Celastrol attenuates inflammatory responses in adipose tissues and improves skeletal muscle mitochondrial functions in high fat diet-induced obese rats via upregulation of AMPK/SIRT1 signaling pathways

Bakar, Mohamad Hafizi Abu; Shariff, Khairul Anuar; Tan, Joo Shun; Lee, Lai Kuan

doi:10.1016/j.ejphar.2020.173371

Cited by 33 publications

(38 citation statements)

References 48 publications

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“…21 Other reports found that celastrol reduces weight gain through suppressing adipocytes differentiation 46 and mitigating oxidative stress. 26,47 Nevertheless, subsequent investigations did not fully in agreement with previous investigations regarding the weight loss effects of celastrol, 48,49 suggesting these weight loss properties exhibited by celastrol are still debatable. In the present study, we observed that the final body weight and serum leptin level was significantly decreased in the HFrD-fed rats supplemented with 3 mg/kg of celastrol, suggesting attributive effect of celastrol on weight loss with improved circulating leptin level, which are comparable to the control group.…”

Section: Discussionmentioning

confidence: 87%

“…Celastrol, a pentacyclic triterpene bioactive compound derived from the roots of the Tripterygium wilfordii has been shown to exhibit great potential against obesity, inflammation, insulin resistance, and other cardiometabolic complications through multiple target actions of cellular responses and signaling pathways. [20][21][22][23][24] Celastrol has been demonstrated to possess in vivo and in vitro ameliorative properties to counteract high fat diet-induced obesity and insulin resistance through significant improvement of mitochondrial functions and attenuated inflammatory conditions in skeletal muscle, 25,26 hepatocytes 27 and adipose tissues. 26,28 Furthermore, celastrol administration in fructose-induced hypertensive rats remarkably attenuated hypertension-induced inflammation and oxidative stress in the isolated primary vascular smooth muscle cell (VSMC) via induction of heme oxygenase-1.…”

Section: Introductionmentioning

confidence: 99%

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Celastrol attenuates high‐fructose diet‐induced inflammation and insulin resistance via inhibition of 11β‐hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues

et al. 2021

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High fructose consumption has been linked to low-grade inflammation and insulin resistance that results in increased intracellular 11ß-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. Celastrol, a pentacyclic triterpene, has been demonstrated to exhibit multifaceted targets to attenuate various metabolic diseases associated with inflammation. However, the underlying mechanisms by which celastrol exerts its attributive properties on high fructose diet (HFrD)-induced metabolic syndrome remain elusive. Herein, the present study was aimed to elucidate the mechanistic targets of celastrol co-administrations upon HFrD in rats and evaluate its potential to modulate 11β-HSD1 activity. Celastrol remarkably improved glucose tolerance, lipid profiles, and insulin sensitivity along with suppression of hepatic glucose production. In rat adipose tissues, celastrol attenuated nuclear factor-kappa B (NF-κB)-driven inflammation, reduced c-Jun Nterminal kinases (JNK) phosphorylation, and mitigated oxidative stress via upregulated genes expression involved in mitochondrial biogenesis. Furthermore, insulin signaling pathways were significantly improved through the restoration of Akt phosphorylation levels at Ser473 and Thr308 residues. Celastrol exhibited a potent, selective and specific inhibitor of intracellular 11β-HSD1 towards oxidoreductase activity (IC 50 value = 4.3 nM) in comparison to other HSD-related enzymes. Inhibition of 11β-HSD1 expression in rat adipose microsomes reduced the availability of its cofactor NADPH and substrate H6PDH in couple to upregulated mRNA and protein

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Celastrol attenuates high‐fructose diet‐induced inflammation and insulin resistance via inhibition of 11β‐hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues

et al. 2021

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“…Numerous evidences supported that obesity is strongly associated with MAFLD development ( Fabbrini et al, 2010 ). The liver protective effect and molecular mechanism of celastrol on high fat diet (HFD) induced MAFLD animal models have been well-investigated ( Wang et al, 2014 ; Ma et al, 2015 ; Zhang et al, 2017a ; Hu et al, 2017 ; Luo et al, 2017 ; Kyriakou et al, 2018 ; Pfuhlmann et al, 2018 ; Zhang et al, 2018 ; Feng et al, 2019a ; Zhao et al, 2019a ; Feng et al, 2019b ; Chellappa et al, 2019 ; Fang et al, 2019 ; Abu Bakar et al, 2020 ; Hu et al, 2020 ; Zhu C. et al, 2021 ; Zhu Y. et al, 2021 ; Hua et al, 2021 ; Ouyang et al, 2021 ; Yang et al, 2021 ).…”

Section: Celastrol and Liver Diseasesmentioning

confidence: 99%

Celastrol: An Update on Its Hepatoprotective Properties and the Linked Molecular Mechanisms

Xie

Wang

et al. 2022

Front. Pharmacol.

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The liver plays an important role in glucose and lipid homeostasis, drug metabolism, and bile synthesis. Metabolic disorder and inflammation synergistically contribute to the pathogenesis of numerous liver diseases, such as metabolic-associated fatty liver disease (MAFLD), liver injury, and liver cancer. Celastrol, a triterpene derived from Tripterygium wilfordii Hook.f., has been extensively studied in metabolic and inflammatory diseases during the last several decades. Here we comprehensively review the pharmacological activities and the underlying mechanisms of celastrol in the prevention and treatment of liver diseases including MAFLD, liver injury, and liver cancer. In addition, we also discuss the importance of novel methodologies and perspectives for the drug development of celastrol. Although celastrol has been claimed as a promising agent against several metabolic diseases, both preclinical and clinical studies are highly required to accelerate the clinical transformation of celastrol in treating different liver illness. It is foreseeable that celastrol-derived therapeutics is evolving in the field of liver ailments.

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“…It has been reported that celastrol can improve mitochondrial dysfunction and insulin sensitivity through reducing mitochondrial oxidative stress and thus enhance fatty acid oxidation in palmitic-acid-induced C3A human hepatocytes ( Abu et al, 2017 ). Importantly, celastrol can stimulate mitochondrial biogenesis and increase cell antioxidant capacity by activating AMPK-SIRT1 signaling pathways, which is associated with increased SIRT1 deacetylation activity and activation of PGC-1α and coactivation of nuclear respiratory factor 1 (NRF1) expression ( Abu et al, 2020 ). In addition, Hu et al also found that celastrol could promote Nur77, a nuclear receptor, translocation from the nucleus into mitochondria.…”

Section: Introductionmentioning

confidence: 99%

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

Shen

Yuan

et al. 2021

Front. Pharmacol.

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Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, and its prevalence is still growing rapidly. However, the efficient therapies for this liver disease are still limited. Mitochondrial dysfunction has been proven to be closely associated with NAFLD. The mitochondrial injury caused reactive oxygen species (ROS) production, and oxidative stress can aggravate the hepatic lipid accumulation, inflammation, and fibrosis. which contribute to the pathogenesis and progression of NAFLD. Therefore, pharmacological therapies that target mitochondria could be a promising way for the NAFLD intervention. Recently, natural products targeting mitochondria have been extensively studied and have shown promising pharmacological activity. In this review, the recent research progress on therapeutic effects of natural-product-derived compounds that target mitochondria and combat NAFLD was summarized, aiming to provide new potential therapeutic lead compounds and reference for the innovative drug development and clinical treatment of NAFLD.

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Celastrol attenuates inflammatory responses in adipose tissues and improves skeletal muscle mitochondrial functions in high fat diet-induced obese rats via upregulation of AMPK/SIRT1 signaling pathways

Cited by 33 publications

References 48 publications

Celastrol attenuates high‐fructose diet‐induced inflammation and insulin resistance via inhibition of 11β‐hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues

Celastrol attenuates high‐fructose diet‐induced inflammation and insulin resistance via inhibition of 11β‐hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues

Celastrol: An Update on Its Hepatoprotective Properties and the Linked Molecular Mechanisms

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

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