4-Acetylantroquinonol B ameliorates nonalcoholic steatohepatitis by suppression of ER stress and NLRP3 inflammasome activation

Yen, I-Chuan; Tu, Qain-Wen; Chang, Tsu‐Chung; Lin, Pei-Hsun; Li, Yao‐Feng; Lee, Shih‐Yu

doi:10.1016/j.biopha.2021.111504

Cited by 20 publications

(14 citation statements)

References 57 publications

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“…Moreover, 4-AAQB inhibited the activation of NLRP3 inflammasomes, responses of inflammatory cytokines, and ER stress in various in vitro and in vivo models. Furthermore, Sirtuin 1 and Nrf2 signaling pathways were increased and protected the liver from injury ( Yen et al, 2021 ). Hence, current data indicate that treatment with 4-AAQB represents an accessible therapeutic strategy for NAFLD control.…”

Section: Pharmacological Agents Associated With Nlrp3 Inflammasome Su...mentioning

confidence: 99%

The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment

Wang

et al. 2022

Front. Pharmacol.

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Non-alcoholic fatty liver disease (NAFLD) is among the most prevalent primary liver diseases worldwide and can develop into various conditions, ranging from simple steatosis, through non-alcoholic steatohepatitis (NASH), to fibrosis, and eventually cirrhosis and hepatocellular carcinoma. Nevertheless, there is no effective treatment for NAFLD due to the complicated etiology. Recently, activation of the NLPR3 inflammasome has been demonstrated to be a contributing factor in the development of NAFLD, particularly as a modulator of progression from initial hepatic steatosis to NASH. NLRP3 inflammasome, as a caspase-1 activation platform, is critical for processing key pro-inflammatory cytokines and pyroptosis. Various stimuli involved in NAFLD can activate the NLRP3 inflammasome, depending on the diverse cellular stresses that they cause. NLRP3 inflammasome-related inhibitors and agents for NAFLD treatment have been tested and demonstrated positive effects in experimental models. Meanwhile, some drugs have been applied in clinical studies, supporting this therapeutic approach. In this review, we discuss the activation, biological functions, and treatment targeting the NLRP3 inflammasome in the context of NAFLD progression. Specifically, we focus on the different types of therapeutic agents that can inhibit the NLRP3 inflammasome and summarize their pharmacological effectiveness for NAFLD treatment.

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Section: Pharmacological Agents Associated With Nlrp3 Inflammasome Su...mentioning

confidence: 99%

The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment

Wang

et al. 2022

Front. Pharmacol.

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“…It is a unique parasitic fungal species that grows slowly in the tree Cinnamomum kanehirai [ 2 ]. Previous studies have found AC mycelium (ACM) provides many beneficial pharmacological activities including anti-inflammation [ 3 ], anti-obesity [ 4 ], anti-cancer [ 5 ], reduction of mild hypertension [ 6 ] and improvement of nonalcoholic steatohepatitis [ 7 , 8 ]. Ethanolic extract of AC contains several bioactive constituents which display promising anti-tumor effects in several types of cancers [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound

Lin

et al. 2021

Molecules

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Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.

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“…4-Acetylantroquinonol B (4-AAQB) improved ALT, AST, and NAFLD activity score (NAS) in MCD-fed mice. 4-AAQB decreased inflammatory responses, ER stress, and NLRP3 inflammasome activation, but elevated Nrf2 and SIRT1 signaling pathways in vitro and in vivo [ 62 ]. By inhibiting the NF-B/NLRP3 signaling pathway, kinsenoside is able to reduce fibrosis and inflammation in experimental NASH mice [ 63 ].…”

Section: Source and Defense System For Mitochondria-mediated Oxidativ...mentioning

confidence: 99%

Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases

Park

Rahman

et al. 2022

Antioxidants

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Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) which are leading causes of liver cirrhosis and hepatocellular carcinoma. The generation of reactive oxygen species (ROS) in response to oxidative stress is caused by mitochondrial dysfunction and is considered critical for treatment. The role of oxidative stress, lipid toxicity, and inflammation in NAFLD are well known. NAFLD is a chronic liver disease that commonly progresses to cirrhosis and chronic liver disease, and people with obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension are at a higher risk of developing NAFLD. NAFLD is associated with a number of pathological factors, including insulin resistance, lipid metabolic dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. As a result, the improvement in steatosis and inflammation is enough to entice researchers to look into liver disease treatment. However, antioxidant treatment has not been very effective for liver disease. Additionally, it has been suggested that the beneficial effects of herbal medicines on immunity and inflammation are governed by various mechanisms for lipid metabolism and inflammation control. This review provided a summary of research on herbal medicines for the therapeutic implementation of mitochondria-mediated ROS production in liver disease as well as clinical applications through herbal medicine. In addition, the pathophysiology of common liver disorders such as ALD and NAFLD would be investigated in the role that mitochondria play in the process to open new therapeutic avenues in the management of patients with liver disease.

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4-Acetylantroquinonol B ameliorates nonalcoholic steatohepatitis by suppression of ER stress and NLRP3 inflammasome activation

Cited by 20 publications

References 57 publications

The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment

The NLRP3 Inflammasome in Non-Alcoholic Fatty Liver Disease and Steatohepatitis: Therapeutic Targets and Treatment

Patient-Derived Tumor Chemosensitization of GKB202, an Antrodia Cinnamomea Mycelium-Derived Bioactive Compound

Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases

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