Exploring mechanism of Banxia Baizhu Tianma Decoction in intervening methamphetamine addiction from PI3K-Akt pathway and cell verification based on network pharmacology and cell verification
- VernacularTitle:基于网络药理学和细胞验证从PI3K-Akt通路探讨半夏白术天麻汤干预甲基苯丙胺成瘾的作用机制
- Author:
Han-Cheng LI
1
;
Zhao JIANG
;
Yang-Kai WU
;
Jie-Yu LI
;
Yi-Ling CHEN
;
Ming ZENG
;
Zhi-Xian MO
Author Information
- Keywords: drug addiction; Banxia Baizhu Tianma Decoction; PI3K-Akt pathway; SH-SY5Y cells; net-work pharmacology; methamphetamine
- From: Chinese Pharmacological Bulletin 2024;40(10):1971-1978
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the mechanism of Banxia Baizhu Tianma Decoction(BBTD)in interfer-ing methamphetamine(MA)addiction using network pharmacology.Methods The mechanism of BBTD intervention in MA addiction was analyzed using net-work pharmacology,and MA-dependent SH-SY5Y cell model was further constructed to observe the effects of BBTD on cell model and PI3K-Akt pathway.Results A total of 88 active ingredients and 583 potential tar-gets of BBTD were screened.KEGG analysis showed that BBTD might intervene in MA addiction through PI3K-Akt,cAMP and other pathways.The molecular docking results showed that key active ingredients ex-hibited strong binding ability with core targets of PI3K-Akt pathway.In vitro experiments showed that MA-de-pendent model cells had shorter synapses,tended to be elliptical in morphology,had blurred cell boundaries,showed typical cell damage morphology,and had high intracellular expression of cAMP(P<0.01)and low expression of 5-HT(P<0.05).BBTD intervention could counteract the above morphology,cAMP,and 5-HT changes,suggesting that it had therapeutic effects on MA-dependent model cells.Western blot showed that MA modeling elevated the p-PI3K/PI3K(P<0.05)and p-Akt/Akt(P<0.01);BBTD inter-vention decreased their relative expression.Conclu-sions Gastrodin and other active ingredients in BBTD have therapeutic effects on MA addiction,and the mechanism may be related to regulation of PI3K-Akt pathway relevant targets.