Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response

Yang, Qiaoling; Shu, Fangfang; Gong, Junting; Ding, Ping; Cheng, Rong-Rong; Tong, Renchao; Ding, Lili; Sun, Huajun; Huang, Wendong; Wang, Zhengtao; Yang, Li

doi:10.1016/j.jep.2020.112556

Cited by 33 publications

(24 citation statements)

References 40 publications

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“…The results suggest the possibility of an effective clinical application of sweroside to NASH patients. Consistently, Yang Q et al reported that sweroside reduced hepatic lipid accumulation and serum lipid levels with decreased hepatic and serum levels of pro-inflammatory cytokines and chemokines in high fat diet-induced obese mice, showing that sweroside improved NAFLD symptoms mediated through the regulation of lipid metabolism-and inflammation-related genes [28].…”

Section: Discussionmentioning

confidence: 68%

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

Yang

Jang

Kim

et al. 2020

IJMS

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Non-alcoholic steatohepatitis (NASH), a type of non-alcoholic fatty liver disease, is characterized as steatosis and inflammation in the liver. NLRP3 inflammasome activation is associated with NASH pathology. We hypothesized that suppressing the NLRP3 inflammasome could be effective in preventing NASH. We searched substances that could inhibit the activation of the NLRP3 inflammasome and identified sweroside as an NLRP3 inhibitor. We investigated whether sweroside can be applied to prevent the pathological symptoms associated with NASH in a methionine–choline-deficient (MCD) diet-induced NASH mouse model. The activation of the NLRP3 inflammasome was determined by detecting the production of caspase-1 and IL-1β from pro-caspase-1 and pro-IL-1β in primary mouse macrophages and mouse liver. In a NASH model, mice were fed an MCD diet for two weeks with daily intraperitoneal injections of sweroside. Sweroside effectively inhibited NLRP3 inflammasome activation in primary macrophages as shown by a decrease in IL-1β and caspase-1 production. In a MCD diet-induced NASH mouse model, intraperitoneal injection of sweroside significantly reduced serum aspartate transaminase and alanine transaminase levels, hepatic immune cell infiltration, hepatic triglyceride accumulation, and liver fibrosis. The improvement of NASH symptoms by sweroside was accompanied with its inhibitory effects on the hepatic NLRP3 inflammasome as hepatic IL-1β and caspase-1 were decreased. Furthermore, sweroside blocked de novo synthesis of mitochondrial DNA in the liver, contributing to suppression of the NLRP3 inflammasome. These results suggest that targeting the NLRP3 inflammasome with sweroside could be beneficially employed to improve NASH symptoms.

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Section: Discussionmentioning

confidence: 68%

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

Yang

Jang

Kim

et al. 2020

IJMS

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“…In addition, depending on the dose, alterations in liver X receptor-α expression were observed. Hypolipidemic and antioxidant activity of iridoids through the stimulation of PPAR-α was noted also in different studies [ 36 , 65 , 66 , 67 , 68 ].…”

Section: Impact Of Iridoidsmentioning

confidence: 65%

The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

Danielewski

Matuszewska

Szeląg

et al. 2021

IJMS

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Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.

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“…Sweroside, a main active component of S. pseudochinensis Hara, has also been reported to exert multiple pharmacotherapeutic actions. 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).…”

Section: Discussionmentioning

confidence: 99%

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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Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response

Cited by 33 publications

References 40 publications

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

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

The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

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

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