作者: Chen, De-Ta ; Sheng, Xiao-Ping ; Qiu, Min-Lei ; Xie, Xiao-Liang ; Gu, Jing-Liang ; Fan, Tian-You ; Rao, Wu ; Li, Yu-Mei ; Pan, Yan-Bin ; Chen, Lin ; Zhu, Hai-Xia ; Shen, Xue

Objective:The objective of this study is to analyze and verify the main drug components and targets of "Fuzi-Guizhi" in the treatment of osteoarthritis by using the network pharmacology platform.Methods:The integrated pharmacology of "Fuzi-Guizhi" was analyzed by using the platform of integrated pharmacology of traditional Chinese medicine to explore its mechanism in the treatment of osteoarthritis. By establishing an arthritis model in vitro, the pharmacological effect of "aconitecassia twigs" on articular cartilage was evaluated and conducted for molecular docking.Results:28 candidate active components, 37 compound targets, and 583 osteoarthritis-related potential targets were screened, and 10 key target processes were screened in the protein interaction network model. Enrichment analysis showed that the 10 core targets involved 958 GO biologic function items and 76 KEGG signal pathways, which were mainly related to apoptosis and mitochondrial functional metabolism. And "Fuzi-Guizhi" drug-containing serum inhibited the expression of Caspase-3 mRNA and protein in chondrocytes and promoted the synthesis of ATP.Conclusion:Our research is preliminary that the mechanism of action of "Fuzi-Guizhi" may inhibit chondrocyte degeneration by resisting mitochondrial apoptosis, and further experimental research is required to determine.

2023-03-01·Journal of Ethnopharmacology

Inhibition Ras/MEK/ERK pathway: An important mechanism of Baihu Jia Guizhi Decoction ameliorated rheumatoid arthritis

Article

作者: Yang, Jinming ; Chen, Huan ; Chen, Qi ; Xu, Shi-Jun ; Liu, Panwang ; Pan, Ting

ETHNOPHARMACOLOGICAL RELEVANCEAlleviating rheumatism by inhibiting synovitis is a routine treatment for rheumatoid arthritis (RA). Baihu Jia Guizhi Decoction (BHJGZ) is a classic prescription and has a long history of application for treating RA with a good anti-inflammatory action. However, the underlying molecular mechanisms have not been fully elucidated.AIM OF THE STUDYThis work aimed to decipher the potential mechanism of BHJGZ against RA focusing on Ras/MEK/ERK pathway.MATERIALS AND METHODSBased on the prediction of network pharmacology, the inhibition action of BHJGZ on Ras/MEK/ERK pathway was firstly validated in vivo and in vitro. Moreover, the affinity with the ingredients of BHJGZ in serum and the targets of Ras/MEK/ERK pathway were evaluated. Finally, the efficacy of BHJGZ for relieving RA was assessed in AA rats.RESULTSThe Ras/MEK/ERK pathway was predicted by network pharmacology as one of important mechanisms of BHJGZ to treat RA. The high expression of Ras protein in synovitis of AA rats was significantly reduced by the treatment with BHJGZ, and the activation of Ras/MEK/ERK pathway in vivo and in vitro was also markedly inhibited (p < 0.05 or p < 0.01). Moreover, the level of p-ERK/ERK, IL-6 and TNF-α in vitro were further suppressed after Ras or MEK was inhibited by mirdametinib or lonafarnib respectively (p < 0.01). Furthermore, the results of molecular docking showed a good affinity and stable binding with the ingredients of BHJGZ in serum and multiple key proteins of the Ras/MEK/ERK pathway. Finally, paw swelling, paw circumference and pathological changes of joint synovitis were significantly reduced by BHJGZ in AA rats (p < 0.05).CONCLUSIONThe inhibition of Ras/MEK/ERK pathway is one of crucial mechanisms of BHJGZ for ameliorating synovitis of RA.

2022-09-01·Phytomedicine

A promising drug combination of mangiferin and glycyrrhizic acid ameliorates disease severity of rheumatoid arthritis by reversing the disturbance of thermogenesis and energy metabolism

Article

作者: Ding, Zihe ; Wang, Kexin ; Wang, Qian ; Ma, Zhaochen ; Chen, Wenjia ; Liu, Yudong ; Li, Congchong ; Mao, Xia ; Lin, Na ; Zhang, Yanqiong ; Li, Weijie ; Wang, Xiaoyue

BACKGROUNDActivation of immune system in rheumatoid arthritis (RA) consumes amount of energy, and the energy metabolic signals may be a potential target for RA therapy. Baihu-Guizhi decoction (BHGZD) achieves satisfactory therapeutic effects in RA in clinics by recovering the adjacent articular cartilage and bone destruction, and abnormal articular temperature. However, its pharmacological material basis and molecular mechanisms have not been fully elucidated.PURPOSEThis study focused on exploring the potential acting mechanism of BHGZD against RA, and identifying its main bioactive compounds (BACs) of the combination of mangiferin and glycyrrhizic acid.METHODSKey putative targets of BHGZD acting on adjuvant-induced arthritis (AIA)-M rats were screened by the transcriptomic profiling of the whole blood cells and synovium tissues collected from rats in normal control, AIA-M model and AIA-M-BHGZD treatment groups. Then, BACs of BHGZD against RA were identified using Ultra Performance Liquid Chromatography-Mass spectrum/Mass spectrum, molecular docking, surface plasmon resonance and pharmacokinetic analysis. In vivo experiments based on AIA-M rats and in vitro experiments based on 3T3-L1 preadipocytes were performed to verify the pharmacological effects of BACs against RA and the corresponding mechanisms.RESULTSPKA-ADCY5-PPARγ-PGC 1α-UCP1-PRDM16 signal axis was demonstrated to be the candidate targets of BHGZD against RA and was involved in maintaining the balance of thermogenesis and energy metabolism, according to the transcriptional regulatory network analysis based on "herbs-putative targets-disease interaction network". Then, mangiferin from Rhizoma Anemarrhenae and glycyrrhizic acid from Radix Glycytthizae were identified as the main BACs of BHGZD against RA due to their highly accumulation in the blood in vivo, strong binding affinities with the two candidate targets of BHGZD against RA-ADCY5 and PPARγ, as well as the in vivo and in vitro strong regulation effects on energy metabolism disturbance.CONCLUSIONSThese findings offer evidence that the combination of mangiferin and glycyrrhizic acid from BHGZD may be a promising candidate drug for RA therapy, and also provide an important reference for the development and modernization of traditional Chinese formulae.

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适应症	国家/地区	公司	日期
急性关节炎	日本	Sanwa Shoyaku Co., Ltd.	1986-07-18
慢性关节炎	日本	Sanwa Shoyaku Co., Ltd.	1986-07-18
偏头痛	日本	Sanwa Shoyaku Co., Ltd.	1986-07-18
神经痛	日本	Sanwa Shoyaku Co., Ltd.	1986-07-18
类风湿关节炎	日本	Sanwa Shoyaku Co., Ltd.	1986-07-18