Objective To isolate high-purity gentiopicroside from the Chinese herbal Gentiana officinalis and investigate its anti-inflammatory activity against iNOS and COX-2 targets. Methods The purity and structures of gentiopicroside was determined by HPLC, IR, NMR, and MS. We investigated the anti-inflammatory effects of gentiopicroside by in vivo， in vitro and molecular experiments. Results In vitro experiment results showed that gentiopicroside inhibited nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) production in mouse macrophages RAW 264.7 stimulated by lipopolysaccharide. In vivo experiment found xylene-induced mouse ear swelling was inhibited by gentiopicroside with an inhibition rate of 34.17%. Molecular docking of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) with gentiopicroside showed that hydrogen bonds (H-bonds) were formed between the sugar fragments in gentiopicroside structure with Tyr355, Ser353, Leu352, Ser530, Arg120, and His90 of COX-2, and Glu377, Asp382, Tyr373, Tyr347, Gln263, Asn370, and Gly371 of iNOS. Thus, gentiopicroside had a lower docking score and displayed satisfactory anti-inflammatory activities. Conclusion These results suggested that the mechanism of anti-inflammatory activity of gentiopicroside was associated with the downregulation of inflammatory cytokines, such as NO, PGE2, and IL-6, and the suppression of iNOS and COX-2. Therefore, gentiopicroside is a potential and selective iNOS and COX-2 inhibitor.
关键词:
龙胆苦苷;抗炎活性;环氧合酶-2;一氧化氮合酶;炎症靶点
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Project Supported:
We sincerely thank Lanzhou University Dr. Huan-xiang Liu gave us great help in molecular docking experiments. National Natural Science Foundation of China (No. 81660577, No. 21562001, and No. 81560716) and National Natural Science Foundation of Gansu Province (1506RJZA036).
Qi-Li Zhang,, Jian Zhang, Peng-Fei Xia, Xue-Jing Peng, Hai-Long Li, Hua Jin, Jie Yang, Lei Zhao. Anti-inflammatory activities of gentiopicroside against iNOS and COX-2 targets[J]. Chinese Herbal Medicines (CHM),2019,11(1):108-112
