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

Li, Mengzhen; Xie, Faren; Wang, Lu; Zhu, Guoxue; Qi, Lian‐Wen; Jiang, Shujun

doi:10.3389/fphar.2022.857956

Cited by 7 publications

(10 citation statements)

References 118 publications

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“…ConA‐induced hepatitis is characterized by acute immune responses with rapid infiltration of various immune cells and an explosive release of cytokines 23 . It has been previously reported that celastrol effectively suppressed the inflammatory response in liver injury induced by other chemicals 10 . Therefore, we investigated the effects of celastrol on ConA‐induced hepatitis.…”

Section: Resultsmentioning

confidence: 99%

“…The progression of ConA‐induced hepatitis is involved with the infiltration of a great number of cytokines, leading to liver injury, including hepatocyte apoptosis and necrosis 27–30 . Previous studies demonstrated that celastrol played a protective role in APAP‐induced, ANIT‐induced, and CCL4‐induced liver injuries by inhibiting proinflammatory responses 10 . Here, we investigated the effect of celastrol on ConA‐induced hepatitis.…”

Section: Discussionmentioning

confidence: 95%

“…Celastrol is a triterpene derived from Tripterygium wilfordii Hook F. 10 It has been reported to exert hepatoprotective effects in a variety of liver diseases, including metabolic-associated fatty liver disease 11 ; liver injury induced with chemicals such as acetaminophen (APAP), 12 α-naphthyl isothiocyanate (ANIT), 13 and carbon tetrachloride (CCL4) 14,15 ; and hepatocellular carcinoma. 16,17 As a triterpene compound, celastrol was found to exhibit immunoregulatory functions via various mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Celastrol pretreatment attenuates concanavalin A‐induced hepatitis in mice by suppressing interleukin‐6/STAT3‐interleukin‐17 signaling

Chen

Lin

et al. 2023

J of Gastro and Hepatol

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Background and Aim Celastrol is extracted from Tripterygium wilfordii Hook F. It has been reported to have protective effects against various liver diseases and immune regulation of autoimmune diseases. However, little is known about whether celastrol protects against immune‐mediated hepatitis. This study aimed to investigate the effect of celastrol on liver injury induced by concanavalin A (ConA) and the potential mechanisms. Methods Intravenous administration of ConA was applied to induce acute liver injury in mice with or without pretreatment of celastrol. The effects of celastrol on ConA‐induced liver injury were further demonstrated by biochemical and histopathological assessments, immunoblotting, and flow cytometry analysis. Results Both biochemical and histopathological observations showed that pretreatment of celastrol significantly ameliorated liver injury induced by ConA. Moreover, the hepatocyte apoptosis and inflammatory responses induced by ConA were also improved in celastrol‐pretreated mice. Further studies revealed that these improvements were characterized as the celastrol‐mediated suppression of total interleukin (IL)‐17 from liver mononuclear cells in ConA‐treated mice. Flow cytometry analysis suggested that celastrol specifically decreased IL‐17 production by CD4+ T cells but not by CD8+ T cells. Fundamentally, pretreatment with celastrol inhibited both the IL‐6 produced by F4/80+ macrophages and the IL‐6 receptor on Th17 cells in the liver, which further led to the downregulated activation of STAT3, thus accounting for blocked Th17 signaling. Conclusions Celastrol may exhibit immune regulatory effects by regulating IL‐6/STAT3‐IL‐17 signaling in ConA‐induced hepatitis, which suggested new potentials for celastrol to be applied in treating immune‐mediated liver diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Celastrol pretreatment attenuates concanavalin A‐induced hepatitis in mice by suppressing interleukin‐6/STAT3‐interleukin‐17 signaling

Chen

Lin

et al. 2023

J of Gastro and Hepatol

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“…Celastrolis a natural triterpenoid found in Tripterygium wilfordii that has been used to treat a variety of common diseases because of its strong anti-inflammatory activity ( Jing et al, 2021 ; Zhu et al, 2021 ; Li M. et al, 2022 ). Celastrol can inhibit the upregulation of IL-6andTNF-α expression in NP cells induced by IL-1β ( Chen et al, 2017 ).…”

Section: Phytochemicals For the Treatment Of Idd By Targeting Inflamm...mentioning

confidence: 99%

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

et al. 2022

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Low back pain is a major cause of disability worldwide that declines the quality of life; it poses a substantial economic burden for the patient and society. Intervertebral disc (IVD) degeneration (IDD) is the main cause of low back pain, and it is also the pathological basis of several spinal degenerative diseases, such as intervertebral disc herniation and spinal stenosis. The current clinical drug treatment of IDD focuses on the symptoms and not their pathogenesis, which results in frequent recurrence and gradual aggravation. Moreover, the side effects associated with the long-term use of these drugs further limit their use. The pathological mechanism of IDD is complex, and oxidative stress and inflammation play an important role in promoting IDD. They induce the destruction of the extracellular matrix in IVD and reduce the number of living cells and functional cells, thereby destroying the function of IVD and promoting the occurrence and development of IDD. Phytochemicals from fruits, vegetables, grains, and other herbs play a protective role in the treatment of IDD as they have anti-inflammatory and antioxidant properties. This article reviews the protective effects of phytochemicals on IDD and their regulatory effects on different molecular pathways related to the pathogenesis of IDD. Moreover, the therapeutic limitations and future prospects of IDD treatment have also been reviewed. Phytochemicals are promising candidates for further development and research on IDD treatment.

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“…In addition to its role in digestion, the liver is involved in the biochemical processes of development, nutrition, energy production, and reproduction. It contributes to carbohydrate and fat metabolism, bile secretion, and vitamin storage [ 2 ]. The liver disease is still one of the significant threats to public health and a global problem because of these functions [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective Effect of Kaempferol: A Review of the Dietary Sources, Bioavailability, Mechanisms of Action, and Safety

Alkandahri

Pamungkas

Oktoba

et al. 2023

Advances in Pharmacological and Pharmaceutical Sciences

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The liver is the body’s most critical organ that performs vital functions. Hepatic disorders can affect the physiological and biochemical functions of the body. Hepatic disorder is a condition that describes the damage to cells, tissues, structures, and functions of the liver, which can cause fibrosis and ultimately result in cirrhosis. These diseases include hepatitis, ALD, NAFLD, liver fibrosis, liver cirrhosis, hepatic failure, and HCC. Hepatic diseases are caused by cell membrane rupture, immune response, altered drug metabolism, accumulation of reactive oxygen species, lipid peroxidation, and cell death. Despite the breakthrough in modern medicine, there is no drug that is effective in stimulating the liver function, offering complete protection, and aiding liver cell regeneration. Furthermore, some drugs can create adverse side effects, and natural medicines are carefully selected as new therapeutic strategies for managing liver disease. Kaempferol is a polyphenol contained in many vegetables, fruits, and herbal remedies. We use it to manage various diseases such as diabetes, cardiovascular disorders, and cancers. Kaempferol is a potent antioxidant and has anti-inflammatory effects, which therefore possesses hepatoprotective properties. The previous research has studied the hepatoprotective effect of kaempferol in various hepatotoxicity protocols, including acetaminophen (APAP)-induced hepatotoxicity, ALD, NAFLD, CCl4, HCC, and lipopolysaccharide (LPS)-induced acute liver injury. Therefore, this report aims to provide a recent brief overview of the literature concerning the hepatoprotective effect of kaempferol and its possible molecular mechanism of action. It also provides the most recent literature on kaempferol’s chemical structure, natural source, bioavailability, and safety.

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

Cited by 7 publications

References 118 publications

Celastrol pretreatment attenuates concanavalin A‐induced hepatitis in mice by suppressing interleukin‐6/STAT3‐interleukin‐17 signaling

Celastrol pretreatment attenuates concanavalin A‐induced hepatitis in mice by suppressing interleukin‐6/STAT3‐interleukin‐17 signaling

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

Hepatoprotective Effect of Kaempferol: A Review of the Dietary Sources, Bioavailability, Mechanisms of Action, and Safety

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