Objective: Kigelia africana, a tropical tree, which has long been used in African traditional medicine. The objective of the current study has been identifying the constituents of K. africana and verifying its utiliti...Objective: Kigelia africana, a tropical tree, which has long been used in African traditional medicine. The objective of the current study has been identifying the constituents of K. africana and verifying its utilities in traditional medicine. Materials and Methods: The methanol extract of K. africana fruits was subjected to chromatographic fractionation utilizing different techniques. The methanol extract together with the isolated compounds were tested for their bioactivities in a series of cell-based assays. Results: The current work led to isolation and characterization of nine constituents including iridoid glycosides, phenylpropanoid derivatives, and a eucommiol derivative. The hexanes extract caused inhibition of the opportunistic yeast; Cryptococcus neoformans Pinh. The chloroform extract exhibited substantial antileishmanial activity of Leishmania donovani. Verminoside(1) showed weak inhibition of the CB1, CB2, and Kappa opioid receptors. Compound 4 exhibited weak inhibition of the Kappa and Mu opioid receptors. The hexanes and the chloroform extracts of K. africana exhibited inhibitory activity against the pathogenic parasite Trypanosoma brucei. The ethyl acetate extract showed the same activity. Conclusions: This is the first report on the isolation of coniferyl 4-0-(3-D-glucopyranoside(7), a eucommiol derivative(crescentin IV)(6), and 6-feruloylcatalpol(4) from the genus Kigelia. It is also the first report on the separation of ajugol(2), catalpol(3), and specioside(5) from the fruits of K. africana. Revision of the^1 H and ^(13)C-NMR spectra of 6-feruloylcatalop(4) and 6-p-hydroxycinnamoylcatalpol(5, specioside) is described. Further, the results of the in vitro assays corroborate the traditional utility of this plant in medicine.展开更多
目的探究利拉鲁肽治疗早期2型糖尿病患者应用大麻素受体1型基因(CNR1)多态性对临床疗效的影响。方法选取2018年1月至2019年1月本院收治的230例确诊为早期2型糖尿病作为研究对象。所有患者均通过皮下注射方案给予利拉鲁肽,比较治疗前后...目的探究利拉鲁肽治疗早期2型糖尿病患者应用大麻素受体1型基因(CNR1)多态性对临床疗效的影响。方法选取2018年1月至2019年1月本院收治的230例确诊为早期2型糖尿病作为研究对象。所有患者均通过皮下注射方案给予利拉鲁肽,比较治疗前后患者的体重指数(BMI)、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1C),对CNR1基因1260G>A位点进行基因分型,比较不同基因分型的mRNA表达及不良反应发生率。结果GG型188例,GA型39例,AA型3例,其中等位基因频率最小为0.098。治疗后,患者BMI、FPG、2 h PG及HbA1c均低于治疗前(P<0.05)。GG型患者CNR1 mRNA表达水平与GA/AA型患者比较差异有统计学意义(P<0.05)。不同基因分型患者的药物治疗不良反应发生率比较差异无统计学意义。结论应用利拉鲁肽药物治疗早期2型糖尿病患者可取得良好的干预效果,其中CNR1基因1260G>A位点表达为GA型、AA型患者,其基因表达可能影响药物疗效。展开更多
Sulfur dioxide（SO_2） pollution in the atmospheric environment causes brain inflammatory insult and inflammatory-related microvasculature dysfunction.However,there are currently no effective medications targeting the...Sulfur dioxide（SO_2） pollution in the atmospheric environment causes brain inflammatory insult and inflammatory-related microvasculature dysfunction.However,there are currently no effective medications targeting the harmful outcomes from chemical inhalation.Endocannabinoids（eCBs） are involved in neuronal protection against inflammation-induced neuronal injury.The 2-arachidonoylglycerol（2-AG）,the most abundant eCBs and a full agonist for cannabinoid receptors（CB1 and CB2）,is also capable of suppressing proinflammatory stimuli and improving microvasculature dysfunction.Here,we indicated that endogenous 2-AG protected against neuroinflammation in response to SO_2 inhalation by inhibiting the activation of microglia and astrocytes and attenuating the overexpression of inflammatory cytokines,including tumor necrosis factor alpha（TNF-a）,interleukin（IL）-1β,and inducible nitric oxide synthase（iNOS）.In addition,endogenous 2-AG prevented cerebral vasculature dysfunction following SO_2 inhalation by inhibiting endothelin 1（ET-1）,vascular cell adhesion molecule-1（VCAM-1） and intercellular adhesion molecule 1（ICAM-1） expression,elevating endothelial nitric oxide synthase（eNOS） level,and restoring the imbalance between thromboxane A2（TXA2） and prostaglandin 12（PGI2）.In addition,the action of endogenous 2-AG on the suppression of inflammatory insult and inflammatory-related microvasculature dysfunction appeared to be mainly mediated by CB1 and CB2 receptors.Our results provided a mechanistic basis for the development of new therapeutic approaches for protecting brain injuries from SO_2 inhalation.展开更多
文摘Objective: Kigelia africana, a tropical tree, which has long been used in African traditional medicine. The objective of the current study has been identifying the constituents of K. africana and verifying its utilities in traditional medicine. Materials and Methods: The methanol extract of K. africana fruits was subjected to chromatographic fractionation utilizing different techniques. The methanol extract together with the isolated compounds were tested for their bioactivities in a series of cell-based assays. Results: The current work led to isolation and characterization of nine constituents including iridoid glycosides, phenylpropanoid derivatives, and a eucommiol derivative. The hexanes extract caused inhibition of the opportunistic yeast; Cryptococcus neoformans Pinh. The chloroform extract exhibited substantial antileishmanial activity of Leishmania donovani. Verminoside(1) showed weak inhibition of the CB1, CB2, and Kappa opioid receptors. Compound 4 exhibited weak inhibition of the Kappa and Mu opioid receptors. The hexanes and the chloroform extracts of K. africana exhibited inhibitory activity against the pathogenic parasite Trypanosoma brucei. The ethyl acetate extract showed the same activity. Conclusions: This is the first report on the isolation of coniferyl 4-0-(3-D-glucopyranoside(7), a eucommiol derivative(crescentin IV)(6), and 6-feruloylcatalpol(4) from the genus Kigelia. It is also the first report on the separation of ajugol(2), catalpol(3), and specioside(5) from the fruits of K. africana. Revision of the^1 H and ^(13)C-NMR spectra of 6-feruloylcatalop(4) and 6-p-hydroxycinnamoylcatalpol(5, specioside) is described. Further, the results of the in vitro assays corroborate the traditional utility of this plant in medicine.
文摘目的探究利拉鲁肽治疗早期2型糖尿病患者应用大麻素受体1型基因(CNR1)多态性对临床疗效的影响。方法选取2018年1月至2019年1月本院收治的230例确诊为早期2型糖尿病作为研究对象。所有患者均通过皮下注射方案给予利拉鲁肽,比较治疗前后患者的体重指数(BMI)、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1C),对CNR1基因1260G>A位点进行基因分型,比较不同基因分型的mRNA表达及不良反应发生率。结果GG型188例,GA型39例,AA型3例,其中等位基因频率最小为0.098。治疗后,患者BMI、FPG、2 h PG及HbA1c均低于治疗前(P<0.05)。GG型患者CNR1 mRNA表达水平与GA/AA型患者比较差异有统计学意义(P<0.05)。不同基因分型患者的药物治疗不良反应发生率比较差异无统计学意义。结论应用利拉鲁肽药物治疗早期2型糖尿病患者可取得良好的干预效果,其中CNR1基因1260G>A位点表达为GA型、AA型患者,其基因表达可能影响药物疗效。
基金supported by the National Science Foundation of China(Nos.91543203,21477070,21377076,21307079)the Research Project Supported by Shanxi Scholarship Council of China(No.2015-006)
文摘Sulfur dioxide（SO_2） pollution in the atmospheric environment causes brain inflammatory insult and inflammatory-related microvasculature dysfunction.However,there are currently no effective medications targeting the harmful outcomes from chemical inhalation.Endocannabinoids（eCBs） are involved in neuronal protection against inflammation-induced neuronal injury.The 2-arachidonoylglycerol（2-AG）,the most abundant eCBs and a full agonist for cannabinoid receptors（CB1 and CB2）,is also capable of suppressing proinflammatory stimuli and improving microvasculature dysfunction.Here,we indicated that endogenous 2-AG protected against neuroinflammation in response to SO_2 inhalation by inhibiting the activation of microglia and astrocytes and attenuating the overexpression of inflammatory cytokines,including tumor necrosis factor alpha（TNF-a）,interleukin（IL）-1β,and inducible nitric oxide synthase（iNOS）.In addition,endogenous 2-AG prevented cerebral vasculature dysfunction following SO_2 inhalation by inhibiting endothelin 1（ET-1）,vascular cell adhesion molecule-1（VCAM-1） and intercellular adhesion molecule 1（ICAM-1） expression,elevating endothelial nitric oxide synthase（eNOS） level,and restoring the imbalance between thromboxane A2（TXA2） and prostaglandin 12（PGI2）.In addition,the action of endogenous 2-AG on the suppression of inflammatory insult and inflammatory-related microvasculature dysfunction appeared to be mainly mediated by CB1 and CB2 receptors.Our results provided a mechanistic basis for the development of new therapeutic approaches for protecting brain injuries from SO_2 inhalation.
