Mitochondrial Targeting Therapeutics: Promising Role of Natural Products in Non-alcoholic Fatty Liver Disease

Xu, Jing; Shen, Jiayan; Yuan, Ruolan; Jia, Bona; Wang, Sijian; Zhang, Yi; Li, Mengyang; Wang, Tao

doi:10.3389/fphar.2021.796207

Cited by 26 publications

(17 citation statements)

References 131 publications

(143 reference statements)

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“…The balance between mitochondrial biogenesis, mitochondrial fission/fusion, and mitochondrial autophagy is essential for mitochondrial homeostasis. Emerging evidence suggests that cellular functions are at risk when mitochondrial homeostasis is disrupted [95,96].…”

Section: Mitochondria and Nafldmentioning

confidence: 99%

Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease

Ramanathan

Ali

Ibdah

2022

IJMS

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Nonalcoholic fatty liver disease (NAFLD) is a global pandemic that affects one-quarter of the world’s population. NAFLD includes a spectrum of progressive liver disease from steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis and can be complicated by hepatocellular carcinoma. It is strongly associated with metabolic syndromes, obesity, and type 2 diabetes, and it has been shown that metabolic dysregulation is central to its pathogenesis. Recently, it has been suggested that metabolic- (dysfunction) associated fatty liver disease (MAFLD) is a more appropriate term to describe the disease than NAFLD, which puts increased emphasis on the important role of metabolic dysfunction in its pathogenesis. There is strong evidence that mitochondrial dysfunction plays a significant role in the development and progression of NAFLD. Impaired mitochondrial fatty acid oxidation and, more recently, a reduction in mitochondrial quality, have been suggested to play a major role in NAFLD development and progression. In this review, we provide an overview of our current understanding of NAFLD and highlight how mitochondrial dysfunction contributes to its pathogenesis in both animal models and human subjects. Further we discuss evidence that the modification of mitochondrial function modulates NAFLD and that targeting mitochondria is a promising new avenue for drug development to treat NAFLD/NASH.

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Section: Mitochondria and Nafldmentioning

confidence: 99%

Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease

Ramanathan

Ali

Ibdah

2022

IJMS

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“…Moreover, since mitochondrial dysfunction is a major contributor to the development and progression of NAFLD [ 144 ], it might be a likely cause for the increased susceptibility of steatotic livers to I/R injury. During NAFLD, loss of hepatic mitochondrial homeostasis leads to increased oxidative stress that impairs mitochondrial respiration, causes lipid peroxidation, increases the secretion of cytokines, and eventually leads to hepatocyte death [ 145 ]. Indeed, higher generation of superoxide was observed during reperfusion in fatty rat livers than in lean rat livers, which is thought to be linked to increased lipid peroxidation and higher susceptibility to LIRI [ 41 ].…”

Section: Impact Of Liver Conditions On Lirimentioning

confidence: 99%

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

2023

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Liver ischemia-reperfusion injury (LIRI) is a major cause of the development of complications in different clinical settings such as liver resection and liver transplantation. Damage arising from LIRI is a major risk factor for early graft rejection and is associated with higher morbidity and mortality after surgery. Although the mechanisms leading to the injury of parenchymal and non-parenchymal liver cells are not yet fully understood, mitochondrial dysfunction is recognized as a hallmark of LIRI that exacerbates cellular injury. Mitochondria play a major role in glucose metabolism, energy production, reactive oxygen species (ROS) signaling, calcium homeostasis and cell death. The diverse roles of mitochondria make it essential to preserve mitochondrial health in order to maintain cellular activity and liver integrity during liver ischemia/reperfusion (I/R). A growing body of studies suggest that protecting mitochondria by regulating mitochondrial biogenesis, fission/fusion and mitophagy during liver I/R ameliorates LIRI. Targeting mitochondria in conditions that exacerbate mitochondrial dysfunction, such as steatosis and aging, has been successful in decreasing their susceptibility to LIRI. Studying mitochondrial dysfunction will help understand the underlying mechanisms of cellular damage during LIRI which is important for the development of new therapeutic strategies aimed at improving patient outcomes. In this review, we highlight the progress made in recent years regarding the role of mitochondria in liver I/R and discuss the impact of liver conditions on LIRI.

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“…BBR has potent antioxidant activity by increasing the antioxidant superoxide dismutase (SOD) enzyme and the AMPK pathway. BBR can also increase mitochondrial uncoupling protein 2 (UCP2), which uncouples and separates ATP from oxidative phosphorylation through modulation of mitochondrial proton outflow (Xu, Shen et al 2021 ). BBR attenuates ED by regulating NO/ROS balance in rats with erectile dysfunction (Alorabi et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The role of berberine in Covid-19: potential adjunct therapy

et al. 2022

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Coronavirus disease 2019 (Covid-19) is a global diastrophic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 leads to inflammatory, immunological, and oxidative changes, by which SARS-CoV-2 leads to endothelial dysfunction (ED), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and multi-organ failure (MOF). Despite evidence illustrating that some drugs and vaccines effectively manage and prevent Covid-19, complementary herbal medicines are urgently needed to control this pandemic disease. One of the most used herbal medicines is berberine (BBR), which has anti-inflammatory, antioxidant, antiviral, and immune-regulatory effects; thus, BBR may be a prospective candidate against SARS-CoV-2 infection. This review found that BBR has anti-SARS-CoV-2 effects with mitigation of associated inflammatory changes. BBR also reduces the risk of ALI/ARDS in Covid-19 patients by inhibiting the release of pro-inflammatory cytokines and inflammatory signaling pathways. In conclusion, BBR has potent anti-inflammatory, antioxidant, and antiviral effects. Therefore, it can be utilized as a possible anti-SARS-CoV-2 agent. BBR inhibits the proliferation of SARS-CoV-2 and attenuates the associated inflammatory disorders linked by the activation of inflammatory signaling pathways. Indeed, BBR can alleviate ALI/ARDS in patients with severe Covid-19. In this sense, clinical trials and prospective studies are suggested to illustrate the potential role of BBR in treating Covid-19.

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Mitochondrial Targeting Therapeutics: Promising Role of Natural Products in Non-alcoholic Fatty Liver Disease

Cited by 26 publications

References 131 publications

Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease

Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

The role of berberine in Covid-19: potential adjunct therapy

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