文献类型：期刊文献

英文题名：Tibetan medicine Bawei Chenxiang Wan attenuates chronic mountain sickness by targeting the AKT/FOXO3a/CAT axis to inhibit oxidative stress

作者：Li, Xiaoya[1];Zhang, Shujing[1];Qiu, Yuehua[1];Wang, Yuyan[1];Hou, Jianchen[1];Ji, Xuenian[1];Ge, Fei[1];Zhang, Xin[1];Sun, Qingqing[1];Song, Haochong[5];Ciwang, Renzeng[2];Luo, Yamin[3];Tao, Xiaohua[1,4]

第一作者：Li, Xiaoya

通讯作者：Tao, XH[1];Ciwang, R[2];Luo, YM[3]

机构：[1]Beijing Univ Chinese Med, Coll Tradit Chinese Med, 11 North Third Ring Rd East, Beijing 100029, Peoples R China;[2]Tibet Univ Tibetan Med, Coll Tibetan Med, 10 Middle Dangre Rd, Lhasa 850000, Peoples R China;[3]Beijing Univ Chinese Med, Bejing Res Inst Chinese Med, 11 North Third Ring Rd East, Beijing 100029, Peoples R China;[4]Minist Educ, Philosophy & Social Sci Lab, BUCM Lab Digital Intelligence & Humanities Innovat, Beijing 100029, Peoples R China;[5]Beijing Union Univ, Coll Special Educ, Beijing 100029, Peoples R China

第一机构：Beijing Univ Chinese Med, Coll Tradit Chinese Med, 11 North Third Ring Rd East, Beijing 100029, Peoples R China

通讯机构：[1]corresponding author), Beijing Univ Chinese Med, Coll Tradit Chinese Med, 11 North Third Ring Rd East, Beijing 100029, Peoples R China;[2]corresponding author), Tibet Univ Tibetan Med, Coll Tibetan Med, 10 Middle Dangre Rd, Lhasa 850000, Peoples R China;[3]corresponding author), Beijing Univ Chinese Med, Bejing Res Inst Chinese Med, 11 North Third Ring Rd East, Beijing 100029, Peoples R China.

年份：2026

卷号：364

起止页码：121481

外文期刊名：JOURNAL OF ETHNOPHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001715555500001)】；

基金：This research was financially supported by a grant from Central Guidance Fund for Local Scientific and Technological Development of the Tibet Autonomous Region [grant number. XZ202101YD0003C] , The Fundamental Research Funds for the Central Universities in China [grant number. 2025-JYB-JBGS-029] , National Natural Science Foun-dation of China [grant number. 81974542] and Beijing Union University New Doctoral Incubation Project of China [grant number. ZK80202006] .

语种：英文

外文关键词：Bawei chenxiang wan; Chronic mountain sickness; Oxidative stress balance; Weighted gene co-expression network analysis; Random forest; AKT/FOXO3a/CAT signaling axis

摘要：Ethnopharmacological relevance: Bawei Chenxiang Wan (BWCX) is a classical Tibetan medicinal formula originating from the canonical Tibetan medical text The Four Tantras. It is traditionally used to activate qi circulation, nourish the heart, tranquilize the mind and enhance intelligence. It has been applied for over a thousand years on the Qinghai-Tibet Plateau to treat cardio-cerebral hypoxic syndromes such as high-altitude (HA) adverse qi flow and mental trance, which are attributed to an imbalance among the three humors (rlung, mkhris-pa, and badkan). The traditional applications of BWCX closely align with the clinical manifestations of modern Chronic Mountain Sickness (CMS). However, its effective components and mechanisms of action anti-CMS remain unclear. Aim of the study: This study aims to systematically elucidate the material basis of BWCX anti-CMS and its underlying mechanism of cardio-cerebral protection through the regulation of oxidative stress. Materials and methods: Chemical constituents of BWCX were characterized by UHPLC-MS. To identify core therapeutic targets, we employed network pharmacology and analyzed CMS patient transcriptomes (GSE145774, GSE103940) by combining weighted gene co-expression network analysis (WGCNA) with the random forest (RF) algorithm. Molecular docking was used to validate interactions between active components and predicted targets. A physiologically relevant CMS model was established by exposing 60 mice to a natural HA environment (Lhasa, 3650 m) for 8 weeks. Hematological parameters were measured; oxidative stress markers (malondialdehyde [MDA], Catalase [CAT], Total Superoxide Dismutase [T-SOD], glutathione peroxidase [GSH-Px], total antioxidant capacity [T-AOC]) and energy metabolism (adenosine triphosphate [ATP]) in cardiac tissues were assessed by ELISA; and the expression of core targets was analyzed using RT-qPCR and Western blot to verify the regulatory effect of BWCX on the AKT1/FOXO3a/CAT signaling axis, and the binding situation of FOXO3a to the promoter region of CAT was analyzed using ChIP-qPCR to verify the regulatory relationship of FOXO3a on CAT. Results: A total of 78 chemical components were identified, including 18-beta-glycyrrhetinic acid, beta-asarone and quassin. Integrative bioinformatics analysis pinpointed AKT1, FOXO3 and CAT as core targets of BWCX anti CMS, with significant enrichment in oxidative stress-related pathways. Molecular docking results showed that the binding energies of costunolide with AKT1, FOXO3a, CAT and ESR2 were -9.5, -8.8, -11.1 and -9.9 kcal/ mol, respectively; while those of 18-beta-glycyrrhetinic acid with the above targets were -9.1, -8.2, -10.2 and -9.2 kcal/mol, respectively, indicating their strong potential for target binding. Animal experiments demonstrated that BWCX intervention significantly reversed CMS-induced hematological abnormalities [increased red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT) and platelets (PLT)], ameliorated cardiac oxidative stress (reduced MDA; elevated T-AOC, T-SOD, GSH-Px, CAT, ATP), and corrected the dysregulated molecular expression: it suppressed the upregulation of AKT1 mRNA/protein and p-AKT1/AKT1 ratio, while restoring the downregulated mRNA/protein expression of FOXO3a and CAT and the p-FOXO3a/FOXO3a ratio in cardiac and hippocampal tissues (P < 0.05). RT-qPCR analysis of AKT1, FOXO3a, and CAT mRNA expression in vitro revealed trends consistent with those observed in the in vivo experiments. It was also verified that significant enrichment of FOXO3a was detected in the CAT promoter region under hypoxic stress (P < 0.05). FOXO3a binds to the CAT promoter in H9C2 cells, thereby confirming that CAT is a direct transcriptional target of FOXO3a. Conclusions: This study provides the first evidence that BWCX alleviates CMS-induced cardio-cerebral hypoxic injury by modulating the AKT1/FOXO3a/CAT signaling axis, thereby rebalancing oxidative stress and improving hemorheology. These findings provide a modern pharmacological interpretation of its traditional cardiocerebral protective effect, offer a paradigm for ethnomedicine research modernization, and lay a scientific foundation for its clinical application and quality control.