Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the...Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic receptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.展开更多
[Objectives]To study the clinical effect of Chaigui decoction(CGD)on Jueyin type hypertension based on the theory of Five Yun Six Qi.[Methods]52 patients with Jueyin type hypertension in Wuxi Hospital Affiliated to Na...[Objectives]To study the clinical effect of Chaigui decoction(CGD)on Jueyin type hypertension based on the theory of Five Yun Six Qi.[Methods]52 patients with Jueyin type hypertension in Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine from January,2020 to March,2021 were randomly divided into Western medicine control group(18 cases)and CGD group(34 cases).CGD group was treated with CGD,while the control group was treated with irbesartan or amlodipine.[Results]After treatment,the systolic blood pressure(SBP)of the two groups decreased significantly,the difference was statistically significant(P<0.05).After treatment,the diastolic blood pressure(DBP)of CGD group was significantly lower than that of the control group(P<0.05).[Conclusions]Based on the theory of Five Yun Six Qi,CGD has significant effect on Jueyin type hypertension,and the effect of reducing DBP is better than that of Western medicine control group.展开更多
Objective: To decipher the antidepression effect of Chaigui Granules(CGKL) from the relationship between depression and microbial molecules based on multi-omics.Methods: Male SD rats were subjected to chronic unpredic...Objective: To decipher the antidepression effect of Chaigui Granules(CGKL) from the relationship between depression and microbial molecules based on multi-omics.Methods: Male SD rats were subjected to chronic unpredictable mild stress(CUMS) for seven weeks. The antidepressants CGKL extract and CGKL were administered for the following four weeks. The behavior test and the content of monoamine neurotransmitters were used to evaluate the efficacy of CGKL. The 16S rRNA sequencing, LC-MS technology and molecular biological techniques were used to explore the pharmacological mechanism of CGKL.Results: CGKL treatment obviously alleviated the depressive behavioral indicators and regulated the content of monoamine neurotransmitters, and presented dose-dependent manner. CGKL could also improve the arginine metabolism disorder of gut microbiota in the jejunum. Meanwhile, the contents of arginine and its metabolites in the serum and hippocampus were regulated to normal levels. Further investigation indicated that the expression of related rate-limiting enzyme genes and proteins in the hippocampus was validated by qRT-PCR and Western blotting. The results showed that the gut microbiota, metabolites, and genes or proteins of rate-limiting enzymes involved in the arginine pathway were significantly regulated by CGKL.Conclusion: The present study demonstrates that CGKL might exert antidepressant effects through regulating arginine metabolism, and its mechanism may be related to modulating the gut microbiota and related metabolic enzyme.展开更多
基金This work was financially supported by the National Natural Science Foundation of China(Grant Nos.:82074323 and 81673572)Key Research and Development Program of Shanxi Province(Grant No.:202102130501010)+2 种基金Innovation Project for Graduate Students in Shanxi Province(Grant No.:2022Y162)the Major Science and Technology Project for“Significant New Drugs Creation”(Grant No.:2017ZX09301047)Research Project Supported by Shanxi Scholarship Council of China(Grant No.:2020019).
文摘Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic receptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.
基金Fund of Wuxi Municipal Health Commission top young and middle-aged talents funding scheme(BJ2020064).
文摘[Objectives]To study the clinical effect of Chaigui decoction(CGD)on Jueyin type hypertension based on the theory of Five Yun Six Qi.[Methods]52 patients with Jueyin type hypertension in Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine from January,2020 to March,2021 were randomly divided into Western medicine control group(18 cases)and CGD group(34 cases).CGD group was treated with CGD,while the control group was treated with irbesartan or amlodipine.[Results]After treatment,the systolic blood pressure(SBP)of the two groups decreased significantly,the difference was statistically significant(P<0.05).After treatment,the diastolic blood pressure(DBP)of CGD group was significantly lower than that of the control group(P<0.05).[Conclusions]Based on the theory of Five Yun Six Qi,CGD has significant effect on Jueyin type hypertension,and the effect of reducing DBP is better than that of Western medicine control group.
基金supported by the National Natural Science Foundation of China (No. 82074147, 82374153)the Science and Technology of Shanxi Province (No. 202103021224026)the Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province (No. 202105D121009)。
文摘Objective: To decipher the antidepression effect of Chaigui Granules(CGKL) from the relationship between depression and microbial molecules based on multi-omics.Methods: Male SD rats were subjected to chronic unpredictable mild stress(CUMS) for seven weeks. The antidepressants CGKL extract and CGKL were administered for the following four weeks. The behavior test and the content of monoamine neurotransmitters were used to evaluate the efficacy of CGKL. The 16S rRNA sequencing, LC-MS technology and molecular biological techniques were used to explore the pharmacological mechanism of CGKL.Results: CGKL treatment obviously alleviated the depressive behavioral indicators and regulated the content of monoamine neurotransmitters, and presented dose-dependent manner. CGKL could also improve the arginine metabolism disorder of gut microbiota in the jejunum. Meanwhile, the contents of arginine and its metabolites in the serum and hippocampus were regulated to normal levels. Further investigation indicated that the expression of related rate-limiting enzyme genes and proteins in the hippocampus was validated by qRT-PCR and Western blotting. The results showed that the gut microbiota, metabolites, and genes or proteins of rate-limiting enzymes involved in the arginine pathway were significantly regulated by CGKL.Conclusion: The present study demonstrates that CGKL might exert antidepressant effects through regulating arginine metabolism, and its mechanism may be related to modulating the gut microbiota and related metabolic enzyme.
