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HgS Inhibits Oxidative Stress Caused by Hypoxia through Regulation of 5-HT Metabolism Pathway

Authors

Keywords:

hypoxia, reactive oxygen species, oxidative stress, 5-Hydroxytryptamine, cinnabar

Abstract

This study aims to reveal the potential relationship between 5-HT and oxidative stress in the organism. Our in vitro experiments in RIN-14B cells showed that anoxia leads the cells to the state of oxidative stress. Administration of exogenous 5-HT exacerbated this effect, whereas the inhibition of Tph1, LP533401 alleviated the oxidative stress. Several research articles reported that Cinnabar (consists of more than 96% mercury sulfide, HgS), which is widely used in both Chinese and Indian traditional medicine prescriptions, has been involved in the regulation of 5-HT. The present research revealed that HgS relieved the level of oxidative stress of RIN-14B cells. This pharmacological activity was also observed in the prescription drug Zuotai, in which HgS accounts for 54.5%, and these effects were found to be similar to LP533401, an experimental drug to treat pulmonary hypertension. Further, our in vivo experiments revealed that the administration of cinnabar or prescription drug Zuotai in zebrafish reduced the reactive oxygen species (ROS) induced by hypoxia and cured behavioral abnormalities. Taken together, in organisms with hypoxia induced oxidative stress 5-HT levels were found to be abnormally elevated, indicating that 5-HT could regulate oxidative stress, and the decrease in the 5-HT levels, behavioral abnormalities after treatment with cinnabar and Zuotai, we may conclude that the therapeutic and pharmacologic effect of cinnabar and Zuotai may be based on the regulation of 5-HT metabolism and relief of oxidative stress. Even though they aren’t toxic at the present dosage in both cell lines and zebrafish, their dose dependent toxicities are yet to be evaluated. Keywords: hypoxia, reactive oxygen species, oxidative stress, 5-Hydroxytryptamine, cinnabar

Author Biographies

Qiangqiang He, Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810008, China; [email protected] (Q.H.); [email protected] (Y.D.)

University of Chinese Academy of Sciences, Beijing 100049, China

Jing Dong, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; [email protected] (J.M.); [email protected] (P.K.K.); [email protected] (L.Z.); [email protected] (J.Z.); [email protected] (J.D.)

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China

Junyi Zhu, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; [email protected] (J.M.); [email protected] (P.K.K.); [email protected] (L.Z.); [email protected] (J.Z.); [email protected] (J.D.)

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China

Liangliang Zhou, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; [email protected] (J.M.); [email protected] (P.K.K.); [email protected] (L.Z.); [email protected] (J.Z.); [email protected] (J.D.)

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China

Praveen Kalavagunta, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; [email protected] (J.M.); [email protected] (P.K.K.); [email protected] (L.Z.); [email protected] (J.Z.); [email protected] (J.D.)

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China

Ji Ma, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; [email protected] (J.M.); [email protected] (P.K.K.); [email protected] (L.Z.); [email protected] (J.Z.); [email protected] (J.D.)

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China

Jing Shang, Qinghai Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810008, China; [email protected] (Q.H.); [email protected] (Y.D.)

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China

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