Dissecting the Molecular Mechanism of Wang-Bi Capsule in the Treatment of Experimental Rheumatoid Arthritis Based on Synovial Tissue Proteomic Analysis

Wang-Bi capsule (WB) is a traditional Chinese medicine formula and has been applied for rheumatoid arthritis (RA) treatment for many years. However, its underlying molecular mechanisms still remain unclear. In this study, collagen-induced arthritis (CIA) rats were used to observe the therapeutic effect of WB used at different time points, and the proteomic analysis of synovial tissue was applied to reveal its basic molecular mechanisms. The results demonstrated that WB not only effectively ameliorated the symptoms and synovitis, but also downregulated the serum levels of inflammatory cytokines/chemokines in CIA rats. Furthermore, the proteomic analysis of synovial tissue showed that WB could regulate several signaling pathways associated with inflammation or cell migration, such as “IL-1 signaling,” “IL-8 signaling,” and “CXCR4 signaling.” The expression levels of proteins including matrix metalloproteinase 3 (MMP3), MMP19, lipopolysaccharide-binding protein (LBP), serine/threonine kinase interleukin-1 receptor-associated kinase 4 (IRAK4), and actin-related protein 2/3 complex subunit 5 (ARPC5) in these pathways were downregulated significantly by WB when compared with the model group. In sum, this study indicated that WB had obvious inhibitory effects on synovitis of CIA rats, and the mechanisms of which may be involved in downregulating the expression levels of several key proteins including MMP3, MMP19, LBP, IRAK4, and ARPC5.

Wang-Bi Tablet Ameliorates DMM-Induced Knee Osteoarthritis through Suppressing the Activation of p38-MAPK and NF-κB Signaling Pathways in Mice

Background. Traditional Chinese medicine (TCM) exhibits outstanding therapeutic effects on the treatment of osteoarthritis (OA). Wang-Bi tablets (WBTs) have been used in clinics to treat knee osteoarthritis (KOA) by alleviating joint swelling and paining, and thus, the quality of life in patients with KOA was improved. However, its underlying molecular mechanism of anti-inflammatory response remains unclear. Therefore, further investigation is required. Purpose. This study aimed to explore the function of WBT in KOA mice and uncover the possible molecular mechanisms. Study Design. A KOA model was constructed by destabilizing the medial meniscus (DMM). IL-1β-treated chondrocytes were used to investigate the precise mechanism in vitro. Methods. (1) C57BL/6 male mice (8-week-old) were divided into Model, Sham, WBT-L, WBT-M, and WBT-H groups. After intragastric administration of 0.5% CMC-Na or WBT for 4 weeks, inflammation and pathological change were analyzed by ELISA, RT-qPCR, hematoxylin and eosin (H & E) and safranine O staining. (2) Isolated chondrocytes were stimulated with IL-1β followed by WBT-containing serum treatment, and then, the expression of inflammatory cytokines was analyzed by ELISA and RT-qPCR. (3) The effects of WBT on inflammatory signaling cascades in mice knee joint and chondrocytes were detected by WB. Results. The results indicated that WBT could alleviate inflammation and prevent cartilage injury in KOA mice. Compared with 0.5% CMC-Na-treated mice, the serum glycosaminoglycans (GAG) level in WBT-treated mice was notably increased, while the proinflammatory cytokine interleukin- (IL-) 6 level was decreased. In addition, WBT treatment suppressed the activation of NF-κB and p38 signaling pathways both in vivo and in vitro. Conclusion. WBT can effectively inhibit articular cartilage injury and inflammatory response in KOA mice. The protective role of WBT in mice KOA was a result of the downregulation of NF-κB and p38-MAPK signal pathways.

Identification of the Main Active Components and Mechanism of Wang Bi Tablet in Treating Rheumatoid Arthritis Based on Integrative Pharmacology

Wang Bi tablet (WBT) is used to treat rheumatoid arthritis (RA) in China. We employed integrative pharmacology, including rapid analysis of chemical composition, pharmacological experiment, and network pharmacology analysis, to elucidate the active components and mechanism underlying the effect of WBT against RA. The chemical fingerprint of WBT was revealed by UPLC-QTOF-MS/MS, and the chemical composition was identified. The anti-inflammatory effect of WBT was evaluated in TNF-α-stimulated RAW264.7 cells by ELISA and transcriptome sequencing. Network pharmacology analysis, functional enrichment analysis, and network visualization were performed. A total of 293 chemical constituents were preliminarily identified or tentatively characterized in WBT extract, and they effectively inhibited inflammatory response in TNF-α-stimulated RAW264.7 cells. Forty-eight key active constituents were identified based on high-frequency binding to hub targets and their corresponding targets number. Next, 135 corresponding hub genes, which may be the putative targets of WBT in treating RA, were selected. Functionally, the putative targets were significantly associated with the inflammatory immune response regulation module, energy metabolism regulation module, and cell function regulation module, corresponding to the traditional efficacy of WBT. In summary, this study revealed, for the first time using integrative pharmacology, that WBT may attenuate RA through the inflammation-immune regulation system.

Introduction

The most obvious trace of perfect governance is seen in the Imperial Temple. 王道之可觀者‎，莫盛乎宗廟。‎ —Wang Bi 王弼‎ (226–249)1 Ancestral worship and related ancestral rituals played a central role in Chinese culture. Historically, ancestral rites and ceremonies in imperial China underwent both social and intellectual developments. Traditional Chinese—including elites—emphasized taking care of the world of ancestral spirits through funeral rites and sacrificial ceremonies....

Laozi

This chapter lay out a centrist interpretation of the Laozi on the basis of the Wang Bi recension, and then asks how much of this account needs to be adjusted in view of evidence from the Guodian manuscripts. Laozi is one of the few classical Chinese texts for which a theory of accretion might fit the facts. Currently, there is only one set of undisputedly pre-imperial Laozi texts: the so-called Laozi A, B, and C manuscripts from Guodian, each of which contains a small number of passages that are found, with some variation, in the Wang Bi recension. Laozi is also discussed in this chapter because its philosophy marks a major turning point: the conceptualization of “the Way” (dao) as a cosmic principle. Although it is not certain that Laozi was the very first text to use the word dao in its radically new sense, the text is representative of intellectual trends that emerged around the fourth century BC.

Wang-Bi Capsule Alleviates the Joint Inflammation and Bone Destruction in Mice with Collagen-Induced Arthritis

Wang-Bi Capsule (WB), a traditional Chinese medicine- (TCM-) based herbal formula, is currently used in clinic for the treatment of rheumatoid arthritis (RA) with positive clinical effects. However, its pharmacological mechanism of action in RA is still obscure. Therefore, this study established a collagen-induced arthritis (CIA) mice model to examine the efficacy of WB by using arthritis score, histological analysis, and micro-CT examination. Proinflammatory cytokines expression, osteoclast number, OPG/RANKL system, and NF-κB activation were then detected to further investigate the mechanism of WB in RA treatment. The results indicated that WB could alleviate the erythema and swelling of paws in CIA mice. It also inhibited the infiltration of inflammatory cells and bone destruction and increased bone density in joints of CIA mice. Mechanistic studies showed that WB treatment decreased the production of IL-1β, IL-6, and TNF-α in serum and joints of CIA mice. Moreover, it reduced the osteoclast number, increased OPG level, decreased RANKL level, and inhibited the activation of NF-κB in joints of CIA mice. In conclusion, this study demonstrated that WB could effectively alleviate disease progression of CIA mice by decreasing the IL-1β, IL-6, and TNF-α levels, modulating the OPG/RANKL system, and inhibiting the activation of NF-κB.

Finding Hope and Certainty: Wang Bi’s Commentaries on the Yijing

In this article, I analyze Wang Bi’s (226–249) essays in General Comments on the Changes of the Zhou (Zhouyi Lueli 《周易略例》). I argue that these essays reveal Wang Bi’s unique approach to finding hope and certainty in an ever-changing world. Taking trigrams and hexagrams as symbols of forces that shape our life, Wang Bi creates a philosophical framework that includes two components: (1) a dynamic ontology that stresses the codependence of part and whole, and (2) an attitude of life that views contingency as a reinvigorating force rather than a devastating force.