The mechanism of the anti-inflammatory effect of Oldenlandia diffusa on arthritis model rats: a quantitative proteomic and network pharmacologic study

Abstract

Background: In China, Oldenlandia diffusa (OD) has been prescribed as a therapeutic herb for rheumatoid arthritis (RA). We previously conducted a preliminary study of the anti-inflammatory effect of OD, and the purpose of this study is to further investigate its mechanism.Methods: We performed a quantitative proteomic analysis of synovium, identified the differentially expressed proteins, and performed bioinformatics analyses. With the help of network pharmacology, we aimed to find the key synovial proteins which OD or its key compound might influence. To verify the result, liquid chromatography-mass spectrometry (LC-MS) was applied to quantify and qualify the absorbable potential compounds of OD. The anti-inflammatory effect was evaluated by morphological, histopathological, and cytokine analyses. Target proteins were observed by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA).Results: MMP3 and CAV1 were identified as 2 of the differentially expressed proteins in RA synovium, and might be influenced by quercetin, the active compound of OD. MMP3 might be altered through atherosclerosis signaling, while CAV1 might be altered through caveolar-mediated endocytosis signaling. According to our verification, quercetin was identified as the absorbed and effective compound of OD, and it could exert an anti-inflammatory effect on the collagen induced arthritis (CIA) model, including serum cytokine expression, synovial hyperplasia and lymphocyte infiltration, articular cartilage lesion. Quercetin could also down-regulate the synovial expression of MMP3 and CAV1, and could exert better effects at a high dose.Conclusions: Quercetin was the main active compound of OD in the treatment of RA. OD might alleviate inflammatory responses in CIA rats by suppressing the expression of MMP3 and CAV1 through quercetin, and at a high dose, quercetin could exert a better anti-inflammatory effect.

Network pharmacology and bioinformatics were used to construct a prognostic model and immunoassay of core target genes in the combination of quercetin and kaempferol in the treatment of colorectal cancer

“…This study preliminarily explored the molecular mechanisms of these two components in the treatment of CRC, laying a foundation for further studies of their biomolecular mechanisms. From the results of the gene function analysis, it can be seen that the combination of quercetin and kaempferol is effective in the treatment of colorectal cancer because they have similar roles in multiple molecular pathways and gene functions, for instance inhibiting the expression of MMP3 [123][124][125][126][127][128]. However, in CRC, whether kaempferol can inhibit MMP3 activity, thereby affecting the development, progression, and migration of CRC?…”

Therapeutic potential of Coptis chinensis for arthritis with underlying mechanisms

“…The regulation of IL-17 signaling pathway in chondrocytes could inhibit the overexpression and activation of key proteins, such as IL-17RA, ACT1 and TRAF6, which could improve the occurrence of cartilage inflammation in OA. Research has shown that aryl hydrocarbon receptor (AHR), caveolin-1 (CAV1), c-reactive protein (CRP), C-X-C motif chemokine 2 (CXCL2), interferon regulatory factor-1 (IRF1), secreted phosphoprotein 1 (SPP1) and other targets are key targets in the pathogenesis of arthritis ( Chen et al, 2022 ; Wang et al, 2022 ; Sakthiswary et al, 2022 ; Zhu et al, 2022 ; Li et al, 2023 ; Yang et al, 2023 ), but role of them in the treatment of arthritis by CC has not been verified and further clarification is needed.…”