Objective:Xiaoyao san(XYS)is a classic traditional Chinese medicinal formula.It has been clinically administered to regulate liver function.However,its mechanisms in glucocorticoid-induced hepatic steatosis are unknow...Objective:Xiaoyao san(XYS)is a classic traditional Chinese medicinal formula.It has been clinically administered to regulate liver function.However,its mechanisms in glucocorticoid-induced hepatic steatosis are unknown.This study aimed to investigate whether XYS protects against corticosterone(CORT)-induced hepatic steatosis,and to explore its mechanism.Methods:High-fat diet mice induced with hepatic steatosis by 2mg/kg CORT were administered 2.56 g/kg or 5.12 g/kg XYS daily for 7 weeks.The effects of XYS on hepatic steatosis in mice were evaluated by H&E and Oil Red O staining and by measuring their plasma lipids(triglyceride,total cholesterol,and free fatty acids).The mechanism of XYS against hepatic steatosis was investigated by network pharmacology,immunohistochemistry,western blotting,and gain-of-function/loss-offunction experiments.Results:XYS alleviated CORT-induced steatosis,decreased plasma lipids,and inhibited glucocorticoid receptor(GR)activation in the liver.Network pharmacology data indicated that XYS may have mitigated hepatic steatosis via GR which mediated adipose differentiation-related protein(ADFP).Gain-of-function/loss-of-function experiments in vitro confirmed that GR positively regulated ADFP expression.Conclusions:XYS ameliorated CORT-induced hepatic steatosis by downregulating the GR/ADFP axis and inhibiting lipid metabolism.Our studies implicate that XYS is promising as a therapy for CORT-induced hepatic steatosis,and lay the foundation for designing novel prophylactic and therapeutic strategies on CORT-induced hepatic steatosis.展开更多
Objectives: To assess the efficacy and safety of modified Xiaoyao San (XYS) for treating Perimenopausal syndrome (PMS). Methods: Literature searches were carried out on PubMed, Cochrane Library, CNKI Database, Chinese...Objectives: To assess the efficacy and safety of modified Xiaoyao San (XYS) for treating Perimenopausal syndrome (PMS). Methods: Literature searches were carried out on PubMed, Cochrane Library, CNKI Database, Chinese Biomedical Literature Database, Wan Fang Database, and VIP Database up to December 2018. Hand search for further references was conducted. Study selection, data extraction, quality assessment, and data analyses were performed as request of the Cochrane standards. Results: Nine publications in total were suitable for inclusion. There was evidence that modified XYS was tested to be more effective in improving overall symptoms compared with HRT (odds ratio 3.50, 95% CI 2.56 to 4.78). Whereas HRT was more sensitive and direct in decreasing FSH (WMD 6.69, 95% CI 5.60 to 9.52) and LH (WMD 7.00, 95% CI, 5.75 to 8.25) in comparison with XYS group. It was also strongly supported that XYS had less adverse effect than HRT (odds ratio 0.07, 95% CI 0.05 to 0.10). Conclusion: Modified XYS might be more effective and safer in treatment of perimenopausal syndrome. However, due to poor methodological quality in the majority of included studies, the potential benefit and safety about XYS need to be confirmed in rigorously designed, multi-centre, and large-scale trials.展开更多
Objective: This study aimed to investigate the therapeutic effects of Xiaoyao San(XYS), a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chro...Objective: This study aimed to investigate the therapeutic effects of Xiaoyao San(XYS), a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chronic unpredictable mild stress(CUMS).Methods: A total of 24 male SD rats were randomly divided into four groups: control group(C), CUMS control group(M), Venlafaxine positive treatment group(V), and XYS treatment group(X). Depressive behaviour and exercise capacity of rats were assessed by body weight, sugar-water preference test, open field test, pole test, and rotarod test. The liver mitochondria metabolomics were analyzed by using liquid chromatography-mass spectrometry(LC-MS) method. TCMSP database and Gene Cards database were used to screen XYS for potential targets for depression, and GO and KEGG enrichment analyses were performed.Results: Compared with C group, rats in M group showed significantly lower body weight, sugar water preference rate, number of crossing and rearing in the open field test, climbing down time in the pole test,and retention time on the rotarod test(P < 0.01). The above behaviors and exercise capacity indices were significantly modulated in rats in V and X groups compared with M group(P < 0.05, 0.01). Compared with C group, a total of 18 different metabolites were changed in the liver mitochondria of rats in M group.Nine different metabolites and six metabolic pathways were regulated in the liver mitochondria of rats in X group compared with M group. The results of network pharmacology showed that 88 intersecting targets for depression and XYS were obtained, among which 15 key targets such as IL-1β, IL-6, and TNF were predicted to be the main differential targets for the treatment of depression. Additionally, a total of 1 553 GO signaling pathways and 181 KEGG signaling pathways were identified, and the main biological pathways were AGE-RAGE signaling pathway, HIF-1 signaling pathway, and calcium signaling pathway.Conclusion: XYS treatment could improve depressive symptoms, enhance exercise capacity, positively regulate the changes of mitochondrial metabolites and improve energy metabolism in the liver of depressed rats. These findings suggest that XYS exerts antidepressant effects through multi-target and multi-pathway.展开更多
Jiawei Xiaoyao San(JWXYS)has shown excellent clinical efficacy in anxiety disorder,but has not yet attracted widespread attention.The animal experiments,clinical trials and mechanism studies of JWXYS were reviewed in ...Jiawei Xiaoyao San(JWXYS)has shown excellent clinical efficacy in anxiety disorder,but has not yet attracted widespread attention.The animal experiments,clinical trials and mechanism studies of JWXYS were reviewed in this article,which may provide a reference for developing new anxiolytic drugs based on this prescription.The literature was searched in PubMed and CNKI and the documents written in English or with English abstracts were selected.JWXYS could reduce the anxiety symptoms of patients alone and reduce the adverse reactions when it is used in combination with other drugs in the clinic.In preclinical studies,JWXYS also showed therapeutic effects in reducing anxiety-like behavior.The mechanisms may include improving the hypothalamic–pituitaryadrenal(HPA)axis and hormone disorders,increasing neurotransmitter content,neurogenesis,and regulating the synthesis of related enzymes.This article shows that JWXYS could effectively treat anxiety disorders by regulating the central nervous system.In the future,with the participation of more researchers,it is expected to develop innovative drugs for the treatment of anxiety disorders based on JWXYS.展开更多
Objective Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes.Current research is focused on the possible role of adiponectin in regulating common biological mechanisms.Xiaoy...Objective Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes.Current research is focused on the possible role of adiponectin in regulating common biological mechanisms.Xiaoyao San(XYS),a classic Chinese medicine compound,has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders.However,the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.Methods An in vivo animal model of depression was established by chronic social defeat stress(CSDS).XYS and fluoxetine were administered by gavage to the drug intervention group.Depression-like behaviors were analyzed by the social interaction test,open field test,forced swim test,and elevated plus maze test.Glucose levels were measured using the oral glucose tolerance test.The involvement of certain molecules was validated by immunofluorescence,histopathology,and Western blotting.In vitro,hypothalamic primary neurons were exposed to high glucose to induce neuronal damage,and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay.Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1(AdipoR1),adenosine 5’-monophosphate-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase(ACC)and other related proteins.Results XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin.XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage.In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.Conclusion Adiponectin may be a key regulator linking depression and metabolic disorders;regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.展开更多
[目的]探讨加味丹栀逍遥散对慢性不可预知性温和应激(CUMS)抑郁小鼠模型的干预作用及可能机制.[方法]C57BL/6N小鼠分为正常组、模型组、加味丹栀逍遥散组和氟西汀组.采用CUMS复制抑郁模型,模型成功后灌胃给药4周.末次给药后进行行为学测...[目的]探讨加味丹栀逍遥散对慢性不可预知性温和应激(CUMS)抑郁小鼠模型的干预作用及可能机制.[方法]C57BL/6N小鼠分为正常组、模型组、加味丹栀逍遥散组和氟西汀组.采用CUMS复制抑郁模型,模型成功后灌胃给药4周.末次给药后进行行为学测试,采用串联质谱标签法(TMT)蛋白质组学分析小鼠肝脏差异蛋白的表达谱,通过Kyoto encyclopedia of genes and genomes(KEGG)通路富集加味丹栀逍遥散抗抑郁的相关通路和蛋白;血液生化检测总胆固醇及总胆汁酸含量.[结果]与正常组相比,模型组小鼠糖水偏好率下降,自主活动次数减少,加味丹栀逍遥散给药后上调小鼠糖水偏好率及自主活动次数.蛋白组学结果显示模型组与加味丹栀逍遥散给药组之间肝脏差异表达蛋白20个,其中上调11个,下调9个.KEGG通路富集分析发现差异表达蛋白主要参与了胆固醇代谢、初级胆汁酸的合成等.生化检测发现,与正常组相比,模型组总胆固醇含量下降而胆汁酸含量升高,加味丹栀逍遥散给药能显著增加总胆固醇含量而减少总胆汁酸含量.[结论]加味丹栀逍遥散具有良好的抗抑郁效应,其机制可能与调节肝脏胆固醇异常代谢、降低血液总胆汁酸有关.展开更多
目的:观察针刺董氏奇穴联合内服中药治疗混合性焦虑抑郁障碍(Mixed Anxiety and Depressive Disorder,MADD)痰气郁结证的疗效。方法:选择2020年4月至2021年10月江海区中西医结合医院治疗的MADD患者90例,随机分为对照组、观察A组、观察B...目的:观察针刺董氏奇穴联合内服中药治疗混合性焦虑抑郁障碍(Mixed Anxiety and Depressive Disorder,MADD)痰气郁结证的疗效。方法:选择2020年4月至2021年10月江海区中西医结合医院治疗的MADD患者90例,随机分为对照组、观察A组、观察B组各30例。对照组予口服氟哌噻吨美利曲辛片,观察A组予内服温胆汤合丹栀逍遥散加减,观察B组在观察A组治疗的基础上予针刺董氏奇穴,均治疗12周,治疗后对比三组患者的医院焦虑抑郁量表(Hospital Anxiety and Depression Scale,HADS)评分、中医证候评分、临床疗效及不良反应。结果:治疗前,三组患者的HADS评分、痰气郁结证评分对比,差异无统计学意义(P>0.05);治疗后,三组患者的HADS评分、痰气郁结证评分均较治疗前下降(P<0.05),其中观察A组、观察B组的HADS评分、痰气郁结证评分均明显低于对照组(P<0.05),观察B组的HADS评分、痰气郁结证评分均明显低于观察A组(P<0.05)。观察B组的总有效率(93.33%)高于观察A组(86.67%)、对照组(73.33%)(P<0.05)。治疗期间,对照组不良反应发生率为13.33%,观察A组为6.67%,观察B组为10.00%,差异无统计学意义(P>0.05)。结论:针刺董氏奇穴联合内服中药具有行气开郁、化痰散结、清肝泻火之功效,治疗MADD痰气郁结证安全有效,值得在临床中推广应用。展开更多
基金the National Natural Science Foundation of China(Nos.81630104 and 81622050).
文摘Objective:Xiaoyao san(XYS)is a classic traditional Chinese medicinal formula.It has been clinically administered to regulate liver function.However,its mechanisms in glucocorticoid-induced hepatic steatosis are unknown.This study aimed to investigate whether XYS protects against corticosterone(CORT)-induced hepatic steatosis,and to explore its mechanism.Methods:High-fat diet mice induced with hepatic steatosis by 2mg/kg CORT were administered 2.56 g/kg or 5.12 g/kg XYS daily for 7 weeks.The effects of XYS on hepatic steatosis in mice were evaluated by H&E and Oil Red O staining and by measuring their plasma lipids(triglyceride,total cholesterol,and free fatty acids).The mechanism of XYS against hepatic steatosis was investigated by network pharmacology,immunohistochemistry,western blotting,and gain-of-function/loss-offunction experiments.Results:XYS alleviated CORT-induced steatosis,decreased plasma lipids,and inhibited glucocorticoid receptor(GR)activation in the liver.Network pharmacology data indicated that XYS may have mitigated hepatic steatosis via GR which mediated adipose differentiation-related protein(ADFP).Gain-of-function/loss-of-function experiments in vitro confirmed that GR positively regulated ADFP expression.Conclusions:XYS ameliorated CORT-induced hepatic steatosis by downregulating the GR/ADFP axis and inhibiting lipid metabolism.Our studies implicate that XYS is promising as a therapy for CORT-induced hepatic steatosis,and lay the foundation for designing novel prophylactic and therapeutic strategies on CORT-induced hepatic steatosis.
文摘Objectives: To assess the efficacy and safety of modified Xiaoyao San (XYS) for treating Perimenopausal syndrome (PMS). Methods: Literature searches were carried out on PubMed, Cochrane Library, CNKI Database, Chinese Biomedical Literature Database, Wan Fang Database, and VIP Database up to December 2018. Hand search for further references was conducted. Study selection, data extraction, quality assessment, and data analyses were performed as request of the Cochrane standards. Results: Nine publications in total were suitable for inclusion. There was evidence that modified XYS was tested to be more effective in improving overall symptoms compared with HRT (odds ratio 3.50, 95% CI 2.56 to 4.78). Whereas HRT was more sensitive and direct in decreasing FSH (WMD 6.69, 95% CI 5.60 to 9.52) and LH (WMD 7.00, 95% CI, 5.75 to 8.25) in comparison with XYS group. It was also strongly supported that XYS had less adverse effect than HRT (odds ratio 0.07, 95% CI 0.05 to 0.10). Conclusion: Modified XYS might be more effective and safer in treatment of perimenopausal syndrome. However, due to poor methodological quality in the majority of included studies, the potential benefit and safety about XYS need to be confirmed in rigorously designed, multi-centre, and large-scale trials.
基金supported by the National Natural Science Foundation of China,China(No.82074147)the Project of Natural Science Research of the Shanxi Province,China(No.202103021224027).
文摘Objective: This study aimed to investigate the therapeutic effects of Xiaoyao San(XYS), a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chronic unpredictable mild stress(CUMS).Methods: A total of 24 male SD rats were randomly divided into four groups: control group(C), CUMS control group(M), Venlafaxine positive treatment group(V), and XYS treatment group(X). Depressive behaviour and exercise capacity of rats were assessed by body weight, sugar-water preference test, open field test, pole test, and rotarod test. The liver mitochondria metabolomics were analyzed by using liquid chromatography-mass spectrometry(LC-MS) method. TCMSP database and Gene Cards database were used to screen XYS for potential targets for depression, and GO and KEGG enrichment analyses were performed.Results: Compared with C group, rats in M group showed significantly lower body weight, sugar water preference rate, number of crossing and rearing in the open field test, climbing down time in the pole test,and retention time on the rotarod test(P < 0.01). The above behaviors and exercise capacity indices were significantly modulated in rats in V and X groups compared with M group(P < 0.05, 0.01). Compared with C group, a total of 18 different metabolites were changed in the liver mitochondria of rats in M group.Nine different metabolites and six metabolic pathways were regulated in the liver mitochondria of rats in X group compared with M group. The results of network pharmacology showed that 88 intersecting targets for depression and XYS were obtained, among which 15 key targets such as IL-1β, IL-6, and TNF were predicted to be the main differential targets for the treatment of depression. Additionally, a total of 1 553 GO signaling pathways and 181 KEGG signaling pathways were identified, and the main biological pathways were AGE-RAGE signaling pathway, HIF-1 signaling pathway, and calcium signaling pathway.Conclusion: XYS treatment could improve depressive symptoms, enhance exercise capacity, positively regulate the changes of mitochondrial metabolites and improve energy metabolism in the liver of depressed rats. These findings suggest that XYS exerts antidepressant effects through multi-target and multi-pathway.
基金supported by the National Natural Science Foundation of China(No.81173541).
文摘Jiawei Xiaoyao San(JWXYS)has shown excellent clinical efficacy in anxiety disorder,but has not yet attracted widespread attention.The animal experiments,clinical trials and mechanism studies of JWXYS were reviewed in this article,which may provide a reference for developing new anxiolytic drugs based on this prescription.The literature was searched in PubMed and CNKI and the documents written in English or with English abstracts were selected.JWXYS could reduce the anxiety symptoms of patients alone and reduce the adverse reactions when it is used in combination with other drugs in the clinic.In preclinical studies,JWXYS also showed therapeutic effects in reducing anxiety-like behavior.The mechanisms may include improving the hypothalamic–pituitaryadrenal(HPA)axis and hormone disorders,increasing neurotransmitter content,neurogenesis,and regulating the synthesis of related enzymes.This article shows that JWXYS could effectively treat anxiety disorders by regulating the central nervous system.In the future,with the participation of more researchers,it is expected to develop innovative drugs for the treatment of anxiety disorders based on JWXYS.
基金This work was financially supported by the National Natural Science Foundation of China(No.81904091,No.81973748 and No,82174278)the National Natural Science Foundation of Guang-dong,China(No.2021A1515011212)+2 种基金Province Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong(No.20202039)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University.Key.Area Research and Development Program of Guangdong Province(No.20208111100001)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine.China.
文摘Objective Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes.Current research is focused on the possible role of adiponectin in regulating common biological mechanisms.Xiaoyao San(XYS),a classic Chinese medicine compound,has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders.However,the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.Methods An in vivo animal model of depression was established by chronic social defeat stress(CSDS).XYS and fluoxetine were administered by gavage to the drug intervention group.Depression-like behaviors were analyzed by the social interaction test,open field test,forced swim test,and elevated plus maze test.Glucose levels were measured using the oral glucose tolerance test.The involvement of certain molecules was validated by immunofluorescence,histopathology,and Western blotting.In vitro,hypothalamic primary neurons were exposed to high glucose to induce neuronal damage,and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay.Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1(AdipoR1),adenosine 5’-monophosphate-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase(ACC)and other related proteins.Results XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin.XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage.In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.Conclusion Adiponectin may be a key regulator linking depression and metabolic disorders;regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.
文摘[目的]探讨加味丹栀逍遥散对慢性不可预知性温和应激(CUMS)抑郁小鼠模型的干预作用及可能机制.[方法]C57BL/6N小鼠分为正常组、模型组、加味丹栀逍遥散组和氟西汀组.采用CUMS复制抑郁模型,模型成功后灌胃给药4周.末次给药后进行行为学测试,采用串联质谱标签法(TMT)蛋白质组学分析小鼠肝脏差异蛋白的表达谱,通过Kyoto encyclopedia of genes and genomes(KEGG)通路富集加味丹栀逍遥散抗抑郁的相关通路和蛋白;血液生化检测总胆固醇及总胆汁酸含量.[结果]与正常组相比,模型组小鼠糖水偏好率下降,自主活动次数减少,加味丹栀逍遥散给药后上调小鼠糖水偏好率及自主活动次数.蛋白组学结果显示模型组与加味丹栀逍遥散给药组之间肝脏差异表达蛋白20个,其中上调11个,下调9个.KEGG通路富集分析发现差异表达蛋白主要参与了胆固醇代谢、初级胆汁酸的合成等.生化检测发现,与正常组相比,模型组总胆固醇含量下降而胆汁酸含量升高,加味丹栀逍遥散给药能显著增加总胆固醇含量而减少总胆汁酸含量.[结论]加味丹栀逍遥散具有良好的抗抑郁效应,其机制可能与调节肝脏胆固醇异常代谢、降低血液总胆汁酸有关.
文摘目的:观察针刺董氏奇穴联合内服中药治疗混合性焦虑抑郁障碍(Mixed Anxiety and Depressive Disorder,MADD)痰气郁结证的疗效。方法:选择2020年4月至2021年10月江海区中西医结合医院治疗的MADD患者90例,随机分为对照组、观察A组、观察B组各30例。对照组予口服氟哌噻吨美利曲辛片,观察A组予内服温胆汤合丹栀逍遥散加减,观察B组在观察A组治疗的基础上予针刺董氏奇穴,均治疗12周,治疗后对比三组患者的医院焦虑抑郁量表(Hospital Anxiety and Depression Scale,HADS)评分、中医证候评分、临床疗效及不良反应。结果:治疗前,三组患者的HADS评分、痰气郁结证评分对比,差异无统计学意义(P>0.05);治疗后,三组患者的HADS评分、痰气郁结证评分均较治疗前下降(P<0.05),其中观察A组、观察B组的HADS评分、痰气郁结证评分均明显低于对照组(P<0.05),观察B组的HADS评分、痰气郁结证评分均明显低于观察A组(P<0.05)。观察B组的总有效率(93.33%)高于观察A组(86.67%)、对照组(73.33%)(P<0.05)。治疗期间,对照组不良反应发生率为13.33%,观察A组为6.67%,观察B组为10.00%,差异无统计学意义(P>0.05)。结论:针刺董氏奇穴联合内服中药具有行气开郁、化痰散结、清肝泻火之功效,治疗MADD痰气郁结证安全有效,值得在临床中推广应用。