Metabolomics combined with network pharmacology to study the mechanism of Shentong Zhuyu decoction in the treatment of rheumatoid arthritis

Jiang, Yanping; Yang, Zheng; Qin, Dong; Liao, Wan; Pang, Lan; Chen, Jiao; He, Qinman; Zhang, Jinming; Luo, Yuanhong; Li, Jiaxin; Fu, Chaomei; Fu, Qiang

doi:10.1016/j.jep.2021.114846

Cited by 12 publications

(4 citation statements)

References 76 publications

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“…Rheumatoid arthritis (RA) is a chronic immune disease, which involves multiple systems. The hallmark pathological features of RA include the proliferation of synovial lining cells, significant inflammatory cell infiltration into the interstitium, regeneration of microvessels, pannus formation, damage of both cartilage and bone tissue, as well as reported metabolic disorders ( Liu et al, 2021 ; Jiang et al, 2021 ). Globally, the prevalence of RA is relatively high, about 0.5–1.0% ( Tobon et al, 2010 ; Ardalan and Vahed, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Traditional Tibetan Medicine Twenty-Five Wei’er Tea Pills Ameliorate Rheumatoid Arthritis Based on Chemical Crosstalk Between Gut Microbiota and the Host

Nie

et al. 2022

Front. Pharmacol.

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Twenty-Five Wei’er Tea Pills (TFP), a traditional Tibetan medicine, has shown to have a promising therapeutic effect in patients with Rheumatoid arthritis (RA), as well as being safe. Nonetheless, there have been limited pharmacological studies that have explored this therapeutic option. As gut microbiota has been proven to have a critical role in the pathogenesis of RA, this study aims to explore and reveal relevant ways by which TFP interacts with the chemical crosstalk between the gut microbiome and its host. 16S rRNA sequencing, combined with un-targeted metabolomics, were conducted on collagen-induced arthritis (CIA) rats. CIA model rats treated with TFP showed significant improvement in weight gain, pathological phenomena in joints, as well as decreased serum levels of TNF-α, IL-6 and increased level of IL-4 and IL-10. Significant dysfunction in the gut microbiome and alteration in serum metabolites were observed in CIA model rats, which were restored by TFP treatment. Coherence analysis indicated that TFP modulated the pathways of histidine metabolism, phenylalanine metabolism, alanine, aspartate, glutamate metabolism, amino sugar and nucleotide sugar metabolism owing to the abundances of Lactobacillus, Bacteroides, Prevotellaceae_UCG-001 and Christensenellaceae_R-7_group in the gut microflora. The corresponding metabolites involved L-histidine, histamine, phenylethylamine, asparagine, L-aspartic acid, D-fructose 1-phosphate, D-Mannose 6-phosphate, D-Glucose 6-phosphate, and Glucose 1-phosphate. In conclusion, this study reveals the ameliorative effects of TFP on RA through the chemical crosstalk that exists between the gut microbiota and its host, and also further enriches our understandings of the pathogenesis of RA.

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Section: Introductionmentioning

confidence: 99%

Traditional Tibetan Medicine Twenty-Five Wei’er Tea Pills Ameliorate Rheumatoid Arthritis Based on Chemical Crosstalk Between Gut Microbiota and the Host

Nie

et al. 2022

Front. Pharmacol.

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“…This approach can effectively reveal the synergistic effects of novel combination drugs, assist in multi-target drug development, and provide new perspectives for disease treatment. Jiang et al, 2022 used an integrated strategy combining metabolomics and network analysis to investigate the mechanism of Shentong Zhuyu decoction (STZYD) against rheumatoid arthritis (RA), including Ligusticum capillaceum H. Wolff ( Apiaceae ; “Chuanxiong” Rhizoma ), Carthamus tinctorius L. ( Asteraceae; Carthami Flos ), Prunus persica (L.) Batsch ( Rosaceae ; Persicae Semen ), Achyranthes bidentata Blume ( Amaranthaceae ; Achyranthis Bidentatae Radix ), Gentiana macrophylla Pall. ( Gentianaceae ; Gentianae Radix et Rhizoma ), P. lactiflora Pall.…”

Section: Approaches For Establishing Amctmentioning

confidence: 99%

Section: Elucidating Synergistic Mechanismsmentioning

confidence: 99%

Active metabolites combination therapies: towards the next paradigm for more efficient and more scientific Chinese medicine

Gao,

Wu,

Chen

et al. 2024

Front. Pharmacol.

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Traditional Chinese medicine (TCM) formulae have been studied extensively in various human diseases and have proven to be effective due to their multi-component, multi-target advantage. However, its active metabolites are not clear and the specific mechanisms are not well established, which limits its scientific application. Recently, combination therapies are attracting increasing attention from the scientific community in the past few years and are considered as the next paradigm in drug discovery. Here, we tried to define a new concept of “active metabolites combination therapies (AMCT)” rules to elucidate how the bioactive metabolites from TCMs to produce their synergistic effects in this review. The AMCT rules integrate multidisciplinary technologies like molecular biology, biochemistry, pharmacology, analytical chemistry and pharmacodynamics, etc. Meanwhile, emerging technologies such as multi-omics combined analysis, network analysis, artificial intelligence conduce to better elucidate the mechanisms of these combination therapies in disease treatment, which provides new insights for the development of novel active metabolites combination drugs. AMCT rules will hopefully further guide the development of novel combination drugs that will promote the modernization and international needs of TCM.

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“…Therefore, the integration of metabolomics and network pharmacology for mechanistic studies allows them to complement and validate each other. This approach has emerged as a promising tool for investigating drug therapy for diseases in recent years 18,[29][30][31] . These two research methods are similar to the "holistic concept" in TCM.…”

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confidence: 99%

Integrated network pharmacology and metabolomics reveal the mechanisms of Jasminum elongatum in anti-ulcerative colitis

Qiu,

Xiao,

Yang

et al. 2023

Sci Rep

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Jasminum elongatum (JE), an ethnic Chinese medicine, is widely used in the Lingnan region of China, because of its analgesic and antidiarrheal action, as well as its anti-inflammatory effects in gastrointestinal diseases. However, whether JE could against ulcerative colitis (UC) remains unclear. This research aims to reveal JE in treating UC and clarify the underlying mechanism. We used the 2.5% dextran sulfate sodium (DSS)-induced UC mice (C57BL/6J) to evaluate the therapeutic effects of JE. Metabolomics of serum and network pharmacology were combined to draw target-metabolite pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using immunohistochemistry. The pharmacodynamic results, including disease activity index (DAI), histological evaluation, and inflammatory cytokines in colon tissues, demonstrated that JE significantly relieved the physiological and pathological symptoms of UC. Network pharmacology analysis indicated 25 core targets, such as TNF, IL-6, PTGS2 and RELA, and four key pathways, including the NF-κB signaling pathway and arachidonic acid metabolism pathway, which were the key connections between JE and UC. Metabolomics analysis identified 45 endogenous differential metabolites and 9 metabolic pathways by enrichment, with the arachidonic acid metabolism pathway being the main metabolism pathway, consistent with the prediction of network pharmacology. IκB, p65 and COX-2 were identified as key targets and this study demonstrated for the first time that JE reverses 2.5% DSS-induced UC in mice via the IκB/p65/COX-2/arachidonic acid pathway. This study reveals the complex mechanisms underlying the therapeutic effects of JE on UC and provides a new approach to identifying the underlying mechanisms of the pharmacological action of Chinese natural medicines such as JE.

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Metabolomics combined with network pharmacology to study the mechanism of Shentong Zhuyu decoction in the treatment of rheumatoid arthritis

Cited by 12 publications

References 76 publications

Traditional Tibetan Medicine Twenty-Five Wei’er Tea Pills Ameliorate Rheumatoid Arthritis Based on Chemical Crosstalk Between Gut Microbiota and the Host

Traditional Tibetan Medicine Twenty-Five Wei’er Tea Pills Ameliorate Rheumatoid Arthritis Based on Chemical Crosstalk Between Gut Microbiota and the Host

Active metabolites combination therapies: towards the next paradigm for more efficient and more scientific Chinese medicine

Integrated network pharmacology and metabolomics reveal the mechanisms of Jasminum elongatum in anti-ulcerative colitis

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