Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress

Jang, Min-Kyung; Nam, Jeong Soo; Kim, Ji Ha; Yun, Ye‐Rang; Han, Chang Woo; Kim, Byung Joo; Jeong, Hyein; Ha, Ki‐Tae; Jung, Myeong Ho

doi:10.1016/j.jep.2016.03.021

Cited by 51 publications

(29 citation statements)

References 33 publications

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“…Previously, we found that S. chinensis extract inhibited ER stress and prevented the development of hepatic steatosis [12]. This supports the hypothesis that S. chinensis extract can be used as a potential therapeutic agent for treatment of ER stress-induced diseases, including hepatic steatosis.…”

Section: Discussionsupporting

confidence: 84%

Gomisin A Ameliorates Endoplasmic Reticulum Stress-induced Hepatic Steatosis

Yun¹,

Jung²

2017

Journal of Life Science

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Previously, we have shown that Schisandra chinensis (Turcz.) Baill. (S. chinensis) has a protective effect against endoplasmic reticulum (ER) stress-induced hepatic steatosis. Gomisin A is a bioactive phytoestrogen derived from S. chinensis. In the present study, the in vitro and in vivo effects of gomisin A on ER stress and hepatic steatosis were investigated. We quantified the expression of markers of ER stress, including glucose regulated protein 78 (GRP78), C/EBP homolog protein (CHOP), and X-boxbinding protein-1 (XBP-1), in HepG2 cells treated with tunicamycin or palmitate. Tunicamycin treatment in HepG2 cells induced the expression of markers of ER stress, including GRP78, CHOP, and XBP-1c. However, treatment with gomisin A reduced the expression of markers of ER stress. These inhibitory effects were also observed in palmitate-incubated HepG2 cells. The in vivo inhibitory effects of gomisin A were assessed in mice injected with tunicamycin or fed with a high fat diet (HFD). Gomisin A reduced the expression of markers of ER stress and decreased triglyceride levels in the livers of mice after tunicamycin injection or HFD feeding. Furthermore, gomisin A decreased the expression of inflammatory genes in palmitate-incubated HepG2 cells and the liver of HFD-fed obese mice. These results suggest that gomisin A inhibits ER stress and ameliorates hepatic steatosis induced by ER stress.

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Section: Discussionsupporting

confidence: 84%

Gomisin A Ameliorates Endoplasmic Reticulum Stress-induced Hepatic Steatosis

Yun¹,

Jung²

2017

Journal of Life Science

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“…ER stress is known to activate hepatic de novo lipogenesis, inhibit VLDL secretion, promote IR and inflammatory process, and promote cell apoptosis through pathways including CHOP/Caspase. ER stress increases the level of fat accumulation and worsens the NAFLD to a more serious hepatic state (Ferré & Foufelle, ; Jang et al, ). Studies showed that CHOP deletion protected from diet‐induced steatohepatitis (Tamaki et al, ).…”

Section: Discussionmentioning

confidence: 99%

Zingiber officinaleextract and omega‐3 fatty acids ameliorate endoplasmic reticulum stress in a nonalcoholic fatty liver rat model

et al. 2019

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Endoplasmic reticulum (ER) stress was reported to play a major role in non‐alcoholic fatty liver disease (NAFLD) induction and progression. Here, we study the effect of Zingiber officinale and omega‐3 fatty acids on ER stress for treating NAFLD. Male Wistar rats were fed on a normal diet (control group) or high‐fat diet (HFD) for 8 weeks. The HFD rats were later treated with vehicle, omega‐3 or with Z. officinale extract. HFD group demonstrated significantly more body weight gain and higher plasma lipid profile, glucose, and hepatic enzymes. The expressions of lipogenic ChREBP and ER stress genes CHOP, XBP1, and GRP78 were increased. This was accompanied by intrahepatic fat accumulation visualized by hepatic morphology and H&E‐stained sections. Treatment with Z. officinale and omega‐3 fatty acids reverted these changes into a normal healthy state. From these results, we prove that both therapeutic approaches can be potential drugs for treating NAFLD besides other ER stress‐associated diseases. Practical applications The effect of Zingiber officinale extract and omega‐3 fatty acid on ER stress associated with NAFLD was investigated. The results revealed that Z. officinale extract and omega‐3 fatty acids significantly inhibited ER stress and intrahepatic fat accumulation with the upper hand for Z. officinale extract. Both can be used as future promising therapies for the treatment of NAFLD patients and also treating different diseases that involve ER stress as a pathological modulator like diabetes mellitus, Alzheimer's disease, Parkinson's disease, and cancer.

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“…Gomisin N (GN) is a lignan from S. chinensis and was reported to exhibit hepatoprotective18, anticancer19, and anti-inflammatory effects20. Very recently, we have reported that S. chinensis and GN show protective effects against the endoplasmic reticulum (ER) stress-induced hepatic steatosis2122.…”

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confidence: 99%

Gomisin N inhibits adipogenesis and prevents high-fat diet-induced obesity

Jang

Yun

Kim

et al. 2017

Sci Rep

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Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition. GN inhibited the extracellular signal-regulated kinase and phosphoinositide 3-kinase/protein kinase B signaling in the MCE process and activated AMP-activated protein kinase. Furthermore, GN downregulated CCAT/enhancer-binding protein β (C/EBPβ) and histone H3K9 demethylase JMJD2B during early stages of adipogenesis, and therefore repressed the expression of C/EBPβ-targeted cell cycle genes. In addition, GN also repressed the expression of histone H3K4 methyltransferase MLL4 and reduced PPARγ expression. Moreover, GN effectively lowered the final body weight, adipose tissue mass, and reduced the serum levels of glucose, total triglyceride, and cholesterol in the HFD-induced obese mice. GN also markedly reduced hepatic triglyceride level induced by HFD. Collectively, these findings suggest that GN has potential as a novel agent for the prevention and treatment of obesity.

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Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress

Cited by 51 publications

References 33 publications

Gomisin A Ameliorates Endoplasmic Reticulum Stress-induced Hepatic Steatosis

Gomisin A Ameliorates Endoplasmic Reticulum Stress-induced Hepatic Steatosis

Zingiber officinaleextract and omega‐3 fatty acids ameliorate endoplasmic reticulum stress in a nonalcoholic fatty liver rat model

Gomisin N inhibits adipogenesis and prevents high-fat diet-induced obesity

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