Beta-sitosterol and its derivatives repress lipopolysaccharide/d-galactosamine-induced acute hepatic injury by inhibiting the oxidation and inflammation in mice

Yin, Yongxia; Liu, Xiaofeng; Liu, Jinping; Cai, Enbo; Zhu, Hongyan; Li, Haijun; Zhang, Lianxue; Li, Pingya

doi:10.1016/j.bmcl.2018.03.073

Cited by 54 publications

(35 citation statements)

References 37 publications

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“…Oxidative Medicine and Cellular Longevity reduction of protein expression of Pparα and Cpt1a, two important regulators administering FA β-oxidation, was prevented by PS-ALA supplementation. Others suggested that beta-sitosterol repressed acute hepatic injury by inhibiting oxidative stress in mice [50]. Evidence from a clinical study showed that dietary 0.945 g/d n-3 PUFA (21% eicosapentaenoic (EPA), 16% docosahexaenoic (DHA) acids, and 64% ALA) for 6 months significantly improved hepatic Each bar denotes the mean ± standard error of the mean (n = 6).…”

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confidence: 99%

Plant Sterol Ester of α-Linolenic Acid Attenuates Nonalcoholic Fatty Liver Disease by Rescuing the Adaption to Endoplasmic Reticulum Stress and Enhancing Mitochondrial Biogenesis

Han

Guo

et al. 2019

Oxidative Medicine and Cellular Longevity

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Nonalcoholic fatty liver disease (NAFLD) is becoming more common in the world and is presenting a great challenge concerning prevention and treatment. Plant sterol ester of α-linolenic acid (PS-ALA) has a potential benefit to NAFLD. To examine the effect of PS-ALA on NAFLD, C57BL/6J mice were given a control diet, high fat and high cholesterol diet (HFD), and HFD plus 2% PS, 1.3% ALA, or 3.3% PS-ALA for 16 weeks. Our results showed that PS-ALA treatment suppressed hepatic steatosis, ameliorated lipid disorder, attenuated inflammatory response, and inhibited oxidative stress. In the molecular level, PS-ALA downregulated high transcriptional and translational levels of endoplasmic reticulum (ER) stress markers (Grp78 and Chop) leading to decreased protein expression of transcription factor and key enzymes involved in de novo lipogenesis (Srebp-1c and Fas) and cholesterol synthesis (Srebp-2 and Hmgcr). In parallel, PS-ALA blocked Nlrp3 activation and reduced release of IL-1β and IL-18 via inhibiting ER stress-induced sensitization of unfolded protein response sensors (Ire1α and Xbp1s). Finally, PS-ALA improved HFD-induced mitochondrial damage and fatty acid accumulation as exhibited by higher protein and mRNA expression of key genes administering mitochondrial biogenesis (Pgc-1α, Nrf1, and Tfam) and fatty acid β-oxidation (Pparα and Cpt1a). In conclusion, our study originally demonstrated that PS-ALA rescued ER stress, enhanced mitochondrial biogenesis, and thus ameliorated NAFLD.

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mentioning

confidence: 99%

Plant Sterol Ester of α-Linolenic Acid Attenuates Nonalcoholic Fatty Liver Disease by Rescuing the Adaption to Endoplasmic Reticulum Stress and Enhancing Mitochondrial Biogenesis

Han

Guo

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…β-sitosterol applies its anti-tumor properties via MPK/PTEN/HSP90 axis in AGS human gastric adenocarcinoma cells (Shin et al 2018). Antioxidant and anti-inflammatory effects of β-sitosterol derivatives on acute hepatic injury was reported by Yin et al (2018). In addition, treatment with β-sitosterol in patients with benign prostatic hyperplasia improves urinary flow measure which may be due to antiinflammatory properties or cholesterol metabolism (Wilt et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Other phytopharmacological extract in the bark of elm tree is β-sitosterol, which has a structure and function similar to cholesterol and is referred as "key of life". Solubility of β-sitosterol is low that restricts its use (AbuMweis et al 2014;Yin et al 2018). Based on the best available evidence in literature, various pharmacological properties for phytosterol have been studied (Wilt et al 1999;Shin et al 2018;Yin et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Solubility of β-sitosterol is low that restricts its use (AbuMweis et al 2014;Yin et al 2018). Based on the best available evidence in literature, various pharmacological properties for phytosterol have been studied (Wilt et al 1999;Shin et al 2018;Yin et al 2018). β-sitosterol applies its anti-tumor properties via MPK/PTEN/HSP90 axis in AGS human gastric adenocarcinoma cells (Shin et al 2018).…”

Section: Discussionmentioning

confidence: 99%

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Ulmus minor bark hydro-alcoholic extract ameliorates histological parameters and testosterone level in an experimental model of PCOS rats

Hoseinpour

Ghanbari

Azad

et al. 2019

Endocrine Regulations

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Objective. Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with female factor infertility. Ulmus minor bark (UMB) is one of the medicinal plants used in Persian folklore as a fertility enhancer. In the current study, we aimed to elucidate the effect of UMB hydro-alcoholic extract on histological parameters and testosterone condition in an experimental model of PCOS rats.Methods. Thirty female rats were randomly divided into five groups: (1) control, (2) vehicle, (3) PCOS/50 mg [6 mg/kg dehydroepiandrosterone (DHEA) + 50 mg/kg UMB hydro-alcoholic extract], (4) PCOS/150 mg (6 mg/kg DHEA + 150 mg/kg UMB hydro-alcoholic extract), and (5) PCOS (6 mg/kg DHEA). All interventions were performed for 21 days. Afterwards, stereological analysis was done for determination of ovarian volume and follicle number. The serum level of testosterone was measured by ELISA kit.Results. UMB hydro-alcoholic extract improved the total number of the corpus luteum in the treatment groups when compared to the PCOS group (p<0.05). PCOS/150 mg and PCOS/50 mg groups showed significantly lower total number of the primordial, primary, and secondary follicles as well as testosterone level compared to the PCOS group (p<0.05). The total number of antral follicles and volume of ovary did not differ significantly between groups.Conclusion. UMB extract may be an effective and good alternative in improving PCOS histological and testosterone disturbances although further studies are warranted to confirm the safety of UMB plant in human.

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“…Recent research showed that stigmasterol inhibited LPS-induced acute liver injury with a dose-dependent manner [21]. β-Sitosterol was mentioned to decrease hepato brosis, inhibit the oxidation and in ammation against LPS/D-GalN -induced acute hepatic failure and protect against CCl4-induced hepatotoxicity in animal models [22,23].…”

Section: Discussionmentioning

confidence: 99%

Uncovering bioactive compounds and potential mechanisms of Jieduan-Niwan Formula against liver failure

Ma¹,

Zhang²,

Gao³

et al. 2020

Preprint

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Background Liver failure is considered as the inability of the liver to perform its normal synthetic and metabolic function. Our previous data showed that Jieduan-Niwan formula (JDNW) induced liver failure, while its underlying mechanism remains unknown. Methods In the present study, we performed a network pharmacology to analyze the bioactive ingredients and related targets. Compound and target data of JDNW formula were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and targets related to liver diseases were obtained from DisGeNET database. Information of protein protein interaction were retrieved from STRING database. Network construction and degree calculation were used Cytoscape software. Metascape web-server was used for GO and KEGG pathway enrichment. A microarray data series (GSE72081) was obtained from Gene Expression Omnibus database and analyzed using R project and Connectivity Map. Ledock was used for molecular docking. Results A total of 114 unduplicated active ingredients were identified after ADME screening. After construction of a target-liver disease network, 28 targets were identified for anti-liver failure effect. These targets were significantly enriched in fluid shear stress and atherosclerosis, pathways in cancer, IL-17 signaling pathway, HIF-1 signaling pathway, insulin resistance, toxoplasmosis, prostate cancer, microRNAs in cancer, NF-kappa B signaling pathway, Chemical carcinogenesis, VEGF signaling pathway and complement and coagulation cascades pathways. After analyzing a public microarray data of quercetin, we found biological action of some NFκB inhibitors was similar to quercetin. Molecular docking study showed that quercetin possessed a capability to bind on IKKβ and inhibited NFκB activation. Conclusions JDNW formula treated liver failure via multiple targets and multiple pathways, including NFκB signal. Quercetin was identified as a key bioactive ingredient of JDNW formula and its anti-liver failure effect may involve in NFκB inhibition.

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Beta-sitosterol and its derivatives repress lipopolysaccharide/d-galactosamine-induced acute hepatic injury by inhibiting the oxidation and inflammation in mice

Cited by 54 publications

References 37 publications

Plant Sterol Ester of α-Linolenic Acid Attenuates Nonalcoholic Fatty Liver Disease by Rescuing the Adaption to Endoplasmic Reticulum Stress and Enhancing Mitochondrial Biogenesis

Plant Sterol Ester of α-Linolenic Acid Attenuates Nonalcoholic Fatty Liver Disease by Rescuing the Adaption to Endoplasmic Reticulum Stress and Enhancing Mitochondrial Biogenesis

Ulmus minor bark hydro-alcoholic extract ameliorates histological parameters and testosterone level in an experimental model of PCOS rats

Uncovering bioactive compounds and potential mechanisms of Jieduan-Niwan Formula against liver failure

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