이희주 Park, Eun-Jin Ryu, Byeol Cho, Hyo-Moon Nghiem, Duc-Trong Pham, Ha-Thanh-Tung PAN, CHEOL HO Oh, Won-Keun 2024-01-12T02:35:09Z 2024-01-12T02:35:09Z 2022-11-29 2022-11 1424-8247 https://pubs.kist.re.kr/handle/201004/75927 Limacia scandens is traditionally used to treat depression and affective disorders in Malaysia. The chemical compositions have been reported to include bisbenzylisoquinoline and aporphine-type alkaloids in the genus Limacia Lour., but studies on the components of L. scandens have rarely been reported. Therefore, this study was conducted to determine new benzylisoquinoline alkaloid derivatives with autophagy regulation activity from this plant. Bioactivity-guided isolation was applied to various column chromatography methods using RP-18, Sephadex LH-20 open column chromatography, and preparative HPLC. The chemical structures of the isolated compounds were elucidated through spectroscopic data analysis, including NMR, HR-ESI-MS, and ECD data. In addition, isolated compounds were tested for autophagy-regulating activity in HEK293 cells expressing GFP-L3. Three new dimeric benzylisoquinoline alkaloids (1？3), one new 4-hydroxybenzoic acid-conjugated benzylisoquinoline alkaloid (4), and six known compounds (5？10) were isolated from the stems of L. scandens. All compounds (1？10) were screened for autophagy regulation in HEK293 cells stably expressing the GFP-LC3 plasmid. Among the isolated compounds, 1, 2, and 4 showed autophagic regulation activity that blocked the process of combining autophagosomes and lysosomes. They also inhibit the protein degradation process from the autolysosome as inhibitors of autophagy. Novel benzylisoquinoline alkaloids from L. scandens showed potent potency for the inhibition of autophagic flux. This study provides potential candidates for developing natural autophagy inhibitors for disease prevention and treatment. English Multidisciplinary Digital Publishing Institute (MDPI) Benzylisoquinoline Alkaloids from the Stems of Limacia scandens and Their Potential as Autophagy Inhibitors Article 10.3390/ph15111332 1 Pharmaceuticals, v.15, no.11, pp.1332 Pharmaceuticals 15 11 1332 Y scie scopus 000882676400001 Chemistry, Medicinal Pharmacology & Pharmacy Pharmacology & Pharmacy Article CELL-DEATH DISEASE FLUX Limacia scandens dimeric benzylisoquinoline alkaloids autophagy inhibitor