SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway

Kim, Da Eun; Chang, Bo Yoon; Jeon, Byeong Min; Baek, Jong-In; Kim, Sun Chang; Kim, Sung Yeon

doi:10.3390/ijms21124534

Cited by 17 publications

(15 citation statements)

References 62 publications

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“…AMPK activation is reported to facilitate the nuclear expression of Nrf2 through its downstream signaling to alleviate cellular oxidative stress ( Wu et al, 2018 ). In addition, several reports have shown that liver protection can be achieved by activating the AMPK/Nrf2/HO-1 pathway ( Shen et al, 2019 ; Kim et al, 2020 ). Notably, it has been shown that CAV1 regulates AMPK activation ( Salani et al, 2012 ; Liu et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 Alleviates Acetaminophen-Induced Fat Accumulation in Non-Alcoholic Fatty Liver Disease by Enhancing Hepatic Antioxidant Ability via Activating AMPK Pathway

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for acute liver injury caused by overuse of acetaminophen (APAP). Caveolin-1 (CAV1), a regulator of hepatic energy metabolism and oxidative stress, was found to have a protective effect against NAFLD in our previous study. However, it remains unclear whether CAV1 has a protective effect against APAP-induced hepatotoxicity in NAFLD. The aim of this study was to determine whether CAV1 inhibits oxidative stress through the AMPK/Nrf2/HO-1 pathway to protect the liver from fat accumulation exacerbated by APAP in NAFLD. In this study, seven-week-old C57BL/6 male mice (18–20 g) were raised under similar conditions for in vivo experiment. In vitro, L02 cells were treated with A/O (alcohol and oleic acid mixture) for 48 h, and APAP was added at 24 h for further incubation. The results showed that the protein expression of the AMPK/Nrf2 pathway was enhanced after CAV1 upregulation. The effects of CAV1 on fat accumulation, ROS, and the AMPK/Nrf2 anti-oxidative pathway were reduced after the application of CAV1-siRNA. Finally, treatment with compound C (an AMPK inhibitor) prevented CAV1 plasmid-mediated alleviation of oxidative stress and fat accumulation and reduced the protein level of Nrf2 in the nucleus, demonstrating that the AMPK/Nrf2/HO-1 pathway was involved in the protective effect of CAV1. These results indicate that CAV1 exerted a protective effect against APAP-aggravated lipid deposition and hepatic injury in NAFLD by inhibiting oxidative stress. Therefore, the upregulation of CAV1 might have clinical benefits in reducing APAP-aggravated hepatotoxicity in NAFLD.

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Section: Discussionmentioning

confidence: 99%

Caveolin-1 Alleviates Acetaminophen-Induced Fat Accumulation in Non-Alcoholic Fatty Liver Disease by Enhancing Hepatic Antioxidant Ability via Activating AMPK Pathway

et al. 2021

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“…48,49 Also, a ginsenoside F2-enhanced mixture (SGL 121) reduced hepatic lipidosis in a high-fat and high-carbohydrate diet-induced non-alcoholic fatty liver disease model by increasing the phosphorylation of AMPK and ACC. 28 Therefore, AMPK signaling may play a key role in the anti-obesity effect of GF2. GF2 Promoted the Biosynthesis of the Mitochondria in 3T3-L1 Adipocytes.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…23 GF2 reportedly has pharmacological effects on gastric carcinoma, 24 breast cancer, 25 inflammation, 26 and hepatoprotectivity. 27,28 Notably, GF2 prevented obesity by directly binding to PPARγ, thus inhibiting adipocyte differentiation. 29 However, the mechanism by which GF2 alleviates obesity is unclear.…”

Section: ■ Introductionmentioning

confidence: 99%

“…20(S)-ginsenoside F2 (GF2) is a minor saponin from natural Panax ginseng or obtained by biotransformation of major PPD-type saponins, such as Rb1, Rb2, Rb3, and Rc . GF2 reportedly has pharmacological effects on gastric carcinoma, breast cancer, inflammation, and hepatoprotectivity. , Notably, GF2 prevented obesity by directly binding to PPARγ, thus inhibiting adipocyte differentiation . However, the mechanism by which GF2 alleviates obesity is unclear.…”

Section: Introductionmentioning

confidence: 99%

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Ginsenoside F2 Suppresses Adipogenesis in 3T3-L1 Cells and Obesity in Mice via the AMPK Pathway

Zhou

et al. 2021

J. Agric. Food Chem.

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Ginsenoside F2 (GF2) is a protopanaxdiol saponin from Panax ginseng leaves and possesses many potential pharmacological properties. GF2 may prevent obesity by directly binding to the peroxisome proliferator-activated receptor-γ (PPARγ) and inhibiting adipocyte differentiation. However, the mechanism by which GF2 alleviates obesity is unknown. We therefore explored the anti-adipogenesis and anti-obesity effects of GF2 in vitro and in vivo. GF2 inhibited differentiation and reduced the triglyceride (TG) content of 3T3-L1 preadipocytes in the early stage of adipogenesis. Administration of GF2 (50 and 100 mg/kg) to obese mice for 4 weeks reduced the body weight gain, weight of adipose tissues, adipocyte size, and total cholesterol, TG, and AST levels in serum. RNA sequencing and real-time quantitative PCR indicated that GF2 decreased the expression levels of adipokines, including PPARγ, fatty acid synthase, and adiponectin. KEGG enrichment and western blot analyses demonstrated that GF2 accelerated the phosphorylation of AMPK and ACC in vitro and in vivo. Moreover, GF2 promoted the biosynthesis of mitochondria in 3T3-L1 adipocytes and increased the expression of antioxidant enzymes such as SOD and GSH-Px in the liver of obese mice. Therefore, GF2 suppressed adipogenesis and obesity by regulating the expression of adipokines and activating the AMPK pathway. Hence, the findings suggest that GF2 may have potential therapeutic implications to treat obesity.

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“…Protopanaxadiol (PPD), an aglycon of dammarene-type ginsenosides, possesses anti-cancer, anti-inflammatory, anti-oxidant, hepatoprotectant, anti-lipogenic, wound-healing, and anti-obesity activity [ 1 , 2 , 3 , 4 , 5 ]. Despite having high pharmacological potency, the application of these ginsenosides as drugs and pharmaceuticals is limited because Panax ginseng cultivation is slow, and the ginsenoside content of ginseng is low [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

CRISPRi-Guided Metabolic Flux Engineering for Enhanced Protopanaxadiol Production in Saccharomyces cerevisiae

Lim

Baek

Jeon

et al. 2021

IJMS

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Protopanaxadiol (PPD), an aglycon found in several dammarene-type ginsenosides, has high potency as a pharmaceutical. Nevertheless, application of these ginsenosides has been limited because of the high production cost due to the rare content of PPD in Panax ginseng and a long cultivation time (4–6 years). For the biological mass production of the PPD, de novo biosynthetic pathways for PPD were introduced in Saccharomyces cerevisiae and the metabolic flux toward the target molecule was restructured to avoid competition for carbon sources between native metabolic pathways and de novo biosynthetic pathways producing PPD in S. cerevisiae. Here, we report a CRISPRi (clustered regularly interspaced short palindromic repeats interference)-based customized metabolic flux system which downregulates the lanosterol (a competing metabolite of dammarenediol-II (DD-II)) synthase in S. cerevisiae. With the CRISPRi-mediated suppression of lanosterol synthase and diversion of lanosterol to DD-II and PPD in S. cerevisiae, we increased PPD production 14.4-fold in shake-flask fermentation and 5.7-fold in a long-term batch-fed fermentation.

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SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway

Cited by 17 publications

References 62 publications

Caveolin-1 Alleviates Acetaminophen-Induced Fat Accumulation in Non-Alcoholic Fatty Liver Disease by Enhancing Hepatic Antioxidant Ability via Activating AMPK Pathway

Caveolin-1 Alleviates Acetaminophen-Induced Fat Accumulation in Non-Alcoholic Fatty Liver Disease by Enhancing Hepatic Antioxidant Ability via Activating AMPK Pathway

Ginsenoside F2 Suppresses Adipogenesis in 3T3-L1 Cells and Obesity in Mice via the AMPK Pathway

CRISPRi-Guided Metabolic Flux Engineering for Enhanced Protopanaxadiol Production in Saccharomyces cerevisiae

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