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 a...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.展开更多
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, neuroc...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.展开更多
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 co...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.展开更多
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-f...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.展开更多
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...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.展开更多
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 pr...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展开更多
Background:Diabetic wounds pose significant clinical challenges due to impaired healing processes,often resulting in chronic,nonhealing ulcers.Asiaticoside(AC),a natural triterpene derivative from Centella asiatica,ha...Background:Diabetic wounds pose significant clinical challenges due to impaired healing processes,often resulting in chronic,nonhealing ulcers.Asiaticoside(AC),a natural triterpene derivative from Centella asiatica,has demonstrated notable anti-inflammatory and wound-healing properties.However,the synergistic effects of nitric oxide(NO)-a recognized promoter of wound healing-combined with AC in treating diabetic wounds remain inadequately explored.Methods:Ultraperformance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was utilized to identify differential metabolites and dysregulated metabolic pathways associated with diabetic wounds.Molecular docking analyses were conducted to confirm the binding affinity of AC to key therapeutic targets.The effects of asiaticoside-nitric oxide hydrogel(ACNO)on gene and protein expression were evaluated using reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and western blotting.In vitro experiments using sarcoma(SRC)agonists and inhibitors were performed to investigate the impact of ACNO therapy on the expression of SRC,STAT3,and other proteins in HaCaT cells.Results:Metabolomic profiling revealed that diabetic wounds in mice exhibited marked metabolic dysregulation,which was attenuated by ACNO treatment.Key metabolites modulated by ACNO included mandelic acid,lactic acid,and 3-hydroxyisovaleric acid.The primary metabolic pathways involved were methyl histidine metabolism and the malate-aspartate shuttle.Immunofluorescence staining confirmed that ACNO therapy enhanced angiogenesis,promoted cellular proliferation,and facilitated diabetic wound closure.RT-qPCR data demonstrated that ACNO regulated the transcription of critical genes(SRC,STAT3,EGFR,and VEGFA).Notably,ACNO attenuated SRC/STAT3 pathway activation while concurrently upregulating EGFR and VEGFA expression.Conclusions:These findings emphasize the therapeutic potential of ACNO hydrogel in diabetic wound healing through the modulation of metabolic pathways and the SRC/STAT3 signaling axis.By correlating altered metabolites with molecular targets,this study elucidates the pharmacodynamic foundation for ACNO's preclinical application and provides valuable insights into the development of targeted therapies for diabetic wound management.展开更多
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 skeleto...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.展开更多
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 ...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.展开更多
Centella asiatica(CA)has been reported to exert pharmacological effects on inflammatory diseases.In particular,CA possesses anti-inflammatory effects on macrophages;however,the precise intracellular mechanisms remain ...Centella asiatica(CA)has been reported to exert pharmacological effects on inflammatory diseases.In particular,CA possesses anti-inflammatory effects on macrophages;however,the precise intracellular mechanisms remain unclear.This study aimed to investigate the anti-inflammatory activity and intracellular signaling mechanism of a CA-active extract in a LPS-induced macrophage model of inflammation.In addition,FTIR spectra and RP-HPLC were used to analyze the centelloid compounds with known anti-inflammatory activity.We found that 70%EtOH extract(CA-70E)from CA alleviated oxidative damage and inflammation by reducing intracellular ROS forma-tion and the secretion of pro-inflammatory factors(NO,TNF-α,MCP-1,and IL-6).CA-70E inhibited the mRNA expression of inflammatory factors(iNOS,TNF-α,MCP-1,IL-6,IL-12,and COX-2)as well as phagocytic activity.Additionally,it suppressed the phosphorylation cascade of pro-inflammatory proteins and nuclei translocation of activated p65 protein in MAPK and NF-κB signaling system.The antagonistic study using anti-PRRs revealed that CA-70E decreased the secretion of TNF-α,MCP-1,and IL-6 by binding to TLR4,CR3,CD14,and dectin-1 re-ceptors.Meanwhile,FTIR spectra and RP-HPLC analyses showed that among the major centelloids,asiaticoside was the most abundant in CA-70E.We suggest that 70%EtOH extract of C.asiatica,with asiaticoside as a major compound,suppresses the phosphorylation in MAPK and NF-κB signaling pathways primarily via its action on TLR4,CR3,CD14,and dectin-1 receptors,thus decreasing the secretion of TNF-α,IL-6,and MCP-1.展开更多
基金supported by the Yeungnam University research grant in 2017。
文摘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.
基金supported by the National Natural Science Foundation of China,No.31271126,81372606
文摘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.
基金supported by the National Foundation for Science and Technology Development(NAFOSTED)of Vietnam(Grant No.106.16-2012.80)
文摘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.
基金Supported by the General Project of Anhui Provincial Health and Construction Commission,No.AHWJ2022b056.
文摘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.
文摘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.
文摘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
基金supported by the National Natural Science Foundation of China(No.82160770,82460792)the Outstanding Young Scientific and Technological Talents Project of Guizhou Province(No.2021-5639)+1 种基金the Zunyi Science and Technology Talent Platform Carrier Construction Project(No.ZSKRPT2023-1)scholarships from the China Scholarship Council(No.CSC-202008520012).
文摘Background:Diabetic wounds pose significant clinical challenges due to impaired healing processes,often resulting in chronic,nonhealing ulcers.Asiaticoside(AC),a natural triterpene derivative from Centella asiatica,has demonstrated notable anti-inflammatory and wound-healing properties.However,the synergistic effects of nitric oxide(NO)-a recognized promoter of wound healing-combined with AC in treating diabetic wounds remain inadequately explored.Methods:Ultraperformance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was utilized to identify differential metabolites and dysregulated metabolic pathways associated with diabetic wounds.Molecular docking analyses were conducted to confirm the binding affinity of AC to key therapeutic targets.The effects of asiaticoside-nitric oxide hydrogel(ACNO)on gene and protein expression were evaluated using reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and western blotting.In vitro experiments using sarcoma(SRC)agonists and inhibitors were performed to investigate the impact of ACNO therapy on the expression of SRC,STAT3,and other proteins in HaCaT cells.Results:Metabolomic profiling revealed that diabetic wounds in mice exhibited marked metabolic dysregulation,which was attenuated by ACNO treatment.Key metabolites modulated by ACNO included mandelic acid,lactic acid,and 3-hydroxyisovaleric acid.The primary metabolic pathways involved were methyl histidine metabolism and the malate-aspartate shuttle.Immunofluorescence staining confirmed that ACNO therapy enhanced angiogenesis,promoted cellular proliferation,and facilitated diabetic wound closure.RT-qPCR data demonstrated that ACNO regulated the transcription of critical genes(SRC,STAT3,EGFR,and VEGFA).Notably,ACNO attenuated SRC/STAT3 pathway activation while concurrently upregulating EGFR and VEGFA expression.Conclusions:These findings emphasize the therapeutic potential of ACNO hydrogel in diabetic wound healing through the modulation of metabolic pathways and the SRC/STAT3 signaling axis.By correlating altered metabolites with molecular targets,this study elucidates the pharmacodynamic foundation for ACNO's preclinical application and provides valuable insights into the development of targeted therapies for diabetic wound management.
基金supported by the Guangxi Science and Technology Base and Talent Special Project(AD23026030)the Guiding Funds of Central Government for Supporting the Development of the Local Science and Technology(ZY23055032)+2 种基金the National Natural Science Foundation of China(22277095)to Y.YResearch in the Z.L.group is supported by a Key Project at the Central Government level:the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(2060302)the National Technologies Key R&D Program of China(2022YFC2602000)。
文摘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.
文摘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.
基金supported by the"Regional Innovation Strategy(RIS)"through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(MOE)(2021RIS-001).
文摘Centella asiatica(CA)has been reported to exert pharmacological effects on inflammatory diseases.In particular,CA possesses anti-inflammatory effects on macrophages;however,the precise intracellular mechanisms remain unclear.This study aimed to investigate the anti-inflammatory activity and intracellular signaling mechanism of a CA-active extract in a LPS-induced macrophage model of inflammation.In addition,FTIR spectra and RP-HPLC were used to analyze the centelloid compounds with known anti-inflammatory activity.We found that 70%EtOH extract(CA-70E)from CA alleviated oxidative damage and inflammation by reducing intracellular ROS forma-tion and the secretion of pro-inflammatory factors(NO,TNF-α,MCP-1,and IL-6).CA-70E inhibited the mRNA expression of inflammatory factors(iNOS,TNF-α,MCP-1,IL-6,IL-12,and COX-2)as well as phagocytic activity.Additionally,it suppressed the phosphorylation cascade of pro-inflammatory proteins and nuclei translocation of activated p65 protein in MAPK and NF-κB signaling system.The antagonistic study using anti-PRRs revealed that CA-70E decreased the secretion of TNF-α,MCP-1,and IL-6 by binding to TLR4,CR3,CD14,and dectin-1 re-ceptors.Meanwhile,FTIR spectra and RP-HPLC analyses showed that among the major centelloids,asiaticoside was the most abundant in CA-70E.We suggest that 70%EtOH extract of C.asiatica,with asiaticoside as a major compound,suppresses the phosphorylation in MAPK and NF-κB signaling pathways primarily via its action on TLR4,CR3,CD14,and dectin-1 receptors,thus decreasing the secretion of TNF-α,IL-6,and MCP-1.
