Objective: The analgesic effect of Paeonia Lactiflora has been widely accepted in traditional Chinese medicine. But little is known about the potential mechanism. This study aims to elucidate the effective components ...Objective: The analgesic effect of Paeonia Lactiflora has been widely accepted in traditional Chinese medicine. But little is known about the potential mechanism. This study aims to elucidate the effective components and analgesic mechanism based on network pharmacology. Methods: TCMSP was screened to collect the possible active ingredients and their CAS and SMILES was searched in Pubchem and further be used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Pain-related molecules were obtained from GeenCards database, and the predicted targets of Paeonia Lactiflora for pain treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, the GO analysis and KEGG analysis were conducted in DAVID. Results: Through GO analysis and KEGG analysis, we found that the pain related signaling pathways mainly involved in serotonergic synapse, calcium signaling pathway, inflammatory mediator TRP channels. Using network-based systems biology and molecular docking analyses, we predicted that 11 active ingredients in Paeonia Lactiflora has the analgesic effects with 97 potential targets. PRKCA, CASP3, ALOX15, SLC6A4, PRKCG, ALOX5, PRKCB, ALOX12, EGFR, ADRB2, RYR3, RYR1, NOS2, PTAFR, PRKCQ, and PRKCD were involved in the analgesic effects of Paeonia Lactiflora. Conclusion: Paeonia Lactiflora may alleviate pain through inflammatory mediator regulation of TRP channels, Ca2+ signaling pathway and 5-HT receptor. PRKCA, PRKCB, PRKCD,PRKCQ, and PRKCG may be new targets for pain treatment.展开更多
Ulcerative colitis(UC)is characterized by chronic relapsing intestinal inflammation.Currently,there is no effective treatment for the disease.According to our preliminary data,1,8-cineole,which is the main active comp...Ulcerative colitis(UC)is characterized by chronic relapsing intestinal inflammation.Currently,there is no effective treatment for the disease.According to our preliminary data,1,8-cineole,which is the main active compound of Amomum compactum Sol.ex Maton volatile oil and an effective drug for the treatment of pneumonia,showed remarkable anti-inflammatory effects on colitis pathogenesis.However,its mechanism of action and direct targets remain unclear.This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate sodium salt-induced colitis mouse model.The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells.In addition,1,8-cineole targets were revealed by drug affinity responsive target stability,thermal shift assay,cellular thermal shift assay,and heat shock protein 90(HSP90)adenosine triphosphatases(ATPase)activity assays.The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function.Mechanistically,1,8-cineole directly interacted with HSP90 and decreased its ATPase activity,also inhibited nucleotide-binding and oligomerization domain-,leucine rich repeat-,and pyrin domain-containing 3(NLRP3)binding to HSP90 and suppressor of G-two allele of SKP1(SGT1)and suppressed NLRP3 inflammasome activation in macrophages.These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.展开更多
基金the National Natural Science Foundation of China (Grant No. 81874404).
文摘Objective: The analgesic effect of Paeonia Lactiflora has been widely accepted in traditional Chinese medicine. But little is known about the potential mechanism. This study aims to elucidate the effective components and analgesic mechanism based on network pharmacology. Methods: TCMSP was screened to collect the possible active ingredients and their CAS and SMILES was searched in Pubchem and further be used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Pain-related molecules were obtained from GeenCards database, and the predicted targets of Paeonia Lactiflora for pain treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, the GO analysis and KEGG analysis were conducted in DAVID. Results: Through GO analysis and KEGG analysis, we found that the pain related signaling pathways mainly involved in serotonergic synapse, calcium signaling pathway, inflammatory mediator TRP channels. Using network-based systems biology and molecular docking analyses, we predicted that 11 active ingredients in Paeonia Lactiflora has the analgesic effects with 97 potential targets. PRKCA, CASP3, ALOX15, SLC6A4, PRKCG, ALOX5, PRKCB, ALOX12, EGFR, ADRB2, RYR3, RYR1, NOS2, PTAFR, PRKCQ, and PRKCD were involved in the analgesic effects of Paeonia Lactiflora. Conclusion: Paeonia Lactiflora may alleviate pain through inflammatory mediator regulation of TRP channels, Ca2+ signaling pathway and 5-HT receptor. PRKCA, PRKCB, PRKCD,PRKCQ, and PRKCG may be new targets for pain treatment.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81830114,82004232,82174253,and 82104707)Guangdong Basic and Applied Basic Research Foundation,China(Grant Nos.:2021A1515011215 and 2022A1515110827)+6 种基金Guangzhou Basic and Applied Basic Research Foundation,China(Grant No.:2023A1515011149)China Postdoctoral Science Foundation(Grant Nos.:2020M683206 and 2021M701443)the Key Area Research and Development Program of Guangdong Province,China(Grant No.:2020B1111100010)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,China(Grant No.:202102010014)the Cross-disciplinary Special Project of Jinan University,China(Grant No.:21621115)the State Key Laboratory of Dampness Syndrome of Chinese Medicine,China(Grant No.:SZ2021KF13)the Outstanding Innovative Talents Cultivation Funded Programs for Doctoral Students of Jinan University,China(Grant No.:2021CXB024).
文摘Ulcerative colitis(UC)is characterized by chronic relapsing intestinal inflammation.Currently,there is no effective treatment for the disease.According to our preliminary data,1,8-cineole,which is the main active compound of Amomum compactum Sol.ex Maton volatile oil and an effective drug for the treatment of pneumonia,showed remarkable anti-inflammatory effects on colitis pathogenesis.However,its mechanism of action and direct targets remain unclear.This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate sodium salt-induced colitis mouse model.The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells.In addition,1,8-cineole targets were revealed by drug affinity responsive target stability,thermal shift assay,cellular thermal shift assay,and heat shock protein 90(HSP90)adenosine triphosphatases(ATPase)activity assays.The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function.Mechanistically,1,8-cineole directly interacted with HSP90 and decreased its ATPase activity,also inhibited nucleotide-binding and oligomerization domain-,leucine rich repeat-,and pyrin domain-containing 3(NLRP3)binding to HSP90 and suppressor of G-two allele of SKP1(SGT1)and suppressed NLRP3 inflammasome activation in macrophages.These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.
