Screening of prostaglandin E2 receptor 4 antagonist from active compounds of <i>Baeckea frutescens</i> L. and its anti-rheumatoid arthritis effect <i>in vivo</i>

LIN Xiaobing; WANG Hao; ZHANG Junhan; LIN Zihao; YAN Ming; AN Xiaofei

doi:10.11665/j.issn.1000-5048.20210113

Journal of China Pharmaceutical University > 2021 > 52(1): 92-99. > DOI: 10.11665/j.issn.1000-5048.20210113

LIN Xiaobing, WANG Hao, ZHANG Junhan, LIN Zihao, YAN Ming, AN Xiaofei. Screening of prostaglandin E2 receptor 4 antagonist from active compounds of Baeckea frutescens L. and its anti-rheumatoid arthritis effect in vivo[J]. Journal of China Pharmaceutical University, 2021, 52(1): 92-99. DOI: 10.11665/j.issn.1000-5048.20210113

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Screening of prostaglandin E2 receptor 4 antagonist from active compounds of Baeckea frutescens L. and its anti-rheumatoid arthritis effect in vivo

1.
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009
2.
Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009
3.
Department of Endocrinology, Jiangsu Provincal Hospital of Chinese Medicine, Nanjing 210029, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81774248)

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Received Date: October 16, 2020
Revised Date: December 09, 2020

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Abstract

The objectives of the study were to screen prostaglandin E2 receptor 4 antagonist from active compounds of Baeckea frutescens L. and to explore its anti-rheumatoid arthritis effect.The HEK293T-EP4 cell antagonist screening model was established in vitro. Homogeneous time-resolved fluorescence (HTRF) technique was used to screen the active compounds of Baeckea frutescens L..SPF grade ICR male mice were randomly divided into control group, model group, methotrexate group, and Baeckea frutescens L.compound BF-2 (100, 50 and 25 mg/kg) groups. The collagen-induced arthritis (CIA) mouse model was established in vivo. The swelling volume of the toes of mice was measured, and the pathological examination was analyzed by staining with hematoxylin and eosin.SPF grade ICR mice, male, were randomly divided into control group, BF-2 (100, 50 and 25 mg/kg) group, and aspirin group.The acetic acid-induced body writhing test was observed.The EP4 in vitro antagonist screening model was successfully established.The preliminary screening results found that BF-2, BF-20, BF-11 and BF-12 had strong EP4 antagonistic activity [(102.11 ± 3.45)%, (90.31 ± 3.59)%, (75.72 ± 1.79)% and (76.84 ± 1.64)%], and BF-2 had the strongest antagonistic activity (IC₅₀ = 0.99 ± 0.08 μg/mL).BF-2 could significantly inhibit the toe swelling of CIA mice, and relieve the degradation of articular cartilage matrix and inflammatory cell infiltration.At the same time, compared with the control group, the writhing times of the mice in each dose of BF-2 were significantly reduced.In this study, BF-2 of Baeckea frutescens L.was selected as an EP4 antagonist, which has potential anti-rheumatoid arthritis activity.
- Baeckea frutescens L.,
- compounds,
- rheumatoid arthritis,
- prostaglandin E2 receptor 4,
- inflammatory response

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References

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Screening of prostaglandin E2 receptor 4 antagonist from active compounds of Baeckea frutescens L. and its anti-rheumatoid arthritis effect in vivo

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