JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Yanping Jiang,Yongfeng Zheng,Qin Dong,Wan Liao,Lan Pang,Jiao Chen,Qinman He,Jinming Zhang,Yuanhong Luo,Jiaxin Li,Chaomei Fu,Qiang Fu
Ethnopharmacological relevance Shentong Zhuyu decoction (STZYD) was first recorded in the classic of “ Yilin Gaicuo ” written by Wang Qingren, and recognized by the Chinese National Administration of Traditional Chinese Medicine as one of the 100 classic formulas. The formula has been widely used in the treatment of rheumatoid arthritis (RA) with significant clinical effects. However, its mechanism of action is not completely clear. Aim of the study This study aimed to explore the mechanism of STZYD in the treatment of RA by network pharmacology and metabolomics. Materials and methods The effects of STZYD anti-RA were investigated by paw swelling, arthritis score, cytokine level, histopathological and micro-CT analysis in adjuvant-induced arthritis (AIA) rats. The chemical constituents of STZYD and absorbed constituents in AIA rat serum were analyzed by UPLC-Q-Exactive MS/MS. Based on the characterized chemical components, the network pharmacology was used to find potential targets and signaling pathways of STZYD in RA treatment. Meanwhile, the predicted pathway was determined by the Western blot (WB). Subsequently, non-targeted metabolomics of serum was performed to analyze metabolic profiles, potential biomarkers, and metabolic pathways of STZYD in the treatment of RA based on LC-MS technology. Results STZYD significantly alleviated RA symptoms by improving paw redness and swelling, bone and cartilage damage, synovial hyperplasia , and infiltration of inflammatory cells, and decreased the generation of pro-inflammatory cytokines IL-1β, IL-6, IL-17A and TNF-α in AIA rats. Totally, 59 chemical components of STZYD and 24 serum migrant ingredients were identified. A total of 655 genes of potential bioactive components in STZYD and 1025 related genes of RA were obtained. TNF signaling pathway was considered to one of the main signaling pathways of STZYD anti-RA by KEGG analysis, including a wide range intracellular signaling pathways. NF-κB signaling pathway regulates inflammation and immunity in the TNF signaling pathway. STZYD markedly inhibited the expression of NF-κB signaling pathway. Ten potential biomarkers were found in metabolomics based on LC-MS technology. Alanine , aspartate and glutamate metabolism, arachidonic acid metabolism are the most related pathways of STZYD anti-RA. Conclusion The study based on serum pharmacochemistry, network pharmacology and metabolomics indicated that STZYD can improve RA through regulating inflammation and immunity related pathways, and provided a new possibility for treatment of RA.
研究领域:
药理学
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中医
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免疫学
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风湿病学
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代谢组学
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网络药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Li Yang,Ronghua Liu,Aiguo Fan,Guoyue Zhong,Junwei He
Ethnopharmacological relevance The root of Dendropanax dentiger (Harms) Merr. is a pivotal folk Chinese medicine against rheumatoid arthritis (RA) with no scientific validation. Aim of the study This study was conducted to explore the anti-RA effect of the D. dentiger extract on complete Freund's adjuvant-induced arthritis (AIA) in rats and identified its major bio-constituents. Materials and methods Dendropanax dentiger roots extracts (127.5, 255.0 and 510.0 mg/kg, once daily) were orally at day 7 post-administration adjuvant and lasting for 22 days. The therapeutic effects of D. dentiger roots extract on AIA rats were investigated by body weight growth, arthritis score, thymus and spleen indices, and histopathological analysis. Moreover, the levels of rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and matrix metalloproteinase-2 (MMP-2) were also evaluated. Finally, the major constituents were isolated and identified from D. dentiger roots extract with COX-2 inhibitory and antioxidant activities . Results Dendropanax dentiger roots extract remarkably alleviated the histological lesions of knee joint, increased body weight growth, decreased arthritis score, and reduced thymus and spleen indices in model rats. In parallel, the levels of RF, CRP, TNF-α, IL-1β, IL-6, IL-17, COX-2, 5-LOX and MMP-2 were observably downregulated, while the levels of IL-4 and IL-10 were prominently upregulated in D. dentiger roots extract-treated rats. Meanwhile, 14 compounds were isolated and identified from D. dentiger roots extract, and four phenol derivatives ( 1 , 4 , 6 and 7 ) exhibited remarkable COX-2 inhibitory and antioxidant activities. Conclusions Dendropanax dentiger roots extract possessed persuasive anti-RA effect may be partly responsible for phenol derivatives via modulation of inflammatory biomarkers, and supports the traditional folk use of D. dentiger in China.
研究领域:
药理学
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免疫学
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民族药理学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Yuling Liu,Xin Nie,Yihan Wu,Longfei Lin,Qian Liao,Jingjing Li,Simon Ming-Yuen Lee,Hui Li,Jinming Zhang
Introduction: The insufficient targeting delivery of therapeutic agents greatly impeded the treatment outcomes of rheumatoid arthritis (RA). Despite the recognized therapeutic advantages of gambogic acid (GBA) in inflammatory diseases, its high delivery efficiency to inflammatory site still limits its clinical application. Self-assembly of drug dimers into carrier-free nanoparticles (NPs) has become a straightforward and attractive approach to develop nanomedicines for RA treatment. Herein, homodimers of GBA were designed to form the carrier-free NPs by self-assembly for RA treatment.
Methods: The synthetic gambogic acid dimers (GBA2) were self-assembled into NPs using a one-step solvent evaporation method. The size distribution, morphology, drug-loading efficiency (DLE) and storage stability were evaluated. A molecular dynamic simulation was conducted to gain further insight into the self-assembly mechanisms of GBA2/NPs. Besides, we investigated the cytotoxicity, apoptosis and cellular uptake profiles of GBA2/NPs in macrophages and osteoclasts. Finally, the specific biodistribution on the ankles of adjuvant-induced arthritis (AIA) mice, and the anti-RA efficacy of the AIA rat model were assessed.
Results: GBA2/NPs exhibited the uniform spherical structure, possessing excellent colloidal stability, high self-assembly stability, high drug loading and low hemolytic activity. Comparing with GBA, GBA2/NPs showed higher cytotoxicity, cellular uptake and apoptosis rate against osteoclasts. In addition, GBA2/NPs exhibited much higher accumulation in ankle joints in vivo. As expected, the systematic administration of GBA2/NPs resulted in the greater alleviation of arthritic symptoms, cartilage protection, and inflammation, notably the reduced systemic toxicity compared to free GBA.
Conclusion: GBA2/NPs formed GBA dimers exhibited the superior accumulation in the inflamed joint and anti-RA activity, potentially attributing to the similar extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (""ELVIS"") effects in inflamed joint and the enhanced cellular uptake in macrophages and osteoclasts. Our findings provide substantial evidence that self-assembly of GBA2/NPs would be a promising therapeutic alternative for RA treatment.
研究领域:
药学
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纳米技术
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风湿病学
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药物递送系统
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）