Ziwan-Taoren herb pair can exert an therapeutical effect in primary Sjogren’s syndrome through inhibiting the TLR/NF-κB pathway  

作　　者：Kuok-Tong Lei Yun-Xia Wu Yun Lu Zi-Shan Wang Thi-Huong Nguyen Qiu-Ying Cai Wen Zhu Yue Wang 

机构地区：[1]First Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210000,China [2]Faculty of Traditional Medicine,Phenikaa University,Ha Noi 100803,Vietnam [3]Department of Rheumatology and Immunology,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210000,China

出　　处：《Traditional Medicine Research》2024年第8期11-22,共12页TMR传统医学研究

基　　金：grants from the National Natural Science Foundation of China(82274454).

摘　　要：Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still unknown.This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS.Methods:Firstly,the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis.Secondly,the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques.Finally,efficacy and mechanism were conducted through in vivo experiments,such as water intake,spleen index,hematoxylin-eosin staining pathological changes,ELISA,Western Blot analysis,and immunofluorescence staining.Results:Nine active compounds were extracted from network pharmacology,including quercitrin,luteolin,kaempferol,β-sitosterol,isorhamnetin,galangin,hederagenin,diosmetin and gibberellin 7.Seven disease targets were identified:RELA,TP53,AKT1,interleukin(IL)6,MAPK1,ESR1,IL10;with RELA being the most core target.KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process.preliminary results of molecular docking showed that ZT’s active compounds bind well to the RELA(p65)receptor.In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice.The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased,while levels of inflammatory factors such as tumor necrosis factor-α,IL-6,and IL-1βalong with protein expressions including toll-like receptor4,p-p65 and p-IKKα/βin NF-κB pathway were reduced.Conclusions:The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS,potentially attributed to its capacity for suppressin

关 键 词：traditional Chinese medicine primary Sjogren’s syndrome NF-κB RELA 

分 类 号：R285.5[医药卫生—中药学]