Abstract
Odontites vulgaris Moench has the effect of clearing away heat, detoxification, dispelling wind, and clearing dampness. In this study, the potential anti-inflammatory compounds of O. vulgaris were investigated using ultra-high-performance liquid chromatography–mass spectrometry (UPLC–MS/MS) combined with the network pharmacology approach and further confirmed on an LPS-activated RAW 264.7 macrophage model. Monomer compounds were prepared from the active fraction using modern advanced separation and purification methods. UPLC–Q-Exactive HRMS was used to identify the chemical compounds in the active fractions of O. vulgaris. D-mannitol, geniposidic acid, salidroside, shanzhiside methyl ester, eleutheroside B, geniposide, 7,8-dihydroxycoumarin, gardoside methyl ester, arenarioside, vanillic acid, p-hydroxy-cinnamic acid, melampyroside, syringaresinol, tricin, and diosmetin were isolated from O. vulgaris for the first time. A compound database of O. vulgaris was established based on the existing literature to predict the mechanism of O. vulgaris in the treatment of rheumatoid arthritis. The results suggest that the PI3K-Akt pathway mediates O. vulgaris and deserves more attention in the treatment of RA. Finally, the anti-rheumatoid arthritis effects of the four target compounds were validated with the decreased levels of NO, TNF-α, IL-6 and IL-1β in RAW 264.7 macrophage cells treated with LPS. The present study explored the potential targets and signaling pathways of O. vulgaris in the treatment of RA, which may help to illustrate the mechanisms involved in the action of O. vulgaris and may provide a better understanding of the relationship between O. vulgaris and RA. This study provides novel insights into the development of new drugs and utilization of Mongolian traditional Chinese medicine resources.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial hyperplasia, inflammatory infiltration, pannus formation, and bone erosion, which may lead to joint deformity, disability, and death (Li et al, 2019a; Li et al, 2019b; Guo et al, 2020)
Determination of Indomethacin Concentration The results showed that indomethacin could significantly inhibit the content of nitric oxide (NO) (p < 0.0001), and the inhibitory effect was proportional to the concentration of indomethacin
There were no significant differences in cell proliferation between the control group and the RAW 264.7 cells subjected to the different polar fractions of O. vulgaris (25, 50, 100, and 200 μg/ml) (Figure 4A; p > 0.05)
Summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial hyperplasia, inflammatory infiltration, pannus formation, and bone erosion, which may lead to joint deformity, disability, and death (Li et al, 2019a; Li et al, 2019b; Guo et al, 2020). Nonsteroidal anti-inflammatory drugs are commonly used for the treatment of such patients. Biological blockers that suppress inflammation, such as that mediated by anti-tumor necrosis factor-α, may lead to a higher risk of infection owing to their role in weakening the immune system (Wang et al, 2020a). In recent years, owing to the low level of ethnopharmacological adverse reactions, Ethnopharmacological Mongolian medicine has attracted attention as an alternative treatment for inflammation (Wang et al, 2020b). These Mongolian medicinal treatments exert anti-inflammatory effects through the NF-κB, MAPK, PI3K-Akt, arachidonic acid metabolism, inflammasome, and other pathways (Mao et al, 2019)
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