MADECASSOSIDE

UVB exposure induces oxidative damage and accelerates skin photoaging. Madecassoside (MA), a triterpenoid saponin from Centella asiatica (L.) Urban, has antioxidant and anti-inflammatory properties, but its role in ferroptosis remains unclear. This study aims to investigate the effects of MA against UVB-induced ferroptosis and elucidate its underlying mechanisms. Skin cells and a UVB-irradiated mouse model were established to assess the effects of MA on UVB-induced ferroptosis and skin damage. Skin cells and a UVB-irradiated mouse model were used to assess MA's effects on ferroptosis. ROS, lipid ROS, mitochondrial membrane potential and antioxidant enzyme activity were measured. Protein and gene expression of ferroptosis markers were analyzed via Western blot and qPCR. Transmission electron microscopy (TEM) examined mitochondrial morphology. UVB irradiation induced ferroptosis in human skin cells, characterized by lipid peroxidation, ROS accumulation, mitochondrial dysfunction, and antioxidant depletion. MA treatment significantly inhibited ferroptosis and restored redox balance. In mice, topical MA application enhanced collagen deposition, reduced epidermal thickening, and alleviated ferroptosis. Mechanistically, MA bound to and downregulated the NADPH-cytochrome P450 reductase (POR), a key regulator of ferroptosis and POR overexpression negated MA's protective effects. This study demonstrates that MA protects against UVB-induced ferroptosis via POR inhibition, highlighting its potential for therapeutic and cosmetic applications in preventing ferroptosis.

Platinum-based materials exhibit diverse biological activities, but their application in skincare is limited by poor targeting and low efficacy in treating inflammation and sensory irritation. Herein, we developed madecassoside-functionalized platinum (Pt-MAD) particles by integrating the bioactive plant-derived compound madecassoside (MAD) with platinum to enhance anti-inflammatory and neurogenic-soothing effects. These Pt-MAD complexes were encapsulated within liposomes to improve dispersion stability and transdermal delivery for dermatological applications. In vitro studies demonstrated that Pt-MAD liposomes outperformed conventional Pt-PVP liposomes in reducing inflammation, itch, and redness. MAD surface functionalization enabled targeted modulation of multiple inflammatory mediators, including TNF-α, IL-1β, and IL-17, thereby promoting rapid soothing while supporting epidermal barrier homeostasis through sustained regulation of neurogenic inflammatory pathways. To explore the underlying mechanism, AI-driven docking simulations were performed, revealing that Pt-MAD exhibited strong binding affinities toward key inflammatory receptors, including TRPV1, TRPA1, NK1R, H1R, ETAR. These findings highlight the therapeutic potential of Pt-MAD liposomes as a targeted and effective strategy for managing sensitive skin, offering rapid relief while supporting barrier homeostasis through IL-17-associated inflammatory modulation.

Madecassoside, one of the main bioactive compounds found in Centella asiatica extract, has long been used in the cosmetic regime for skin care with doubtful effects. The main objectives of this study are to investigate the effects of Madecassoside on skin wound healing, UVB-induced keratinocyte damages, and to search for its pharmacological mechanism. Here, using fully differentiated keratinocyte-like HaCaT cell monolayers as an in vitro model, we found that Madecassoside enhanced wound healing and protected against UVB-induced keratinocyte apoptosis and reduction of cell viability. Indeed, these pharmacological effects of Madecassoside were completely abolished by pretreatment of an intracellular Ca 2+ chelator (BAPTA), inhibitors of AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and extracellular signal-regulated kinase (ERK). In addition, our Western blotting analyses strongly indicated that Madecassoside-induced ERK phosphorylation was suppressed by pretreatment of BAPTA, inhibitors of AMPK and mTOR signaling. Collectively, these data suggested that Madecassoside promotes wound healing and reduces keratinocyte apoptosis after being damaged by UVB radiation, at least in part, via Ca 2+ /AMPK- and mTOR-dependent ERK phosphorylation.

Centella asiatica L. Urban (CA) is traditionally used in skin wound healing, and stable cultivation-related studies are currently being conducted to meet the growing demand in the food, cosmetics, and pharmaceutical industries. This study aimed to analyze the growth rate and target bioactive compound levels of a novel variety, giant CA (BT-care), according to cultivation period, and to compare the effects of extracts harvested at specific cultivation periods on skin health in human keratinocytes with those of general CA. Although yields increased with prolonged BT-care cultivation, the levels of madecassoside, asiaticoside, total polyphenols and radical scavenging activity were significantly higher at 75 days post-transplantation. Compared to general CA, BT-care extracts obtained at day 75 significantly enhanced glutathione peroxidase expression among antioxidant-associated genes in ultraviolet B (UVB)-irradiated HaCaT cells. In addition, BT-care dose-dependently upregulated gene expression involved in collagen synthesis, wrinkle prevention, and skin barrier reinforcement. Furthermore, the high-concentration of BT-care significantly reduced the phosphorylation of c-JUN NH 2 -terminal protein kinase and p38 mitogen-activated protein kinases. After 75 days of cultivation, BT-care significantly modulated protein levels associated with skin homeostasis, recovery, collagen synthesis, and skin barrier-related gene expression, which may be attributed to the elevated levels of active compounds. These findings indicate that BT-care may serve as a promising resource for food, cosmetic, and pharmaceutical applications aimed at promoting skin health.

Current acne therapies face major limitations, including antibiotic resistance and skin irritancy. In this study, a synergistic strategy combining cryptotanshinone and madecassoside was developed through functional complementarity. Antibacterial activity against Cutibacterium acnes was evaluated using minimum inhibitory concentration (MIC) and inhibition zone assays, while cytotoxicity was assessed using human keratinocytes (HaCaTs). Anti-inflammatory efficacy was quantified by measuring tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and prostaglandin E 2 (PGE 2 ) in lipopolysaccharide-stimulated macrophages and a copper sulfate (CuSO 4 )-induced zebrafish inflammatory model. Systemic safety was examined in zebrafish models (developmental toxicity and sodium dodecyl sulfate-induced irritation). Finally, macroscopic severity, histopathology, and serum cytokines were used to assess an oleic acid-induced rat acne model. Cryptotanshinone inhibited Cutibacterium acnes (minimum inhibitory concentration = 62.5 μg/mL) but exhibited cytotoxicity (>5 μg/mL) and irritancy (≥1000 μg/mL). Madecassoside eliminated cryptotanshinone-induced cytotoxicity and reduced irritation. Importantly, the combination maintained antibacterial efficacy while synergistically enhancing anti-inflammatory effects, achieving a 94% reduction in follicular hyperkeratosis compared with 39% for cryptotanshinone alone ( p < 0.01), alongside normalization of histopathology and cytokine levels. In conclusion, madecassoside functionally complements cryptotanshinone by neutralizing its cytotoxicity and irritancy, enabling a safe, synergistic therapy that concurrently targets antibacterial and anti-inflammatory pathways in acne pathogenesis.

C. asiatica (L.) Urban is a medicinal plant widely used in traditional Asian medicine with potential geroprotective properties. Its major bioactive compounds-including asiaticoside, madecassoside, asiatic acid, and madecassic acid-exhibit antioxidant, anti-inflammatory, regenerative, neuroprotective, and cytoprotective activities. Experimental studies demonstrate modulation of signaling pathways involved in oxidative stress, inflammation, apoptosis, extracellular matrix remodeling, and cellular survival, including NF-κB, PI3K/Akt/mTOR, MAPK, Nrf2/HO-1, and TGF-β/Smad pathways. Preclinical evidence further indicates attenuation of cellular senescence, improvement of mitochondrial function, enhanced collagen synthesis, and regulation of cytokine production. In experimental models, C. asiatica has shown beneficial effects on wound healing, skin aging, neuroinflammation, β-amyloid aggregation, neuroplasticity, metabolic dysfunction, and vascular protection. Preliminary preclinical findings also suggest possible effects on telomerase activity and telomere maintenance. However, clinical translation remains limited due to insufficient randomized controlled trials, low oral bioavailability of triterpenoids, variability in extract standardization, and limited pharmacokinetic and long-term safety data. This narrative review summarizes the phytochemistry, molecular mechanisms, pharmacological activities, and potential geroprotective applications of c. asiatica, highlighting its translational relevance in healthy aging and age-related disorders while emphasizing the need for standardized clinical studies.

Centella asiatica has emerged as a strategic biomass for the sustainable production of high-value biochemicals at the interface of traditional medicine and modern biotechnology. This review consolidates the current knowledge on its phytochemical diversity, emphasizing triterpenoid saponins-asiaticoside, madecassoside, asiatic acid, and madecassic acid-as core bioactive molecules relevant to pharmaceutical, dermatological, nutraceutical, and functional-ingredient applications. Advances in green extraction technologies, including ultrasound-assisted, microwave-assisted, ohmic-heating, and supercritical CO 2 systems, have demonstrated superior efficiency in recovering high-purity biochemicals while significantly reducing solvent use, energy demand, and environmental impact compared with conventional methods. Complementary analytical and standardization platforms, such as HPLC, UPLC, and GC-MS, enable rigorous quality control across the entire value chain, supporting the development of reproducible and regulatory-compliant biochemical extracts. From a biomass valorization and biorefinery perspective, C. asiatica offers multiple metabolite streams that align with circular economy and field-to-market sustainability principles. Key challenges remain, including agronomic variability, scaling up green extraction, and supply chain resilience. However, emerging solutions, such as Good Agricultural and Collection Practices (GACP) guided cultivation, plant tissue culture, metabolic engineering, and integrated biorefinery frameworks, show strong potential for establishing a reliable and environmentally responsible production system. Collectively, C. asiatica represents a model species for sustainable biochemical production, combining scientific efficacy with industrial, economic, and ecological relevance.

This study presents the development and evaluation of Centella Asiatica (CA)-loaded transfersomes (CANP) as a novel nanocarrier for transdermal delivery. CANP were prepared using an oil-in-water emulsion method, producing nanoparticles with a size of 135.22 ± 4.80 nm, a polydispersity index of 0.22 ± 0.01, and a zeta potential of -26.13 ± 0.58 mV. Stability tests confirmed consistent physicochemical properties under various storage conditions, with encapsulation efficiencies above 68% for madecassoside and 89% for asiaticoside. Ex vivo permeation studies using porcine skin showed significantly improved skin penetration compared to liposomes and niosomes, attributed to the high deformability index (1.31 ± 0.21 mg/cm 2 ). In vitro cytotoxicity assays indicated cell viability above 80% across concentrations. Functionally, CANP reduced nitric oxide production in LPS-stimulated RAW 264.7 cells, demonstrating superior anti-inflammatory effects over native CA. CANP also promoted fibroblast proliferation and collagen production by 91.9% and 213.3% at days 7 and 14, respectively, exceeding vitamin C. Wound healing assays confirmed enhanced fibroblast migration and closure rates similar to fibroblast growth factor. In vivo , CANP hydrogels accelerated healing, with early fibroblast activity and collagen deposition between days 7-14, supporting epithelial regeneration over 21 days. Compared to controls, they more effectively reduced inflammation and increased dermal growth factor expression. These findings support CANP as a promising transdermal nanocarrier with enhanced skin penetration, anti-inflammatory activity, and regenerative potential. Encapsulating CA into transfersomes boosts its therapeutic efficacy, making it a strong candidate for advanced dermal applications.

Photorejuvenation is commonly employed to improve skin appearance but frequently leads to transient irritation and temporary impairment of skin barrier function. Incorporating platinum (Pt)-liposome technology along with soothing ingredients such as panthenol, dipotassium glycyrrhizate, madecassoside, and Portulaca oleracea extract is expected to offer enhanced reparative and anti-inflammatory effects, helping to alleviate post-procedural skin sensitivity and restore barrier integrity. This study aimed to evaluate the efficacy of a Pt-liposome-based facial mask in promoting skin recovery and soothing irritation post-photorejuvenation. Furthermore, the study assessed potential synergistic benefits from combining Pt-liposomes with established soothing agents. We initially assessed the reparative effects of Pt-liposomes using a 3D epidermal skin model and normal human epidermal keratinocytes (NHEK), evaluating parameters such as stratum corneum thickness, cholesterol content, ceramide chain length, and inflammatory responses (IL-8 mRNA expression) following lipopolysaccharide (LPS) stimulation. A randomized, split-face clinical trial involving 30 subjects who underwent photorejuvenation treatment was then conducted. Each participant applied the Pt-liposome-infused facial mask to one side of the face and a control product on the other side. Skin hydration, transepidermal water loss (TEWL), and erythema, tightness, dryness, and scaliness were assessed using objective instrumentation and subjective evaluations at baseline and various intervals up to 14 days post-treatment. In vitro testing showed that Pt-liposomes significantly increased stratum corneum thickness, cholesterol levels, and ceramide chain length (p < 0.01). Pt-liposomes also reduced histamine-induced calcium influx in NHEK cells (p < 0.01). In LPS-stimulated THP-1 cells, combined treatment with Pt-liposomes and soothing agents resulted in a greater reduction in IL-8 mRNA expression compared to either component alone (p < 0.01). Clinical measurements indicated that the application of the Pt-liposome-based facial mask significantly increased skin hydration and reduced TEWL compared to control (p < 0.001) from Day 1 to Day 14. Subjective and dermatological evaluations showed statistically significant improvements in erythema, tightness, dryness, and scaliness on the treated side at all measured time points. No adverse reactions were reported. The Pt-liposome-infused facial mask can effectively promote skin barrier repair, alleviate irritation, and enhance hydration following photorejuvenation. Its synergistic combination with soothing ingredients provides rapid relief from irritation and sustained therapeutic benefits, supporting its potential as a safe and effective option for post-procedural skincare.

The stratum corneum, which has a "brick-and-mortar" structure, serves as an impermeable barrier against pathogens while enabling gas and moisture exchange. Conventional wound dressings strive to reconcile these needs. They, often prioritize excessively porous structures, which compromise the barrier efficacy, or occlusive designs that hinder substance exchange. This leads to complications like infection, dehydration, or exudate accumulation. A biomimetic dual-layer dressing with an advanced barrier layer and regenerative bioactive components has been developed to address these limitations. Inspired by the brick-and-mortar structure, the barrier layer (Cu@KSF) was constructed using keratin microspheres (KM) and methacrylated silk fibroin, which was reinforced by photo-crosslinking and sandwich-like β-crystallites. The coordination of Cu 2+ with keratin carboxyl groups provided a bacterial barrier and inhibition, while maintaining optimal moisture transmission (1481.3-2246.1 g m -2 day -1 ) and oxygen permeability (258.4-401.5 mg m -2 day -1 ), outperforming the commercial Tegaderm™. Also, the bioactive layer (Mas@PKM) integrated the polydopamine-coated KM (PKM) with madecassoside-loaded liposomes, enabling pH-responsive drug release, rapid exudate absorption, and antioxidative activity. Furthermore, the Cu@KSF/Mas@PKM demonstrated biocompatibility while promoting cell migration, angiogenesis, anti-inflammatory effects, and collagen remodeling. It thereby accelerated infected and scald wound healing with reduced scarring. Combining the brick-and-mortar barrier and regenerative bioactivity, this degradable dressing resolved the trade-off between barrier functionality and substance exchange, providing a scalable solution for complex wound management.

Facial laser procedures may result in compromised skin barrier function and associated discomfort. It is essential to address these issues to facilitate a swift recovery and enhance patient satisfaction. To evaluate the efficacy and safety of a panthenol-enriched mask, incorporating centella asiatica extract (madecassoside) and bisabolol, in repairing the skin barrier after 1550 and 1927 nm dual-wavelength non-ablative fractional laser therapy. A total of 60 subjects were enrolled in this double-blind randomized study and were divided into Control group (CG) and Mask group (MG). Both groups received standard post-operative care, the MG receiving the Mask, while the CG received a saline dressing. Skin barrier repair was assessed using a skin physiological detection instrument, colorimetry, and a skin imaging analyzer (VISIA). The incidence of adverse reactions was also monitored. The MG exhibited significantly lower erythema index and hyperpigmentation index at D3, D7, and D14, compared to the CG. The MG had significantly higher sebum content than the CG at D7 and D14. The stratum corneum moisture content in the MG was also higher than in the CG at D3, D7, and D14. Additionally, transepidermal water loss (TEWL) was significantly reduced in the MG at D3, D7, and D14. There was no significant difference in the rate of adverse reactions between the groups. A panthenol-enriched Mask effectively decreased post non-ablative laser erythema, enhanced skin hydration, and promoted skin barrier repair.

The treatment of chronic diabetic wounds faces considerable challenges owing to complex environments in the wound bed, such as chronic inflammation, excessive reactive oxygen species (ROS), impaired extracellular matrix (ECM) and bacterial infection. Current strategies, including bandages, hydrogel dressings and medical devices, that focus solely on a few pathological features have limited success. Herein, a fast self-gelling polyacrylic acid (PAA) derivative/madecassoside (MA) particulate dressing with anti-inflammatory, antioxidative, collagen deposition-promoting and intrinsic antibacterial properties is developed to simultaneously regulate the wound microenvironment and promote tissue regeneration in infected diabetic wounds. The incorporation of N-[Tris(hydroxymethyl)methyl]acrylamides (THMA), a small molecule compound that has three hydroxy groups clustered together, into the PAA backbone confers the copolymer with self-gelation, robust wet tissue adhesion and a strong capacity to load MA via multiple hydrogen bonding. The developed dual-component particulate dressing effectively regulated macrophage polarization towards the anti-inflammatory phenotype, and displayed potent antibacterial activity against both Gram-positive S. aureus (99.2 %) and Gram-negative E. coli (90.8 %) at a dose of 8 mg mL -1 . Further, the dressing obviously accelerated the healing of full-thickness skin wounds compared with commercial fibrin glue in a S. aureus -infected diabetic mouse model. This multifunctional PAA-based wound dressing is potentially valuable for clinical applications towards diabetic foot ulcers, pressure ulcers and other conditions of acute or chronic wounds.