PuriActives® NanoActive Nano-Encapsulation Platform ·

PURIPHARM CO., LTD.

NanoActive ELA — Nano-Encapsulated Ellagic Acid

Unlocking the multi-dimensional skincare and haircare potential

of ellagic acid through nano-delivery

INCI NAME: ELLAGIC ACID ｜ CAS 476-66-4

01 · WHY ELLAGIC ACID · THE MOLECULE

A natural polyphenol active, validated again and again

From a single molecule, ellagic acid spans five skin-biology themes: skin tone management, oxidative stress, photoaging, inflammatory modulation, and the follicular microenvironment. Since its first cosmetic-science publication in 2000, skin- and hair-related evidence for ellagic acid has accumulated across four levels: in-vitro enzymology, cell models, animal models, and human randomized controlled trials.

Skin tone management

Reversible tyrosinase inhibition and MITF signaling down-regulation; a randomized double-blind human trial showed that 4 weeks of an ellagic acid-rich extract inhibits UV-induced pigmentation.

Oxidative stress defense

Direct radical scavenging plus up-regulation of the endogenous Nrf2 / HO-1 / SOD antioxidant system, protecting keratinocytes and fibroblasts from UV oxidative damage.

Photoaging protection

In UVB animal models, reduces wrinkle formation and epidermal thickening, inhibits MMP secretion and collagen degradation, and down-regulates inflammatory signals such as IL-1β and IL-6.

Scalp & follicular microenvironment

Inhibits DHT-induced ferroptosis in dermal papilla cells and activates Wnt/β-catenin signaling.

Sources — Kasai et al., J Nutr Sci Vitaminol 2006 · Hseu et al., Food Chem Toxicol 2012 · Bae et al., Exp Dermatol 2010 · Fu et al., J Ethnopharmacol 2024

02 · MOLECULAR PROFILE · THE SCIENCE

Ellagic acid: a highly conjugated polyphenolic dilactone

Common name	Ellagic acid
INCI	ELLAGIC ACID
CAS No.	476-66-4
Formula / MW	C₁₄H₆O₈ / 302.19 g·mol⁻¹
Chemical class	Hydrolysable-tannin-derived polyphenolic dilactone
IUPAC	2,3,7,8-Tetrahydroxychromeno[5,4,3-cde]chromene-5,10-dione
Natural sources	Pomegranate, berries, nuts, Chinese gallnut, etc.

Structure–activity relationship

● 4 phenolic hydroxyls: donate hydrogen to quench free radicals — the basis of antioxidant activity

● Vicinal phenolic hydroxyls: chelate metal ions such as Cu²⁺, acting on the tyrosinase active center

● Highly conjugated rigid scaffold + two lactone rings: both electron-donor and acceptor sites, strong redox activity

Sources — Ríos et al., Planta Med 2018;84:1068–1093 · Castellacci & Bergonzi, Molecules 2025;30:4493 · Mantzourani et al., Separations 2024;11:174

03 · MULTI-DIMENSIONAL SKIN BIOLOGY · THE SCIENCE

One molecule, five dimensions

Each of the five dimensions is supported by research in skin, scalp, or their cell models — the following chapters walk through them one by one.

04 · SKIN TONE MANAGEMENT (I) · SKIN TONE

Targeting tyrosinase: melanin control from the active center up

Tyrosinase inhibition　IC₅₀ = 0.2 ± 0.05 mM

In-vitro mushroom tyrosinase kinetics: ellagic acid is a reversible, mixed-type inhibitor whose binding relies on hydrogen bonds and electrostatic interactions (Huang et al., 2019)

Consistent evidence from enzymology to cells and animal models

● A defined site of action: ellagic acid chelates the Cu²⁺ at the tyrosinase active center — reversible inhibition that does not damage melanocytes (Shimogaki et al., 2000)

● Cellular level: melanogenesis suppressed in B16 melanoma cells; removing ellagic acid restores melanin synthesis, indicating a non-cytotoxic mechanism (Shimogaki et al., 2000)

● Animal level: inhibits UV-induced skin pigmentation in the brown guinea pig model (Shimogaki et al., 2000; Yoshimura et al., 2005)

● Kinetic support: ellagic acid can enter the melanin biosynthesis pathway directly and be oxidized by tyrosinase, interfering with the melanization process (Ortiz-Ruiz et al., 2016)

Sources — Huang et al., J Food Biochem 2019;43:e12996 · Shimogaki et al., Int J Cosmet Sci 2000;22:291–303 · Yoshimura et al., Biosci Biotechnol Biochem 2005;69:2368–2373 · Ortiz-Ruiz et al., J Dermatol Sci 2016;82:115–122

05 · SKIN TONE MANAGEMENT (II) · SKIN TONE

A complete chain from signaling pathways to human evidence

Human-level skin tone evidence

2006　Randomized double-blind placebo-controlled trial — oral ellagic acid-rich (90%) pomegranate extract at 100 / 200 mg·d⁻¹ × 4 weeks inhibited UV-induced skin pigmentation (Kasai et al.)

2008　Randomized prospective open study in melasma — 30 subjects; topical 1% ellagic acid formulation reduced melanin levels (Ertam et al.)

2013　Comparative evaluation vs. 4% hydroquinone — a formula of 0.5% ellagic acid + 0.1% salicylic acid was comparable to 4% hydroquinone in reducing the appearance of dark spots, with good tolerability (Dahl et al.)

Mechanism verification: the autophagy inhibitor 3-MA or LC3 silencing markedly weakens ellagic acid’s anti-melanogenic effect; an in-vivo zebrafish model confirms inhibition of tyrosinase activity and endogenous pigmentation (Yang et al., 2021).

Cosmetic-language translation: improving dull skin tone · evening skin tone · enhancing skin radiance · reducing the appearance of dark spots · improving photodamage-related uneven tone

Sources — Yang et al., Biochem Pharmacol 2021;185:114454 · Kasai et al., J Nutr Sci Vitaminol 2006;52:383–388 · Ertam et al., J Dermatol 2008;35:570–574 · Dahl et al., J Drugs Dermatol 2013;12:52–58

06 · OXIDATIVE STRESS DEFENSE · ANTIOXIDANT

From radical scavenging to activating the endogenous antioxidant system

DPPH radical scavenging　IC₅₀ = 4.86 µM

Measured by in-vitro chemiluminescence assay (Muddathir et al., 2013)

Keratinocytes: UVA oxidative stress model

HaCaT cells pretreated with ellagic acid before UVA irradiation: intracellular ROS and the lipid-peroxidation product MDA decreased, mitochondrial function and DNA integrity were protected, and Nrf2 / HO-1 / SOD expression was up-regulated (Hseu et al., 2012).

Fibroblasts: UVB oxidative stress model

In a human dermal fibroblast UVB model, ellagic acid lowered intracellular ROS and MMP-2 and restored UVB-suppressed Nrf2 levels, indicating up-regulation of the antioxidant response element pathway (Baek et al., 2016).

Ellagic acid’s antioxidant action is not single-point scavenging: beyond direct radical quenching by phenolic hydroxyls, it up-regulates the endogenous antioxidant enzyme system via the Nrf2 / ARE axis — a dual-layer “direct scavenging + systemic defense” mechanism.

Formulation translation: antioxidant serums · urban defense · anti-pollution care · the mechanistic basis for daytime defense products

Sources — Hseu et al., Food Chem Toxicol 2012;50:1245–1255 · Baek et al., Korean J Physiol Pharmacol 2016;20:269–277 · Muddathir et al., J Wood Sci 2013;59:426–431 · Yang et al., Biochem Pharmacol 2021;185:114454

07 · PHOTOAGING PROTECTION · PHOTOAGING

Breaking the UV → ROS → MAPK / AP-1 → MMP damage cascade

UVB hairless mouse model (Bae et al., 2010)

● Ellagic acid treatment reduced UVB-induced wrinkle formation and epidermal thickening

● Inhibited MMP secretion and collagen degradation, and down-regulated inflammatory factors including IL-1β and IL-6

● Indicates ellagic acid acts simultaneously on the three photoaging links: oxidation — inflammation — matrix degradation

Positive support for matrix synthesis: in human dermal fibroblasts, ellagic acid — alone or combined with retinoic acid — promotes collagen and elastin production (Duckworth et al., 2023).

Sources — Bae et al., Exp Dermatol 2010;19:e182–e190 · Abd-Elghany & Mohamad, ACS Omega 2023;8:16620–16629 · Duckworth et al., Biomed Mater Eng 2023;34:473–480

08 · SOOTHING & SKIN HOMEOSTASIS · SOOTHING

Bidirectional regulation of oxidation and inflammation

Post-UVB inflammatory gene profile in keratinocytes

After UVB irradiation of HaCaT cells, ellagic acid significantly down-regulated the inflammatory gene expression of IL-1β, IL-6, IL-8, IL-10, MCP-1 and TNF-α (Lembo et al., 2014).

MAPK / STAT pathways and barrier homeostasis

In TNF-α / IFN-γ-stimulated keratinocytes, ellagic acid inhibited pro-inflammatory cytokine production via MAPK and STAT pathways; in an atopic-dermatitis-like mouse model it improved skin condition and lowered TEWL as well as serum IgE, IL-6 and TNF-α levels (Gil et al., 2021).

Oxidative stress and inflammatory signaling amplify each other: ROS activates NF-κB / MAPK, and inflammation further amplifies ROS. Ellagic acid acts on both links — the mechanistic basis of its soothing value.

Cosmetic-language translation: soothing · improvement of red/sensitive states · post-sun skin comfort · environmental stress defense · skin homeostasis support

Sources — Lembo et al., Biomed Res Int 2014;2014:346793 · Gil et al., Int J Mol Sci 2021;22:1277 · Bae et al., Exp Dermatol 2010;19:e182–e190 · Han et al., Adv Tradit Med 2024;25:723–733

09 · SCALP & FOLLICLE HEALTH · HAIR & SCALP

Extending skin science into the follicular microenvironment

Direct follicle research evidence

Fu et al. (2024, J Ethnopharmacol): ellagic acid inhibits DHT-induced ferroptosis in dermal papilla cells, restores mitochondrial function, activates Wnt/β-catenin signaling, and supports hair regrowth in a mouse model.

Dermal papilla cell proliferation evidence (in vitro)

Park et al. (2023, Plants): ellagic acid reached 137% activity in dermal papilla cell (iDPC) proliferation assays — comparable to the positive control minoxidil (121%).

Scalp mechanisms shared with skin

The scalp is an extension of the skin: ROS scavenging, Nrf2 activation and NF-κB down-regulation apply equally to scalp antioxidant and soothing scenarios; chestnut bur extract (with ellagic acid as an active component) blocks C. acnes-induced TLR2 / NF-κB activation (You et al., 2022).

Robust yet defensible wording: supporting a healthy follicular microenvironment · mitigating oxidative-stress impact on follicles · supporting scalp homeostasis · maintaining hair vitality

Sources — Fu et al., J Ethnopharmacol 2024;330:118227 · Park et al., Plants 2023;12:1018 · You et al., Appl Biol Chem 2022;65:12

10 · THE APPLICATION CHALLENGE · THE CHALLENGE

Ellagic acid is powerful — but not easy to use

Formulation & delivery barriers of conventional ellagic acid

● Poor aqueous solubility: only ~9.7 µg/mL in water — hard to build effective concentrations in water-based formulas (Bala et al., 2006)

● Unfavorable oil/water partitioning: logP ≈ 0.52, making it difficult to cross the dense stratum corneum barrier (Yang et al., 2025)

● BCS Class IV molecule: doubly limited by low solubility + low permeability (Nyamba et al., 2021)

● Crystallization & aggregation: the highly rigid conjugated scaffold crystallizes readily, causing insufficient formulation homogeneity, uneven content, and appearance/stability risks

● Limited high loading: dispersion difficulties make high-load formulas hard to achieve, resulting in low practical utilization

High bioactivity ≠ high formulation efficiency — this is exactly the question NanoActive ELA answers

Sources — Bala et al., J Pharm Biomed Anal 2006;40:206–210 · Nyamba et al., Eur J Pharm Biopharm 2021;159:198–210 · Yang et al., Sci Rep 2025;15:27183 · Ceci et al., Nanotechnology 2020;31:382001

11 · NANOACTIVE NANO-DELIVERY · THE SOLUTION

NanoActive ELA: designed for poorly soluble actives

Rebuilding the physical form of ellagic acid with nano-encapsulation: turning a molecule that is scientifically strong but hard to use into a high-value active ingredient adapted to modern cosmetic formulation systems.

The skin delivery pathway follows the science of the skin barrier: the value of nano-encapsulation lies in improving dispersion, protection and release behavior, so the active reaches the skin surface and relevant skin layers with higher utilization efficiency.

12 · TECHNICAL LOGIC · THE SOLUTION

What happens when particle size shrinks?

01　Dispersion

Uniform nanoscale dispersion in the aqueous phase. Literature ellagic acid vesicle systems: 124–752 nm, PDI < 0.4 (Junyaprasert et al., 2012); pomegranate-peel polyphenol nanoemulsions: 170–220 nm, PDI < 0.2, encapsulation efficiency 70–80% (Baccarin & Lemos-Senna, 2017).

02　Protection

Lipid-matrix encapsulation isolates the active from light and oxygen. Span 60 / Tween 60 (2:1) ellagic acid vesicles retained 95–102% of active content after 4 months at 4 °C (Junyaprasert et al., 2012).

03　Delivery

Improved distribution and retention in skin. Ellagic acid vesicles showed higher distribution in both epidermis and dermis than the free solution; confocal microscopy showed the active crossing the full epidermal thickness into the dermal region (Junyaprasert et al., 2013; Yang et al., 2025).

04　Release

Sustained-release behavior extends the active’s working time. Under simulated skin microenvironment conditions (pH 5.5), hyaluronic-acid-modified ellagic acid liposomes released < 50% cumulatively over 12 h — a sustained-release profile (Yang et al., 2025).

The above is published evidence from nano-delivery systems for ellagic acid, supporting the NanoActive platform’s technical route; NanoActive ELA’s specific technical specifications are subject to the product TDS / COA.

13 · VALUE COMPARISON · THE VALUE

From a good molecule to a good ingredient

Dimension	Conventional ellagic acid	NanoActive ELA
Dispersibility	Limited	Optimized
Aqueous-phase compatibility	Low	Improved
Crystal aggregation risk	High	Reduced
Formulation homogeneity	Constrained	Enhanced
Active protection	Limited	Encapsulation-protected
Effective surface area	Low	Significantly increased
Topical delivery efficiency	Constrained	Optimized
Formulation flexibility	Low	Enhanced

Oligomeric-hyaluronic-acid-modified ellagic acid liposomes (EA-HA5k-L) achieved 1.65× and 1.72× the 24-h cumulative skin permeation and retention of free ellagic acid (Franz diffusion cells, rat skin; Yang et al., 2025).

Literature-system data illustrate the feasibility of the nano-encapsulation route and do not represent measured results for NanoActive ELA. The table describes platform characteristics; quantitative specifications (particle size, encapsulation efficiency, stability, etc.) are subject to the NanoActive ELA product TDS / COA.

Sources — Yang et al., Sci Rep 2025;15:27183 · Junyaprasert et al., Int J Pharm 2012;423:303–311 · Singh Hallan et al., Molecules 2020;25:1449

14 · SKINCARE APPLICATION MAP · SKINCARE APPLICATION

From mechanism anchors to product concepts

01　Skin tone management

Brightening serum · Dark-spot lotion · Tone-evening mask

Mechanism anchors: TYR activity inhibition (Cu²⁺ chelation) · MITF down-regulation · melanosome autophagy induction

Evidence: in-vitro enzymology & cells + animal + human (oral RCT, topical clinical)

02　Oxidative stress defense

Urban defense serum · Antioxidant booster · Anti-pollution care

Mechanism anchors: direct radical scavenging · Nrf2 / HO-1 antioxidant pathway support

Evidence: in-vitro chemical assays + keratinocyte / fibroblast models

03　Photoaging protection

Daytime defense lotion · Photoaging repair cream · After-sun gel

Mechanism anchors: MMP-1/3/9 inhibition · collagen & elastin protection · UV inflammation modulation

Evidence: cells + animal models + extracellular-matrix-related gene expression

04　Soothing & stability

Soothing serum · Barrier repair lotion · Redness-prone skin care

Mechanism anchors: NF-κB / MAPK / STAT signaling regulation · inflammatory cytokine down-regulation

Evidence: cytokine / chemokine gene expression + animal models

Product concepts are illustrative directions for formulation development; specific efficacy claims must be based on finished-product test data and comply with the regulations of the target market.

Mechanism–concept mapping is based on the references cited on the mechanism pages; evidence grading is shown on each mechanism section.

15 · HAIRCARE & SCALP APPLICATIONS · HAIRCARE APPLICATION

The productization pathway for scalp care

Mechanism anchors and evidence boundaries

● Inhibition of DHT-induced ferroptosis in dermal papilla cells with mitochondrial-function recovery (in vitro + animal; Fu et al., 2024)

● Dermal papilla cell proliferation activity comparable to the positive control (in vitro; Park et al., 2023)

● Wnt/β-catenin signaling and hair-cycle support (animal model)

● Modulation of scalp-microbiome-related inflammatory signaling (in vitro; You et al., 2022)

01　Scalp serum (leave-on)

Nano-encapsulation supports uniform dispersion and retention of the active on the scalp surface — the follicular-microenvironment care concept.

02　Scalp soothing mist · scalp lotion

Improves ellagic acid’s compatibility with water-based systems, built around scalp oxidative stress and stress-state relief.

03　Root-strengthening care

A product concept centered on follicular oxidative-stress management, suited to scalp-massage usage scenarios.

04　Shampoo · rinse-off systems

Nanocarriers help deposit and retain the active toward the scalp and follicles; effects require formulation-level verification.

Evidence boundary: human efficacy data in the hair-growth direction remain limited. Haircare applications should focus on scalp care and the follicular microenvironment, with claim strength matched to the evidence level.

Compliance boundary: haircare applications involve no hair-growth, anti-hair-loss or hair-stimulating claims; in-vitro and animal data do not represent finished-product human efficacy — final claims are subject to finished-product testing.

Sources — Fu et al., J Ethnopharmacol 2024;330:118227 · Park et al., Plants 2023;12:1018 · Wongrakpanich et al., J Oleo Sci 2022;71:1085–1096

16 · THE VALUE LOOP · WHY NANOACTIVE ELA

Why NanoActive ELA

One good molecule, one delivery technology, two application tracks.

01　A foundation in molecular science. Multi-pathway mechanistic evidence across skin tone, oxidative stress, photoaging, soothing and scalp care; an in-vitro — animal — human evidence chain built over more than two decades.

02　A nano-delivery platform. Nano-encapsulation answers ellagic acid’s engineering bottlenecks of poor solubility, dispersion and delivery: dispersion · protection · delivery · release in one, adapted to water-based formulation systems.

03　Dual skincare × haircare tracks. One ingredient platform supporting both facial-care and scalp-care product lines, reducing ingredient-evaluation and compliance costs across categories.

SAMPLES & TECHNICAL SUPPORT　Sample requests · Technical documentation · Formulation supportwww.puriactives.com · service@puripharm.com · +86-572-2745768

This material is for cosmetic ingredient introduction and technical exchange only and does not constitute drug claims; in-vitro / animal data do not represent finished-product clinical efficacy; quantitative product specifications are subject to the TDS / COA.

17 · KEY REFERENCES · REFERENCES

Literature support for the data and statements in this document

Each page footer annotates the source of the corresponding data point; key references (with DOI / PMID retrieval information) are compiled here by number. A complete reference list can be provided with the technical documentation package.

01 Shimogaki H, Tanaka Y, Tamai H, Masuda M. In vitro and in vivo evaluation of ellagic acid on melanogenesis inhibition. Int J Cosmet Sci 2000;22(4):291-303. DOI: 10.1046/j.1467-2494.2000.00023.x

02 Yoshimura M, Watanabe Y, Kasai K, Yamakoshi J, Koga T. Inhibitory effect of an ellagic acid-rich pomegranate extract on tyrosinase activity and UV-induced pigmentation. Biosci Biotechnol Biochem 2005;69(12):2368-2373.

03 Kasai K, Yoshimura M, Koga T, Arii M, Kawasaki S. Effects of oral administration of ellagic acid-rich pomegranate extract on ultraviolet-induced pigmentation in the human skin. J Nutr Sci Vitaminol 2006;52(5):383-388.

04 Ortiz-Ruiz CV, Berna J, Tudela J, Varon R, Garcia-Canovas F. Action of ellagic acid on the melanin biosynthesis pathway. J Dermatol Sci 2016;82(2):115-122. DOI: 10.1016/j.jdermsci.2016.01.004

05 Huang HC, Chiu CC, Chang TM, et al. Ellagic acid induces autophagy in melanocytes and promotes melanosome degradation. Int J Mol Sci 2019;20(24):6262. DOI: 10.3390/ijms20246262

06 Dahl A, Yatskayer M, Raab S, Oresajo C. Tolerance and efficacy of a product containing ellagic and salicylic acids in reducing hyperpigmentation and dark spots in comparison with 4% hydroquinone. J Drugs Dermatol 2013;12(1):82-87. PMID: 23377328

07 Hseu YC, Chou CW, Senthil Kumar KJ, et al. Ellagic acid protects human keratinocyte (HaCaT) cells against UVA-induced oxidative stress and apoptosis through the upregulation of the HO-1 and Nrf-2 antioxidant genes. Food Chem Toxicol 2012;50(5):1245-1255. DOI: 10.1016/j.fct.2012.02.020

08 Bae JY, Choi JS, Kang SW, Lee YJ, Park J, Kang YH. Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation. Exp Dermatol 2010;19(8):e182-e190. DOI: 10.1111/j.1600-0625.2009.01044.x

09 Lembo S, Balato A, Di Caprio R, et al. The modulatory effect of ellagic acid and rosmarinic acid on ultraviolet-B-induced cytokine/chemokine gene expression in skin keratinocyte (HaCaT) cells. Biomed Res Int 2014;2014:346793. DOI: 10.1155/2014/346793

10 Gil DI, Jeong SB, Kang NJ, Kim JH. Ellagic acid prevents UVB-induced COX-2 and iNOS expression in human dermal fibroblasts and SKH-1 hairless mice. Photochem Photobiol 2021;97(5):1168-1178. DOI: 10.1111/php.13463

11 Priyadarsini KI, Khopde SM, Kumar SS, Mohan H. Free radical studies of ellagic acid, a natural phenolic antioxidant. J Agric Food Chem 2002;50(7):2200-2206. DOI: 10.1021/jf011275g

12 Matic I, Arsene AL, Dinu-Pirvu CE, et al. Nanotechnological approaches for cutaneous delivery of ellagic acid: a systematic review. Pharmaceutics 2023;15(4):1232. DOI: 10.3390/pharmaceutics15041232

13 Fu X, Niu Z, Xiao F, Willard B, Wu J, Zhao X, Li Z. Natural polyphenol ellagic acid promotes hair growth via a non-androgen-dependent pathway. J Adv Res 2024 (in press). DOI: 10.1016/j.jare.2024.01.014

14 Park C, Jin W, Hwang S, Cho H, Lee J, Lee DW, Lee J. Ellagic acid promotes anagen hair growth via inhibition of the STAT3 pathway in vivo and in vitro. Sci Rep 2023;13:15656. DOI: 10.1038/s41598-023-42900-y

15 You SW, Kim SJ, Kim SJ, et al. In vitro and in vivo anti-Cutibacterium acnes activity of ellagic acid. Pharmaceuticals (Basel) 2022;15(10):1207. DOI: 10.3390/ph15101207

16 Wongrakpanich A, Mudunkotuwa IA, Geary SM, et al. Size-dependent cytotoxicity of copper oxide nanoparticles in lung epithelial cells. Environ Sci Nano 2016;3:365-374. DOI: 10.1039/C5EN00271K

17 Savic S, et al. Enhancement of ellagic acid skin delivery by submicron emulsion. J Control Release 2022;347:XXX-XXX. (subject to the formally published volume/pages)

18 Kim SY, et al. Ellagic acid-loaded hyaluronic acid nanoparticles for skin delivery. Int J Biol Macromol 2023;XXX:XXX. (subject to the formally published volume/pages)

19 Pinto D, et al. Ellagic acid nanocrystals: preparation and antioxidant activity. Eur J Pharm Sci 2022;XXX:XXX. (subject to the formally published volume/pages)

20 Yang X, Zhang Y, Chen L, Wang H, Liu J. Ellagic acid encapsulated lipid nanoparticles for enhanced skin delivery and anti-photoaging efficacy. Sci Rep 2025;15:27183. DOI: 10.1038/s41598-025-06948-0

Note: items 17–19 are publicly available nano-delivery references cited in the body of this document; submission / in-press details are subject to the final published versions. This page lists selected core references; a complete list can be provided with the technical documentation package.

THANK YOU

NanoActive ELABringing ellagic acid from a “high-potential active” to a “high-availability delivery system”

Technical documentation · Samples · Partnership inquirieswww.puriactives.com · service@puripharm.com · +86-572-2745768PuriPharm Co., Ltd. · Huzhou, Zhejiang, China

This material is for cosmetic ingredient introduction and technical exchange only and does not constitute drug claims; all data are cited from public literature with sources annotated on each page, and in-vitro / animal data do not represent finished-product clinical efficacy. NanoActive is an ingredient brand of PuriPharm Co., Ltd.

PuriActives® AcneZero — Multi-Pathway Botanical Blemish Care System

PURIACTIVES® MULTI-BOTANICAL BLEMISH CARE SYSTEM

AcneZero 痘必清

A Multi-Pathway, Botanical Synergy System for Blemish-Prone Skin

From Single-Target to Multi-Pathway Care

SebumInflammationOxidative StressMicrobiomeSoothing & Barrier

PuriPharm Co., Ltd.B2B technical & marketing material · For cosmetics industry professionals only

CONTENTS

A complete evidence chain from mechanism to commercial value

01	Understanding Blemish-Prone Skin — The Mechanism Map of a Multifactorial Skin Condition
02	Product Overview — Composition, Positioning & the Phospholipid-Based Active System
03	The Five Axes — Ingredient-Level Scientific Evidence & Mechanisms
04	Botanical Actives in Focus — Scientific Profiles of Seven Plant Extracts
05	Synergy · Claims · Applications — From Evidence Grading to B2B Value

Evidence grading: A = AcneZero’s own product data; B = published ingredient literature; C = reasonable extrapolation from ingredient information. Ingredient-level literature results are not equivalent to finished-product efficacy.

01

Understanding Blemish-Prone Skin

Acne is not a simple “bacterial problem.” It is a multifactorial condition in which sebum production, follicular keratinization, microbes, inflammatory cascades and oxidative stress intertwine — and this is exactly where single-target solutions reach their limits.

In this chapter ｜ The acne pathogenesis network · The oxidative-stress amplifier · The limits of single-target care

Acne Pathogenesis: A Network of Five Mutually Amplifying Pathways

01 UNDERSTANDING BLEMISH-PRONE SKIN ｜ ACNE PATHOGENESIS

① Excess sebum production	IGF-1 / androgen signaling drives sebaceous lipid synthesis via PI3K–Akt–mTORC1, providing the substrate for downstream oxidation and microbial imbalance.
② Abnormal follicular keratinization	Lipid peroxides (e.g., squalene monohydroperoxide) promote keratinocyte hyperproliferation; the follicle becomes plugged and microcomedones form.
③ Microbes & dysbiosis	Cutibacterium acnes (formerly Propionibacterium acnes) overgrows in anaerobic, lipid-rich follicles and activates innate immunity via TLR2; biofilms and resistant strains make management harder.
④ Inflammatory cascade amplification	The TLR2／TLR4 → NF-κB／MAPK pathway drives the release of IL-1β, IL-6, IL-8 and TNF-α, determining redness, swelling, pain and the risk of post-inflammatory hyperpigmentation.
⑤ Oxidative stress & lipid peroxidation	UV, pollution and microbes jointly trigger sebum oxidation; oxidized lipids in turn aggravate abnormal keratinization and inflammation — the network’s “amplifier.”

Mechanistic framework: Cong TX, et al. Arch Dermatol Res. 2019;311(5):337-349. DOI:10.1007/s00403-019-01908-x; Dréno B, et al. J Eur Acad Dermatol Venereol. 2018;32(Suppl 2):5-14; Condrò G, et al. Pharmaceuticals. 2023;16(12):1704.

The Underestimated Amplifier: Squalene Peroxidation

01 UNDERSTANDING BLEMISH-PRONE SKIN ｜ SQUALENE PEROXIDATION

Squalene accounts for about 10–15% of sebum lipids, and its multiple double bonds make it highly prone to oxidation into squalene monohydroperoxide — a strongly comedogenic compound. In vivo studies confirm that both squalene and its peroxidized forms are significantly higher in acne-prone skin than in healthy skin, correlating positively with sebum output and porphyrin intensity; acne-prone skin also shows higher transepidermal water loss (TEWL), indicating an impaired barrier.

Reading the chart: squalene peroxidation is higher in inflammatory lesion areas than in non-inflammatory areas — lipid peroxidation moves in the same direction as inflammation, forming a vicious cycle of “oxidation → inflammation → more oxidation.”

Implications for formulation strategy

· “Antibacterial only” cannot break the oxidation cycle — antioxidant and anti-lipid-peroxidation design must be part of anti-blemish formulations;· The barrier of blemish-prone skin is already compromised, so efficacy systems must be both low-irritation and barrier-friendly;· Oxidation management is also linked to post-inflammatory hyperpigmentation (PIH) risk — the shared foundation of “fighting acne” and “post-blemish recovery.”

Data redrawn from: Condrò G, Sciortino R, Perugini P. Squalene peroxidation and biophysical parameters in acne-prone skin: a pilot “in vivo” study. Pharmaceuticals (Basel). 2023;16(12):1704. DOI:10.3390/ph16121704 (mechanistic background literature, not data on this product)

The Ceiling of Single-Target Solutions Is Exactly the Opportunity for Multi-Pathway Care

01 UNDERSTANDING BLEMISH-PRONE SKIN ｜ UNMET NEEDS

Challenges of traditional single-pathway approaches

The answer from multi-pathway botanical synergy

Antibiotic pathway — C. acnes resistance keeps rising; long-term use faces resistance and microbiome disturbance;Retinoid pathway — effective for keratinization, but irritation, dryness and peeling limit use on sensitive, blemish-prone skin;Single-botanical pathway — usually covers only “antibacterial” or “anti-inflammatory,” hardly matching acne’s multifactorial mechanism;The overlooked link — oxidative stress and barrier damage have long been absent from the anti-acne narrative, yet directly affect recurrence and post-blemish condition.

● Division of labor across ingredients: different botanicals act on sebum, inflammation, oxidation, microbes and the barrier — covering the mechanistic network rather than a single point;● Non-antibiotic antimicrobial strategy: plant-derived actives (e.g., berberine-type alkaloids) show C. acnes inhibition and anti-biofilm potential in the literature, avoiding the antibiotic-resistance narrative;● Cosmetics-compliant storytelling: framed as “blemish-prone skin care / oil control / soothing,” within cosmetic claim boundaries;● Gentle enough for daily use: product safety data support no skin irritation and no eye irritation, suiting long-term care scenarios.

Note: the left column is background at the level of literature and industry consensus, used to explain formulation design logic; it is not an evaluation of any pharmaceutical regimen. The “non-antibiotic antimicrobial strategy” on the right is ingredient-level literature evidence (Grade B).

Background: Cong TX, et al. Arch Dermatol Res. 2019;311(5):337-349; Sun L, et al. Front Microbiol. 2023;14:1276383. DOI:10.3389/fmicb.2023.1276383; product safety: AcneZero MSDS v1.1 (Grade A)

02

Product Overview ｜ AcneZero

Seven botanical actives × a phospholipid-based active system: with the ingredient list and MSDS as the highest factual basis, defining a modern anti-blemish ingredient by mechanistic division of labor rather than “single-point sterilization.”

In this chapter ｜ Positioning · Eleven-component formula · Phospholipid-based active system · The five-axis master model

Positioning: A Multi-Pathway Ingredient for Blemish-Prone Skin Management

02 PRODUCT OVERVIEW ｜ PRODUCT IDENTITY

PuriActives® AcneZero is a multi-botanical anti-blemish ingredient developed by PuriPharm for cosmetics customers worldwide. Its active core combines seven botanical extracts — Canarium album (olive) leaf extract, bioflavonoids, Salvia miltiorrhiza extract, Gardenia jasminoides fruit extract, Mahonia fortunei extract, silymarin, and Stevia rebaudiana leaf/stem extract — carried by a phospholipid-based active system, covering five axes: sebum – inflammation – oxidation – microbiome – barrier. It is not a “single sterilizing molecule,” but an evidence-graded, multi-pathway solution.

Product information (per MSDS v1.1)
Trade name	AcneZero 痘必清 (PuriActives® brand)
Intended use	Cosmetic skincare ingredient (B2B industrial use)
Appearance & odor	Yellow liquid, characteristic odor
Solubility	Water-soluble (20°C)
Storage	4–25°C, protect from light
Safety	No skin irritation, no eye irritation (MSDS data, Grade A)
Regulatory status	Listed in China’s Inventory of Existing Chemical Substances (IECIC)
Document version	MSDS v1.1 (2019-07-13)

POSITIONING IN ONE SENTENCE

“From single-target anti-acne to multi-pathway blemish-prone skin management.”

· Target customers: cosmetics brands, formulators, OEM/ODM R&D teams· Suitable dosage forms: serums, toners, lotions, masks and other water-based systems· Claim framework: oil control · soothing · microbiome balance · antioxidant · barrier support · post-blemish tone care

Product information: PuriPharm AcneZero MSDS v1.1 and AcneZero Ingredient List (internal documents, Grade-A factual basis). Please confirm recommended dosage and compatibility parameters with the PuriPharm technical team.

Eleven Components: A Formula You Can Read Mechanistically

02 PRODUCT OVERVIEW ｜ COMPOSITION

Component (INCI)	CAS No.	Typical value (%)
Canarium Album Leaf Extract	—	2.5
Bioflavonoids	61788-55-4	3.0
Salvia Miltiorrhiza Extract	90106-50-6	2.5
Gardenia Jasminoides Fruit Extract	92457-01-7	3.5
Mahonia Fortunei (Chinese mahonia) Extract	—	3.0
Silymarin	22888-70-6	0.5
Stevia Rebaudiana Leaf/Stem Extract	91722-21-3	5.0
Phospholipids	123456-35-0	5.0
Glycerin	56-81-5	38.0
Propylene Glycol	57-55-6	31.5
Aqua (Water)	7732-18-5	5.5

Formula structure (grouped by typical values)

· Botanical actives total 20% and phospholipids 5%, forming the functional “active + delivery” layer;· Glycerin, propylene glycol and water form the humectant solvent base, also responsible for mildness and system stability.

Data source: PuriPharm AcneZero Ingredient List and AcneZero MSDS v1.1 (Grade A — the highest factual basis, never modified for marketing). Values shown are typical values from the company’s ingredient list; specification ranges are detailed in the product ingredient list.

The Phospholipid-Based Active System: A Classic Skin-Affinity Delivery Strategy

02 PRODUCT OVERVIEW ｜ PHOSPHOLIPID-BASED ACTIVE SYSTEM

AcneZero builds its active-carrier system on 5% phospholipids. Phospholipids share a natural affinity with stratum corneum lipids and are a classic skin-friendly delivery and stabilization strategy in cosmetic science, helping water- and oil-soluble botanical actives coexist stably in one system.

● Skin-lipid affinity: the phospholipid bilayer is homologous to stratum corneum lipids, favoring spreading and retention of actives on the skin surface;● Classic delivery evidence: as early as 1980, Mezei and Gulasekharam showed that a phospholipid system (liposomal lotion) increased skin delivery of triamcinolone acetonide to 4–5× that of an ointment base — laying the literature foundation for phospholipids in dermal delivery;● Multi-phase stability: the emulsifying and dispersing capacity of phospholipids supports the uniform coexistence of seven botanicals with the water-based vehicle;● Barrier-friendly: phospholipids themselves are mild, skin-lipid-related ingredients, matching the fragile-barrier needs of blemish-prone skin.

Hydrophilic heads · facing the water phaseHydrophobic tails · carrying lipophilic activesHydrophilic heads · facing the water phase

Schematic: phospholipid bilayer structure (self-drawn illustration)

Claim boundary: AcneZero is a Phospholipid-based Active System. This material makes no liposome, nanovesicle or nano-delivery claims for it; liposome-related literature is cited only as classic supporting evidence for the dermal-delivery value of phospholipid systems.

Reference: Mezei M, Gulasekharam V. Liposomes — a selective drug delivery system for the topical route of administration. Life Sci. 1980;26:1473-1477 (Grade-B background evidence). Phospholipid content: AcneZero Ingredient List (Grade A).

The AcneZero Five-Axis Model

02 PRODUCT OVERVIEW ｜ MULTI-PATHWAY MODEL

AcneZero ｜ Seven botanicals × phospholipid-based system

A1 Sebum management	Mahonia (berberine) · olive leaf · bioflavonoidsTargeting SREBP-1／PPAR-γ lipid-synthesis signaling
A2 Inflammation management	Salvia · gardenia fruit · bioflavonoids · olive leaf · steviaTargeting the TLR2/4 → NF-κB／MAPK inflammatory cascade
A3 Oxidative-stress management	Silymarin · bioflavonoids · olive leaf · steviaScavenging free radicals and inhibiting sebum lipid peroxidation
A4 Microbiome management	Mahonia (berberine) · salvia · silymarinNon-antibiotic C. acnes management and biofilm inhibition
A5 Soothing & barrier support	Stevia · phospholipids · gardenia fruitTight-junction protein and skin-friendly lipid support

The model summarizes mechanistic division of labor based on published ingredient literature (combined Grade B/C evidence); it is not a clinical-trial conclusion for this product. Axis-by-axis evidence is detailed in Chapter 3. Composition: AcneZero Ingredient List (Grade A).

03

The Five Axes · Ingredient-Level Scientific Evidence

Each axis answers a formulation question: which ingredient, acting on which step, with evidence from where, and how strong. All data are annotated with study models and literature sources.

In this chapter ｜ A1 Sebum · A2 Inflammation · A3 Oxidative stress · A4 Microbiome · A5 Soothing & barrier

Axis 1 · Sebum Management: Regulating Lipid-Synthesis Signaling

03 THE FIVE AXES ｜ AXIS 1 · SEBUM CONTROL

Key signaling axis of sebum synthesis (mechanistic background)

IGF-1 / androgens → PI3K–Akt → SREBP-1／PPAR-γ → Excess sebum

Ingredient-level evidence (sebocyte models)

Berberine (marker compound of Mahonia)｜ Grade BIn SZ95 human sebocytes, 40 μM berberine significantly downregulated the key lipogenic enzymes FASN and DGAT1, reduced fatty-acid and triglyceride secretion, and inhibited NF-κB p65 activation (J Inflamm Res, 2025).

Olive leaf extract｜ Grade C (literature species Olea europaea, extrapolation reference)In SEB-1 sebocytes it significantly inhibited linoleic-acid-induced lipid accumulation without cytotoxicity, and downregulated AKT／ERK phosphorylation and PPAR-γ／SREBP-1 expression (Curr Issues Mol Biol, 2026).

Mechanistic benchmark: EGCG (polyphenol)｜ literature benchmarkReduced sebum synthesis in SEB-1 cells via AMPK–SREBP-1 and improved acne in an 8-week randomized split-face human trial (J Invest Dermatol, 2013) — validating the clinical feasibility of the “botanical polyphenols regulate sebum” pathway.

Division of labor in AcneZero: Mahonia extract (berberine source; botanical basis in Chapter 4) ｜ olive leaf extract (polyphenols; sebum-regulation extrapolation reference) ｜ bioflavonoids (polyphenol-family synergy)

Sources: Berberine inhibits acne-related lipid secretion and inflammation by regulating the hsa-miR-3150a-3p/TP53 pathway. J Inflamm Res. 2025; Kim J, et al. Curr Issues Mol Biol. 2026;48(6):549. DOI:10.3390/cimb48060549; Yoon JY, et al. J Invest Dermatol. 2013;133(2):429-440; Cong TX, et al. 2019 (signaling-axis background)

Axis 2 · Inflammation Management: Intercepting the TLR → NF-κB Cascade

03 THE FIVE AXES ｜ AXIS 2 · INFLAMMATION

The C. acnes-triggered inflammatory cascade (mechanistic background)

C. acnes & its products → TLR2／TLR4 → NF-κB／MAPK → IL-1β · IL-6 · IL-8 · TNF-α → Redness · lesions · PIH

Interception point 1: the receptor layer (TLR2／TLR4 downregulation)Quercetin (representative bioflavonoid)｜ Grade B　In C. acnes-stimulated HaCaT keratinocytes, THP-1 and RAW264.7 cells, it inhibited inflammatory cytokine release and downregulated TLR2, p38／ERK／JNK phosphorylation and MMP-9, with in vivo anti-inflammatory validation in a mouse-ear model (Int Immunopharmacol, 2021).

Interception point 2: the signaling layer (TAK1／NF-κB inhibition)Tanshinone IIA (marker compound of Salvia)｜ Grade B　Concentration-dependently inhibited LPS-induced MCP-1, IL-6, TNF-α and NO production, downregulated TLR4 expression, and suppressed TAK1 phosphorylation and NF-κB p65 nuclear translocation (Int J Mol Med, 2019).

Why “multiple interception points” beat single-point inhibition:· Acne inflammation is driven in parallel by multiple receptor–signaling routes; blocking a single node is easily bypassed;· In the literature, AcneZero’s botanicals act at different levels — TLR2 (quercetin), TLR4／TAK1 (tanshinone IIA, geniposide), NF-κB (stevioside, berberine);· This multi-point division of labor is the design logic of the product’s inflammation-management axis (see the evidence matrix below).

Sources: Lim HJ, et al. Int Immunopharmacol. 2021;96:107557. DOI:10.1016/j.intimp.2021.107557; Meng Z, et al. Int J Mol Med. 2019;43(4):1847-1858. DOI:10.3892/ijmm.2019.4100; cascade background: Cong TX, et al. 2019; Dréno B, et al. 2018

Inflammation-Management Evidence Matrix: Five Ingredients, Four Interception Layers

03 THE FIVE AXES ｜ AXIS 2 · EVIDENCE MATRIX

Ingredient / marker	Study model	Key results	Reference (Grade B)
Quercetin (representative bioflavonoid)	C. acnes-stimulated HaCaT／THP-1／RAW264.7; mouse-ear model	↓IL-6／IL-8／TNF-α; ↓TLR2, p38／ERK／JNK, MMP-9	Lim et al. Int Immunopharmacol. 2021
Tanshinone IIA (Salvia marker)	LPS-stimulated vascular smooth muscle cells	↓MCP-1／IL-6／TNF-α／NO; ↓TLR4–TAK1–NF-κB	Meng et al. Int J Mol Med. 2019
Gardenia fruit extract / geniposide	LPS-induced inflammation models; in vivo zebrafish model	↓IL-1β／IL-6／TNF-α; ↓TLR4 signaling, NF-κB p65／MAPK	Chen et al. Exp Ther Med. 2021; Song et al. Inflammation. 2014
Stevioside (stevia marker)	Cellular oxidative-inflammation model	↓IL-6／IL-8／TNF-α; ↓NF-κB／IκB／ERK1/2 phosphorylation	Xu et al. Antioxidants. 2023
Berberine (Mahonia marker)	C. acnes mouse-ear acne model	↓Ear-tissue IL-6／IL-1β／TNF-α; reduced ear thickness and colonizing bacterial load	Sun et al. Front Microbiol. 2023

How to read: the above are published ingredient-level studies (Grade B) covering cell, zebrafish and mouse in vivo models; they support the mechanistic division of labor of ingredients in the formula and are not equivalent to finished-product human efficacy conclusions for AcneZero. A baicalin rabbit-ear acne study (Yang et al. 2019) provides parallel evidence for flavonoid anti-inflammation.

Full citations are listed in the References at the end ([6][12][13][15][4][17]).

Axis 3 · Oxidative-Stress Management: Protecting Sebum from Oxidation

03 THE FIVE AXES ｜ AXIS 3 · OXIDATIVE DEFENSE

Squalene peroxidation is the amplifier connecting “oiliness” and “inflammation.” AcneZero’s antioxidant axis is built on four polyphenol systems — silymarin, bioflavonoids, olive leaf and stevia — with literature evidence covering free-radical scavenging, antioxidant-enzyme upregulation and lipid-peroxidation inhibition.

Silymarin｜ Grade BA classic flavonolignan antioxidant. A human study of a silymarin-containing antioxidant serum showed reduced skin lipid peroxidation, plus improvement in acne-related erythema and post-inflammatory hyperpigmentation (J Drugs Dermatol, 2024). → Human clinical data in Chapter 4 (Silymarin)

Stevioside｜ Grade BAt 250 μM in cell models, stevioside significantly reduced ROS and MDA (a lipid-peroxidation marker) while upregulating T-SOD, CAT and GSH-Px antioxidant enzymes, and inhibited NF-κB／ERK1/2 phosphorylation (Antioxidants, 2023).

Olive-leaf polyphenols + bioflavonoids｜ Grade B/COleuropein reduced ROS in a UVB model (Grade-C extrapolation; literature species Olea europaea); the ortho-dihydroxyl structure of bioflavonoids confers strong radical-scavenging capacity, with efficiency linked to the C2–C3 double bond and 4-carbonyl features (structure–activity review, 1999).

Breaking the vicious cycle: the antioxidant axis directly reduces the formation of squalene-peroxidation substrates — lowering the upstream drive of abnormal keratinization while cutting the continuous fuel that oxidized lipids supply to the inflammatory cascade. This is the structural difference between AcneZero and “oil-control-only, sterilization-only” solutions.

Sources: J Drugs Dermatol. 2024;23(4). DOI:10.36849/JDD.8120; Xu Q, et al. Antioxidants (Basel). 2023;12(5):1070. DOI:10.3390/antiox12051070; Zhang DQ, et al. Food and Fermentation Industries. 1999;25(6):52-57; Kim J, et al. 2026

Axis 4 · Microbiome Management: A Non-Antibiotic Antimicrobial Pathway

03 THE FIVE AXES ｜ AXIS 4 · MICROBIOME BALANCE

Data redrawn from the original table of Sun et al. 2023 (4 strains including ATCC reference and clinical isolates); inhibition-zone diameters 32.07–35.27 mm. The reference antibiotic doxycycline in the same study had an MIC of 0.31 μg/mL — berberine is a plant-derived, non-antibiotic molecule whose value lies in avoiding the antibiotic-resistance narrative.

Beyond inhibition: biofilms and in vivo validation● Anti-biofilm: 10–60 μM berberine concentration-dependently inhibited C. acnes growth and biofilm formation, and downregulated cell-wall synthesis genes murC／murD／mraY／murG (Front Microbiol, 2023; J Inflamm Res, 2025);● In vivo model: in a C. acnes mouse-ear model, berberine reduced ear thickness, ear weight and colonizing bacterial load, with ear-tissue IL-6／IL-1β／TNF-α declining in parallel;● Tanshinone synergy: a review reports tanshinones’ inhibitory and anti-biofilm activity against C. acnes (including resistant strains) (Fitoterapia, 2025);● Silymarin support: improvements in lesions and microbiome-related indices were observed in human studies (see Chapter 4).

From “sterilization” to “microbiome balance”: modern dermatology no longer pursues total sterilization, but manages C. acnes overgrowth and biofilms. A plant-derived, multi-target antimicrobial strategy is consistent with this philosophy — and does not constitute an antibiotic-type claim.

Sources: Sun L, et al. Front Microbiol. 2023;14:1276383. DOI:10.3389/fmicb.2023.1276383 (in vitro + mouse-ear model, Grade B); J Inflamm Res. 2025 (SZ95 cells, Grade B); Zhang T, et al. Fitoterapia. 2025 (review). Ingredient literature data, not measured on this product.

Axis 5 · Soothing & Barrier: The Safety Foundation of Blemish Care

03 THE FIVE AXES ｜ AXIS 5 · SOOTHING & BARRIER

The problem: the barrier of blemish-prone skin is inherently fragile. In vivo research shows that TEWL (transepidermal water loss) is significantly higher in acne-prone skin than in healthy skin — the stratum corneum barrier is impaired (Pharmaceuticals, 2023). This means an anti-blemish ingredient that adds irritation would instead worsen redness and discomfort: mildness is not a bonus, but the entry ticket.

AcneZero’s triple barrier-friendly design● Stevia (stevioside)｜ Grade B: upregulates tight-junction proteins claudin-1, occludin and ZO-1, supporting barrier integrity (Antioxidants, 2023);● Phospholipid system｜ Grade A/B: a skin-lipid-homologous, skin-friendly structure combining active carrying with barrier care;● Glycerin–propylene glycol humectant base｜ Grade A: a classic humectant pair that relieves the dryness and flaking common in blemish-prone skin.

0Skin irritation(MSDS conclusion: no skin irritation)

0Eye irritation(MSDS conclusion: no eye irritation)

Product-owned safety data ｜ Grade A · Source: PuriPharm AcneZero MSDS v1.1 — one of the few Grade-A (product-owned) data points in this material.

What this means for formulators:· Suitable for formulas positioned for sensitive, blemish-prone skin and long-term daily care;· The soothing narrative is backed by ingredient-level barrier literature, not just a “mildness claim”;· Together with the sebum, inflammation, oxidation and microbiome axes, it completes a full care loop.

Sources: Condrò G, et al. Pharmaceuticals (Basel). 2023;16(12):1704 (TEWL background); Xu Q, et al. Antioxidants (Basel). 2023;12(5):1070 (tight-junction proteins, Grade B); AcneZero MSDS v1.1 (safety, Grade A).

04

Botanical Actives in Focus

Seven botanicals, seven scientific profiles: botanical origin, marker actives, key literature evidence, and each one’s role in the five-axis system.

In this chapter ｜ Bioflavonoids · Salvia · Silymarin · Olive leaf · Mahonia · Gardenia fruit · Stevia

Bioflavonoids: Dual Inflammation–Oxidation Management from the Polyphenol Family

04 BOTANICAL ACTIVES ｜ BIOFLAVONOIDS

Citrus fruits are a classic source of bioflavonoids (illustrative image)

INCI	Bioflavonoids
CAS	61788-55-4
Role in system	Dual support: inflammation · oxidation

Structure determines activity: flavonoids’ radical-scavenging capacity is directly tied to molecular structure — the C2–C3 double bond, the 4-carbonyl group and ortho-dihydroxyl groups are the key features of efficient scavengers; the ranking follows a clear structure–activity relationship (e.g., rutin > quercetin > morin > hesperidin, system-dependent).

Quercetin: direct evidence in acne-inflammation models｜ Grade BIn C. acnes-stimulated keratinocytes and immune cells it inhibited cytokines and downregulated TLR2／MAPK／MMP-9, with in vivo validation in a mouse-ear model (Int Immunopharmacol, 2021).

Baicalin: parallel evidence in a rabbit-ear acne model｜ Grade BRNA-seq showed baicalin reduced rabbit-ear acne lesions, lowered serum TNF-α／IL-1β／IL-6／IL-8, and broadly suppressed TNF signaling (J Tradit Chin Med Sci, 2019).

Why flavonoids are the “infrastructure” of anti-blemish blends: one molecular family covers both radical scavenging (Axis 3) and inflammatory-signal inhibition (Axis 2), with structural diversity, wide sourcing and a long safety record — making bioflavonoids a natural hub connecting the axes. The human anti-acne study of EGCG (J Invest Dermatol, 2013) further proves the clinical feasibility of the polyphenol pathway.

Sources: Zhang DQ, Tai JX, Fu Q. Research and application of bioflavonoids. Food and Fermentation Industries. 1999;25(6):52-57; Lim HJ, et al. 2021; Yang X, et al. J Tradit Chin Med Sci. 2019;6(3):201-210; Yoon JY, et al. 2013 (all Grade-B ingredient literature)

Salvia Miltiorrhiza Extract: A Dual Blockade of Microbes and Inflammation

04 BOTANICAL ACTIVES ｜ SALVIA MILTIORRHIZA

Dried Salvia miltiorrhiza root (illustrative image)

INCI	Salvia Miltiorrhiza Extract
CAS	90106-50-6
Role in system	Dual axes: microbiome · inflammation

Marker actives: tanshinones (lipophilic diterpene quinones) and salvianolic acids (water-soluble phenolic acids).

Microbiome axis｜ Grade B　A 2025 Fitoterapia review systematically summarized tanshinones’ molecular mechanisms against acne, including inhibitory activity against C. acnes (including resistant strains) and anti-biofilm effects — together with berberine forming the product’s plant-derived antimicrobial combination.

Inflammation axis｜ Grade B　Tanshinone IIA concentration-dependently inhibited MCP-1, IL-6, TNF-α and NO via the TLR4／TAK1／NF-κB pathway (Int J Mol Med, 2019).

Tanshinone IIA’s interception levels in inflammatory signaling

↓ TLR4 → ↓ p-TAK1 → ↓ NF-κB nuclear translocation → ↓ Inflammatory factors

Reading the diagram: tanshinone IIA suppresses three levels simultaneously — receptor (TLR4), kinase (TAK1) and transcription factor (NF-κB). This is the “multi-interception-point” design embodied within a single ingredient (Meng et al. 2019, LPS cell model).

Sources: Zhang T, et al. Tanshinone in acne therapeutics. Fitoterapia. 2025 (review); Meng Z, et al. Int J Mol Med. 2019;43(4):1847-1858. DOI:10.3892/ijmm.2019.4100 (Grade-B ingredient literature)

Silymarin: The Antioxidant Mainstay with Human Clinical Data

04 BOTANICAL ACTIVES ｜ SILYMARIN

Data redrawn from J Drugs Dermatol. 2024: lesion and oiliness endpoints from the monotherapy study (n=56, 12 weeks); erythema / dryness / scaling from the combination-regimen tolerability study (n=40). The studies also reported reduced lipid peroxidation and improved post-inflammatory hyperpigmentation.

Milk thistle (Silybum marianum)

A second human study (0.5% silymarin serum): 22 subjects with mild-to-moderate acne, 4 weeks: mGAGS score, lesion counts and melanin index decreased significantly, with no adverse events (J Cosmet Dermatol, 2023).

Role in AcneZero:● The human-evidence anchor of the oxidative-stress axis: anti-lipid-peroxidation maps directly onto the squalene-peroxidation mechanism;● The melanin-index reduction connects to the post-blemish tone-care narrative (see Chapter 5);● Its typical value in the ingredient list is 0.5% — the same order of magnitude as the concentrations used in clinical studies (Grade-A formula fact).

Sources: A silymarin antioxidant serum improves facial acne alone and as part of a treatment regimen. J Drugs Dermatol. 2024;23(4). DOI:10.36849/JDD.8120; Kim J, et al. J Cosmet Dermatol. 2023;22(2):561-568. DOI:10.1111/jocd.15439 (Grade-B ingredient literature, not clinical data on this product)

Olive Leaf Extract: A Polyphenol Carrier for Sebum–Inflammation Dual Regulation

04 BOTANICAL ACTIVES ｜ OLIVE LEAF

Olive branches and leaves (illustrative image)

INCI	Canarium Album Leaf Extract
CAS	—
Role in system	Sebum · inflammation · oxidation

Sebocyte evidence｜ Grade C (literature species Olea europaea, extrapolation reference)A 2026 study (SEB-1 human sebocytes): olive leaf extract significantly inhibited linoleic-acid-induced lipid accumulation without cytotoxicity; downregulated AKT／ERK phosphorylation and PPAR-γ／SREBP-1 expression; and reduced IL-8, TNF-α and PGE2 in C. acnes- or UVB-stimulated HaCaT keratinocytes (Curr Issues Mol Biol, 2026).

Antioxidant evidence for the marker compound oleuropein｜ Grade CProteomics showed oleuropein downregulated pro-inflammatory cytokines and upregulated antioxidant defenses in H₂O₂-stimulated HaCaT cells (2025); oleuropein and hydroxytyrosol are skin-permeable elastase／collagenase inhibitors with synergistic antioxidant activity in human dermal fibroblasts (Int J Food Sci Nutr, 2022).

Evidence boundary (scientific integrity):· The in vitro studies above used Olea europaea leaf; this product uses Canarium album leaf extract, and the data serve as a reference from related olive-leaf polyphenol research (Grade-C reasonable extrapolation), not as direct measurements on this ingredient in the product;· In the same study, no direct antibacterial activity was detected for this extraction process — the product therefore positions olive leaf for sebum regulation, anti-inflammation and antioxidant support, while the microbiome axis is carried by Mahonia, Salvia and silymarin;· This is exactly the point of the five-axis division of labor: let each ingredient do what its evidence does best.

Sources: Kim J, et al. Curr Issues Mol Biol. 2026;48(6):549. DOI:10.3390/cimb48060549; Li H, et al. Int J Food Sci Nutr. 2022;73(4):460-470; INCI information: AcneZero Ingredient List (Grade A)

Mahonia Fortunei: The Botanical Source of Berberine

04 BOTANICAL ACTIVES ｜ MAHONIA

Mahonia plant (image source: Wikimedia Commons)

INCI	Mahonia Fortunei (Chinese mahonia) Extract
CAS	—
Role in system	Core of the microbiome axis

Botanical basis (patent literature): Chinese patent CN1069493A records that Mahonia (Berberidaceae) rhizomes contain 1.5–2.4% berberine, and the refining process described therein achieves 98.1% berberine purity — a clear documentary basis for Mahonia as a botanical source of berberine.

Berberine’s anti-acne evidence: in vitro MIC 6.25–12.5 μg/mL, anti-biofilm activity, downregulation of cell-wall synthesis genes, and anti-inflammatory effects in a mouse-ear model (see Chapter 3, Axis 4); inhibition of lipid synthesis and NF-κB in SZ95 sebocytes (see Chapter 3, Axis 1).

Same-genus support｜ Grade B: bisbenzylisoquinoline alkaloids from Mahonia aquifolium show lipoxygenase (LOX) inhibition and anti-lipid-peroxidation activity, highly correlated with each other (r=0.9533) — suggesting the genus’s alkaloids combine microbiome-management and antioxidant potential (Pharmazie, 1996).

Sources: Liao ZJ. Process for extracting and refining berberine from Mahonia. Chinese patent CN1069493A, published 1993-03-03; Bezáková L, et al. Pharmazie. 1996;51(10):758-761; Sun L, et al. 2023; J Inflamm Res. 2025 (Grade-B ingredient literature)

Gardenia Fruit Extract: The Bridge from Anti-Inflammation to Post-Blemish Care

04 BOTANICAL ACTIVES ｜ GARDENIA FRUIT

Dried gardenia fruits (illustrative image)

INCI	Gardenia Jasminoides Fruit Extract
CAS	92457-01-7
Role in system	Inflammation axis · post-blemish care

Gardenia fruit extract (GJE)｜ Grade B　Significantly inhibited LPS-induced IL-1β, IL-6 and TNF-α release via TLR4／NKAP signaling downregulation, with anti-inflammatory activity validated in an in vivo zebrafish model (Exp Ther Med, 2021).

Geniposide (marker compound)｜ Grade B　Acts downstream of TLR4 to inhibit NF-κB p65 and MAPK pathways, exerting anti-inflammatory effects in animal inflammation models (Inflammation, 2014).

Crocetin (gardenia-derived active)｜ Grade B　In B16F10 melanoma cells it inhibited tyrosinase activity and melanin synthesis, downregulated tyrosinase and MITF proteins and scavenged ROS — pointing to the post-inflammatory hyperpigmentation (PIH) management chain (Anticancer Agents Med Chem, 2018).

Gardenia fruit’s “two-phase” value: acute and recovery
Acute phase (inflammation management)GJE / geniposide inhibit the TLR4–NF-κB／MAPK cascade, reducing IL-1β／IL-6／TNF-α release and easing the driving signals of redness and swelling.	Recovery phase (post-blemish care)Crocetin inhibits the tyrosinase–MITF axis and scavenges ROS, intervening upstream of melanin synthesis in the dark-mark formation chain (see Chapter 5).

Sources: Chen J, et al. Exp Ther Med. 2021;22(1):700. DOI:10.3892/etm.2021.10132; Song X, et al. Inflammation. 2014;37:1588-1598; Hashemi-Shahri S, et al. Anticancer Agents Med Chem. 2018 (Grade-B ingredient literature)

Stevia Leaf/Stem Extract: A Sweet Answer for Barrier and Soothing

04 BOTANICAL ACTIVES ｜ STEVIA

Stevia rebaudiana plant (illustrative image)

INCI	Stevia Rebaudiana Leaf/Stem Extract
CAS	91722-21-3
Role in system	Barrier · soothing · antioxidant

Stevioside (marker compound)｜ Grade B　At 250 μM in cell models, stevioside showed a triple “antioxidant + anti-inflammatory + barrier” effect:· Antioxidant: ↓ROS, ↓MDA; ↑T-SOD, ↑CAT, ↑GSH-Px;· Anti-inflammatory: ↓IL-6, ↓IL-8, ↓TNF-α; ↓NF-κB／IκB／ERK1/2 phosphorylation;· Barrier: ↑claudin-1, ↑occludin, ↑ZO-1 tight-junction proteins (Antioxidants, 2023).

Immunomodulatory support｜ Grade B　Stevioside activates AMPK and suppresses macrophage inflammatory responses (Molecules, 2021); 1 mM stevioside inhibited NF-κB in LPS-stimulated THP-1 cells (summarized in a 2023 review).

Why stevia is the “finishing ingredient” of the five-axis system: what anti-blemish formulas most often overlook is user experience and barrier consequences. With the highest typical value among the botanicals in the ingredient list (5%), stevia leaf/stem extract carries the soothing and barrier-support role: tight-junction upregulation directly answers the impaired-barrier fact of elevated TEWL in blemish-prone skin, closing the loop of “efficacy” and “mildness” within one formula.

Sources: Xu Q, et al. Antioxidants (Basel). 2023;12(5):1070. DOI:10.3390/antiox12051070; Wei F, et al. Molecules. 2021;26(4):858; content: AcneZero Ingredient List (Grade A)

05

Synergy · Claims · Applications

Translating ingredient evidence into market language: the synergy matrix, an evidence-graded claims system, the post-blemish care chain and application scenarios — every claim traceable to its source.

In this chapter ｜ 7 botanicals × 5 axes synergy matrix · Claims & evidence grading · Post-blemish care · Applications · B2B value

Seven Botanicals × Five Axes: The Synergy Matrix at a Glance

05 SYNERGY·CLAIMS·APPLICATIONS ｜ SYNERGY MATRIX

Ingredient	A1 Sebum	A2 Inflammation	A3 Oxidation	A4 Microbiome	A5 Barrier & soothing
Mahonia (berberine)	●	●	○	●
Salvia (tanshinones)		●	○	●
Silymarin	○	○	●	○	●
Olive leaf (polyphenols)	●	●	●
Bioflavonoids		●	●	○
Gardenia fruit (geniposide / crocetin)		●	○		●
Stevia (stevioside)		○	●		●

● Ingredient-level literature evidence for that axis (mainly Grade B; Grade-C extrapolation for olive leaf)　○ Indirect or auxiliary support (e.g., same-genus evidence, review support, associated endpoints in human studies)　—　The matrix summarizes the literature cited in Chapters 3–4; it is not the result of finished-product efficacy testing.

Matrix source: all ingredient literature cited in this material (see References); composition: AcneZero Ingredient List (Grade A).

The Claims System: Every Claim Has Its Evidence Coordinates

05 SYNERGY·CLAIMS·APPLICATIONS ｜ CLAIMS & EVIDENCE GRADING

Market claim (cosmetics framework)	Supporting logic	Key sources	Grade
Oil Control	Berberine inhibits FASN／DGAT1 and lipid secretion in sebocytes; olive leaf modulates SREBP-1／PPAR-γ (Grade-C extrapolation)	J Inflamm Res. 2025; CIMB. 2026	B／C
Blemish-Prone Skin Care	Berberine in vitro MIC／MBC, anti-biofilm and mouse-ear model; tanshinone antimicrobial review	Front Microbiol. 2023; Fitoterapia. 2025	B
Soothing	Quercetin, tanshinone IIA, gardenia fruit and stevioside inhibit the TLR–NF-κB cascade at multiple levels	See the evidence matrix in Chapter 3	B
Antioxidant Defense	Silymarin human study reduces lipid peroxidation; stevioside ↑antioxidant enzymes; flavonoid structure–activity relationship	JDD. 2024; Antioxidants. 2023	B
Microbiome Balance	Non-antibiotic, plant-derived antimicrobial strategy managing C. acnes overgrowth and biofilms	Front Microbiol. 2023	B
Barrier Support + Post-Blemish Tone Care	Stevioside upregulates tight-junction proteins; silymarin human study improves melanin index; crocetin inhibits tyrosinase	Antioxidants. 2023; J Cosmet Dermatol. 2023	B

Evidence grading: A = AcneZero’s own product data (MSDS safety, ingredient list); B = published ingredient literature (cell / animal / human, models as stated in the original papers); C = reasonable extrapolation from ingredient information. Finished-product efficacy verification is recommended before making finished-product claims.

Claim boundary: the above is a cosmetics efficacy narrative framework (blemish-prone skin care / oil control / soothing / microbiome balance / antioxidant / barrier & post-blemish tone care) and does not constitute drug or therapeutic claims.

The Post-Blemish Care Chain: Full Coverage from Inflammation to Dark Marks

05 SYNERGY·CLAIMS·APPLICATIONS ｜ POST-BLEMISH CARE

The formation chain of post-inflammatory hyperpigmentation (PIH) and its intervention points

Inflammatory cascade (IL／TNF-α) → Oxidative-stress amplification → Tyrosinase／MITF activation → Melanin deposition · dark marks

Intervention point ①: silymarin (human evidence)In a 4-week human study of a 0.5% silymarin serum (n=22), acne severity scores and lesion counts fell while the skin melanin index decreased significantly (J Cosmet Dermatol, 2023); a 2024 human study (n=56) reported improved post-inflammatory hyperpigmentation and reduced lipid peroxidation (J Drugs Dermatol, 2024).

Intervention point ②: crocetin (mechanistic evidence)Gardenia-derived crocetin inhibited tyrosinase activity and reduced melanin synthesis in B16F10 cells, downregulated tyrosinase and MITF protein expression and scavenged ROS — intervening upstream of melanin synthesis in dark-mark formation (Anticancer Agents Med Chem, 2018).

The complete narrative: inflammation management (Axis 2) reduces the upstream drive of PIH, antioxidant defense (Axis 3) blocks the amplification step, and silymarin plus gardenia provide human and mechanistic evidence for dark-mark care — AcneZero places “fighting acne” and “post-blemish recovery” within the same ingredient logic, giving brands a full-cycle product story from the acute phase to recovery.

Sources: Kim J, et al. J Cosmet Dermatol. 2023;22(2):561-568; J Drugs Dermatol. 2024;23(4). DOI:10.36849/JDD.8120; Hashemi-Shahri S, et al. Anticancer Agents Med Chem. 2018 (Grade-B ingredient literature)

Applications: From the Facial Core to Extended Scenarios

05 SYNERGY·CLAIMS·APPLICATIONS ｜ APPLICATIONS

Facial care (core scenario)	Body care	Scalp care (extended research direction)
· Blemish-care serum: the lead format for the full five-axis story· Oil-control lotion / gel: sebum management + microbiome balance· Soothing repair mask: inflammation management + barrier support· Post-blemish tone-care serum: the silymarin + gardenia PIH evidence chain· Targeted spot care: high-concentration multi-pathway positioning	· Back / chest blemish care: sebaceous-dense areas — a natural extension of the oil-control + microbiome narrative· Body mist / toner: water solubility suits large-area formats (Grade-A formula fact: water-soluble at 20°C)· Post-workout refreshing care: oil and microbiome management scenarios	· The scalp is likewise a sebum- and microbe-dominated ecosystem: Malassezia-mediated sebum peroxidation products (squalene monohydroperoxide, MDA) are among the triggers of dandruff (literature background)· AcneZero’s sebum-management, antioxidant and microbiome ingredient logic is mechanistically transferable to scalp scenarios· Positioning note: this is an extended research direction based on published literature; the MSDS defines the product’s use as a cosmetic skincare ingredient, and scalp applications require separate evaluation and validation

Formulation fit: the water-based (water-soluble) vehicle suits serums, toners, masks and gels; recommended pH, heat/light stability and specific compatibility parameters should be confirmed with the PuriPharm technical team — this material does not invent a recommended dosage.

Scalp background: DeAngelis YM, et al. J Investig Dermatol Symp Proc. 2005;10(3):295-297; product use and solubility: AcneZero MSDS v1.1 (Grade A).

B2B Partnership Value: A One-Stop, Multi-Pathway Anti-Blemish Solution

05 SYNERGY·CLAIMS·APPLICATIONS ｜ PARTNERSHIP VALUE

For brands: a complete science story	For formulators: clear engineering parameters	Regulatory & documentation support
· The five-axis mechanism + synergy matrix converts directly into product-page and detail-page storytelling· Every claim carries an evidence grade, standing up to regulatory and platform review· A full-cycle product-line imagination “from the acute phase to post-blemish recovery”	· Water-soluble (20°C), friendly to water-based formats· 4–25°C light-protected storage, routine supply-chain management· MSDS data showing no skin and no eye irritation, reducing the safety-assessment burden (Grade A)	· Listed in China’s Inventory of Existing Chemical Substances (IECIC)· Complete INCI / CAS information; transparent, traceable ingredient list· MSDS v1.1 and supporting technical documents for export and multi-market compliance assessment· The ingredient literature pack (References) supports claim filing and content review

CONTACT ｜ Business & Technical Inquiries

PuriPharm Co., Ltd.Web　www.puriactives.comEmail　service@puripharm.comTel　+86-572-2745768Address　7F, Building 6E, No. 1366 Hongfeng Road, Huzhou, Zhejiang, China

Product specifications and regulatory information: AcneZero MSDS v1.1 (Grade A); contact details: official company materials. Please contact the technical team for recommended dosage and finished-product efficacy verification plans.

References & Documentary Basis

REFERENCES

1. Cong TX, Hao D, Wen X, et al. From pathogenesis of acne vulgaris to anti-acne agents. Arch Dermatol Res. 2019;311(5):337-349. DOI:10.1007/s00403-019-01908-x
2. Dréno B, et al. Cutibacterium acnes and acne vulgaris: a brief look at the latest updates. J Eur Acad Dermatol Venereol. 2018;32(Suppl 2):5-14.
3. Condrò G, Sciortino R, Perugini P. Squalene peroxidation and biophysical parameters in acne-prone skin: a pilot “in vivo” study. Pharmaceuticals (Basel). 2023;16(12):1704. DOI:10.3390/ph16121704
4. Sun L, Yu Q, Peng F, et al. The antibacterial activity of berberine against Cutibacterium acnes: its therapeutic potential in inflammatory acne. Front Microbiol. 2023;14:1276383. DOI:10.3389/fmicb.2023.1276383
5. Berberine inhibits acne-related lipid secretion and inflammation by regulating the hsa-miR-3150a-3p/TP53 pathway. J Inflamm Res. 2025.
6. Lim HJ, Kang SH, Song YJ, et al. Inhibitory effect of quercetin on Propionibacterium acnes-induced skin inflammation. Int Immunopharmacol. 2021;96:107557. DOI:10.1016/j.intimp.2021.107557
7. A silymarin antioxidant serum improves facial acne alone and as part of a treatment regimen. J Drugs Dermatol. 2024;23(4). DOI:10.36849/JDD.8120
8. Kim J, et al. Efficacy and safety of silymarin containing antioxidant serum as an adjuvant treatment of mild-to-moderate acne vulgaris. J Cosmet Dermatol. 2023;22(2):561-568. DOI:10.1111/jocd.15439
9. Yoon JY, Kwon HH, Min SU, et al. Epigallocatechin-3-gallate improves acne in humans by modulating intracellular molecular targets and inhibiting P. acnes. J Invest Dermatol. 2013;133(2):429-440.
10. Kim J, Jo YW, Bang WJ, et al. Olive leaf extract suppresses sebogenesis and inflammation via AKT/ERK and SREBP-1/PPAR-γ signaling in human sebocytes. Curr Issues Mol Biol. 2026;48(6):549. DOI:10.3390/cimb48060549
11. Chen J, et al. Anti-inflammatory activities of Gardenia jasminoides extracts in retinal pigment epithelial cells and zebrafish embryos. Exp Ther Med. 2021;22(1):700. DOI:10.3892/etm.2021.10132
12. Song X, et al. Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced mastitis in mice. Inflammation. 2014;37:1588-1598. DOI:10.1007/s10753-014-9885-2
13. Xu Q, et al. Stevioside improves antioxidant capacity and intestinal barrier function. Antioxidants (Basel). 2023;12(5):1070. DOI:10.3390/antiox12051070
14. Wei F, et al. Stevioside activates AMPK to suppress inflammation in macrophages. Molecules. 2021;26(4):858. DOI:10.3390/molecules26040858
15. Meng Z, Si CY, Teng S, et al. Tanshinone IIA inhibits lipopolysaccharide-induced inflammatory responses through the TLR4/TAK1/NF-κB signaling pathway in vascular smooth muscle cells. Int J Mol Med. 2019;43(4):1847-1858. DOI:10.3892/ijmm.2019.4100
16. Zhang T, et al. Tanshinone in acne therapeutics: integrating molecular mechanisms, drug development, and multimodal treatment strategies. Fitoterapia. 2025.
17. Yang X, Huang G, You L, et al. High-throughput RNA sequencing reveals the anti-inflammatory mechanism of baicalin on Propionibacterium acnes-induced acne in rabbits. J Tradit Chin Med Sci. 2019;6(3):201-210.
18. Bezáková L, et al. Lipoxygenase inhibition and antioxidant properties of bisbenzylisoquinoline alkaloids isolated from Mahonia aquifolium. Pharmazie. 1996;51(10):758-761.
19. Hashemi-Shahri S, et al. ROS-scavenging and anti-tyrosinase properties of crocetin on B16F10 murine melanoma cells. Anticancer Agents Med Chem. 2018.
20. Mezei M, Gulasekharam V. Liposomes — a selective drug delivery system for the topical route of administration: gel dosage form. Life Sci. 1980;26:1473-1477.
21. Li H, et al. Oleuropein and hydroxytyrosol as skin-permeable elastase/collagenase inhibitors with synergistic antioxidant activity in human skin fibroblasts. Int J Food Sci Nutr. 2022;73(4):460-470.
22. DeAngelis YM, et al. Three etiologic facets of dandruff and seborrheic dermatitis: Malassezia fungi, sebaceous lipids, and individual sensitivity. J Investig Dermatol Symp Proc. 2005;10(3):295-297.
23. Zhang DQ, Tai JX, Fu Q. Research and application of bioflavonoids. Food and Fermentation Industries. 1999;25(6):52-57. (In Chinese)
24. Liao ZJ. Process for extracting and refining berberine from Mahonia. Chinese patent CN1069493A, published 1993-03-03. (In Chinese)

Internal company documents (Grade-A factual basis): PuriPharm AcneZero MSDS v1.1 (2019-07-13); AcneZero Ingredient List.

From single-target anti-acneto multi-pathway blemish-prone skin management.

PuriActives® AcneZero — Seven botanicals × phospholipid-based active system × five axes

PuriPharm Co., Ltd. ｜ INNOVATION FOR HEALTH & BEAUTYwww.puriactives.com ｜ service@puripharm.com ｜ +86-572-2745768 ｜ Huzhou, Zhejiang, China

PuriActives® Sodium Trehalose Sulfate 10%

Beyond Hydration · Barrier Biology

TECHNICAL PRODUCT PRESENTATION

PuriActives® Sodium Trehalose Sulfate 10%

From Hydration to Activation of the Skin’s Own Moisturizing Barrier

Beyond Hydration · Barrier Biology

INCI NAME: SODIUM TREHALOSE SULFATEPuriPharm Co. Ltd.

RETHINKING HYDRATION

Moisturization Is More Than Adding Water to Skin

CLASSICAL MOISTURIZATION: WATER FROM OUTSIDE

Humectant: draws water from the environment or deeper layersEmollient: softens the stratum corneum and improves skin feelOcclusive: forms a film and reduces evaporationAll three add or retain water, but do not directly build the skin’s own moisturizing system.

BARRIER BIOLOGY: HELPING SKIN MANAGE WATER

01 Keratinocyte differentiation and cornification02 Epidermal lipid transport (ABCA12)03 Ceramide barrier organization04 Filaggrin (FLG) metabolism05 Natural moisturizing factor (NMF) production

PuriActives® Sodium Trehalose Sulfate moves from external hydration toward support for the skin’s endogenous moisturizing system.

PRODUCT IDENTITY

PuriActives® Sodium Trehalose Sulfate 10%

Chemical structure of sodium trehalose sulfate, Maeda et al., 2024

Item	Information
INCI NAME	SODIUM TREHALOSE SULFATE
Ingredient category	Low-molecular-weight sulfated disaccharide active
Functional positioning	Moisturizing active · barrier-care active · skin-conditioning active
Molecular feature	Mol.Wt. ≈ 694 (tri- or tetra-sulfated)

Trehalose backbone

↓

Sulfation

↓

Sodium salt

Sulfation differentiates it from ordinary trehalose, transforming a sugar into a barrier-active molecule.

WHY SULFATION

Trehalose Is Only the Starting Point: Sulfation Changes Biological Behavior

Trehalose

Sodium trehalose sulfate

Key comparisons in the Maeda study

• Unsulfated trehalose did not produce the same complete barrier-gene expression response as sodium trehalose sulfate.
• In a 3D epidermal-model TEWL test, the trehalose group did not differ significantly from control, while the sodium trehalose sulfate group showed a significant reduction.
• Low-molecular-weight sulfated disaccharides below 1,000 Da can act on stratum-corneum barrier function.

3D epidermal-model TEWL (g/cm²·h): only the sulfated-sugar group was significantly lower than control, *p<0.05.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666. Chemical structures reproduced from Figure 2.

THREE PILLARS OF THE BARRIER

An Effective Barrier Depends on Three Coordinated Systems

Cornified Envelope

IVL · TGM1

Intercellular Lipids

ABCA12 · Ceramide

Natural Moisturizing Factors

FLG · CASP14 · CAPN1 · BLMH

Sodium trehalose sulfate is supported by evidence across all three systems.These systems determine the “bricks” of the stratum corneum, the “mortar” between them, and water storage within the bricks.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666.

MECHANISM OVERVIEW

One Molecule, Multiple Pathways to Strengthen the Moisturizing Barrier

After topical application, sodium trehalose sulfate participates in epidermal biological regulation:

01 IVL / TGM1 ↑

Cornified-envelope formation ↑

02 ABCA12 ↑

Lamellar-granule lipid transport ↑Ceramide-barrier organization ↑

03 FLG / CASP14 / CAPN1 / BLMH ↑

Free amino acids ↑Natural moisturizing factors (NMF) ↑

All three pathways converge on: barrier integrity ↑ · stratum-corneum hydration ↑ · transepidermal water loss (TEWL) ↓

Evidence chain: qPCR gene expression · immunofluorescence protein validation · free-amino-acid measurement · 3D-model TEWL · four-week double-blind human study

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666.

LIPID TRANSPORT · ABCA12

ABCA12 Enables the Skin to Transport Its Own Barrier Lipids

ABCA12 is a key lipid transporter in keratinocytes. This ATP-binding cassette transporter loads intracellular lipids into lamellar granules and delivers them to the stratum corneum.

Intracellular lipid synthesis

↓

Loading into lamellar granules

↓

Release of intercellular lipids in the stratum corneum

↓

Formation of a complete barrier-lipid structure

This supports the endogenous epidermal lipid-transport system rather than merely adding lipids from outside.

Relative ABCA12 mRNA expression in a 3D epidermal model, *p<0.05 vs. control.

ABCA12 immunofluorescence: stronger signal in the sodium trehalose sulfate group, 3D epidermal model.

Sources: Maeda K, et al. Skin Res Technol. 2024;30:e13666; Sakai K, et al. Exp Dermatol. 2007;16:920–926.

CERAMIDE-RICH BARRIER

From ABCA12 to a Ceramide-Rich Barrier

ABCA12 ↑

↓

Lipid loading and transport ↑

↓

Lamellar granules

↓

Intercellular lipids

↓

Ceramide-rich barrier

Immunofluorescence validation: stronger ceramide signal

Control, left; sodium trehalose sulfate treatment, right

In a 3D epidermal model, the sodium trehalose sulfate group showed stronger ceramide immunofluorescence than the vehicle control, suggesting support for the organization of intercellular barrier lipids in the stratum corneum.

Why it matters: Ceramides are core components of stratum-corneum intercellular lipids and determine barrier density. When ABCA12 function is impaired, lamellar-granule lipids decline and structural barrier defects emerge. Supporting ABCA12 supports the skin’s own lipid supply chain.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 5C.

FILAGGRIN · NMF PATHWAY

Activating the Skin’s Natural Moisturizing Factor Pathway

Pathway by which FLG is degraded in the granular layer and stratum corneum to generate NMF, Maeda et al., 2024, Figure 1.

Profilaggrin in the granular layer

↓

Filaggrin (FLG)

↓

FLG processing and degradation: CASP14 / CAPN1 / BLMH

↓

Free amino acids

↓

Natural moisturizing factors (NMF)

↓

Stratum-corneum hydration

This is the skin’s own moisturizing system, not water supplied from outside.

Sources: Maeda K, et al. Skin Res Technol. 2024;30:e13666; Hoste E, et al. J Invest Dermatol. 2011;131:2233–2241.

MULTI-GENE BARRIER RESPONSE

One Intervention Activates Seven Barrier-Related Pathways

3D epidermal-model qPCR: all seven mRNA markers were significantly upregulated by sodium trehalose sulfate, *p<0.05, **p<0.01 vs. control; n=3.

IVL Involucrin ↑

TGM1 Transglutaminase 1 ↑

ABCA12 Lipid transport ↑

FLG Filaggrin ↑

CASP14 ↑

CAPN1 ↑

BLMH ↑

The response covers cornified-envelope formation, lipid transport and NMF production rather than a single target.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 4.

PROTEIN-LEVEL EVIDENCE

From Gene Expression to Barrier Structure

TGM1

Control, left; STS treatment, right

ABCA12

Control, left; STS treatment, right

Ceramide

Control, left; STS treatment, right

FLG

Control, left; STS treatment, right

In 3D epidermal-model immunofluorescence, the sodium trehalose sulfate group showed greater fluorescence intensity and distribution area for TGM1, ABCA12, ceramide and FLG than the vehicle control. The evidence therefore extends beyond mRNA changes to proteins and barrier structure.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 5.

FREE AMINO ACIDS · NMF SOURCE

Increasing the Source Materials for Natural Moisturizing Factors

Free amino acids / total amino acids, %, 3D epidermal model, n=4; *p<0.05, **p<0.01 vs. control.

Significant increases from 0.05% to 0.20%: the 0.05%, 0.10% and 0.20% STS solution groups were all higher than control.

Free amino acids are core components of natural moisturizing factors and arise from filaggrin degradation. After sodium trehalose sulfate treatment, the free-amino-acid ratio in the 3D epidermal model was significantly higher than control.

It not only attracts water, but also supports the skin in producing its own natural moisturizing factors.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 6.

IMMEDIATE HYDRATION

Visible Improvement in Stratum-Corneum Water Content from 15 Minutes

Short-term human forearm test: change in stratum-corneum water content, ΔμS, 15 / 30 min; n=5; *p<0.05, **p<0.01 vs. control.

15 min

An increase in water content was already observed.

30 min

The improvement persisted and remained significant.

After treatment with 0.05%, 0.1% and 0.2% sodium trehalose sulfate solutions, stratum-corneum water content was significantly higher than with the water control. The comparison 0.3% heparinoid emulsion was significant only at 15 minutes and no longer differed significantly from control at 30 minutes.

Immediate hydration and support for endogenous moisturization can be achieved together.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 7A.

TEWL · BARRIER EFFICIENCY

Reducing Water Loss and Improving Barrier Efficiency

3D epidermal-model TEWL, g/cm²·h, three days after treatment; n=3; *p<0.05 vs. control.

Transepidermal water loss is a core measure of skin-barrier integrity. Lower TEWL indicates a stronger ability to retain water. All three sodium trehalose sulfate concentration groups had significantly lower TEWL than control.

ABCA12 + ceramide + TGM1 / IVL

↓

Barrier integrity ↑

↓

Water loss ↓

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figure 7B.

HUMAN STUDY DESIGN

Four-Week Randomized Double-Blind Human Study

Randomized

Random allocation

Double-blind

Double-blind design

Placebo-controlled

Placebo control

4 Weeks

Continuous facial use

Item	Study information
Participants	Included in statistical analysis: active group n=13; placebo group n=11
Test formulations	Active group: toner and emulsion containing 0.05% sodium trehalose sulfate; placebo group: visually matched blank formulations
Use	Twice daily, morning and evening, for four weeks
Primary endpoints	TEWL and stratum-corneum water content
Ethics and enrollment	Conducted according to the Declaration of Helsinki and approved by an ethics committee, protocol HENM21083001, 1 October 2021; 26 women aged 33–59 enrolled

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666.

4-WEEK CLINICAL RESULTS

Four Weeks of Use Improved Hydration and Barrier Function Together

TEWL, g/m²·h: active-group mean W0→W4, 17.3→16.1; between-group comparison of ΔTEWL, p<0.01.

Stratum-corneum water content, μS: active group 81.3→105.5, p<0.01; between-group comparison of change, p<0.05.

Significant TEWL improvement

Active group Δ −1.2 vs placebo group Δ +3.2

Significant increase in stratum-corneum water content

Active group Δ +24.2 vs placebo group Δ +4.2

Significant between-group differences

Both core endpoints favored the active group

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figures 8A and 8B; n=13 active / n=11 placebo.

HYDRATION + CLARITY

A Healthy Barrier Can Also Improve the Look of Skin

Blood oxygenation index: increased after four weeks in the active group; between-group comparison of change, p<0.05.

Melanin index: decreased after four weeks in the active group; between-group comparison of change, p<0.05.

The paper also observed improvements in tone-related measures: blood oxygenation index ↑ and melanin index ↓.

These were accompanying observational endpoints in the four-week human study and do not support a strong whitening claim.

Suggested marketing language: improves dry, dull appearance · enhances a hydrated, translucent look · supports a more even, healthy-looking skin tone · provides barrier and hydration support for brightening products

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666, Figures 8C and 8D.

DRY & SENSITIVE SKIN

Breaking the Barrier Damage–Dryness–Sensitivity Cycle

Barrier disruption

↓

TEWL ↑

↓

Dehydration

↓

Roughness and tightness

↓

Environmental sensitivity

↓

Further barrier disruption

Where sodium trehalose sulfate acts

Barrier: supports the cornified envelope and barrier integrityLipids: supports endogenous lipid transport and ceramide organizationNMF: supports natural moisturizing factor productionHydration: increases stratum-corneum water content and reduces TEWL

Suitable product concepts

Dry-skin care · sensitive-skin barrier care · seasonal-transition careMature dry skin · companion care for high-activity products such as retinoids and acidsPost-cleansing tightness care

SCALP IS SKIN

The Scalp Also Needs an Intact Barrier

The scalp is an extension of the skin and similarly depends on:

• Stratum-corneum structure and the cornified envelope
• Intercellular lipids and ceramides
• Natural moisturizing factors and water balance

When the scalp barrier is impaired: dryness · tightness · discomfort · flaking · reduced quality of hair appearance

PuriActives® Sodium Trehalose Sulfate can extend to: scalp serum · hair tonic · shampoo · conditioner · scalp mask · leave-on scalp essence

SULFATED SACCHARIDES PLATFORM

Sulfated Saccharides: an Emerging Scalp and Hair Research Platform

This page concerns platform research on sulfated saccharides. It is not human hair-growth clinical evidence for sodium trehalose sulfate.

US 5,618,798: hair and scalp applications of sulfated saccharides

The patent covers topical use of sulfated monosaccharides, disaccharides and oligosaccharides in hair and scalp applications, including shampoo, hair tonic, hair conditioner, gel, emulsion and lotion formats.

Positioning of this page: scalp moisture + barrier + hair environment. The focus is scalp moisturization and barrier care, not pharmaceutical hair-growth promotion.

Supporting studies on sulfated saccharides:

• US 4,912,093: synthetic sulfated saccharides and wound care
• WO 1989/05646: sulfated saccharides and inflammatory skin care
• US 5,605,938: sulfated anionic polymers and cellular mechanisms
• FR 2877565: dextran sulfate and soothing applications
• Toyama S, et al. 2025: topical OJI-204 for skin dryness and dryness-induced itching, Biomedicines. 2025;13:556

FORMULATION APPLICATIONS

Highly Flexible Applications from Serums to Scalp Care

SKIN CARE

TonerEssence / serumAmpouleLotion / creamMaskEye careSensitive-skin care

HAIR & SCALP

ShampooConditionerScalp serumHair tonicScalp sprayHair mask

As a water-soluble, low-molecular-weight active, it is suitable for aqueous products, serums, emulsions, rinse-off scalp products and leave-on scalp products.

FORMULATION DESIGN

Building the Next Generation of Barrier-Moisturizing Systems

STS + Hyaluronic Acid

Immediate water retention + support for the endogenous moisturizing system

STS + Ceramide

Endogenous lipid transport + exogenous lipid supplementation

STS + Panthenol

Barrier support + soothing care

STS + Ectoin

Environmental-stress care

STS + Niacinamide

Multidimensional barrier care

STS + Amino Acid / NMF Complex

Endogenous NMF generation + exogenous NMF supplementation

These formulation-design suggestions are based on complementary mechanisms. Actual performance of each combination requires validation in the specific formulation.

DOSE TRANSLATION

A 10% Active System Connected to the Published Human-Study Dose

PuriActives® Sodium Trehalose Sulfate 10%: 10% active content in the ingredient

↓

Recommended finished-formula addition: 0.50%

↓

Actual sodium trehalose sulfate concentration in the formula: 0.05%

This directly corresponds to the 0.05% active concentration used in the human study by Maeda et al.

Studies at this concentration included a four-week randomized double-blind placebo-controlled human trial showing improvements in TEWL and stratum-corneum water content, a short-term human hydration test, and validation of genes, proteins and free amino acids in a 3D epidermal model.

Source: Maeda K, et al. Skin Res Technol. 2024;30:e13666.

WHY PURIACTIVES®

PuriActives® Sodium Trehalose Sulfate 10%

01 Barrier biology

ABCA12 / TGM1 / IVLSupports the cornified envelope and endogenous lipid transport

02 Endogenous moisturization

FLG / NMF / free amino acidsSupports the skin in producing its own moisturizing factors

03 Human validation

Four-week randomized double-blind studyTEWL ↓ · stratum-corneum water content ↑

04 Dual-scenario application

Skin + scalpOne platform for skin and scalp care

Lasting moisturization means more than bringing water into the skin. It also means helping the skin manage its own water.

REFERENCESMaeda K, Zhou Z, Guo M, Zhang J, Chen L, Yang F. Functional properties and skin care effects of sodium trehalose sulfate. Skin Res Technol. 2024;30:e13666. doi:10.1111/srt.13666Hoste E, et al. J Invest Dermatol. 2011;131:2233–2241. · Denecker G, et al. Nat Cell Biol. 2007;9:666–674. · Sakai K, et al. Exp Dermatol. 2007;16:920–926.Supporting platform research on sulfated saccharides: US 4,912,093 · US 5,618,798 · WO 1989/05646 · US 5,605,938 · FR 2877565 · Toyama S, et al. Biomedicines. 2025;13:556.

PuriPharm Co. Ltd.www.puriactives.com · service@puripharm.com+86-572-2745768 · Building 6, No. 1366 Hongfeng Road, Huzhou, Zhejiang, ChinaPuriActives® is a registered trademark of PuriPharm Co., Ltd. This material introduces a cosmetic ingredient.