PMID- 34481877 OWN - NLM STAT- MEDLINE DCOM- 20220128 LR - 20220128 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 910 DP - 2021 Nov 5 TI - 1, 8-cineole protects against ISO-induced heart failure by inhibiting oxidative stress and ER stress in vitro and in vivo. PG - 174472 LID - S0014-2999(21)00626-9 [pii] LID - 10.1016/j.ejphar.2021.174472 [doi] AB - Sugemule-3 is widely adopted in clinical practice to manage cardio-cerebral diseases. 1, 8-cineole is the main ingredient of Sugemule-3, however, the underlying cellular mechanisms for its protective effect are poorly understood. 1, 8-cineole improved the survival of H9C2 cardiomyocytes during isoproterenol (ISO) injury and reduced ISO-induced apoptosis. Compared to the ISO group, 1, 8-cineole highly attenuated the generation of ISO-induced reactive oxygen species (ROS), the depolarization of big up tri, openpsim, suppression of the Bax/Bcl-2 ratio, and p-caspase 3 expression, in vitro. Furthermore, 1, 8-cineole treatment in H9C2 cardiomyocytes lowered the expressions of 78-kDa glucose-regulated protein (GRP78), p-protein kinase-like ER kinase (PERK), activation of transcription factor (ATF) 4, and ER stress effector protein C/EBP and homologous protein (CHOP). These findings implied that 1, 8-cineole contribute to cardioprotection via the GRP78/CHOP pathways. Using animal models, 1, 8-cineole was revealed to markedly alleviate ISO-induced heart injury, and reduce cardiac hypertrophy, formation of the cytoplasmic vacuole, loss of myofiber, and fibrosis by inhibiting oxidative stress and ER stress. 1, 8-cineole reduces apoptosis by inhibiting signaling pathways related to oxidative stress and ER stress. These findings implicate 1, 8-cineole as a potential therapeutic target for cardiac hypertrophy-related heart diseases, including heart failure. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - Wang, Yu AU - Wang Y AD - Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. FAU - Zhang, Xuan AU - Zhang X AD - Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. FAU - Fu, Yao AU - Fu Y AD - Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. FAU - Fu, Danni AU - Fu D AD - Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. FAU - Zhen, Dong AU - Zhen D AD - Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. FAU - Xing, An AU - Xing A AD - Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. FAU - Chen, Yu AU - Chen Y AD - Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. FAU - Gong, Guohua AU - Gong G AD - Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China; Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China. Electronic address: gongguohua0211@163.com. FAU - Wei, Chengxi AU - Wei C AD - Medicinal Chemistry and Pharmacology Institute, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, PR China. Electronic address: weichengxi1224@163.com. LA - eng PT - Journal Article DEP - 20210902 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Protective Agents) RN - L628TT009W (Isoproterenol) RN - RV6J6604TK (Eucalyptol) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Cell Line MH - Disease Models, Animal MH - Endoplasmic Reticulum Stress/drug effects MH - Eucalyptol/*pharmacology/therapeutic use MH - Heart Failure/chemically induced/pathology/*prevention & control MH - Humans MH - Isoproterenol/administration & dosage/toxicity MH - Myocytes, Cardiac/drug effects/pathology MH - Oxidative Stress/drug effects MH - Protective Agents/*pharmacology/therapeutic use MH - Rats MH - Signal Transduction/drug effects OTO - NOTNLM OT - 1 OT - 8-Cineole OT - Cardiac hypertrophy OT - ER stress OT - Oxidative stress EDAT- 2021/09/06 06:00 MHDA- 2022/01/29 06:00 CRDT- 2021/09/05 20:36 PHST- 2021/05/14 00:00 [received] PHST- 2021/08/20 00:00 [revised] PHST- 2021/09/01 00:00 [accepted] PHST- 2021/09/06 06:00 [pubmed] PHST- 2022/01/29 06:00 [medline] PHST- 2021/09/05 20:36 [entrez] AID - S0014-2999(21)00626-9 [pii] AID - 10.1016/j.ejphar.2021.174472 [doi] PST - ppublish SO - Eur J Pharmacol. 2021 Nov 5;910:174472. doi: 10.1016/j.ejphar.2021.174472. Epub 2021 Sep 2.