Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study

BACKGROUND Diabetic nephropathy(DN)is a severe microvascular complication of diabetes characterized by inflammation,oxidative stress,and renal fibrosis.Asiaticoside(AC)exhibits anti-inflammatory,antioxidant,and anti-fibrotic properties,suggesting potential therapeutic benefits for DN.This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2(NRF2)/heme oxygenase-1(HO-1)antioxidant pathway.METHODS The effects of AC on high glucose(HG)-induced proliferation,inflammation,oxidative stress,and fibrosis were evaluated in rat glomerular mesangial cells(HBZY-1)in vitro.A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury,inflammation,oxidative stress,and fibrosis.The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model.RESULTS AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats,including reduced body weight,and elevated blood glucose,serum creatinine,blood urea nitrogen,and 24-h urine protein.Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin(IL)-6,IL-8,tumor necrosis factor-alpha,reactive oxygen species,and malondialdehyde levels while increasing superoxide dismutase activity.Additionally,AC suppressed the expression of fibrogenic markers such as collagen I,collagen IV,and fibronectin.AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase(Quinone)1 protein expression in renal tissues and HG-induced HBZY-1 cells.CONCLUSION AC improves DN by reducing inflammation,oxidative stress,and fibrosis through the activation of the NRF2/HO-1 signaling pathway.These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.

Development of polyurethane foam dressing containing silver and asiaticoside for healing of dermal wound

Polyurethane foam dressings for dermal wounds were formulated with natural polyols in order to improve the foam characteristics and the release of 2 active agents,silver and asiaticoside(AS)as an antimicrobial agent and an herbal wound healing agent,respectively.The foam was instantly formed by interaction of polyols and diisocyanate.Hydroxypropyl methylcellulose,chitosan and sodium alginate were individually mixed with themain polyols,polypropylene glycol,in the formulation while the active componentswere impregnated into the obtained foam dressing sheets.Although the type and amount of the natural polyols slightly affected the pore size,water sorption-desorption profile and compression strength of the obtained foam sheets,a prominent effect was found in the release of both active components.Among natural polyols formulations,foam sheets with alginate showed the highest silver and AS release.Non-cytotoxicity of these foam sheets to human fibroblast cells was confirmed.Antimicrobial testing on four bacteria strains showed that 1mg/cm^2 silver in formulations with 6%of natural polyols and without natural polyols had sufficient content of the silver release with comparable inhibition zone and significantly larger zone than other formulations.In pig study,the foam dressing with 6%alginate,1mg/cm^2 silver and 5%AS could improve wound healing in both the percentage of the wound closure and histological parameters of the dermal wound without any dermatologic reactions.In conclusion,this innovative foam dressing had potential to be a good candidate for wound treatment.

Neuroprotective effects of Asiaticoside

In the central nervous system, Asiaticoside has been shown to attenuate in vitro neuronal damage caused by exposure to β-amyloid. In vivo studies demonstrated that Asiaticoside could attenuate neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion animals. In addition, Asiaticoside showed anxiolytic effects in acute and chronic stress animals. However, its potential neuroprotective properties in glutamate-induced excitotoxicity have not been fully studied. We investigated the neuroprotective effects of Asiaticoside in primary cultured mouse cortical neurons exposed to glutamate-induced excitotoxicity invoked by N-methyl-D-aspartate. Pretreatment with Asiaticoside decreased neuronal cell loss in a concentration-dependent manner and restored changes in expression of apoptotic-related proteins Bcl-2 and Bax. Asiaticoside pretreatment also attenuated the upregulation of NR2B expression, a subunit of N-methyl-D-aspartate receptors, but did not affect expression of NR2A subunits. Additionally, in cultured neurons, Asiaticoside significantly inhibited Ca^2＋ influx induced by N-methyl-D-aspartate. These experimental findings provide preliminary evidence that during excitotoxicity induced by Nmethyl-D-aspartate exposure in cultured cortical neurons, the neuroprotective effects of Asiaticoside are mediated through inhibition of calcium influx. Aside from its anti-oxidant activity, down-regulation of NR2B-contalning N-methyl-D-aspartate receptors may be one of the underlying mechanisms in Asiaticoside neuroprotection.

Production of asiaticoside from centella(Centella asiatica L.Urban)cells in bioreactor

Objective:To investigate the effects of some culture conditions on production of asialicoside from centella(Centella asiatica L.Urban)cells cultured in 5-L bioreactor.Methods:The centell cell suspension culture was conducted in 5-L bioreactor to investigate the growth and asiaticoside accumulation under various conditions.Asiaticoside content was determined by HPLC analysis.Results:The results showed that the cell growth and asiaticoside accumulation peaked after 24d of culture at an agitation speed of 150 r/min and aeration rate of 2.5 L/min.The cell biomass reached a maximum value of 302.45 g fresh weight(31.43 g dry weight)and growth index of 3.03with inoculum size of 100 g.However,asiaticoside content was the highest(60.08 mg/g dry weight)when culture was initiated with an inoculum size of 50 g.Conclusions:The present study found the suitable conditions for growth of centella cells and their asiaticoside production in bioreactor.

Enzymatic pretreatment and microwave extraction of asiaticoside from Centella asiatica

The extraction of asiaticoside from Centella asiatica by enzymatic pretreatment and microwave extraction (EPME) was studied in this article. The effects of several important factors such as temperature of enzymatic pretreatment, liquid to solid ratio and microwave radiation time were investigated by quadric regression orthogonal design experiment and were analyzed by response surface. An extraction model with well forecast performance was then established. The results indicate that the optimum extraction condition was as follows: liquid to solid ratio was 36mL/g, temperature of enzymatic pretreatment was 45℃, enzymatic time was 30min, and microwave ra-diation time was

The biosynthesis of asiaticoside and madecassoside reveals tandem duplication-directed evolution of glycoside glycosyltransferases in the Apiales

Certain plant species within the Apiales order accumulate triterpenoid saponins that feature a distinctive glucose-glucose-rhamnose(G-G-R)sugar chain attached at the C-28 position of the pentacyclic triterpene skeleton.Until recently,the genomic basis underlying the biosynthesis and evolution of this sugar chain has remained elusive.In this study,we identified two novel glycoside glycosyltransferases(GGTs)that can sequentially install the sugar chain’s second D-glucose and third L-rhamnose during the biosynthesis of asiaticoside and madecassoside,two representative G-G-R sugar chain-containing triterpenoid saponins produced by Centella asiatica.Enzymatic assays revealed the remarkable substrate promiscuity of the two GGTs and the key residues crucial for sugar-donor selectivity of the glucosyltransferase and rhamnosyltransferase.We further identified syntenic tandem gene duplicates of the two GGTs in the Apiaceae and Araliaceae families,suggesting a well-conserved genomic basis underlying sugar chain assembly that likely has evolved in the early ancestors of the Apiales order.Moreover,expression patterns of the two GGTs in pierced leaves of C.asiatica were found to be correlated with the production of asiaticoside and madecassoside,implying their involvement in host defense against herbivores and pathogens.Our work sheds light on the biosynthesis and evolution of complex saponin sugars,paving the way for future engineering of diverse bioactive triterpenoids with unique glycoforms.

Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were examined.Results:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities.Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity.Furthermore,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal.Conclusions:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.

A review on phytopharmaceutical importance of asiaticoside

Herbal plant materials have huge potential in the field of medicine,nutraceuticals,perfumery,beverages,fragrances,cosmetics and dyeing industry.Centella asiatica(L.)Urban(family:Apiaceae)(C.asiatica)is a very popular medicinal herb in Sri Lanka,Madagascar,India and other parts of Asia.Gotu kola,Brahmi and Mandukparniin are the synonyms of C.asiatica which is mainly used for improving memory power.The pharmacological importance of C.asiatica is mainly because of triterpenes such as asiatic acid,asiaticoside,madecassoside and madecassic acid,etc.C.asiatica is mainly used for the treatment of mental fatigue,anxiety,epidermal wound,eczema,leprosy,asthma,psoriasis,ulcers and vein diseases.Asiaticoside is a pentacyclic triterpenoid saponin having anti-depression,anti-tumor,anti-inflammatory,antioxidant properties and further it also possesses wound healing,antiulcer and anti-hepatofibrotic activities.It improved cognitive impairment in diabetic condition because of the decreased oxidative stress.Quantification of asiaticoside in C.asiatica has been done by several methods which were mainly based on high performance liquid chromatography methods using different compositions of mobile phase sand detection systems.In these days scientists are trying to discover novel medicine from natural sources for the development of better drugs.In this review we have collected information of asiaticoside in respect to its medicinal values,pharmacological activities,extraction,isolation,and other analytical aspects.So the present review will be supportive to the scientists who are trying to develop some novel medicines from asiaticoside for the better health prospects.