苦杏仁苷是存在于苦杏仁等蔷薇科植物中的一种含氰基糖苷化合物。近年研究显示苦杏仁苷具有较好的抗纤维化作用,主要与调控相关细胞凋亡、控制有关胶原蛋白表达等密切相关。此外,苦杏仁苷抗肿瘤、抗炎等药理作用也取得明显进展,其通过...苦杏仁苷是存在于苦杏仁等蔷薇科植物中的一种含氰基糖苷化合物。近年研究显示苦杏仁苷具有较好的抗纤维化作用,主要与调控相关细胞凋亡、控制有关胶原蛋白表达等密切相关。此外,苦杏仁苷抗肿瘤、抗炎等药理作用也取得明显进展,其通过抑制细胞周期、诱导肿瘤细胞凋亡、调节免疫反应等抑制肿瘤生长,通过抑制炎症介质[白细胞介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)]表达,调节MAPK/NF-κB等信号通路,减轻炎症反应。但苦杏仁苷被β-葡萄糖苷代谢分解后形成有害物质氢氰酸,导致其临床应用受到限制。为解决苦杏仁苷生物利用度低、稳定性差限制其应用的问题,有研究将其开发成新型制剂,如自微乳化药物递送系统、纳米制剂、凝胶等,实现靶向递送并调控代谢路径,有效提高其稳定性和安全性,对提升苦杏仁苷的临床用药疗效具有重要的应用价值。该文基于国内外对苦杏仁苷的研究现状,通过检索中国知网、维普、PUBMED、Web of Science等国内外数据库,综述苦杏仁苷的药理作用及其制剂的研发进展,为苦杏仁苷的研究开发和临床应用提供科学依据。展开更多
Stigmasterol is a plant sterol with anti-apoptotic,anti-oxidative and anti-inflammatory effect through multiple mechanisms.In this study,we further assessed whether it exerts protective effect on human brain microvess...Stigmasterol is a plant sterol with anti-apoptotic,anti-oxidative and anti-inflammatory effect through multiple mechanisms.In this study,we further assessed whether it exerts protective effect on human brain microvessel endothelial cells(HBMECs)against ischemia-reperfusion injury and explored the underlying mechanisms.HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion(OGD/R)model,while a middle cerebral artery occlusion(MCAO)model of rats were constructed.The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance(SPR)and cellular thermal shift assay(CETSA).The results showed that 10μmol·L−1 stigmasterol significantly protected cell viability,alleviated the loss of tight junction proteins and attenuated the blood-brain barrier(BBB)damage induced by OGD/R in the in vitro model.Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites,including T692,a critical gatekeep residue of this receptor.Exogenous ephrin-A1(an EPHA2 ligand)exacerbated OGD/R-induced EPHA2 phosphorylation at S897,facilitated ZO-1/claudin-5 loss,and promoted BBB leakage in vitro,which were significantly attenuated after stigmasterol treatment.The rat MCAO model confirmed these protective effects in vivo.In summary,these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability,reducing the loss of tight junction proteins,and attenuating the BBB damage.These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.展开更多
文摘苦杏仁苷是存在于苦杏仁等蔷薇科植物中的一种含氰基糖苷化合物。近年研究显示苦杏仁苷具有较好的抗纤维化作用,主要与调控相关细胞凋亡、控制有关胶原蛋白表达等密切相关。此外,苦杏仁苷抗肿瘤、抗炎等药理作用也取得明显进展,其通过抑制细胞周期、诱导肿瘤细胞凋亡、调节免疫反应等抑制肿瘤生长,通过抑制炎症介质[白细胞介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)]表达,调节MAPK/NF-κB等信号通路,减轻炎症反应。但苦杏仁苷被β-葡萄糖苷代谢分解后形成有害物质氢氰酸,导致其临床应用受到限制。为解决苦杏仁苷生物利用度低、稳定性差限制其应用的问题,有研究将其开发成新型制剂,如自微乳化药物递送系统、纳米制剂、凝胶等,实现靶向递送并调控代谢路径,有效提高其稳定性和安全性,对提升苦杏仁苷的临床用药疗效具有重要的应用价值。该文基于国内外对苦杏仁苷的研究现状,通过检索中国知网、维普、PUBMED、Web of Science等国内外数据库,综述苦杏仁苷的药理作用及其制剂的研发进展,为苦杏仁苷的研究开发和临床应用提供科学依据。
基金supported by the Key Research Project of the Science&Technology Department of Sichuan Province,China(Nos.2021YFS0131 and 2020YFS0414).
文摘Stigmasterol is a plant sterol with anti-apoptotic,anti-oxidative and anti-inflammatory effect through multiple mechanisms.In this study,we further assessed whether it exerts protective effect on human brain microvessel endothelial cells(HBMECs)against ischemia-reperfusion injury and explored the underlying mechanisms.HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion(OGD/R)model,while a middle cerebral artery occlusion(MCAO)model of rats were constructed.The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance(SPR)and cellular thermal shift assay(CETSA).The results showed that 10μmol·L−1 stigmasterol significantly protected cell viability,alleviated the loss of tight junction proteins and attenuated the blood-brain barrier(BBB)damage induced by OGD/R in the in vitro model.Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites,including T692,a critical gatekeep residue of this receptor.Exogenous ephrin-A1(an EPHA2 ligand)exacerbated OGD/R-induced EPHA2 phosphorylation at S897,facilitated ZO-1/claudin-5 loss,and promoted BBB leakage in vitro,which were significantly attenuated after stigmasterol treatment.The rat MCAO model confirmed these protective effects in vivo.In summary,these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability,reducing the loss of tight junction proteins,and attenuating the BBB damage.These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.
