PMID- 32431178 OWN - NLM STAT- MEDLINE DCOM- 20200917 LR - 20200917 IS - 1793-6853 (Electronic) IS - 0192-415X (Linking) VI - 48 IP - 4 DP - 2020 TI - Ginsenoside Rb2 Ameliorates LPS-Induced Inflammation and ER Stress in HUVECs and THP-1 Cells via the AMPK-Mediated Pathway. PG - 967-985 LID - 10.1142/S0192415X20500469 [doi] AB - Inflammation and endoplasmic reticulum (ER) stress have been documented to contribute to the development of atherosclerosis. Ginsenoside Rb2 has been reported to exhibit antidiabetic effects. However, the effects of Rb2 on atherosclerotic responses such as inflammation and ER stress in endothelial cells and monocytes remain unclear. In this study, the expression of inflammation and ER stress markers was determined using a Western blotting method. Concentrations of tumor necrosis factor alpha (TNF[Formula: see text]) and monocyte chemoattractant protein-1 (MCP-1) in culture media were assessed by enzyme-linked immunosorbent assay (ELISA) and apoptosis was evaluated by a cell viability assay and a caspase-3 activity measurement kit. We found that exposure of HUVECs and THP-1 monocytes to Rb2 attenuated inflammation and ER stress, resulting in amelioration of apoptosis and THP-1 cell adhesion to HUVECs under lipopolysaccharide (LPS) condition. Increased AMPK phosphorylation and heme oxygenase (HO)-1 expression, including GPR120 expression were observed in Rb2-treated HUVECs and THP-1 monocytes. Downregulation of both, AMPK phosphorylation and HO-1expression rescued these observed changes. Furthermore, GPR120 siRNA mitigated Rb2-induced AMPK phosphorylation. These results suggest that Rb2 inhibits LPS-mediated apoptosis and THP-1 cell adhesion to HUVECs by GPR120/AMPK/HO-1-associated attenuating inflammation and ER stress. Therefore, Rb2 can be used as a potential therapeutic molecule for treatment of atherosclerosis. FAU - Sun, Jaw Long AU - Sun JL AD - Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. FAU - Abd El-Aty, A M AU - Abd El-Aty AM AD - Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, Turkey. AD - Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt. FAU - Jeong, Ji Hoon AU - Jeong JH AD - Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. FAU - Jung, Tae Woo AU - Jung TW AD - Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. LA - eng PT - Journal Article DEP - 20200520 PL - Singapore TA - Am J Chin Med JT - The American journal of Chinese medicine JID - 7901431 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (FFAR4 protein, human) RN - 0 (Ginsenosides) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Tumor Necrosis Factor-alpha) RN - 11021-13-9 (ginsenoside Rb2) RN - EC 1.14.14.18 (HMOX1 protein, human) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Apoptosis/drug effects/genetics MH - Atherosclerosis/chemically induced/*drug therapy/genetics MH - Chemokine CCL2/genetics/metabolism MH - Endoplasmic Reticulum Stress/*drug effects/*genetics MH - Gene Expression/drug effects MH - Ginsenosides/*pharmacology/*therapeutic use MH - Heme Oxygenase-1/genetics/metabolism MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Inflammation MH - Lipopolysaccharides/*adverse effects MH - Phosphorylation/drug effects MH - *Phytotherapy MH - Receptors, G-Protein-Coupled/genetics/metabolism MH - Signal Transduction/*drug effects/*genetics MH - THP-1 Cells MH - Tumor Necrosis Factor-alpha/genetics/metabolism OTO - NOTNLM OT - AMPK OT - Apoptosis OT - Atherosclerosis OT - Ginsenoside OT - HO-1 OT - Inflammation OT - Rb2 EDAT- 2020/05/21 06:00 MHDA- 2020/09/18 06:00 CRDT- 2020/05/21 06:00 PHST- 2020/05/21 06:00 [pubmed] PHST- 2020/09/18 06:00 [medline] PHST- 2020/05/21 06:00 [entrez] AID - 10.1142/S0192415X20500469 [doi] PST - ppublish SO - Am J Chin Med. 2020;48(4):967-985. doi: 10.1142/S0192415X20500469. Epub 2020 May 20.