Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome

Yang, Gabsik; Jang, Joo Hyeon; Kim, Sung Wook; Han, Sung-Hyun; Ho, Kyung; Jang, Jae-Ki; Kang, Han Chang; Cho, Yong‐Yeon; Lee, Hye Suk; Lee, Joo Young

doi:10.3390/ijms21082790

Cited by 47 publications

(31 citation statements)

References 41 publications

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“…In the present study, we found that sweroside inhibited the expression levels of NLRP3, ASC, IL-1β, and cleaved caspase-1, which suggested that sweroside could repress NLRP3 inflammasome-mediated pyroptosis. This was consistent with findings by Yang et al ( 21 ). In the process of IR, ROS largely accumulate in the tissue and induce NLRP3 inflammasome activation ( 34 ).…”

Section: Discussionsupporting

confidence: 94%

“…Yang et al revealed that sweroside alleviated non-alcoholic fatty liver disease in obese mice via the modulation of lipid metabolism and inflammation ( 29 ). In addition, Yang et al indicated that sweroside protected against non-alcoholic steatohepatitis by inhibiting NLRP3 inflammasome-mediated pyroptosis ( 21 ). More interestingly, sweroside has been found to prevent myocardial cells against aconitine-induced cardiac toxicity ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

“…It also has been found that sweroside could prevent against lipopolysaccharide (LPS) or interleukin (IL)-1β-induced inflammation via suppression of NF-kappaB (NF-κB) signaling pathway ( 19 , 20 ). Notably, a recent study has demonstrated that sweroside could lead to suppression of NLRP3 inflammasome activation ( 21 ). However, the detailed mechanism has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Sweroside Protects Against Myocardial Ischemia–Reperfusion Injury by Inhibiting Oxidative Stress and Pyroptosis Partially via Modulation of the Keap1/Nrf2 Axis

Zhao

Zhu

et al. 2021

Front. Cardiovasc. Med.

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Aims: Sweroside, a secoiridoid glucoside extracted from Swertia pseudochinensis Hara, is reported to possess antioxidant and anti-inflammatory activities. However, whether sweroside has a protective effect on myocardial ischemia–reperfusion (IR) injury is yet to be elucidated. The present study aimed to confirm the cardioprotective effect of sweroside and to identify its underlying mechanism.Methods and Results: H9c2 cells were pretreated with sweroside and then underwent hypoxia–reoxygenation. Cell Counting Kit-8, creatine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) assays were conducted to detect cell viability and myocardial injury, respectively. The Langendorff method was used to induce myocardial IR injury ex vivo. Triphenyltetrazolium chloride staining was performed to detect myocardial infarct size, while protein expression was analyzed using western blotting. Overall, the results indicated that sweroside pretreatment dose-dependently led to a significant enhancement in cell viability, a decrease in release of CK-MB and LDH, a reduction in infarct size, and an improvement in cardiac function. Additionally, sweroside pretreatment caused a marked suppression of oxidative stress, as evidenced by the fact that sweroside decreased the accumulation of reactive oxygen species and malondialdehyde, while enhancing the activities of superoxide dismutase and glutathione peroxidase. Moreover, sweroside was found to notably repress pyroptosis, as sweroside blocked pore formation in the cell membrane, inhibited caspase-1 and interleukin (IL)-1β activity, and decreased the expression levels of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, cleaved caspase-1, and IL-1β. Mechanistically, it was found that sweroside inhibited Kelch-like ECH-associated protein 1 (Keap1) and induced nuclear factor E2-associated factor 2 (Nrf2) nuclear translocation. Furthermore, the inhibition of oxidative stress and pyroptosis by sweroside could be abrogated via the inhibition of Nrf2 expression, which suggested that the protective effect induced by sweroside was Nrf2-dependent.Conclusions: The present study demonstrated that sweroside pretreatment could protect against myocardial IR injury by inhibiting of oxidative stress and NLRP3 inflammasome-mediated pyroptosis partially via modulation of the Keap1/Nrf2 axis.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sweroside Protects Against Myocardial Ischemia–Reperfusion Injury by Inhibiting Oxidative Stress and Pyroptosis Partially via Modulation of the Keap1/Nrf2 Axis

Zhao

Zhu

et al. 2021

Front. Cardiovasc. Med.

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“…It can effectively inhibit NLRP3 inflammasome activation in bone marrow-derived macrophages (BMDMs). Additionally, in a mouse model of nonalcoholic steatohepatitis (NASH) induced by a methionine-choline-deficient (MCD) diet, sweroside significantly attenuates NASH symptoms (including liver fibrosis) through the suppression of NLRP3 inflammasome activation in the liver, partially by inhibiting de novo synthesis of mitochondrial DNA (mtDNA), which can be oxidized to serve as the ultimate NLRP3 ligand, or at least a part of it, thus activating NLRP3 inflammasome complexes after exposure to LPS and NLRP3 activators (Zhong et al, 2018;Yang et al, 2020).…”

Section: Monoterpenoidsmentioning

confidence: 99%

Natural Products that Target the NLRP3 Inflammasome to Treat Fibrosis

Ding

Wei

et al. 2020

Front. Pharmacol.

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Fibrosis is a common pathway followed by different organs after injury, and it can lead to parenchymal scarring, cellular dysfunction, and even organ failure. The NLRP3 inflammasome is a multiprotein complex composed of the sensor molecule NLRP3, the adaptor apoptosis-associated speck-like protein containing a CARD (ASC), and the effector protease caspase-1. Overactivation of the NLRP3 inflammasome triggers the abundant secretion of IL-1β and IL-18, induces pyroptosis, and promotes the release of a swathe of proinflammatory proteins, all of which contribute to fibrogenic processes in multiple organs. In recent years, screening bioactive natural compounds for NLRP3 inhibitors to alleviate fibrosis has gained broad interest from the scientific community because of the associated cost-effectiveness and easy access. In this review, we systematically and comprehensively summarize the natural products, including terpenoids, phenols, and alkaloids, among others, and the plant-derived crude extracts, that have been reported to ameliorate fibrosis via inhibiting NLRP3 inflammasome activation and highlight the underlying mechanisms. Among all the compounds, diterpenoids is the most promising candidates for inhibiting NLRP3 inflammasome activation and improving fibrosis, as they possess combined inhibitory effect on NLRP3 inflammasome assembly and NF-κB signaling pathway. All the information may aid in the development of therapeutic strategies for the treatment of fibrotic diseases.

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“…Therefore, the discovery of inhibitors of NLRP3 inflammasome activation from bioactive compounds derived from natural substances might be a promising future strategy for the prevention and treatment of neurodegenerative diseases. Our study showed that β-carotene, sweroside, and sulforaphane [ 57 , 58 , 59 ], acting as NLRP3 inhibitors, might be applicable to the prevention of AD and PD.…”

Section: Discussionmentioning

confidence: 99%

A Novel Treatment Strategy by Natural Products in NLRP3 Inflammasome-Mediated Neuroinflammation in Alzheimer’s and Parkinson’s Disease

Lee

Kim

et al. 2021

IJMS

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Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases. Many studies have demonstrated that the release of NLRP3 inflammasome-mediated proinflammatory cytokines by the excessive activation of microglia is associated with the pathogenesis of AD and PD and suggested that the NLRP3 inflammasome plays an important role in AD and PD development. In both diseases, various stimuli, such as Aβ and α-synuclein, accelerate the formation of the NLRP3 inflammasome in microglia and induce pyroptosis through the expression of interleukin (IL)-1β, caspase-1, etc., where neuroinflammation contributes to gradual progression and deterioration. However, despite intensive research, the exact function and regulation of the NLRP3 inflammasome has not yet been clearly identified. Moreover, there have not yet been any experiments of clinical use, although many studies have recently been conducted to improve treatment of inflammatory diseases using various inhibitors for NLRP3 inflammasome pathways. However, recent studies have reported that various natural products show improvement effects in the in vivo models of AD and PD through the regulation of NLRP3 inflammasome assembly. Therefore, the present review provides an overview of natural extraction studies aimed at the prevention or treatment of NLRP3 inflammasome-mediated neurological disorders. It is suggested that the discovery and development of these various natural products could be a potential strategy for NLRP3 inflammasome-mediated AD and PD treatment.

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Sweroside Prevents Non-Alcoholic Steatohepatitis by Suppressing Activation of the NLRP3 Inflammasome

Cited by 47 publications

References 41 publications

Sweroside Protects Against Myocardial Ischemia–Reperfusion Injury by Inhibiting Oxidative Stress and Pyroptosis Partially via Modulation of the Keap1/Nrf2 Axis

Sweroside Protects Against Myocardial Ischemia–Reperfusion Injury by Inhibiting Oxidative Stress and Pyroptosis Partially via Modulation of the Keap1/Nrf2 Axis

Natural Products that Target the NLRP3 Inflammasome to Treat Fibrosis

A Novel Treatment Strategy by Natural Products in NLRP3 Inflammasome-Mediated Neuroinflammation in Alzheimer’s and Parkinson’s Disease

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