Active Ingredients and Anti‐Arthritic Mechanisms of Ba‐Wei‐Long‐Zuan Granule Revealed by¹H‐NMR‐Based Metabolomics Combined with Network Pharmacology Analysis

Abstract

Ba‐Wei‐Long‐Zuan granule (BWLZ) is a traditional herbal preparation. It has been widely used for the treatment of rheumatoid arthritis (RA). However, its active ingredients and mechanisms of action are still unclear. The present study aims to reveal the active compounds and anti‐arthritic mechanisms of BWLZ against collagen‐induced arthritis (CIA) by using 1H‐NMR‐based metabolomics, molecular docking and network pharmacology methods. After 30 days of administration, BWLZ could effectively improve the metabolic disorders in CIA rats. The anti‐arthritic effect of BWLZ was related to its restoration of 16 disturbed serum metabolites. Molecular docking and network analysis showed that 20 compounds present in BWLZ could act on multiple targets. Among them, coclaurine and hesperidin showed the highest hit rates for target proteins related to both metabolic regulation and RA, indicating that these two compounds might be potential active ingredients of BWLZ. Moreover, pathway enrichment analysis suggested that the anti‐arthritic mechanisms of BWLZ might be attributed to its network regulation of several biological processes, such as steroid hormone biosynthesis, mTOR signaling pathway, alanine, aspartate and glutamate metabolism, and synthesis and degradation of ketone bodies. These results provide further evidence for the anti‐arthritic properties of BWLZ and are beneficial for its quality control and clinical application. The potential targets and biological processes found in this study may provide valuable information for further studying the molecular mechanisms of BWLZ against RA. In addition, our work provides new insights for revealing the active ingredients and regulatory mechanisms of complex herbal preparations.

The Role of Natural Products in Rheumatoid Arthritis: Current Knowledge of Basic In Vitro and In Vivo Research

“…Bawei Longzuan granule (also found in the literature as Ba-Wei-Long-Zuan granule) is a representative Zhuang medicine preparation used for the treatment of RA [ 62 ]. A recent study showed that oral administration of 1.25, 2.5, and 5 g/kg for 30 days successfully modulated paw swelling in CIA rats; notably, the higher dose resulted in a rapid decrease after 15 days, which was also slightly observed for the medium dose but not for the lower dose.…”

Revealing the pharmacological effect and mechanism of darutoside on gouty arthritis by liquid chromatography/mass spectrometry and metabolomics

“…Rats were injected by sodium urate emulsion into joint cavity leading to neutrophil infiltration, synovial inflammatory cell infiltration, uric acid deposition, local tissue necrosis, synovial tissue hyperplasia, and inflammatory factor release, which the pathological manifestations are very similar to clinical. The combination of metabolomics and network pharmacology can link endogenous metabolites with disease targets, thereby further revealing the molecular mechanism of TCM with multi-component and multi-target characteristics ( Zhang et al, 2018 ; Fan et al, 2020 ). Recently, some researchers have successfully used the integrated metabolomics and network pharmacology strategies to quest the interaction between organisms and drugs, which has brought great inspiration to the mechanism research of darutoside.…”