| Residential College | true |
| Status | 已發表Published |
| Title | Studies on the Anti-Rheumatoid Arthritis Components and Mechanisms of Glycine tabacina |
| Author | TU Yanbei 
|
| Subtype | 博士Phd |
| Thesis Advisor | Prof. HE CHENGWEI |
| Date Issued | 2021-08 |
| Degree Grantor | University of Macau |
| Place of Conferral | Macau |
| Keyword | Rheumatoid Arthritis Glycine Tabacina Coumestans Signaling Pathways |
| Abstract | The roots of Glycine tabacina (Labill.) Benth (family: Leguminosae), named Yan Dou in Chinese, has been used to treat RA and joint infection for a long time in folk medicine. However, the lack of systemic phytochemical and pharmacological studies makes us know very little about the exact anti-arthritic efficacy and underlyling mechanisms of this species, which severely limits the in-depth medicinal development of this species. Therefore, inspired by its traditional medicinal use, it is of great significance to elucidate the chemical and pharmacological basis of G. tabacina for the development of novel and effective anti-RA drugs from this species. Firstly, we established a collagen-induced arthritis (CIA) rat model to evaluate the anti-RA effect of G. tabacina ethanol extract (GTE). It was found that oral administration of GTE (1.11, 2.22 and 4.44 g dry herb powder per kg body weight of rat) significantly ameliorated the arthritic symptoms in CIA rat, including paw swelling, arthritis index, bone erosion and cartilage destruction. Besides, we found GTE could exhibit its strong anti-CIA activity through inhibiting pro-inflammatory cytokines production (IL-1β, IL-6 and TNF-α) and enchancing antioxidant capacity in rats, suggesting its potential preventive and therapeutic effects on RA. After the confirmation of anti-RA activity of GTE, the subsequent phytochemical research led to the isolation of eight new coumestans, named glytabastan A-H (1-8), together with twenty-three known compounds 9-31. Their structures were elucidated using various spectroscopic methods. The anti-arthritic activities of all isolates were evaluated, and the results showed that compounds 1-6, 8, 11-13, 15 and 16 inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse-derived RAW 264.7 macrophages, compounds 1-6, 8-12, 15 and 16 inhibited IL-1β-induced TNF-α secretion in SW982 human synovial cells, and compounds 1, 2, 9-11, 13, 15 and 16 suppressed receptor activator of nuclear factor (NF) κB ligand (RANKL)-induced osteoclastogenesis. These results suggested that the coumestans and isoflavonoids in G. tabacina might be responsible for the anti-RA activity of this species. Among them, coumestans 1 (glytabastan A), 2 (glytabastan B), 9 (dolichosin A) and 10 (coumestrol) were considered as potential drug candidates for RA treatment. Moreover, network pharmacological analysis was conducted to elucidate the potential anti-RA regulation of GTE holistically, which revealed that the anti-RA effect of G. tabacina involved a complex interaction network consisted of mulit-components, multi-targets, multi-pathways (PI3K/Akt, MAPK pathways etc.) and multiple biological processes (inflammatory response, cytokine-mediated signaling pathways, etc.). We next further determined the anti-RA activity and underlying mechanisms of glytabastan B (GlyB, 2) in vitro and in vivo. It was observed that GlyB (3 and 6 μM) significantly attenuated IL-1β-induced arthritic inflammation in SW982 cells. |
| Language | 英語English |
| Document Type | Thesis |
| Collection | University of Macau |
| Recommended Citation GB/T 7714 | TU Yanbei. Studies on the Anti-Rheumatoid Arthritis Components and Mechanisms of Glycine tabacina[D]. Macau, University of Macau, 2021. |
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