OBJECTIVE: To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.
METHODS: SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes, and histological changes of the thoracic aorta were evaluated using HE staining. In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings, the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine (NE)- and KCl-induced constriction. The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester, indomethacin, zinc protoporphyrin Ⅸ, tetraethyl ammonium chloride, glibenclamide, barium chloride, Iberiotoxin, 4-aminopyridine, or TASK-1-IN-1. The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.
RESULTS: Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology. While not obviously affecting resting aortic rings with intact endothelium, asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE, but its effects differed between endothelium-intact and endothelium-denuded rings. In endothelium-intact aortic rings pretreated with indomethacin, ZnPP Ⅸ, barium chloride, glyburide, TASK-1-IN-1 and 4-aminopyridine, asiaticoside did not produce significant effect on NE-induced vasoconstriction, and tetraethylammonium, Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside. In KCland NE-treated rings, asiaticoside obviously inhibited CaCl2-induced vascular contraction.
CONCLUSIONS: Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening, promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow, thereby reducing systolic blood pressure in rats.

The skin is the largest organ and a crucial barrier for protection against various intrinsic and extrinsic factors. As we age, the skin\'s components become more vulnerable to damage, forming wrinkles. Among different procedures, hyaluronic acid-based hydrogel has been extensively utilized for skin regeneration and reducing wrinkles. However, it has limitations like low retention and weak mechanical properties. In this study, we suggested the poly(l-lactic acid) (PLLA) microparticles containing alkaline magnesium hydroxide and nitric oxide-generating zinc oxide and rejuvenative hyaluronic acid (HA) hydrogels including these functional microparticles and asiaticoside, creating a novel delivery system for skin rejuvenation and regeneration. The fabricated rejuvenative hydrogels have exhibited enhanced biocompatibility, pH neutralization, reactive oxygen species scavenging, collagen biosynthesis, and angiogenesis capabilities in vitro and in vivo. Additionally, an excellent volume retention ability was demonstrated due to the numerous hydrogen bonds that formed between hyaluronic acid and asiaticoside. Overall, our advanced injectable hydrogel containing functional microparticles, with controlled release of bioactive molecules, has a significant potential for enhancing the regeneration and rejuvenation of the skin.

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.

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.

As interest in skin aesthetics increases, treatments to suppress aging are increasing. Among them, a facelift is the most effective procedure for improving wrinkles. However, side effects including inflammatory reactions occur due to the limitations of the PDO thread itself used during the procedure. In this paper, to improve the function of PDO thread, inorganic particles such as magnesium hydroxide (MH) and zinc oxide (ZO) and a biologically active agent, asiaticoside, were coated on the surface of PDO thread using ultrasonic coating technology. The coated thread exhibited excellent biocompatibility, promoted collagen synthesis, reduced inflammation, and stimulated angiogenesis in vitro and in vivo. The multifunctional PDO thread has shown promising potential for skin regeneration without inducing fibrosis. Such a practical coating system and the developed multifunctional PDO thread suggest new possibilities for developing safer and more effective materials in cosmetic and regenerative medicine to prevent aging and improve skin aesthetics.

Excessive abdominal fat deposition in chickens is a major concern in the poultry industry. Nutritional interventions are a potential solution, but current options are limited. Asiaticoside (Asi), a herbal extract, has shown positive effects in animals, but its impact on poultry lipid metabolism is still unknown. In this study, the effects of dietary Asi on yellow-feathered chicken lipid metabolism and its potential mechanisms were investigated. A total of 120 chickens were randomly divided into three groups, with five replicates per group and 8 chickens per replicate. The chickens were fed a basal diet supplemented with 0, 0.01, or 0.05% Asi for 6 wk. The results showed that Asi down-regulated lipogenic gene expression and up-regulated lipid-breakdown-related genes in both the liver and fat tissues of the chickens, which resulted in a half reduction in abdominal fat while not affecting meat yield. Mechanistically, the hepatic and adipose PI3K/AKT pathway may be involved in Asi-induced fat loss in chickens as revealed by computer-aided reverse drug target prediction and gene expression analysis. Moreover, Asi ingestion also significantly modified the cecal microbiota of the chickens, resulting in a reduced Firmicutes to Bacteroidetes ratio and decreased abundance of bacteria positively correlated with abdominal fat deposition such as Ruminococcus, while increasing the abundance of bacteria inversely correlated with abdominal fat deposition such as Lactobacillus, Bacteroides, and Blautia. Collectively, these data suggest that Asi could ameliorate the abdominal fat deposition in yellow-feathered chickens, probably through modulating the PI3K/AKT pathway and gut microbiota function.

Alzheimer\'s disease (AD) is a prevalent neurodegenerative disorder, hallmarked by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles. Due to the uncertainty of the pathogenesis of AD, strategies aimed at suppressing neuroinflammation and fostering synaptic repair are eagerly sought. Asiaticoside (AS), a natural triterpenoid derivative derived from Centella asiatica, is known for its anti-inflammatory, antioxidant, and wound-healing properties; however, its neuroprotective function in AD remains unclear. Our current study reveals that AS, when administered (40 mg/kg) in vivo, can mitigate cognitive dysfunction and attenuate neuroinflammation by inhibiting the activation of microglia and proinflammatory factors in Aβ1-42-induced AD mice. Further mechanistic investigation suggests that AS may ameliorate cognitive impairment by inhibiting the activation of the p38 MAPK pathway and promoting synaptic repair. Our findings propose that AS could be a promising candidate for AD treatment, offering neuroinflammation inhibition and enhancement of synaptic function.

Ischemia/reperfusion injury (I/R) is the major cause of acute kidney injury, which becomes a global health problem. The effects of asiaticoside, as an anti-inflammatory drug, on renal ischemia-reperfusion injury have not been well defined. After the CD4+ cells were treated with asiaticoside, the CD4+CD25+FOXP3+ Treg cell differentiation was detected by flow cytometry. The viability and release of inflammatory factors of CD4+CD25+FOXP3+ Treg cell were detected by CCK-8 and ELISA. Renal I/R injury mice model was established, and the mice were pre-treated with asiaticoside or CD25 antibody or infused with Treg cells. The histological changes of renal tissue were evaluated by Hematoxylin-eosin, PAS, and Masson staining. The renal function markers were evaluated by colorimetry, the release of inflammatory factors was determined by ELISA. The Th17 and Treg cells in the blood and spleen were quantified by flow cytometry. The expressions of FOXP3 and RoR-γt in renal tissues were determined by western blotting. Asiaticoside promoted CD4+CD25+FOXP3+ Treg cell differentiation, increased the cell viability and down-regulated TNF-α, IL-1β, and IL-6, while up-regulated IL-10 of CD4+CD25+FOXP3+ Treg cells. Moreover, asiaticoside ameliorated the histological damage, decreased the Th17 cells and increased Treg cells, and down-regulated the TNF-α, IL-1β, IL-6, blood urea nitrogen, serum creatinine, and RoR-γt, while up-regulated IL-10 and FOXP3 of renal I/R injury mice. Effect of asiaticoside on renal I/R injury mice was reversed by CD25 antibody whose role was further reversed by Treg cell infusing. In conclusion, asiaticoside ameliorated renal I/R injury due to promoting CD4+CD25+FOXP3+ Treg cell differentiation.

The intranasal route of drug administration offers an opportunity to bypass the blood-brain barrier and deliver compounds directly into the brain. Scientific evidence exists for medicinal plants (e.g., Centella asiatica and Mesembryanthemum tortuosum) to treat central nervous system conditions such as anxiety and depression. The ex vivo permeation of selected phytochemicals (i.e., asiaticoside and mesembrine) has been measured across excised sheep nasal respiratory and olfactory tissue. Permeation studies were conducted on individual phytochemicals and C. asiatica and M. tortuosum crude extracts. Asiaticoside exhibited statistically significantly higher permeation across both tissues when applied alone as compared to the C. asiatica crude extract, while mesembrine permeation was similar when applied alone or as M. tortuosum crude extract. Permeation of all the phytocompounds was similar or slightly higher than that of the drug atenolol across the respiratory tissue. Permeation of all the phytocompounds was similar to or slightly lower than that of atenolol across the olfactory tissue. In general, the permeation was higher across the olfactory epithelial tissue than across the respiratory epithelial tissue and therefore showed potential for direct nose-to-brain delivery of the selected psychoactive phytochemicals.

The aim of this study was to investigate the underlying protective mechanisms of asiaticoside (AS) against liver fibrosis (LF) both in vivo and in vitro. A rat model with carbon tetrachloride (CCl4)-induced liver fibrosis is employed to verify the effect and mechanism of AS on the process of liver fibrosis in vivo experiment. Hematoxylin/eosin and sirius red staining was conducted to assess the severity of liver injury and fibrosis. Further, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), glutamyl transferase (GGT), and total bilirubin (TBil) were measured. In addition, LX2 cells were cultured for vitro experiment to investigate the influence of AS on hepatic stellate cells (HSCs). Overproduction of α-smooth muscle actin and type I collagen is characteristic of LF and HSCs, as determined by immunohistochemical and Western blot analyses. The expression levels of molecules associated with the Notch signaling pathway (i.e., Notch-1, Jagged-1, and Delta-like-4) were assessed by Western blot analysis. The results revealed that AS attenuated LF, as defined by reduced deposition of collagen, expression of α-smooth muscle actin and collagen type 1, and expression of biochemical parameters (alanine aminotransferase, aspartate aminotransferase, and hydroxyproline). Notably, AS suppressed the expression levels of Notch-1, Jagged-1, and Delta-like-4 in activated HSCs and LF. Collectively, these results demonstrate that AS prevented the progression of LF by modulating the Notch signaling pathway, indicating that AS has potential therapeutic effects against LF.