Frontiers in Pharmacology
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2023
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IF 5.6
Sun E.,Huang Ran,Ding Ke,Wang Ling,Hou Jian,Tan Xiaobin,Wei Yingjie,Feng Liang,Jia Xiaobin
Introduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and the effect of warming the kidney and enhancing yang is significantly enhanced after heating with suet oil. However, the active compounds, corresponding targets, metabolic pathways, and synergistic mechanism of frying Epimedium in suet oil to promote yang, remain unclear.Methods: Herein, a strategy based on comprehensive GC-TOF/MS metabolomics and network pharmacology analysis was used to construct an “active compounds-targets-metabolic pathways” network to identify the active compounds, targets and metabolic pathways involved. Subsequently, the targets in kidney tissue were further validated by real-time quantitative polymerase chain reaction (RT-qPCR). Histopathological analysis with physical and biochemical parameters were performed.Results: Fifteen biomarkers from urine and plasma, involving five known metabolic pathways related to kidney yang deficiency were screened. The network pharmacology results showed 37 active compounds (13 from Epimedium and 24 from suet oil), 159 targets, and 267 pathways with significant correlation. Importantly, integrated metabolomics and network pharmacologic analysis revealed 13 active compounds (nine from Epimedium and four from suet oil), 7 corresponding targets (ALDH2, ARG2, GSTA3, GSTM1, GSTM2, HPGDS, and NOS2), two metabolic pathways (glutathione metabolism, arginine and proline metabolism), and two biomarkers (Ornithine and 5-Oxoproline) associated with improved kidney yang deficiency by Epimedium fried with suet oil.Discussion: These finds may elucidate the underlying mechanism of yang enhancement via kidney warming effects. Our study indicated that the mechanism of action mainly involved oxidative stress and amino acid metabolism. Here, we demonstrated the novel strategies of integrating metabolomics and network pharmacology in exploring of the mechanisms of traditional Chinese medicines.
研究领域:
药理学
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中医药学
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代谢组学
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系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2024
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IF 3.1
Ling Xin,Mengxin Ren,Yanwei Lou,Huawen Yin,Feng Qin,Zhili Xiong
Gushudan (GSD) was a traditional Chinese prescription with the remarkable effect of kidney-tonifying and bone-strengthening. However, the potential prevention mechanisms of the GSD on kidney-yang-deficiency-syndrome (KYDS) and its regulation on gut microbe metabolism still need to be further systematically investigated. This study established untargeted urinary metabolomics based on RP/HILIC-UHPLC-Q-Orbitrap HRMS and combined with multivariate statistical analysis to discover differential metabolites and key metabolic pathways. And the gut microbe metabolism pathway-targeted metabolomic based on HILIC-UHPLC-MS/MS was developed and validated to simultaneously determine 15 gut microbe-mediated metabolites in urine samples from the control group (CON), KYDS model group (MOD), GSD-treatment group (GSD) and positive group (POS). The results showed that a total of 36 differential metabolites were discovered in untargeted metabolomics. These differential metabolites included proline, cytosine, butyric acid and nicotinic acid, which were primarily involved in the gut microbe metabolism, amino acid metabolism, energy metabolism and nucleotide metabolism. And GSD played a role in preventing KYDS by regulating these metabolic pathways. The targeted metabolomics found that the levels of 10 gut microbe-mediated metabolites had significant differences in different groups. Among them, compared with the CON group, the levels of lysine, tryptophan, phenylacetylglycine and hippuric acid were increased in the MOD group, while the levels of threonine, leucine, dimethylamine, trimethylamine, succinic acid and butyric acid were decreased, which verified the disorders of gut microbe metabolism in the KYDS rats and GSD had a significant regulatory effect on this disorder. As well as by comparing analysis, it was found that the experimental results were consistent with previous metabolomics and microbiomics of fecal samples. Therefore, this integrated strategy of untargeted and targeted metabolomics not only elucidated the potential prevention mechanism of GSD on KYDS, but also provided a scientific basis for GSD preventing KYDS via the “gut-kidney” axis.
研究领域:
药理学
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代谢组学
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中医药
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系统生物学
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肠道微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2025
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IF 4.1
Jiaxin Di,Meifang Guo,Maijiao Peng,Leyao Fang,Junxi Shen,Nenqun Xiao,Zhoujin Tan
Purpose To investigate the therapeutic mechanisms of sodium butyrate combined with SSP in treating diarrhea with kidney-yang deficiency syndrome, providing experimental evidence for the modern application of classical Chinese medicine formulas.Methods A mouse model of diarrhea with kidney-yang deficiency syndrome was established via adenine combined with Folium sennae gavage. After successful model establishment, the drug intervention groups were administered by gavage with 100% SSP decoction, 300 mg/mL sodium butyrate, and 100 mg/kg sodium butyrate + 50% SSP decoction, respectively. General physical conditions and organ indices were assessed. Serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, as well as colonic immunoglobulin A (sIgA) and mucin 2 (MUC2) levels, were determined via ELISA. Kidney and intestinal histology were evaluated via hematoxylin‒eosin (HE) staining. The characteristics of the small intestinal mucosal microbiota under different interventions were analysed via 16S rRNA sequencing.Results Compared with natural recovery, the combination of 100 mg/kg sodium butyrate + 50% SSP significantly restored colonic sIgA levels (p< 0.05) and MUC2 levels, indicating an improvement in intestinal mucosal barrier function. Histological analysis revealed that the combination of 100 mg/kg sodium butyrate + 50% SSP improved renal inflammation and restored intestinal villus length and crypt depth. The combination therapy controlled the relative abundance of Corynebacterium while restoring Dwaynesavagella and Megasphaera_A. Correlation analysis indicated that Mammaliicoccus and Corynebacterium were significantly negatively correlated with sIgA and MUC2 levels and that their relative abundances were inhibited by the combination therapy.Conclusion Sodium butyrate enhanced the therapeutic efficacy of SSP. The combination therapy effectively repaired damaged kidneys and intestines and alleviated diarrhea with kidney-Yang deficiency syndrome by modulating the relative abundance of intestinal microbiota and enhancing intestinal immunity as well as mucosal barrier function. The interaction between the intestinal microbiota and intestinal mucosal protective factors may be a key mechanism in the combined treatment of diarrhea with kidney-yang deficiency syndrome.
研究领域:
药理学
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中医学
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微生物学
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免疫学
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胃肠病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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