Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite.In this study,potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches.I...Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite.In this study,potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches.In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein(P-gp),as well as the inhibition effects on P-gp.Additionally,anti-inflammatory activity of aconitine(AC)combined with active ingredients of liquorice,as well as pharmacokinetic patterns of AC after co-administration was investigated.Anti-inflammatory effect of AC(1 mg/kg)in rats was enhanced in combination with bioactive ingredients of liquorice(10 mg/kg).In the meanwhile,the exposure of AC in vivo was altered,in terms of Cmax and AUC.For instance,the Cmax and AUC were increased to 1.9 and 1.3 folds,respectively,when used in combination with liquiritigenin.The in silico study revealed the potential binding mode with outward facing conformation of P-gp.The resulting data obtained from transport of rhodamine-123(Rh-123)across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice.The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp.The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation,and further the anti-inflammatory effect,which helps clarify the compatibility rationale of these two herbs.展开更多
Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular disease...Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular diseases and alleviate pain.However,the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear.In the present study,the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model.Based on the network pharmacological analysis of 13 bioactive ingredients found in DC,a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained,which was associated with mitogen-activated protein kinase(MAPK)signal pathway,hepatic inflammation and fibrotic response.Furthermore,this hypothesis was verified using carbon tetrachloride(CCl_4)-induced fibrosis model.Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels,inflammatory cell infiltration and collagen deposition caused by CCl_4.The increased expression of liver fibrosis markers,such as collagen 1,fibronectin,α-smooth muscle actin(α-SMA)and transforming growth factor-β(TGF-β),and inflammatory factors,such as chemokine(C-C motif)ligand 2(MCP-1),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2(ERK1/2)-protein kinase B(AKT)signaling pathways.Collectively,these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition,decreasing inflammatory reactions and bile acid accumulation,which provides insights into the mechanisms of herbpair in improving liver fibrosis.展开更多
"Herb-Pairs",also known as pair drugs,refers to a prescription consisted of two relatively fixed traditional Chinese medicine,is the most basic,most simple and most common form of medication prescription in ..."Herb-Pairs",also known as pair drugs,refers to a prescription consisted of two relatively fixed traditional Chinese medicine,is the most basic,most simple and most common form of medication prescription in traditional Chinese medicine compound compatibility.It is not a random combination of two herbs,nor is the simple accumulation of efficacy,but the simple and delicate experience of ancient Chinese medicine practitioners.As a bridge between single drug and prescriptions,it is the embodiment of the regular and dialectical connotation.Therefore,research on Herb-Pairs has always been the most basic and most important entry point for compound compatibility studies.However,the interaction between herbs and herbs is an effect with a downside as well as benefits.The beneficial herb-herb interaction in Herb-Pairs include mutual promotion,mutual enhancement,mutual restraint between two drugs and counteract toxicity of another drug.And the harmful herb-herb interaction in Herb-Pairs includes mutual inhibition and antagonism.Al of these interactions areby means of affecting the metabolism of components to play a therapeutic effect.Using the pharmacokinetic-pharmacodynamic(PK-PD)binding model,the combination of drug metabolism and pharmacodynamics can further elucidate the influence on effect caused by drug concentration and metabolism,which can help elucidate the mechanism of drug action.Consequently,in this review,the herb-herb interactions in terms of pharmacokinetic were summarized to elucidate rule of TCM compatibility.展开更多
Objective： Mahuang-Shigao herb-pair is a famous formula composed of Ephedra and Gypsum. The herb-pair is frequently used for treating cold symptoms and bronchial asthma in the clinical practice of Chinese medicine ...Objective： Mahuang-Shigao herb-pair is a famous formula composed of Ephedra and Gypsum. The herb-pair is frequently used for treating cold symptoms and bronchial asthma in the clinical practice of Chinese medicine （CM）. In the present study, we evaluated evidence for the benefit of combined use of Ephedra and Gypsum by analyzing the antipyretic and anti-asthmatic activities of Ephedra-Gypsum. Methods： The antipyretic effects of Ephedra-Gypsum were evaluated in yeast-induced hyperthermia test. Thirty male Wistar rats were randomly divided into 5 groups, including control group, standard aspirin group, and 3 Ephedra- Gypsum groups of different doses （6, 12, 24 g/kg）. Ephedra-Gypsum extract and asprin were administered orally 6 h after the injection of yeast solution and body temperature was measured every 1 h for 8 h. The anti- asthmatic effects of Ephedra-Gypsum were evaluated using an ovalbumin （OVA）-induced asthmatic rat model. Thirty-six male SD rats were randomly divided into 6 groups. Rats were alternately sensitized and OVA＋Al（OH）3 challenged by exposure to mists of ovalbumin. Ephedra-Gypsum extracts （6, 12, 24 g/kg） or dexamethasone were administered 45 min prior to the allergen challenge for 8 days. Latent period and the weight of wet to dry ratio of lung were determined. In addition, the eosinophils in blood and white blood cell （WBC） were counted by an YZ-Hemavet Analyzer. Results： The Ephedra-Gypsum extracts at test dose （6, 12, 24 g/kg） significantly and dose-dependently attenuated yeast-induced fever in rats. The Ephedra-Gypsum extracts also prolonged the latent period, reduced OVA-induced increases in eosinophils and WBC, and decreased the wet and dry weight ratio of the lungs in the anti-asthmatic test. Conclusions： These findings indicate that the Ephedra-Gypsum extract has antipyretic and anti-asthmatic properties. Hence, the results support additional scientific evidence in prescriptions.展开更多
基金supported by National Key Research and Development Program(Grant2016YFE0121400)National Natural Science Foundation of China(Grant No.81430096)+2 种基金Macao Science and Technology Development Fund(006/2015/AMJ to Y.Xie)the program of Changjiang Scholars and innovative Research Team in University(No.IRT_14R41)Tianjin Natural and Science Foundation(No.17YFZCSY01170)。
文摘Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite.In this study,potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches.In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein(P-gp),as well as the inhibition effects on P-gp.Additionally,anti-inflammatory activity of aconitine(AC)combined with active ingredients of liquorice,as well as pharmacokinetic patterns of AC after co-administration was investigated.Anti-inflammatory effect of AC(1 mg/kg)in rats was enhanced in combination with bioactive ingredients of liquorice(10 mg/kg).In the meanwhile,the exposure of AC in vivo was altered,in terms of Cmax and AUC.For instance,the Cmax and AUC were increased to 1.9 and 1.3 folds,respectively,when used in combination with liquiritigenin.The in silico study revealed the potential binding mode with outward facing conformation of P-gp.The resulting data obtained from transport of rhodamine-123(Rh-123)across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice.The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp.The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation,and further the anti-inflammatory effect,which helps clarify the compatibility rationale of these two herbs.
基金the National Natural Science Foundation of China(No.82004045)the Beijing Nova Program of Science and Technology(No.Z191100001119088)the Beijing University of Chinese Medicine Specific Grant for“Double Top Construction”(No.1000041510168)。
文摘Angelicae Sinensis Radix(Danggui)and Ligusticum Chuanxiong Rhizoma(Chuan Xiong)herb-pair(DC)have been frequently used in Traditional Chinese medicine(TCM)prescriptions for hundreds of years to prevent vascular diseases and alleviate pain.However,the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear.In the present study,the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model.Based on the network pharmacological analysis of 13 bioactive ingredients found in DC,a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained,which was associated with mitogen-activated protein kinase(MAPK)signal pathway,hepatic inflammation and fibrotic response.Furthermore,this hypothesis was verified using carbon tetrachloride(CCl_4)-induced fibrosis model.Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels,inflammatory cell infiltration and collagen deposition caused by CCl_4.The increased expression of liver fibrosis markers,such as collagen 1,fibronectin,α-smooth muscle actin(α-SMA)and transforming growth factor-β(TGF-β),and inflammatory factors,such as chemokine(C-C motif)ligand 2(MCP-1),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2(ERK1/2)-protein kinase B(AKT)signaling pathways.Collectively,these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition,decreasing inflammatory reactions and bile acid accumulation,which provides insights into the mechanisms of herbpair in improving liver fibrosis.
文摘"Herb-Pairs",also known as pair drugs,refers to a prescription consisted of two relatively fixed traditional Chinese medicine,is the most basic,most simple and most common form of medication prescription in traditional Chinese medicine compound compatibility.It is not a random combination of two herbs,nor is the simple accumulation of efficacy,but the simple and delicate experience of ancient Chinese medicine practitioners.As a bridge between single drug and prescriptions,it is the embodiment of the regular and dialectical connotation.Therefore,research on Herb-Pairs has always been the most basic and most important entry point for compound compatibility studies.However,the interaction between herbs and herbs is an effect with a downside as well as benefits.The beneficial herb-herb interaction in Herb-Pairs include mutual promotion,mutual enhancement,mutual restraint between two drugs and counteract toxicity of another drug.And the harmful herb-herb interaction in Herb-Pairs includes mutual inhibition and antagonism.Al of these interactions areby means of affecting the metabolism of components to play a therapeutic effect.Using the pharmacokinetic-pharmacodynamic(PK-PD)binding model,the combination of drug metabolism and pharmacodynamics can further elucidate the influence on effect caused by drug concentration and metabolism,which can help elucidate the mechanism of drug action.Consequently,in this review,the herb-herb interactions in terms of pharmacokinetic were summarized to elucidate rule of TCM compatibility.
基金Supported by the National Natural Science Foundation of China(No.81030066)
文摘Objective： Mahuang-Shigao herb-pair is a famous formula composed of Ephedra and Gypsum. The herb-pair is frequently used for treating cold symptoms and bronchial asthma in the clinical practice of Chinese medicine （CM）. In the present study, we evaluated evidence for the benefit of combined use of Ephedra and Gypsum by analyzing the antipyretic and anti-asthmatic activities of Ephedra-Gypsum. Methods： The antipyretic effects of Ephedra-Gypsum were evaluated in yeast-induced hyperthermia test. Thirty male Wistar rats were randomly divided into 5 groups, including control group, standard aspirin group, and 3 Ephedra- Gypsum groups of different doses （6, 12, 24 g/kg）. Ephedra-Gypsum extract and asprin were administered orally 6 h after the injection of yeast solution and body temperature was measured every 1 h for 8 h. The anti- asthmatic effects of Ephedra-Gypsum were evaluated using an ovalbumin （OVA）-induced asthmatic rat model. Thirty-six male SD rats were randomly divided into 6 groups. Rats were alternately sensitized and OVA＋Al（OH）3 challenged by exposure to mists of ovalbumin. Ephedra-Gypsum extracts （6, 12, 24 g/kg） or dexamethasone were administered 45 min prior to the allergen challenge for 8 days. Latent period and the weight of wet to dry ratio of lung were determined. In addition, the eosinophils in blood and white blood cell （WBC） were counted by an YZ-Hemavet Analyzer. Results： The Ephedra-Gypsum extracts at test dose （6, 12, 24 g/kg） significantly and dose-dependently attenuated yeast-induced fever in rats. The Ephedra-Gypsum extracts also prolonged the latent period, reduced OVA-induced increases in eosinophils and WBC, and decreased the wet and dry weight ratio of the lungs in the anti-asthmatic test. Conclusions： These findings indicate that the Ephedra-Gypsum extract has antipyretic and anti-asthmatic properties. Hence, the results support additional scientific evidence in prescriptions.
