PMID- 36431839 OWN - NLM STAT- MEDLINE DCOM- 20221129 LR - 20221213 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 27 IP - 22 DP - 2022 Nov 10 TI - Antioxidant Effects of Roasted Licorice in a Zebrafish Model and Its Mechanisms. LID - 10.3390/molecules27227743 [doi] LID - 7743 AB - Licorice (Gan-Cao, licorice) is a natural antioxidant and roasted licorice is the most common processing specification used in traditional Chinese medicine prescriptions. Traditional Chinese medicine theory deems that the honey-roasting process can promote the efficacy of licorice, including tonifying the spleen and augmenting "Qi" (energy). The antioxidant activity and mechanisms underlying roasted licorice have not yet been reported. In this study, we found that roasted licorice could relieve the oxidative stress injury induced by metronidazole (MTZ) and could restrain the production of excessive reactive oxygen species (ROS) induced by 2,2'-azobis (2-methylpropionamidine) dihydrochloride (AAPH) in a zebrafish model. It was further found that roasted licorice could exert its oxidative activity by upregulating the expression of key genes such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC) in the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway both in vivo and in vitro. Furthermore, consistent results were obtained showing that rat serum containing roasted licorice was estimated to reduce cell apoptosis induced by H(2)O(2). Then, the UHPLC-Q-Exactive Orbitrap MS analysis results elucidated the chemical composition of rat plasma containing roasted licorice extracts, including ten prototype chemical components and five metabolic components. Among them, six compounds were found to have binding activity with Kelch-like ECH-associated protein 1 (KEAP1), which plays a crucial role in the transcriptional activity of NRF2, using a molecular docking simulation. The results also showed that liquiritigenin had the strongest binding ability with KEAP1. Immunofluorescence further confirmed that liquiritigenin could induce the nuclear translocation of NRF2. In summary, this study provides a better understanding of the antioxidant effect and mechanisms of roasted licorice, and lays a theoretical foundation for the development of a potential antioxidant for use in clinical practice. FAU - Zhou, Qian AU - Zhou Q AD - Shandong Academy of Chinese Medicine, Jinan 250014, China. FAU - Zhang, Shanshan AU - Zhang S AD - Shandong Academy of Sciences, Qilu University of Technology, Jinan 250103, China. FAU - Geng, Xue AU - Geng X AD - Shandong Institute for Food and Drug Control, Jinan 250101, China. AD - School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. FAU - Jiang, Haiqiang AU - Jiang H AD - School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. FAU - Dai, Yanpeng AU - Dai Y AD - Shandong Academy of Chinese Medicine, Jinan 250014, China. FAU - Wang, Ping AU - Wang P AD - Shandong Academy of Chinese Medicine, Jinan 250014, China. FAU - Hua, Min AU - Hua M AD - Shandong Academy of Chinese Medicine, Jinan 250014, China. AD - School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. FAU - Gao, Qi AU - Gao Q AD - Shandong Academy of Chinese Medicine, Jinan 250014, China. FAU - Lang, Shiyue AU - Lang S AD - School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. FAU - Hou, Lijing AU - Hou L AD - Shandong Academy of Chinese Medicine, Jinan 250014, China. AD - School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. FAU - Shi, Dianhua AU - Shi D AD - Shandong Academy of Chinese Medicine, Jinan 250014, China. FAU - Zhou, Meng AU - Zhou M AD - The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China. LA - eng GR - 81603299 and 81700636/National Natural Science Foundation of China/ GR - ZR2020KH021/Key Project of Shandong Provincial Natural Science Foundation/ GR - 2020M672076/China Postdoctoral Science Foundation/ GR - SDZYY20200101001/Major Scientific and Technological Innovation Projects of Shandong/ GR - 2019GSF108150/Key R&D project of Shandong Province/ PT - Journal Article DEP - 20221110 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Antioxidants) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - EC 6.3.2.2 (Glutamate-Cysteine Ligase) RN - BBX060AN9V (Hydrogen Peroxide) RN - 0 (Plant Extracts) RN - 0 (Triterpenes) SB - IM MH - Rats MH - Animals MH - *Glycyrrhiza/chemistry MH - Antioxidants/pharmacology/metabolism MH - NF-E2-Related Factor 2/metabolism MH - Kelch-Like ECH-Associated Protein 1/metabolism MH - Zebrafish/metabolism MH - Glutamate-Cysteine Ligase/metabolism MH - Hydrogen Peroxide/metabolism MH - Molecular Docking Simulation MH - Plant Extracts MH - *Triterpenes PMC - PMC9694442 OTO - NOTNLM OT - KEAP1 OT - NRF2 OT - UHPLC-Q-Exactive Orbitrap MS OT - antioxidant OT - roasted licorice OT - zebrafish model COIS- The authors declare no conflict of interest. EDAT- 2022/11/27 06:00 MHDA- 2022/11/30 06:00 PMCR- 2022/11/10 CRDT- 2022/11/26 01:26 PHST- 2022/10/12 00:00 [received] PHST- 2022/11/06 00:00 [revised] PHST- 2022/11/08 00:00 [accepted] PHST- 2022/11/26 01:26 [entrez] PHST- 2022/11/27 06:00 [pubmed] PHST- 2022/11/30 06:00 [medline] PHST- 2022/11/10 00:00 [pmc-release] AID - molecules27227743 [pii] AID - molecules-27-07743 [pii] AID - 10.3390/molecules27227743 [doi] PST - epublish SO - Molecules. 2022 Nov 10;27(22):7743. doi: 10.3390/molecules27227743.