IMR Press / FBL / Volume 27 / Issue 8 / DOI: 10.31083/j.fbl2708242
Open Access Original Research
Antioxidants Rich Herbal Formula Ger-Gen-Chyn-Lian-Tang Protects Lipotoxicity and Ameliorates Inflammation Signaling through Regulation of Mitochondrial Biogenesis and Mitophagy in Nonalcoholic Fatty Liver Disease Mice
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1 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 33302 Taoyuan City, Taiwan
2 Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, 33302 Taoyuan City, Taiwan
3 Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, 204 Keelung City, Taiwan
4 Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, 11217 Taipei, Taiwan
5 Brion Research Institute of Taiwan, 23143 Taipei, Taiwan
*Correspondence: joyamen@mail.cgu.edu.tw (Tzung-Yan Lee)
Academic Editor: Salvatore Nesci
Front. Biosci. (Landmark Ed) 2022, 27(8), 242; https://doi.org/10.31083/j.fbl2708242
Submitted: 30 April 2022 | Revised: 29 June 2022 | Accepted: 21 July 2022 | Published: 15 August 2022
(This article belongs to the Special Issue Mitochondrial Biology in Health and Disease)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) has become a prevalent issue and a consequence of metabolic syndrome impact on human health. Both of anti-atherosclerosis and anti-hepatic fibrosis capabilities of herbal medicine Ger-Gen-Chyn-Lian-Tang (GGCLT) has attracted attention, but their molecular regulatory mechanisms in a NAFLD model have not been elucidated. The aim of the present study was to explore the bioactivity of db/db mice following treatment with GGCLT. Methods: NAFLD phenotype of db/db mice were treated with GGCLT and lipogenesis, mitochondria dysfunction, mitophagy, macrophage polarization and adipose tissue browning were then evaluated using qRT-PCR and/or Western blot analysis, immunofluorescence, and immunohistochemistry assays, respectively. Results: GGCLT not only decreased serum levels of TG and free fatty acids, but glucose and insulin tolerance test in db/db mice. In parallel, GGCLT reduced lipogenesis and hypoxia-inflammation cascades in NAFLD progression. GGCLT reduced lipid accumulation and was accompanied by the enhanced mitochondria biogenesis, M2 macrophage, and decreased M1 macrophage. The latter two events contributing to the anti-inflammation are resulting from mitochondria dynamics, and the lipotoxicity lowering effect of GGCLT of NAFLD mice is mediated by promoting mitophagy in Parkin-dependent and -independent pathways, by mitochondrial fusion over fission manner. GGCLT also inactivated lipogenesis and decreased lipid accumulation in epididymal white adipose tissue with a higher M2/M1 macrophage ratio. Conclusions: Besides in the liver, modulating of mitochondrial biogenesis and adipose tissue browning were characterized by increased Tmem26, Tfam, and Prdm16 expression by GGCLT in EWAT also contributes to the beneficial action in NAFLD.

Keywords
NAFLD
Ger-Gen-Chyn-Lian-Tang
lipotoxicity
mitochondria biogenesis
mitophagy
adipose tissue browning
Figures
Fig. 1.
Funding
MOST 102-2320-B182-015-MY3/ Ministry of Science and Technology, Taipei, Taiwan
103-2320-B182-002-MY3/ Ministry of Science and Technology, Taipei, Taiwan
106-2320-B-182-005-MY3/ Ministry of Science and Technology, Taipei, Taiwan
109-2320-B-182-023-MY3/ Ministry of Science and Technology, Taipei, Taiwan
CMRPD1B0261/ Chang Gung Memorial Hospital, Linkou, Taiwan
CMRPD1B0262/ Chang Gung Memorial Hospital, Linkou, Taiwan
CMRPD1D0351/ Chang Gung Memorial Hospital, Linkou, Taiwan
CMRPD1D0352/ Chang Gung Memorial Hospital, Linkou, Taiwan
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