机构：[1]State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China[2]The Second Affiliated Hospital, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China[3]School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China[4]Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China[5]Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Department of Biology, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China深圳市康宁医院深圳医学信息中心[6]Shuguang Hospital and School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Epilepsy is a chronic neurological disorder, characterized by recurrent, spontaneous, and transient seizures, and affects more than 70 million people worldwide. Although two dozen antiepileptic drugs (AEDs) are approved and available in the market, seizures remain poorly controlled in one-third of epileptic patients who are suffering from drug resistance or various adverse effects. Recently, the xanthone skeleton has been regarded as an attractive scaffold for the discovery and development of emerging anticonvulsants. We had isolated several dihydroxanthone derivatives previously, including oliganthin H, oliganthin I, and oliganthin N, whose structures were similar and delicately elucidated by spectrum analysis or X-ray crystallographic data, from extracts of leaves of Garcinia oligantha. These xanthone analogues were evaluated for anticonvulsant activity, and a novel xanthone, oliganthin H, has been identified as a sound and effective natural inhibitor of convulsions in zebrafish in vivo. A preliminary structure-activity relationship analysis on the relationship between structures of the xanthone analogues and their activities was also conducted. Oliganthin H significantly suppressed convulsant behavior and reduced to about 25% and 50% of PTZ-induced activity, in 12.5 and 25 μM treatment groups (P < 0.01 and 0.001), respectively. Meanwhile, it reduced seizure activity, velocity, seizure duration, and number of bursts in zebrafish larvae (P < 0.05). Pretreatment of oliganthin H significantly restored aberrant induction of gene expressions including npas4a, c-fos, pyya, and bdnf, as well as gabra1, gad1, glsa, and glula, upon PTZ treatment. In addition, in silico analysis revealed the stability of the oliganthin H-GABAA receptor complex and their detailed binding pattern. Therefore, direct interactions with the GABAA receptor and involvement of downstream GABA-glutamate pathways were possible mechanisms of the anticonvulsant action of oliganthin H. Our findings present the anticonvulsant activity of oliganthin H, provide a novel scaffold for further modifications, and highlight the xanthone skeleton as an attractive and reliable resource for the development of emerging AEDs.
基金：
This work was performed in part at the high-performance
computing cluster (HPCC), which is supported by the
Information and Communication Technology Office (ICTO)
of the University of Macau. Research at the University of
Macau was funded by The Science and Technology Development
Fund, Macau SAR (file nos. 014/2017/A1, 0058/2019/
A1, and 0016/2019/AKP), and the University of Macau
(MYRG2019-00105-ICMS).
第一作者机构：[1]State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China[2]The Second Affiliated Hospital, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China
通讯作者：
通讯机构：[1]State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China[6]Shuguang Hospital and School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China[*1]State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China[*2]Shuguang Hospital and School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
推荐引用方式(GB/T 7714)：
Gong Guiyi,Chen Hanbin,Kam Hiotong,et al.In Vivo Screening of Xanthones from Garcinia oligantha Identified Oliganthin H as a Novel Natural Inhibitor of Convulsions.[J].JOURNAL OF NATURAL PRODUCTS.2020,83(12):3706-3716.doi:10.1021/acs.jnatprod.0c00963.
APA：
Gong Guiyi,Chen Hanbin,Kam Hiotong,Chan Ging,Tang Yue-Xun...&Lee Simon Ming-Yuen.(2020).In Vivo Screening of Xanthones from Garcinia oligantha Identified Oliganthin H as a Novel Natural Inhibitor of Convulsions..JOURNAL OF NATURAL PRODUCTS,83,(12)
MLA：
Gong Guiyi,et al."In Vivo Screening of Xanthones from Garcinia oligantha Identified Oliganthin H as a Novel Natural Inhibitor of Convulsions.".JOURNAL OF NATURAL PRODUCTS 83..12(2020):3706-3716
