Ya-Ru Wu1, Liang Li2, Xian-Chang Sun3, Jun Wang4, Chun-Yan Ma1, Yue Zhang1, Hui-Lin Qu1, Rui-Xia Xu5, Jian-Jun Li6. 1. State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. 2. Department of Surgical Intensive Care Unit, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. 3. Department of CT, The Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China. 4. Tancheng Traditional Chinese Hospital, Tancheng 276100, Shandong Province, China. 5. State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Electronic address: ruixiaxu@sina.com. 6. State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Electronic address: lijianjun@126.com.
Abstract
BACKGROUND AND AIM: Diallyl disulfide (DADS), a volatile sulfide extracted from garlic, has been suggested as a chemical of anti-atherosclerotic drugs, while its molecular mechanism for this benefit has not fully been understood. The aim of the present study was to investigate the effects of DADS on lipid metabolism and its potential mechanisms in HepG2 cells induced by lipopolysaccharides (LPS). METHODS AND RESULTS: HepG2 cells were treated with LPS with or without different concentrations of DADS (0, 20, 40, 80, 160 μg/ml) for 24 h. The cell activity was detected by CCK8, and Dil-LDL uptake assay was used to examine the LDL uptake. Real-time PCR and Western blot were used to detect the expression of LDLR, PCSK9 SREBP2 and HMGCR. In addition, we examined the effect of the combination of DADS with atorvastatin on PCSK9 expression. The results showed that LPS significantly increased PCSK9 and SREBP2 expressions in a dose-dependent manner in HepG2 cells. DADS attenuated PCSK9, SREBP2 and HMGCR expressions and up-regulated the expression of LDLR. Moreover, DADS reversed the expressions of PCSK9, SREBP2, HMGCR and LDLR induced by LPS and DADS could promote the LDL uptake in HepG2 cells. Furthermore, DADS decreased the expression of PCSK9 by activating the PI3K/Akt-SREBP2 signal pathway. Notably, DADS could reduce PCSK9 expression induced by atorvastatin in HepG2 cells. CONCLUSION: DADS could significantly attenuated PCSK9 expression in a dose-dependent manner induced by LPS and increased the LDLR expression in HepG2 cells, which was associated with the activation of PI3K/Akt-SREBP2 signaling pathway.
BACKGROUND AND AIM: Diallyl disulfide (DADS), a volatile sulfide extracted from garlic, has been suggested as a chemical of anti-atherosclerotic drugs, while its molecular mechanism for this benefit has not fully been understood. The aim of the present study was to investigate the effects of DADS on lipid metabolism and its potential mechanisms in HepG2 cells induced by lipopolysaccharides (LPS). METHODS AND RESULTS:HepG2 cells were treated with LPS with or without different concentrations of DADS (0, 20, 40, 80, 160 μg/ml) for 24 h. The cell activity was detected by CCK8, and Dil-LDL uptake assay was used to examine the LDL uptake. Real-time PCR and Western blot were used to detect the expression of LDLR, PCSK9SREBP2 and HMGCR. In addition, we examined the effect of the combination of DADS with atorvastatin on PCSK9 expression. The results showed that LPS significantly increased PCSK9 and SREBP2 expressions in a dose-dependent manner in HepG2 cells. DADS attenuated PCSK9, SREBP2 and HMGCR expressions and up-regulated the expression of LDLR. Moreover, DADS reversed the expressions of PCSK9, SREBP2, HMGCR and LDLR induced by LPS and DADS could promote the LDL uptake in HepG2 cells. Furthermore, DADS decreased the expression of PCSK9 by activating the PI3K/Akt-SREBP2 signal pathway. Notably, DADS could reduce PCSK9 expression induced by atorvastatin in HepG2 cells. CONCLUSION:DADS could significantly attenuated PCSK9 expression in a dose-dependent manner induced by LPS and increased the LDLR expression in HepG2 cells, which was associated with the activation of PI3K/Akt-SREBP2 signaling pathway.
Authors: Rahayu Zulkapli; Mohd Yusmiaidil Putera Mohd Yusof; Suhaila Abd Muid; Seok Mui Wang; Al'Aina Yuhainis Firus Khan; Hapizah Nawawi Journal: Int J Environ Res Public Health Date: 2022-10-08 Impact factor: 4.614