Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems

Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems Retty Handayani1,2 , Raden Maya Febriyanti3, Muhaimin Muhaimin3, Anis Yohana Chearunisaa2,4 1 Doctoral Program, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia 2 Dosage Form Development Research Center, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia 3 Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia 4 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia Corresponding author: Raden Maya Febriyanti ([email protected]); Anis Yohana Chearunisaa (anis.yohan[email protected]) Received 30 July 2025♦ Accepted 23 October 2025♦ Published 3 November 2025 Citation: Handayani R, Febriyanti RM, Muhaimin M, Chearunisaa AY (2025) Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems. Pharmacia 72: 1–13. https://doi.org/10.3897/pharmacia.72.e167217 Abstract Centella asiatica (L.) Urb. is increasingly used in dermatology and cosmeceuticals for wound repair, barrier support, scar modulation, and photoaging. This review synthesizes evidence (2016–May 2025) across molecular mechanisms relevant to cutaneous aging, preclinical efficacy, human clinical outcomes, and delivery systems that improve dermal bioavailability. The principal triterpenoid saponins (asiaticoside, madecassoside) and their aglycones (asiatic acid, madecassic acid), together with polyphenols, act across complementary pathways, including transforming growth factor beta (TGF-β)/small mothers against decapentaplegic proteins (Smad)-driven extracellular matrix (ECM) anabolism; nuclear factor kappa B (NF-κB) and Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) attenuation; mitigation of oxidative/glycation stress; and photoprotection to improve histologic and biophysical skin endpoints. Human studies, though small and heterogeneous, report improvements in hydration, transepidermal water loss (TEWL), elasticity, and wrinkle appearance, as well as benefits in scar parameters, with good topical tolerability. Advanced carriers such as transfersomes, liposomes, niosomes, phytosomes, nanoemulsions, hydrogels, microneedles, and nanofibers enhance skin penetration, stability, and residence of bioactive compounds from C. asiatica. Keywords asiaticoside, cosmeceuticals, madecassoside, nanocarriers, photoaging, wound healing Introduction Centella asiatica (L.) Urb. (Apiaceae) is widely distributed across tropical and subtropical Asia and parts of Africa, including India, Indonesia, Malaysia, China, Korea, Japan, Taiwan, and Madagascar (Park 2021a; Shin et al. 2021; Zeng et al. 2025). In traditional medicine, it has been employed as tea or decoctions for diverse dermatological conditions, including wounds, burns, scars, eczema, psoriasis, and varicose ulcers (Bansal et al. 2024). Over the past decade, these traditional uses have catalyzed intensive research and growing adoption in the dermatology and cosmeceutical sectors, with topical formulations aimed at wound repair, scar modulation, and anti-aging (Khalili Hassanabad et al. 2025). Copyright Handayani R et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Pharmacia 72: 1–13 DOI 10.3897/pharmacia.72.e167217 Review Article Handayani R et al.: Centella asiatica (L.) Urb. in skin health and cosmeceuticals2 The pharmacological activity of C. asiatica is attributed primarily to its secondary metabolites. The aerial parts are rich in pentacyclic triterpenoids – most notably the saponins asiaticoside and madecassoside and their aglycones asiatic acid and madecassic acid – together with sesquiterpenes and monoterpenes in the essential oil (α-humulene, β-caryophyllene, myrcene, bicyclogermacrene, and germacrene-D), plant sterols, phenolic acids (chlorogenic acids), and flavonoids (catechin, epicatechin, quercetin, and kaempferol) (Shin et al. 2021; Kunjumon et al. 2022; Diniz et al. 2023; Johnson et al. 2023). Quantitative analyses have shown considerable variability in these phytoconstituents, with asiatic acid reported in the range of 0.02–3.2%, madecassic acid 0.02–3.06%, asiaticoside 0.018–4.3%, and madecassoside 0.01–4.8%, while accessions from Assam, India, contained up to 21.7 mg/g asiaticoside and 11.2 mg/g madecassoside (Singh et al. 2023). These constituents exert complementary actions relevant to skin biology, including stimulation of collagen synthesis and dermal matrix remodeling, modulation of pro-inflammatory signaling, and attenuation of oxidative and glycation stress that collectively underpin benefits in tissue repair and skin-barrier maintenance (Park 2021a; Diniz et al. 2023; Rashid et al. 2023). In particular, asiaticoside and madecassoside have been linked to transforming growth factor beta (TGF-β)/Smad activation, vascular endothelial growth factor (VEGF)-mediated angiogenesis, and improvements in structural skin integrity (Shin et al. 2021). Recent comprehensive reviews have provided insights into various aspects of C. asiatica research. Sun et al. (2020) presented an extensive overview of systemic pharmacological potentials, including neurological, metabolic, hepatoprotective, and anti-inflammatory activities; however, skin-specific anti-aging mechanisms, dermatological models, and formulation science received only superficial coverage. Bansal et al. (2024) offered a broad therapeutic survey spanning anti-ulcer, anti-cancer, anti-diabetic, neuroprotective, and cardioprotective activities, alongside nanostructured carrier systems, but did not specifically dissect dermatological anti-aging mechanisms or the impact of formulation architectures on skin-related outcomes. In a more recent review, Hein et al. (2025) examined technological advancements in C. asiatica extraction and formulation, emphasizing greener methodologies, process innovations, and delivery systems; however, they provided limited analysis specifically on dermatological and cosmeceutical applications. This narrative review therefore narrows the scope to skin health and aging. Specifically, we synthesize preclinical evidence and human data on C. asiatica in wound repair, photo-induced and intrinsic aging, and selected inflammatory dermatoses. Additionally, we appraise how advanced delivery systems affect dermal bioavailability and clinical outcomes. In contrast to previous reviews that primarily emphasized the pharmacological activities and therapeutic potential of C. asiatica (Sun et al. 2020), its broad therapeutic indications with limited dermatological depth (Bansal et al. 2024), and advances in extraction technologies and phytochemistry without a specific focus on skin applications (Hein et al. 2025), this review concentrates on skin health and cosmetics. The novelty lies in the integration of molecular mechanisms, preclinical and clinical evidence, and innovations in delivery systems within a dermatology-focused framework. By synthesizing detailed pharmacological knowledge with formulation strategies, this review aims to provide actionable, evidence-based guidance for researchers, thereby bridging existing translational gaps and supporting the development of standardized, effective, and safe C. asiatica-based skincare products. Methods A comprehensive literature search was performed on the ScienceDirect, PubMed, and Scopus databases for articles published from 1 January 2016 to 31 May 2025 that investigated C. asiatica in relation to dermatology, formulation, or delivery technology. Inclusion criteria for the articles included original in vitro, in vivo, or human studies in which C. asiatica crude extract, fraction, or purified constituent was used in a single preparation, with outcomes relevant to preclinical efficacy, clinical endpoints, or advanced formulation metrics. Reviews, case reports, multi-herb formulations, non-dermatological indications, non-topical preparations, and articles lacking quantitative data were excluded from further analysis. The search identified 2,731 articles in ScienceDirect (n = 2,387), PubMed (n = 311), and Scopus (n = 33). There were duplicates (n = 501), with a total of 617 articles screened. Articles were excluded due to non-C. asiatica content, herbal combinations, non-dermatological indications, non-topical preparations, and unavailable full text (n = 2,114). An expanded search-strategy report and publication-by-year visualization are provided in Suppl. material 1. Consequently, 51 articles were assessed for eligibility. Furthermore, results were synthesized narratively into four thematic domains, namely: (1) skin health-related molecular mechanisms of C. asiatica bioactive compounds; (2) preclinical studies (animal models); (3) clinical efficacy and safety; and (4) advances in formulation and drug-delivery systems. List of abbreviations C. asiatica Centella asiatica (L.) Urb.; TECA Titrated extract of Centella asiatica; NF-κB Nuclear factor kappa-light-chainenhancer of activated B cells; TGF-β Transforming growth factor beta; TGF-β1 Transforming growth factor beta 1; VEGF Vascular endothelial growth factor; FGF-2 Fibroblast growth factor 2; MMP Matrix metalloproteinase; MMP-1/-9 Matrix metalloproteinase-1/-9; Pharmacia 72: 1–13 3 ECM Extracellular matrix; IL-1β / IL-6 Interleukin-1 beta /interleukin-6; TNF-α Tumor necrosis factor alpha; COX-2 Cyclooxygenase-2; iNOS Inducible nitric oxide synthase; ROS Reactive oxygen species; SOD Superoxide dismutase; AGEs Advanced glycation end products; MITF Microphthalmia-associated transcription factor; JAK/STAT3 Janus kinase/signal transducer and activator of transcription 3; MAPK/ERK Mitogen-activated protein kinase/ extracellular signal-regulated kinase; Wnt/β-catenin Wingless/integrated/beta-catenin pathway; TEWL Transepidermal water loss; HA Hyaluronic acid; SLN Solid lipid nanoparticle; NLC Nanostructured lipid carrier; SLM Solid lipid microparticle; MN Microneedle; PCL/PEO Polycaprolactone/polyethylene oxide; PVA Polyvinyl alcohol; ZnO Zinc oxide; CuO Copper oxide; PECE Poly(ethylene glycol)–poly(εcaprolactone)–poly(ethylene glycol); PVP K30 Polyvinylpyrrolidone K30; ECM–GelMA Extracellular matrix–gelatin methacryloyl; HRIPT Human repeat insult patch test; VSS Vancouver Scar Scale; VAS Visual analog scale; QuickDASH Quick Disabilities of the Arm, Shoulder and Hand; P. acnes Propionibacterium acnes; S. aureus Staphylococcus aureus. Phytoconstituents and mechanisms of C. asiatica in dermatology The dermatological efficacy of C. asiatica derives from a synergistic interplay among multiple phytochemical classes rather than from any single isolated compound. This multicomponent, multitarget pharmacological approach enables the plant to concurrently address several pathological processes in the skin, including inflammation, oxidative stress, extracellular matrix (ECM) remodeling, and pigmentation anomalies (Table 1). Central to the pharmacological activity of C. asiatica are triterpenoid saponins, which upon hydrolysis yield aglycones that promote collagen and hyaluronic acid synthesis, exhibit anti-inflammatory and anti-elastase activities, and possess antioxidative properties critical for scar control and anti-aging benefits (Shen et al. 2019; Kim et al. 2021; Chutoprapat et al. 2024; Zhang et al. 2024; Alam et al. 2025; Tai et al. 2025). Other triterpenoid derivatives, such as ursane and oleanane derivatives and bayogenin, provide additional antioxidant and antifibrotic activities by inhibiting key enzymes like elastase and fibrosis-related signaling molecules (Masi et al. 2022; Gayathri et al. 2024). Flavonoids and phenolics further augment these effects, with compounds like quercetin and kaempferol Table 1. Bioactive compounds of C. asiatica and their skin-related pharmacological activities. Compound Phytochemical class Skin-related activity Mechanism of action References Asiaticoside Triterpenoid saponin Anti-keloid, antifibrotic, antioxidant, wound healing, anti-photoaging, anti-wrinkle Inhibits NF-κB/PI3K–Akt pathways; promotes fibroblast migration and collagen synthesis; modulates apoptosis (Bcl-2/Bax/Caspase-3) (Zhao et al. 2020; Jiang et al. 2022) Centellasiaticoside Triterpenoid ursane Anti-photoaging Enhances HaCaT cell viability; reduces LDH release post-UVB (Dang et al. 2024) Madecassoside Triterpenoid saponin Anti-aging, anti-inflammatory, anti-pollutant, skin hydration, anti-melanogenesis Inhibits elastase, reduces IL-6/TNF-α; enhances collagen and hyaluronic acid synthesis; suppresses JAK/STAT3 pathway (Shen et al. 2019; Kim et al. 2021; Tai et al. 2025) Asiatic acid Triterpenoid aglycone Anti-acne, anti-inflammatory, anti-aging, antibacterial, antifibrotic Inhibits P. acnes and S. aureus; suppresses UVB-induced inflammation and STAT3 pathway; promotes fibroblast proliferation (Chutoprapat et al. 2024, Wu et al. 2025) Madecassic acid Triterpenoid aglycone Antioxidant, tissue protection Reduces pro-inflammatory cytokines (Alam et al. 2025) Isomadecassic acid Triterpenoid Anti-photoaging Reduces LDH release after UVB exposure (Dang et al. 2024) Ursane and Oleanane derivatives Triterpenoid Saponin Antioxidant, anti-inflammatory Inhibits elastase and oxidative stress pathways (Masi et al. 2022) Bayogenin Triterpenoid Antifibrotic Inhibits MAPK-1, binds fibrosis-related targets (Gayathri et al. 2024) Quercetin Flavonoid Antioxidant Scavenges ROS, reduces oxidative stress (Mohapatra et al. 2021) Kaempferol Flavonoid Anti-infection Inhibits pyocyanin, biofilm, protease, and elastase from P. aeruginosa (Vasavi et al. 2016) Tannin Polyphenol Anti-glycation, anti-aging Inhibits AGE formation in proteinfructose models (Borges et al. 2024) Di-O-caffeoylquinic acids Phenolic Antioxidant, depigmentation Inhibits tyrosinase activity (Soun-udom et al. 2024) Handayani R et al.: Centella asiatica (L.) Urb. in skin health and cosmeceuticals4 offering reactive oxygen species (ROS) scavenging capacity and selective modulation of inflammatory pathways such as JAK/STAT3, which are particularly relevant in conditions like psoriasis (Vasavi et al. 2016; Mohapatra et al. 2021; Soun-udom et al. 2024). Additionally, di-O-caffeoylquinic acids exhibit potent tyrosinase inhibition, positioning C. asiatica extracts as beneficial adjuncts for managing photo-induced hyperpigmentation (Soun-udom et al. 2024). Whole-extract matrices have demonstrated superior antiglycation effects compared to isolated triterpenes alone, highlighting the importance of phytochemical synergy within standardized botanical preparations (Borges et al. 2024). At the molecular signaling level, asiaticoside and madecassoside activate the TGF-β/Smad pathway to drive extracellular matrix synthesis, thereby enhancing collagen deposition and improving skin elasticity and hydration (Shen et al. 2019; Kim et al. 2021; Tai et al. 2025). Additionally, preliminary evidence indicates potential interactions with Wnt/β-catenin pathways in chronic wound healing, though such findings warrant further investigation. In the context of inflammation, madecassoside and asiatic acid suppress NF-κB signaling, thereby attenuating the production of pro-inflammatory cytokines and enzymes such as TNF-α, IL-6, COX-2, and iNOS (Shen et al. 2019; Kim et al. 2021). Concurrently, quercetin-mediated modulation of JAK/ STAT3 signaling and the IL-23/IL-17A axis underscores the targeted immunomodulatory potential of flavonoid constituents, particularly in autoimmune-related dermatoses (Rashid et al. 2023). Antioxidant and cytoprotective benefits from C. asiatica are mediated through direct ROS scavenging and upregulation of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase (Zhao et al. 2020; Mohapatra et al. 2021; Jiang et al. 2022). These actions are essential in preventing UV-induced cellular injury, lipid peroxidation, and subsequent ECM degradation. Specific triterpenes such as centellasiaticoside and isomadecassic acid have demonstrated protective effects in keratinocytes under UVB stress, reducing LDH leakage and maintaining cellular viability (Dang et al. 2024). Furthermore, the antimicrobial and anti-acne potential of asiatic acid, particularly against C. acnes and S. aureus, coupled with its ability to inhibit STAT3-linked inflammation, positions C. asiatica favorably for managing acne-prone skin (Chutoprapat et al. 2024; Wu et al. 2025). Kaempferol’s inhibitory effects on virulence factors from P. aeruginosa also support the plant’s broader antimicrobial utility (Vasavi et al. 2016). In antifibrotic contexts, asiaticoside, asiatic acid, and bayogenin collectively contribute to scar limitation by modulating fibrosis-related pathways such as MAPK-1 and maintaining balanced TGF-β/Smad signaling without excessive fibrotic responses (Bisht et al. 2024; Borges et al. 2024; Gayathri et al. 2024; Zhang et al. 2024). Fig. 1 illustrates collective mechanisms of C. asiatica in skin health. Preclinical evidence The preclinical evidence of dermatological benefits of C. asiatica has been reported in various studies (summarized in Table 2). The pharmacological activities span excision and diabetic-ulcer wounds, hypertrophic scars, atopic dermatitis, and UVB-photoaging models, with interventions ranging from crude extracts to phytosomes and NO-releasing gels. Across models, directionally consistent outcomes inTable 2. Summary of preclinical evidence for C. asiatica in dermatology. Model/system Intervention Dose/concentration Key outcomes Reference Rat excision model C. asiatica extract (topical and oral) 50–100 mg/kg ↑ Wound contraction, ↑ hydroxyproline, ↑ tensile strength (Singh et al. 2022) Diabetic rat ulcer model Asiaticoside–NO gel (topical) 2% gel ↑ Wnt/β-catenin, ↓ bacterial load, ↑ wound closure (Park 2021) Mouse hypertrophic scar model C. asiatica extract (topical) 1% cream ↓ TGF-β1, ↓ collagen I/III, ↓ scar thickness (Balevi and Balevi 2023) Mouse atopic dermatitis model C. asiatica phytosome 50 mg/kg ↓ IgE, ↓ NF-κB, ↓ mast cells, ↓ COX-2 (Wang et al. 2024) UVB-induced aging mouse model C. asiatica extract (topical) 0.5–1% formulation ↑ TGF-β/Smad, ↓ MMP-1/-9, ↓ wrinkle depth (Khalili Hassanabad et al. 2025) Vitiligo oxidative model C. asiatica extract 20 µg/mL ↑ melanocyte viability, ↓ oxidative damage (Park 2021) Hair follicle dermal papilla cells C. asiatica extract 10 µg/mL ↑ proliferation, ↑ hair inductive markers (Park 2021a) Figure 1. Molecular mechanisms of C. asiatica in skin health. Abbreviations: ROS, reactive oxygen species; MAPK, mitogen-activated protein kinase; AP-1, activator protein 1; NF-κB, nuclear factor kappa B; TGF-β, transforming growth factor beta; MMP, matrix metalloproteinase (MMP-1, -3, -9, -12). Pharmacia 72: 1–13 5 clude faster closure, improved biomechanical properties, antifibrotic signaling, suppression of inflammatory mediators, and protection against photo-oxidative injury. Wound healing and tissue repair Preclinical studies consistently demonstrate that C. asiatica accelerates wound healing through stimulation of fibroblast activity, collagen synthesis, and angiogenesis. In rodent models of excision and ulcerative wounds, both topical and oral applications of C. asiatica significantly enhance healing through mechanisms such as fibroblast activation, collagen biosynthesis, and angiogenesis. These beneficial effects manifest as accelerated wound contraction, increased hydroxyproline content – an indicator of collagen production – and improved tensile strength of the newly formed tissue (Singh et al. 2022a). Specifically, topical application of asiaticoside enhances dermal vascularization and re-epithelialization, accompanied by increased collagen cross-linking and capillary density. In diabetic ulcer models, topical gels formulated with nitric oxide–releasing asiaticoside demonstrate accelerated wound closure, reduced microbial colonization, and activation of Wnt/β-catenin signaling pathways, highlighting their potential utility in managing chronic and ischemic wounds (Park 2021a). Wound healing mechanisms of asiaticoside are illustrated in Fig. 2. C. asiatica also exhibits notable potential in scar modulation and antifibrotic activity, particularly in hypertrophic and keloid scarring contexts characterized by excessive fibroblast activity and extracellular matrix (ECM) deposition. In murine scar models, treatment with C. asiatica extracts has been shown to downregulate transforming growth factor beta 1 (TGF-β1) expression, decrease collagen I and III synthesis, and reduce overall scar thickness (Balevi and Balevi 2023). Treated wounds consistently display thinner, more organized collagen architecture resembling healthy dermal tissue, attributed mechanistically to the action of asiaticoside in preventing myofibroblast differentiation and suppressing profibrotic cytokine expression (Li et al. 2025). Antioxidant and anti-aging activity Preclinical UVB-exposure models have revealed the potent antioxidant and anti-aging capabilities of C. asiatica. Triterpenoids such as asiaticoside and asiatic acid scavenge reactive oxygen species (ROS) and upregulate endogenous antioxidant enzymes, including superoxide dismutase (SOD) and catalase (Park 2021). Topical application of C. asiatica extract mitigated photoaging by suppressing MMP-1 and MMP-9, enzymes responsible for collagen degradation, while activating TGF-β/Smad signaling to enhance ECM integrity. These findings suggest promising applications in anti-wrinkle and skin-rejuvenating cosmeceuticals. Anti-inflammatory effects in dermatological disorders C. asiatica exerts broad anti-inflammatory actions relevant to multiple inflammatory skin conditions such as acne and atopic dermatitis. Its constituents effectively modulate inflammation through inhibition of nuclear factor kappa B (NF-κB) signaling pathways and suppression of downstream inflammatory mediators. Madecassoside, in particular, has shown the ability to reduce interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and toll-like receptor 2 (TLR2) expression in macrophages stimulated by Cutibacterium acnes, suggesting its immunomodulatory properties extend beyond simple antimicrobial effects. In atopic dermatitis models, phytosomal formulations of C. asiatica have been reported to significantly reduce serum IgE levels, mast cell infiltration, cyclooxygenase-2 (COX-2) activity, and NF-κB signaling, thus rationalizing further clinical exploration as a potential topical immunotherapeutic agent (Park 2021a; Wang et al. 2024a). Clinical evidence and safety Although fewer in number than preclinical studies, early human data show improvements in hydration, transepidermal water loss (TEWL), elasticity, and wrinkle appearance with topical C. asiatica–containing formulations, as well as signals in scar management with triterpenoid-focused carriers. Table 3 provides clinical studies of C. asiatica for its efficacy in dermatological and cosmetic applications. Clinical evidence supports the efficacy of Centella asiatica across a spectrum of dermatological conditions, including wound healing, scar management, skin aging, and barrier dysfunction. A randomized controlled trial (RCT) involving 280 postoperative carpal tunnel release patients demonstrated that twice-daily topical application of a 1% C. asiatica cream significantly improved scar outcomes as measured by the Vancouver Scar Scale (VSS); the mean VSS score was reduced by 2.1 points in the treatFigure 2. Mechanism of action of asiaticoside across the wound healing phases. Handayani R et al.: Centella asiatica (L.) Urb. in skin health and cosmeceuticals6 ment group versus 0.8 in the control group after 8 weeks (p < 0.01), with reduced postoperative pain and improved functional hand outcomes assessed by the QuickDASH questionnaire (Balevi and Balevi 2023). Such findings reinforce the potential of C. asiatica formulations in postoperative scar management. In anti-aging contexts, topical formulations of C. asiatica have yielded promising clinical results. An open-label RCT enrolling 104 periand postmenopausal women found that daily application of an asiaticoside-based serum significantly enhanced skin elasticity (+22%), hydration (+18%), and collagen synthesis, in addition to normalizing skin microbiome composition (Korkina et al. 2024). Similarly, a double-blind RCT involving 60 participants using a 3% C. asiatica emulsion reported a 15–20% reduction in wrinkle depth and increased skin firmness without any observed irritation, emphasizing both efficacy and tolerability (Poomanee et al. 2023). C. asiatica’s effectiveness in promoting wound healing has also been well documented through observational syntheses, particularly for formulations containing asiaticoside (0.2–0.4%) or titrated extract of C. asiatica (TECA; e.g., Madecassol). These preparations have consistently shown increased synthesis of collagen I, fibronectin, and hydroxyproline – critical biomarkers of wound repair – translating to accelerated wound closure rates. Notably, clinical case series with TECA ointment demonstrated wound contraction improvements of 25–40% compared with standard care (Arribas-López et al. 2022). Furthermore, formulations specifically targeting barrier repair and hydration, including creams and hydrogels containing 2.5% and 5% C. asiatica extracts, have demonstrated significant reductions in transepidermal water loss (TEWL) alongside improved hydration of the stratum corneum, further validating the anti-inflammatory and barrier-restorative properties of the plant (Ratz-Łyko 2016). Emerging data from advanced formulations such as extracellular vesicles (EVs) derived from C. asiatica further enhance its dermatological promise. A short-duration study involving 25 participants showed that topical application of C. asiatica–derived EVs significantly reduced pore area and wrinkle depth while simultaneously enhancing skin hydration and dermal density. Notably, these benefits occurred without any irritation, as confirmed by patch testing in additional participants, underscoring both the effectiveness and the favorable safety profile of novel vesicular formulations (Park and Shin 2025). Additionally, C. asiatica demonstrates efficacy in inflammatory skin conditions. Studies utilizing phytosomal formulations of C. asiatica (0.2–0.4%) in models of atopic dermatitis have shown substantial decreases in inflammatory markers such as immunoglobulin E (IgE), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and mast cell counts through modulation of the NF-κB signaling pathway (Park et al. 2017). These findings indicate potential therapeutic utility in managing chronic inflammatory skin disorders. Formulation and advanced delivery systems Optimizing dermal delivery of C. asiatica bioactive compounds – particularly triterpenoids such as asiaticoside and madecassoside – is pivotal for enhancing therapeutic efficacy due to their inherently limited skin permeability and instability in traditional aqueous formulations. Advanced carrier systems, including hydrogels, liposomes, niosomes, phytosomes, transfersomes, exosomes, nanocomposites, microneedles, nanofibers, nanoparticles, and lipid-based delivery platforms, have been developed to overcome these challenges. These novel delivery technologies can significantly enhance dermal penetration, stability, targeted delivery, and overall bioavailability of C. asiatica constituents. The key characteristics, formulation descriptions, and documented benefits of various advanced carrier systems are summarized in Table 4a, b. Table 3. Clinical studies of C. asiatica in dermatology. Study and population Indication Dosage/form Key outcomes References RCT, n = 280 (CTR post-op patients) Scar management 1% topical cream, 2×/day, 6 months ↓ Vancouver Scar Scale (VSS), ↓ VAS pain, improved QuickDASH (Balevi and Balevi 2023) Open-label RCT, n = 104 (peri/postmenopausal women) Skin aging Daily serum (asiaticosidebased) ↑ Elasticity, hydration, collagen; microbiome normalization (Korkina et al. 2024) Double-blind RCT, n = 60 Wrinkles/elasticity 3% C. asiatica emulsion ↓ Wrinkle depth, ↑ skin firmness, no irritation (Poomanee et al. 2023) Observational synthesis Wound healing Asiaticoside 0.2–0.4%, TECA/ Madecassol ↑ Collagen I, fibronectin, hydroxyproline; faster healing (Arribas-López et al. 2022) HR-1 mice and ex vivo study Atopic dermatitis 0.2%–0.4% C. asiatica phytosome ↓ IgE, COX-2, iNOS, TNF-α, mast cells (via NFκB) (Park et al. 2017) 4-week human study (n=25) Hydration/ barrier Cream/hydrogel (2.5% and 5%) ↓ TEWL, ↑ stratum corneum hydration, anti-inflammatory (A. Ratz-Łyko 2016) 2-week human study (n=20, mean age 50.7 years) + patch test (n=30) Anti-aging/wrinkle reduction Ampoule with C. asiaticaderived extracellular vesicles (EVs) ↓ Pore area (−17.9%), ↓ wrinkle depth (−7.8–18.8%), ↑ hydration and dermal density, 0 irritation in 24-h test (Park and Shin 2025) Pharmacia 72: 1–13 7 Table 4. a. Nanoparticle-based delivery systems of C. asiatica for skin applications. b. Lipid-based vesicular delivery systems of C. asiatica for skin applications. System type Formulation description Characteristics Benefit Key outcome References a Nanoparticles Alginate–chitosan asiaticoside nanoparticles Size TEM: 392.4 ± 17.5 nm; DLS: 563.1 ± 18.2 nm; PDI ≈ 0.2 Stability, antiproliferative activity Oncology-relevant delivery model (Liu et al. 2023) Asiaticosideencapsulated alginate– chitosan nanoparticles (ACNPs) Size DLS: 489 nm; PDI: 0.538; Zeta: –13.5 mV; Size EE%: >90% Controlled drug release, improved stability ACNPs showed spherical morphology, high encapsulation (>90%), and controlled release (~10% in 24 h) (Kunjumon et al. 2024) Chemically reduced with citrate/NaBH₄, PEG-SH stabilized 30–32 nm (DLS), <10–30 nm (TEM); Zeta +1.43 mV PEGylated, stable, uniform Homogeneous spherical NPs, sterically stable (Khalili Hassanabad et al. 2025) Nanosuspension 10% nanosuspension (200 nm) with PVP K30 Size DLS: 190–230 nm; PDI < 0.3 5× better skin absorption, fast release Stable and non-irritant for cosmetics (Kim et al. 2021) Nanoemulgel Asiatic acid nanoemulsion + virgin coconut oil in gel Size: 131.8 ± 0.3 nm; EE%: 94.9% 99.86% wound contraction by day 20 Excellent permeation and biocompatibility (Mahadev et al. 2025) Solid Lipid Microparticles (SLM) Lipid microparticles for acne delivery Size: 7.5–38.9 µm; EE%: 31–100%; LA: 90–95% Controlled release, proven anti-acne activity Promising topical therapy (Chutoprapat et al. 2024) Nanostructured lipid carrier (NLC) NLC with glycolate and dry extract of C. asiatica Size: 118–140 nm; PDI ~0.20; Zeta: −28 to −35 mV; EE: dry extract (89–93%), glycolic extract (29–45%); stable up to 180 days Accelerated skin permeation Topical delivery enhancement (da Rocha et al. 2019) Microneedles Chitosan MN patch for C. asiatica Type I: 404 μm height; Type II: 372 μm height Dermal penetration, drug stability Advanced delivery platform (Ryall et al. 2022) 3D-printed microneedles with madecassoside Needle height 1143.97 ± 37.74 μm, base diameter 709.21 ± 53.5 μm, tip diameter 24.25 ± 2.87 μm Site-specific soft tissue delivery Emerging transdermal strategy Suitable for periodontal soft tissue regeneration (He et al. 2025) CS-AS-BSP MNs (chitosan tip + Bletilla striata polysaccharide base), lyophilized Height ~600 μm, bottom diameter ~300 μm Bilayer structure allows control of AS release, penetrating the epidermis Promotes scar-free wound healing and controlled release of AS for 7 days. (Lv et al. 2023) Nanofibers PCL/PEO nanofiber CA-AgNPs Fiber diameters: thin (PEO) 100–150 nm, thick (PCL) 350–600 nm; CAAgNPs size 14.8 ± 7.3 nm, zeta potential −30.4 mV Controlled release, antimicrobial, wound healing Electrospun patch for burn/ wound (Bozkaya et al. 2022) Electrospun PVA nanofibers loaded with Centella asiatica extract Size Fiber diameter 100–450 nm Improved bioavailability, scar-free healing Synergistic scaffold-based design (Manotham et al. 2023) Nanocomposites ZnO-poloxamer + C. asiatica nanocomposite Size ~50 nm; ZP –17.4 mV; EE% 82.5 Angiogenesis, antibacterial, diabetic wound healing Multifunctional; diabetic application (Wang et al. 2024) SiO₂ nanocomposite prepared with 1–10 wt% extract + C. asiatica extract vial ball Milling method Size ↓ with longer milling (qualitative SEM) Antioxidant stable and non-toxic Stable nanocarrier for anti-aging (Ebau et al. 2023) Sol–gel magnetic Nanocomposite Size: 68.57 nm (FE-SEM, ImageJ); Drug loading efficiency: 55.53% (pH 1.2), 57.83% (pH 7.4) Antioxidant and antifungal properties Preclinical only; low dermatological validation (Sahara et al. 2025) Hydrogel/ Nanohydrogel Chitosan–gelatin hydrogel with asiaticoside Sustained release of ~80% in 24 h) Biocompatible scaffold, controlled asiaticoside release, printable and stable Strong in vitro evidence; needs animal/human Validation (Witkowska et al. 2025) Handayani R et al.: Centella asiatica (L.) Urb. in skin health and cosmeceuticals8 System type Formulation description Characteristics Benefit Key outcome References Hydrogel/ Nanohydrogel Asiaticosideloaded polymeric nanoparticles With gelatin-based hydrogel 168.4 nm; PDI 0.09 Enhanced permeability and collagen stimulation Effective in animal wound models (Narisepalli et al. 2023) Asiatic acid + HA/CS/ gelatin hydrogel with ZnO and CuO NPs Porous; ESR 1068%, gel content 85% Burns healing, angiogenesis, reepithelialization, TNF-α Suppression Potential for clinical burns (↑ re-epithelization, collagen, angiogenesis; ↓ TNF-α, ↑ MMP2) (Thanusha et al. 2018) Chitosan–methacrylic acid nanogel madecassoside delivery >95% release at pH 7.4 (24h) pH-responsive release of madecassoside Stable, controlled release (nonFickian diffusion) (Suhail et al. 2024) Controlled-release chitosan hydrogel (containing 3% asiaticoside + 3% chitosan) n/a (not reported) Antimicrobial, skin permeation, hyaluronidase inhibition Multi-functional, strong preclinical basis (good skin permeability (PAMPA); hyaluronidase inhibition; antimicrobial activity; effective wound healing in vitro (Witkowska et al. 2023) C. asiatica–based burn wound hydrogel n/a (not reported) Moisture retention, enhanced healing Topical burn treatment potential (Vajpayee et al. 2024) Biodegradable foam with asiaticoside Pore size: 228–262 μm; density inversely related to pore size Suitable pore size and porosity comparable to commercial wound dressings SEM showed round interconnected pores; Bl foam had slightly larger pores; porosity decreased with higher polymer conc.; density increased with polyols (Namviriyachote et al. 2019) b. Liposome Asiaticoside liposome hydrogel with graphene oxide Size: 179.8–200.1 nm; PDI: 0.144–0.217; Zeta: −15.6 to −20.7 mV; Encapsulation: 62.36–71.25%; Loading efficiency: 5.67–6.48% Reduced scarring, electrostimulation responsive Innovative multifunctional wound patch (Zheng et al. 2020) PECE thermosensitive liposomes with madecassoside Size: 213.43 ± 4.68 nm (range 175–220 nm depending on EPC:PECE ratio); Zeta: −23.8 ± 15.4 mV (stable) Enhanced wound healing Biocompatible, injectable (Liu et al. 2020) Soy lecithin– stigmasterol liposomes Size: 512.7 – 787.8 nm Phenolic stability, antioxidant potential Suitable for cosmeceutical/food delivery (Tripathy and Srivastav 2023) Niosomes Box–Behnken optimized niosomes Size: 127.8 nm; PDI: 0.22; Zeta: +1.3 mV; EE%: RHT = 67.2%, AS = 78.6% Stability, sustained release, transdermal efficacy Rational design; validated in vitro (Hnin et al. 2024) Centella asiatica extract (CAE-Nio) and HA-modified CAE-Nio Size: 155 nm; Zeta: −15 mV; EE%: 71–77% Improved dermal penetration and skin deposition High bioadhesiveness, strong dermal retention (Wichayapre echar et al. 2020) Phytosomes Titrated extract of Centella asiatica (TECA), topical application (0.2–0.4% cream) n/a (not reported) Anti-inflammatory, antioxidant, anti-atopic dermatitis Promising in dermatitis models, improved histopathology (Park et al. 2017) Transfersomes Asiatic acid transfersomal gel (AATG) Size: 27.15–63.54 nm; Zeta: −0.010 to −0.129 mV; %EE: up to 90.84% Clinical improvements in melanin index and hydration Clinical: ↓ melanin index, ↑elasticity (Opatha et al. 2024) Exosomes Topical ampoule of CICA-derived extracellular vesicles (EVs) n/a (not reported) Enhanced skin penetration Natural nanovesicle, anti-aging Clinical: Safe; ↓ pores and wrinkles; ↑ hydration and dermal density (Park and Shin 2025) Hydrogel dressings and nanofiber systems Hydrogel-based platforms for C. asiatica bioactives have been extensively developed to promote moist wound environments and enable controlled release of active compounds. For instance, polyurethane foam dressings infused with asiaticoside demonstrated enhanced wound healing in chronic and burn wounds via improved tissue hydration and antimicrobial action (Namviriyachote et al. 2019). Formulations combining chitosan, gelatin, or hyaluronic acid with asiaticoside or asiatic acid have shown Pharmacia 72: 1–13 9 excellent in vitro and in vivo efficacy, supporting re-epithelialization, angiogenesis, and collagen synthesis while reducing TNF-α and oxidative stress. Electrospun nanofiber mats further enhance wound contact and conformability. Silver nanoparticle–loaded nanofibers and PVAbased systems incorporating C. asiatica extract enabled slow, sustained release, promoted antibacterial activity, and accelerated wound closure in animal models (Bozkaya et al. 2022; Manotham et al. 2023). These systems offer improved physical coverage and topical bioavailability compared to conventional creams or gauze dressings. Vesicular delivery systems Vesicular nanocarriers – particularly liposomes, niosomes, phytosomes, and transfersomes – have proven highly effective in overcoming the skin barrier and enhancing dermal delivery of C. asiatica phytoconstituents. Liposomes, composed of phospholipid bilayers, facilitate the delivery of lipophilic compounds such as asiatic acid while maintaining skin hydration and reducing transepidermal water loss (Liu et al. 2020; Witkowska et al. 2023). Thermoresponsive and graphene oxide–integrated liposomal hydrogels have demonstrated additional functionalities such as electrostimulation responsiveness and scar reduction (Zheng et al. 2020). Niosomes, formed from nonionic surfactants and often surface-modified with hyaluronic acid, have been optimized for enhanced skin deposition. Formulations incorporating asiaticoside showed improved stability, sustained release, and deep epidermal delivery (Hnin et al. 2024; Wichayapreechar et al. 2020). Phytosomes, complexing polar bioactives such as madecassoside with phospholipids, offer enhanced anti-inflammatory action and better skin permeation, as demonstrated by the inhibition of NF-κB, COX-2, iNOS, and IgE in dermatitis models (Park et al. 2017). Transfersomes, known for their ultra-deformable membranes, have shown the highest transdermal efficiency among vesicular systems. Topical gels containing asiatic acid–loaded transfersomes significantly improved skin hydration and elasticity and reduced melanin levels in hypertrophic scar models, supported by early clinical trials (Opatha et al. 2024). Lipid-based nanocarriers and nanoemulsions Solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulgels, and solid lipid microparticles (SLMs) have been extensively utilized to encapsulate C. asiatica actives. These sub-100 nm systems protect unstable compounds from degradation and improve their dermal bioavailability. NLCs containing asiaticoside penetrated the stratum corneum more effectively than free extracts, yielding a 50–60% increase in biological activity – especially in collagen stimulation and wound contraction (da Rocha et al. 2019; Kim et al. 2021; Krzyżostan et al. 2024). Similarly, nanoemulsion formulations based on asiatic acid and natural oils (e.g., virgin coconut oil) achieved near-complete wound closure within 20 days (Mahadev et al. 2025). SLMs, tailored for acne treatment, improved asiatic acid stability and showed controlled release and anti-acne effects in vitro and in vivo (Chutoprapat et al. 2024). These systems are notable for their GRAS-compliant components and scalable manufacturing potential in cosmeceuticals. Microneedle patches Microneedle (MN) arrays fabricated from biodegradable polymers such as chitosan or Bletilla striata represent a transformative technology for transdermal C. asiatica delivery. These arrays bypass the stratum corneum and deliver bioactives directly into the dermis with minimal discomfort (Ryall et al. 2022). Recent studies showed that asiaticoside-loaded dissolvable MNs downregulated TGF-β1 and COL1 expression, supporting scarless wound healing (Lv et al. 2023). Additionally, 3D-printed MNs containing madecassoside offer targeted dermal therapy for localized dermatologic indications (He et al. 2025). This delivery method is particularly promising for regenerative and anti-aging applications where deeper tissue penetration is required. Silica-based and other nanocomposites Nanocomposites utilizing inorganic matrices such as porous silica or metal oxides are increasingly used to stabilize C. asiatica compounds and enable targeted dermal effects. Ebau et al. (2023) developed a silica-based nanocomposite that preserved antioxidant activity and protected keratinocytes from oxidative stress – an essential mechanism in anti-aging therapy. Similar formulations with ZnO or magnetic oxides demonstrated antimicrobial, antioxidant, and angiogenic effects in diabetic wound and fungal models (Wang et al. 2024; Sahara et al. 2025). While these systems show promise, long-term dermatological safety and regulatory pathways remain areas for further investigation. Safety and toxicological profile C. asiatica is widely regarded as safe and well tolerated for both topical and oral use, supported by its long-standing inclusion in traditional medicine and cosmeceutical formulations. Nevertheless, systematic safety evaluation remains critical, particularly in high-concentration extracts, nanoformulations, and prolonged-use topical products targeting sensitive or compromised skin. Adverse reactions to topical C. asiatica are rare and typically mild. The