Zhijin Li1, Yunchao Wang2, Bin Jiang1, Wenliang Li3, Lihua Zheng1, Xiaoguang Yang1, Yongli Bao1, Luguo Sun1, Yanxin Huang1, Yuxin Li4. 1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China. 2. Shijiazhuang No.4 Pharmaceutical Co., ltd, Shijiazhuang 050000, China. 3. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China; School of Pharmaceutical Science, Jilin Medical University, Jilin 132013, China. Electronic address: liwl100@nenu.edu.cn. 4. Jilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of life Sciences, Northeast Normal University, Changchun 130024, China. Electronic address: yxli486@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Armillaria mellea (Vahl. ex. Fr.) Karst is an important traditional Chinese medicine used in dispelling wind and removing obstruction in the meridians, and strengthening tendons and bones. Armillaria mellea has been recorded in the book Caobenshiyi which was written by ancestor for the function of suppressing hyderactive liver for calming endogenous wind medicine. The aim of this study is to investigate the cytotoxic activity for liver cell lines (normal and cancerous) of protoilludane sesquiterpene aryl esters from the mycelium of A. mellea. MATERIALS AND METHODS: A systemic fractionation of the mycelium extracts of A. mellea and relative activity mechanisms were studied. RESULTS: Two new protoilludane sesquiterpene aryl esters named 5'-methoxy-armillasin (1) and 5-hydroxyl-armillarivin (2) were isolated. In addition, eight known protoilludane sesquiterpene aryl esters armillaridin (3), armillartin (4), armillarin (5), melleolide B (6), armillarilin (7), armillasin (8), armillarigin (9) and melleolide (10) were also isolated from the mycelium of A. mellea. The relative configurations of the two new compounds were confirmed by NOESY spectra. Among ten protoilludane sesquiterpene aryl esters, compounds 2, 3, 4, 7, 8, 9 and 10 were active constituents with highly cytotoxic activity against HepG2 cells (4.95-37.65μg/mL). We reported here for the time, that compound 10 (melleolide) showed anti-tumor ability on hepatoma cell. The relative mechanism was assessed on HepG2 cells. CONCLUSIONS: Among all the ten protoilludane sesquiterpene aryl esters, melleolide (10) showed the best cytotoxic activity for HepG2 cells (4.95μg/mL) and lower activity for L02 cells (16.05μg/mL). Mechanism study showed that melleolide decreased the viability of the cancer cells with varying levels of cleaved-caspase 3, caspase 8, caspase 9, Bax and Ki67 expression. On the other hand, melleolide induced HepG2 cell cycle arrest at the G2/M phase.
ETHNOPHARMACOLOGICAL RELEVANCE: Armillaria mellea (Vahl. ex. Fr.) Karst is an important traditional Chinese medicine used in dispelling wind and removing obstruction in the meridians, and strengthening tendons and bones. Armillaria mellea has been recorded in the book Caobenshiyi which was written by ancestor for the function of suppressing hyderactive liver for calming endogenous wind medicine. The aim of this study is to investigate the cytotoxic activity for liver cell lines (normal and cancerous) of protoilludane sesquiterpene aryl esters from the mycelium of A. mellea. MATERIALS AND METHODS: A systemic fractionation of the mycelium extracts of A. mellea and relative activity mechanisms were studied. RESULTS: Two new protoilludane sesquiterpene aryl esters named 5'-methoxy-armillasin (1) and 5-hydroxyl-armillarivin (2) were isolated. In addition, eight known protoilludane sesquiterpene aryl esters armillaridin (3), armillartin (4), armillarin (5), melleolide B (6), armillarilin (7), armillasin (8), armillarigin (9) and melleolide (10) were also isolated from the mycelium of A. mellea. The relative configurations of the two new compounds were confirmed by NOESY spectra. Among ten protoilludane sesquiterpene aryl esters, compounds 2, 3, 4, 7, 8, 9 and 10 were active constituents with highly cytotoxic activity against HepG2 cells (4.95-37.65μg/mL). We reported here for the time, that compound 10 (melleolide) showed anti-tumor ability on hepatoma cell. The relative mechanism was assessed on HepG2 cells. CONCLUSIONS: Among all the ten protoilludane sesquiterpene aryl esters, melleolide (10) showed the best cytotoxic activity for HepG2 cells (4.95μg/mL) and lower activity for L02 cells (16.05μg/mL). Mechanism study showed that melleolide decreased the viability of the cancer cells with varying levels of cleaved-caspase 3, caspase 8, caspase 9, Bax and Ki67 expression. On the other hand, melleolide induced HepG2 cell cycle arrest at the G2/M phase.
Authors: M Todd Hovey; Daniel T Cohen; Daniel M Walden; Paul H-Y Cheong; Karl A Scheidt Journal: Angew Chem Int Ed Engl Date: 2017-07-17 Impact factor: 15.336