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JOURNAL OF ETHNOPHARMACOLOGY · 2021 · IF 4.36

Study on the compatibility effect and active constituents of Atractylodis Rhizoma in Ermiao Wan against Acute Gouty Arthritis

Xiao-Ling Fu,Jie Zhou,Wei-Wei Tang,Yang Liu,Zi-Lu Li,Ping Li,Jun Chen

Ethnopharmacological relevance Ermiao Wan (EMW), composed of Atractylodis Rhizoma (AR) and Phellodendri Chinensis Cortex (PC), is a classical traditional Chinese medicine prescription having been used to treat the disease named “Tong Feng”, which is described as “ache in bones and joints” with the same symptom of modern disease named acute gouty arthritis for many years in TCM clinical practice. Besides, both PC and AR were considered to be effective in anti-inflammatory according to modern pharmacological research. Aim of the study Present study was undertaken to probe the compatibility rationality between the two herbs PC and AR in EMW and the active constituents of AR against acute gouty arthritis (AGA). Materials and methods Rat model of AGA was induced by intra-articular injection of monosodium urate (MSU) crystal suspension, and PC combined with or without different AR extracts were used for AGA treatment. Ankle joint swelling, proinflammatory cytokines in serum and pathological changes of synovium were investigated. Using the developed UHPLC-QQQ-MS method, the plasma concentrations of the primary alkaloids in PC, such as berberine , phellodendrine, magnoflorine , jatrorrhizine , berberrubine , palmatine , and tetrahydropalmatine , in AGA rat were determined, and pharmacokinetics properties were compared following oral administration of PC, PC combined with or without different AR extracts. Results PC, PC combined with AR volatile oil (VO) extract or PC combined with whole AR extract significantly attenuated the ankle joint swelling of AGA rats. Besides, the combination of PC and VO extract of AR showed superior efficacy than other groups in ameliorating ankle joint swelling, reducing the IL-6 expression in serum and improving tissue lesions of ankle joints. Furthermore, it turned out that the VO extract of AR increased the blood exposure level of PC related alkaloids than non-volatile oil (NVO) extract of AR, by comparing the pharmacokinetic results of each group. Conclusions The VO components of AR were the key compatible materials to combine with PC in EMW for AGA treatment. Moreover, the enhanced anti-AGA activity of PC after combining with VO extract of AR may attribute to the influence of VO on the pharmacokinetics of PC. This study may provide useful information for elucidating the compatibility effects of AR in EMW against AGA.

CAS / MDL: 64-86-8
研究领域: 民族药理学 · 中医药 · 药理学 · 炎症研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2023 · IF 3.4

Targeted and non-targeted metabolomics uncovering the effects of Er-Miao-Wan formula on rats with hyperuricemia

Chenhui Gu,Xuewen Hu,Baixi Shan,Xiaojing Wu,Jun Chen

Er-Miao-Wan formula (EMW), composed of Phellodendri Chinensis Cortex and Atractylodis Rhizoma, is widely used in the treatment of hyperuricemia (HUA), gout, and related complications as a classic compound formula. However, its mechanisms for the treatment of HUA still need to be further systematically investigated. The study aimed to perform modern analytical techniques to elucidate the mechanisms of EMW in improving the symptoms of HUA from the perspective of metabolomics. We used a high-fructose diet to establish a rat model of HUA to evaluate the effects of EMW on improving HUA. Next, we established a targeted metabolomics analysis method to quantitatively analyze purine metabolites in plasma by using ultra-high-performance liquid chromatography with ultraviolet and triple quadrupole mass spectrometry (UHPLC-UV-QQQ MS), and combined with plasma non-targeted metabolomics analysis by using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF MS) to clarify the potential mechanisms of EMW to improve HUA. Oral administration of EMW could significantly increase the urinary uric acid and decrease the serum uric acid, and exhibited a remarkable effect on improving HUA. Plasma targeted metabolomics analysis showed that six purine metabolites related to HUA, including uric acid, hypoxanthine , xanthine , deoxyadenosine , deoxyguanosine , and deoxyinosine , were changed in the EMW-treated group. Further, principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA) showed that the mechanism of EMW interfering with purine metabolic pathway in the rats with HUA could be different from that of allopurinol . On the basis of plasma non-targeted metabolomics, PCA and orthogonal partial least squares discriminant analysis (OPLA-DA) screened and identified 23 potential biomarkers in the rats with HUA, and 11 biomarkers showed a trend of reversion after the intervention of EMW. The pathway analysis suggested that EMW might have therapeutic effects on the rats with HUA via the metabolic pathways including phenylalanine metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In this study, a plasma targeted metabolomics method that can simultaneously quantify nine purine metabolites in rats with HUA was established for the first time, which can be used to study diseases closely related to HUA. In addition, we further explored the overall effect of EMW on HUA in combination with the metabonomic method established by non-targeted metabolomics, which was helpful to solve the defect that the pharmacological mechanism caused by multi-components and multi-targets of traditional Chinese medicine was difficult to explain scientifically and comprehensively. In summary, EMW could effectively alleviate the symptoms of high-fructose-induced HUA, and the study provided a reference for the potential therapeutic mechanism of EMW.

研究领域: 药理学 · 代谢组学 · 中医药 · 生物化学
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2019 · IF 2.813

Study on chemical constituents of herbal formula Er Miao Wan and GC–MS based metabolomics approach to evaluate its therapeutic effects on hyperuricemic rats

Bixia Huang,Xuewen Hu,Jiancheng Wang,Ping Li,Jun Chen

Hyperuricemia strongly correlates with an increased risk of the development of gout, and cardiovascular and kidney diseases, etc. Er Miao Wan (EMW) is a classical traditional Chinese medicine (TCM) formula extensively used for the treatment of hyperuricemia and gout. However, the global components and action mechanism of the formula are still unknown. Here, the chemical constituents of EMW extract were identified by ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and gas chromatography–mass spectrometry (GC–MS). A total of 24 alkaloids, 15 organic acids, 4 terpenoids , 3 lactones , 3 glycosides , 46 volatile constituents and 3 other compounds were tentatively identified from the EMW extract. Additionally, based on the hyperuricemic rat model induced by long-term high-fructose feed, a GC–MS based metabolomics approach was conducted to holistically assess the mechanism of EMW. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied for screening differential metabolites. A total of 21 metabolites that markedly changed in hyperuricemic rats were identified. Further univariate analysis showed that 9 differential metabolites among them were profoundly reversed by EMW intervention. Metabolic pathway analysis revealed that the variations of these metabolites were mainly associated with glycerolipid metabolism, amino acid metabolism, primary bile acid metabolism, taurine and hypotaurine metabolism and purine metabolism. It was inferred that EMW possibly induced its anti-hyperuricemic effect through restoring multiple disturbed pathways to the normal state. This study could assist with elucidating the potential mechanisms of EMW.

研究领域: 药理学 · 代谢组学 · 中医药学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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