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Centella asiatica is an ethnomedicinal herbaceous species that grows abundantly in tropical and sub‐tropical regions of China, India, South‐Eastern Asia and Africa. It is a popular nutraceutical that is employed in various forms of clinical and cosmetic treatments. C. asiatica extracts are reported widely in Ayurvedic and Chinese traditional medicine to boost memory, prevent cognitive deficits and improve brain functions. The major bioactive constituents of C. asiatica are the pentacyclic triterpenoid glycosides, asiaticoside and madecassoside, and their corresponding aglycones, asiatic acid and madecassic acid. Asiaticoside and madecassoside have been identified as the marker compounds of C. asiatica in the Chinese Pharmacopoeia and these triterpene compounds offer a wide range of pharmacological properties, including neuroprotective, cardioprotective, hepatoprotective, wound healing, anti‐inflammatory, anti‐oxidant, anti‐allergic, anti‐depressant, anxiolytic, antifibrotic, antibacterial, anti‐arthritic, anti‐tumour and immunomodulatory activities. Asiaticoside and madecassoside are also used extensively in treating skin abnormalities, burn injuries, ischaemia, ulcers, asthma, lupus, psoriasis and scleroderma. Besides medicinal applications, these phytocompounds are considered cosmetically beneficial for their role in anti‐ageing, skin hydration, collagen synthesis, UV protection and curing scars. Existing reports and experimental studies on these compounds between 2005 and 2022 have been selectively reviewed in this article to provide a comprehensive overview of the numerous therapeutic advantages of asiaticoside and madecassoside and their potential roles in the medical future.

Centella asiatica, widely known as Gotu kola, is a traditional herb celebrated for its benefits in skin health and wound healing. Recent research has provided new insights into its efficacy, particularly through topical applications. This review highlights the plant’s mechanisms, focusing on its active compounds such as asiaticoside, madecassoside, asiatic acid, and madecassic acid, which enhance collagen synthesis, modulate inflammation, and offer antioxidant protection. Clinical trials have been collected and summarized that innovative delivery systems, such as hydrogels, nanostructures or microneedles, can accelerate wound healing, reduce wound size, and improve recovery times in various wound types, including diabetic ulcers and burns. Future research will likely refine these technologies and explore new applications, reinforcing the role of C. asiatica in contemporary wound care. Advances in formulation and delivery will continue to enhance the plant’s therapeutic potential, offering promising solutions for effective wound management.

Diabetes mellitus is a chronic disease with a high mortality rate and many complications. A non-healing diabetic foot ulcer (DFU) is one the most serious complications, leading to lower-extremity amputation in 15% of diabetic patients. Nanofibers are emerging as versatile wound dressing due to their unique wound healing properties, such as a high surface area to volume ratio, porosity, and ability to maintain a moist wound environment capable of delivering sustained drug release and oxygen supply to a wound. The present study was aimed to prepare and evaluate a polyvinyl alcohol (PVA)–sodium alginate (SA)–silk fibroin (SF)-based multifunctional nanofibrous scaffold loaded with asiaticoside (AT) in diabetic rats. The SEM findings showed that fibers’ diameters ranged from 100–200 nm, and tensile strengths ranged from 12.41–16.80 MPa. The crosslinked nanofibers were sustained AT over an extended period. The MTT and scratch assay on HaCat cells confirmed low cytotoxicity and significant cell migration, respectively. Antimicrobial tests revealed an excellent anti-microbial efficacy against P. aeruginosa and S. aureus bacteria. In-vivo study demonstrated better wound healing efficacy in diabetic rats. In addition, the histopathological studies showed its ability to restore the normal structure of the skin. The present study concluded that developed multifunctional nanofibers have a great potential for diabetic wound healing applications.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused mainly by immune dysregulation. This study explored the anti-inflammatory and immunomodulatory effects of the Centella asiatica ethanol extract (CA) on an AD-like dermal disorder. Treatment with CA inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in a dose-dependent manner in inflammatory stimulated HaCaT cells by interferon-γ (IFN-γ) and TNF-α-triggered inflammation. Eight-week-old BALB/c mice treated with 2,4-dinitrochlorobenzene (DNCB) were used as a mouse model of AD. In AD induce model, we had two types treatment of CA; skin local administration (80 µg/cm2, AD+CA-80) and oral administration (200 mg/kg/d, AD+CA-200). Interestingly, the CA-treated groups exhibited considerably decreased mast cell infiltration in the ear tissue. In addition, the expression of IL-6 in mast cells, as well as the expression of various pathogenic cytokines, such as TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, iNOS, COX-2, and CXCL9, was reduced in both AD+CA-80 and AD+CA-200 groups. Collectively, our data demonstrate the pharmacological role and signaling mechanism of CA in the regulation of allergic inflammation of the skin, which supports our hypothesis that CA could potentially be developed as a therapeutic agent for AD.

Centella asiatica extract is a valued plant material with known anti-inflammatory and anti-microbiological properties. Using the Design of Experiment (DoE) approach, it was possible to obtain an optimized water/alcoholic extract from Centella asiatica, which allowed the preparation of the final material with biological activity in the wound healing process. Studies on the novel applications of Centella asiatica in conjunction with the multifunctional chitosan carrier have been motivated by the plant’s substantial pharmacological activity and the need to develop new and effective methods for the treatment of chronic wounds. The controlled release of asiaticoside was made possible by the use of chitosan as a carrier. Based on the findings of investigations using the PAMPA skin assay, which is a model imitating the permeability of actives through skin, this compound, characterized by sustained release from the chitosan delivery system, was identified as being well able to permeate biological membranes such as skin. Chitosan and the lyophilized extract of Centella asiatica worked synergistically to block hyaluronidase, exert efficient microbiological activity and take part in the wound healing process, as proven in an in vitro model. A formulation containing 3% extract with 3% medium-molecular-weight chitosan was indicated as a potentially new treatment with high compliance and effectiveness for patients. Optimization of the chitosan-based hydrogel preparation ensured the required rheological properties necessary for the release of the bioactive from the chitosan delivery system and demonstrated a satisfactory antimicrobial activity.

The pharmaceutical and nutraceutical fields are limited in their use of asiaticoside (AS) due to its poor solubility in water. The study used a spray drying technique to design an AS dry nanoemulsion with drug-releasing properties improvement. A combination of high-speed homogenization and ultrasonication methods prepared nanoemulsion. The nanoemulsion formulation containing virgin coconut oil or VCO (13.55%, w/w) as oil phase, sucrose ester (SE) with HLB 3 (2.5%, w/w) as surfactant, and sodium caseinate (SC) (2%, w/w) as co-surfactant. Nanoemulsion formulation followed by spray drying was carried out to improve the physical and chemical characteristics of the product. AS shows the highest solubility in methanol (> 30mg/mL), while the solubility of AS in water is 0.297mg/mL. The in vitro release test of pure AS and dry nanoemulsion in two different media shows significant differences. Compared to pure AS and its physical mixture, the cumulative dissolved AS percentage in dry nanoemulsion is greater, at 51.48% in 0.1 N HCl medium pH 1.2 and 48.72% in phosphate buffer saline (PBS) medium pH 6.8. The nanoparticle morphology of the dried nanoemulsion is spherical with a rough surface. The diffractogram of the dry nanoemulsion shows that AS changed from a crystalline state to an amorphous state. The thermogram of the dried nanoemulsion shows a loss of crystallinity of the AS. The dry nanoemulsion formulation demonstrates superior drug release characteristics compared to the physical mixture and pure form due to its smaller particle size. This enhanced dissolution leads to greater solute availability, potentially resulting in higher oral absorption and bioavailability of AS.

Patients with diabetic foot ulcers usually suffer from inefficient epithelisation and angiogenesis accompanied by chronic wound healing. Diabetic foot ulcers remain a major challenge in clinical medicine; however, traditional treatments are incapable of transdermal drug delivery, resulting in a low drug delivery rate. We report the development of Ti 2 C 3 MXenes-integrated poly-γ-glutamic acid (γ-PGA) hydrogel microneedles to release asiaticoside (MN-MXenes-AS). Asiaticoside was loaded into PGA-MXenes hydrogel to facilitate cell proliferation while regulating angiogenesis. The characterisation and mechanical strength of the microneedles were investigated in vitro, and the wound-healing efficacy of the microneedles was confirmed in diabetic mice. MXenes significantly improved the mechanical strength of microneedles, while γ-PGA hydrogels provided a moist microenvironment for wound healing. Mice treated with MN-MXenes-AS demonstrated obvious improvements in wound healing process. We successfully fabricated an MXenes-integrated microneedle that possesses sufficient rigidity to penetrate the cuticle for subcutaneous drug delivery, thereby accelerating diabetic wound healing. We demonstrated that MN-MXenes-AS is effective in promoting growth both in vivo and in vitro. Collectively, our data show that MN-MXenes-AS accelerated the healing of diabetic foot ulcers, supporting the use of these microneedles in the treatment of chronic wounds. Graphical Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-associated mortality. Asiaticoside (AC) exhibits antitumor effects; however, to the best of our knowledge, the biological function of AC in CRC cells remains unclear. Therefore, the aim of the present study was to investigate the effect of AC on CRC cells. In the present study, CCK-8 and colony formation assays were performed to assess the effects of AV on human CRC cell lines (HCT116, SW480 and LoVo). Mitochondrial membrane potential was examined by JC-1 staining. Cell apoptosis and cell cycle were monitored by flow cytometry, and the expression of genes was evaluated using RT-qPCR and western blot analysis. Furthermore, the biological effect of AC in vivo was detected using a xenograft mouse model. The findings revealed that 2 µM AC suppressed the proliferation of CRC cells in a time- and dose-dependent manner, but had no adverse effects on normal human intestinal FHC cells at a range of concentrations. AC decreased the mitochondrial membrane potential and increased the apoptosis of CRC cells in a dose-dependent manner. Furthermore, AC induced cell cycle arrest at the G0/G1 phase. AC attenuated IκBα phosphorylation in a dose-dependent manner, thereby preventing P65 from entering the nucleus, and resulting in inhibition of the NF-κB signaling pathway. In addition, AC significantly reduced the expression of CDK4 and Cyclin D1 in a dose-dependent manner, significantly upregulated the activation of caspase-9 and caspase-3, and decreased the Bcl-2/Bax mRNA ratio. Furthermore, treatment with the NF-κB signaling pathway inhibitor JSH-23 significantly increased the cytotoxicity of AC in CRC cells. Findings of the xenograft mice model experiments revealed that AC significantly inhibited colorectal tumor growth in a dose-dependent manner. Overall, AC suppressed activation of the NF-κB signaling pathway by downregulating IκBα phosphorylation. This resulted in inhibition of CRC cell viability and an increase of cell apoptosis, which may form the basis of AC use in the treatment of patients with CRC.

Diabetic cardiomyopathy (DCM) is a chronic microvascular complication of diabetes that is generally defined as ventricular dysfunction occurring in patients with diabetes and unrelated to known causes. Several mechanisms have been proposed to contribute to the occurrence and persistence of DCM, in which oxidative stress and autophagy play a non‐negligible role. Diabetic cardiomyopathy is involved in a variety of physiological and pathological processes. The 5′ adenosine monophosphate‐activated protein kinase/nuclear factor‐erythroid 2‐related factor 2 (AMPK/Nrf2) are expressed in the heart, and studies have shown that asiaticoside (ASI) and activated AMPK/Nrf2 have a protective effect on the myocardium. However, the roles of ASI and AMPK/Nrf2 in DCM are unknown. The intraperitoneal injection of streptozotocin (STZ) and high‐fat feed were used to establish the DCM models in 100 C57/BL mice. Asiaticoside and inhibitors of AMPK/Nrf2 were used for intervention. Cardiac function, oxidative stress, and autophagy were measured in mice. DCM mice displayed increased levels of oxidative stress while autophagy levels declined. In addition, AMPK/Nrf2 was activated in DCM mice with ASI intervention. Further, we discovered that AMPK/Nrf2 inhibition blocked the protective effect of ASI by compound C and treatment with ML‐385. The present study demonstrates that ASI exerts a protective effect against DCM via the potential activation of the AMPK/Nrf2 pathway. Asiaticoside is a potential therapeutic target for DCM.

The most important component of intestinal ischemia/reperfusion (II/R) injury is damage to the intestinal mucosal barrier. In II/R injury, damage and restoration occur simultaneously. To develop a treatment for II/R injury, further knowledge about the restoration of intestinal barrier function is needed. Whether asiaticoside (AS) has positive effects on barrier function following II/R injury is unclear, although multiple studies have reported that AS enhances intestinal recovery after injury. In our study, we discovered that AS can reduce the intestinal Chiu score after II/R injury ( P < 0.05), increase intestinal barrier-associated protein expression ( P < 0.05) and increase PCNA and Ki-67 expression after II/R injury ( P < 0.05). Furthermore, following II/R injury, AS primarily activates FoxM1 expression, which promotes cell proliferation and enhances barrier function. TST (a FoxM1 inhibitor) administration significantly reversed the upregulation of FoxM1, as well as the intestinal epithelial proliferation and barrier function induced by AS pretreatment in rats after II/R injury. Therefore, our results reveal that AS promotes cell proliferation and barrier function by activating FoxM1 expression. Our findings may provide a new potential therapeutic approach for treating II/R injury with AS.