The active components and potential mechanisms of Wuji Wan in the treatment of ethanol-induced gastric ulcer: An integrated metabolomics, network pharmacology and experimental validation

Article

作者: Liu, Wen ; Wu, Tiantai ; Wang, Shouli ; Zhao, Qing ; Zhang, Ming ; Lu, Yuan ; Zhang, Huan ; Du, Huakang ; Li, Herong ; Chen, Shuaishuai ; Liu, Ting ; Jin, Yang ; Guo, Weiyu

ETHNOPHARMACOLOGICAL RELEVANCEWuji Wan (WJW) is a traditional Chinese medicine formula that can be found in the "Prescriptions of Taiping Benevolent Dispensary" that has been employed in treating gastric discomfort, burning epigastric pain, and gastric reflux for hundreds of years and has shown promise for treating gastric ulcers (GUs). However, the active components and mechanism of action against GUs remain unclear.AIM OF THE STUDYThe aim of this study was to explore the active components of WJW and elucidate the underlying mechanism involved in treating GUs.MATERIALS AND METHODSInitially, cell viability was measured by a cell counting kit 8 (CCK-8) assay to evaluate the efficacy of WJW-containing serum in vitro. The gastric ulcer index, ulcer inhibition rate, hematoxylin and staining (H&E), and periodic acid-Schiff (PAS) staining were used to evaluate the therapeutic effect of WJW in vivo. Subsequently, the levels of inflammatory factors and oxidative stress factors were determined using an enzyme-linked immunosorbent assays (ELISA) on in vitro and in vivo samples. Additionally, UPLC-Q Exactive Plus Orbitrap HRMS was used to analyze the components that were absorbed into the blood of WJW and its metabolites. Network pharmacology and metabolomics were subsequently used to identify the targets and pathways. Real-time quantitative PCR (RT‒qPCR) and Western blotting were used to verify the mRNA and protein levels of the key targets and pathways. Finally, the active components were identified by molecular docking to verify the binding stability of the components and key targets.RESULTSWJW-containing serum ameliorated ethanol-induced damage in GES-1 cells and promoted cell healing. WJW-containing serum reduced IL-6, TNF-α, MDA, and LDH levels while increasing IL-10, SOD, and T-AOC levels in the cells. Moreover, WJW treatment resulted in decreased IL-6, TNF-α, and MDA levels and increased IL-10, SOD, PGE_2, and NO levels in GUs rats. In addition, eight components of WJW were absorbed into the blood. The network pharmacology results revealed 192 common targets for blood entry components and GUs, and KEGG analysis revealed that apoptosis signaling pathways were the main pathways involved in WJW activity against GUs. Metabolomic screening was used to identify 13 differential metabolites. There were 23 common targets for blood entry components, GUs, and differential metabolites, with the key targets TNF (TNF-α), AKT1, PTGS2 (COX2) and MAPK1. WJW significantly inhibited the expression of Bax, Caspase-9, Caspase-3, cleaved Caspase-9, cleaved Caspase-3, TNF-α, COX2, and p-p44/42 MAPK while promoting the expression of Bcl-2 and p-AKT1. Molecular docking revealed that the active components of WJW for the treatment of GUs are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin.CONCLUSIONSWJW treatment reduces inflammation and oxidative stress injury and inhibits apoptosis signaling pathways. The main active components are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. In this paper, we provide a new strategy for exploring the active components of traditional Chinese medicine formulas for the treatment of diseases based on target mechanisms.

2022-12-01·Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

[Pharmacodynamic substances and therapeutic potential of Wuji Pills:based on UPLC-Q-TOF-MS/MS and network pharmacology].

Article

作者: Sun, Yi ; Li, Yu-Jie ; Yang, Qing ; Zhu, Xiao-Xin ; Cai, Wei-Yan ; Chen, Ying ; Wang, Ya-Jie ; Chen, Li-Na ; Guo, Yu-Xuan ; Zhang, Shu-Han ; Weng, Xiao-Gang ; Wang, An-Qi ; Li, Qi

As a classic prescription, Wuji Pills is composed of Coptidis Rhizoma, Euodiae Fructus Preparata, and stir-fried Paeo-niae Radix Alba at the ratio of 6∶1∶6. The practical application of it is limited compared with other famous Chinese medicine prescriptions. Only one company produces Wuji Pills in China. In this study, ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to analyze and identify 26 identical compounds from Wuji Pills and drug-containing plasma of rats. Based on these components, 46 potential targets were screened out with network pharmacology methods, followed by the component-target network construction, Gene Ontology(GO) term enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and disease prediction. It was concluded that Wuji Pills acted on core targets such as PTGS2, PTSG1, NCOA2, HSP9 OAD1, and RXRA through magnoflorine, hydroxyevodiamine, daucosterol, and berberine and exerted pharmacodynamic effects through various pathways such as calcium ion signaling pathway, phosphatidylinositol-3-kinase-protein kinase B(PI3 K-Akt) signaling pathway, and vascular endothelial growth factor(VEGF) signaling pathway. Thus, Wuji Pills has therapeutic potential for Alzheimer's disease, diabetes mellitus, myocardial ischemia, and other diseases in addition to the conventional disease(irritable bowel syndrome, IBS). The above research results can provide a reference for the comprehensive interpretation of the pharmacodynamic basis of Wuji Pills and the expansion of clinical application. At the same time, a lot of components in serum and the in vivo transformed and metabolized components of Wuji Pills have similar structure and relative molecular weight. In theory, these components may show additive effects and the competitive/antagonistic effects on the same target. According to the hypothesis of "additive effect of multiple components for a single target" in traditional Chinese medicine, multiple similar components may exert the additive effects on local targets. This study can partly prove the scientificity of this hypothesis and provide laboratory evidence.

2014-12-01·Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine

[Treatment of antipsychotic drug-induced phlegm dampness type amenorrhea by Wuji Powder and a small dose aripiprazole: a clinical study].

Article

作者: Zhang, Peng ; Zhang, Ying-Ran ; Xia, Shi-Yan ; Meng, Xu ; Yu, Hong ; Liu, Jun

OBJECTIVETo assess the efficacy and safety of Wuji Powder (WP) and a small dose aripiprazole in treatment of antipsychotic drug-induced phlegm dampness type amenorrhea.METHODSSeventy female schizophrenic patients with antipsychotic drug-induced galactorrhea-amenorrhea syndrome (GAS) were recruited and randomly assigned to the treatment group and the control group, 35 in each group. All patients received antipsychotic drug therapy. Patients in the treatment group additionally took WP, while those in the control group took aripiprazole (at the daily dose of 5 mg, once daily). The therapeutic course for all was 4 weeks. Prolactin levels and obesity indices[body weight, waist aircumstance, body mass index (BMI) and waist-hit ratio (WHR)] were determined before and after treatment. The efficacy was evaluated.RESULTSThe treatment course was completed in 95.71% of patients. The total effective rate of the 33 patients of the treatment group was 93.94% (31/33), while it was 91.18% (31/34) in the 34 patients of the control group. There was no difference in the total effective rate between the two groups (P > 0.05). Prolactin levels in both group after treatment were significantly lower than those of the baseline (P < 0.01). There was no significant difference in prolactin levels between the two groups after treatment (P > 0.05). Compared with before treatment, body weight, BMI, waist circumstance, and waist-hip ratio obviously decreased after treatment, showing significant difference when compared with the control group (P < 0.05). There was no significant difference in body weight, BMI, waist circumstance, and waist-hip ratio in the control group between before and after treatment (P > 0.05).CONCLUSIONSBoth WP and aripiprazole could lower high prolactin levels of schizophrenics with phlegm dampness type amenorrhea. They showed equivalent efficacy. But WP showed more obvious effect in reducing obesity indices.

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适应症	国家/地区	公司	日期
关节痛	日本	Teikoku Seiyaku Co. Ltd.	1987-10-01
普通感冒	日本	Teikoku Seiyaku Co. Ltd.	1987-10-01
痛经	日本	Teikoku Seiyaku Co. Ltd.	1987-10-01
胃肠炎	日本	Teikoku Seiyaku Co. Ltd.	1987-10-01
头痛	日本	Teikoku Seiyaku Co. Ltd.	1987-10-01
腰痛	日本	Teikoku Seiyaku Co. Ltd.	1987-10-01
神经痛	日本	Teikoku Seiyaku Co. Ltd.	1987-10-01