Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD

Yang, Zehong; Yu, Yuanyuan; Sun, Nannan; Zhou, Limian; Zhang, Dong; Chen, Haixin; Miao, Wei; Gao, Weihang; Zhang, Can Yang; Liu, Changhui; Yang, Xiaoying; Wu, Xiaojie; Gao, Yong

doi:10.1016/j.jgr.2020.07.005

Cited by 12 publications

(21 citation statements)

References 35 publications

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“…Although Panax ginseng is a source of plenty of biological active compounds, the molecules with the greatest potential to become drug molecules are ginsenosides. According to data obtained from animal studies, ginsenosides have great potential to be used for the treatment of cardiovascular diseases, hepatic disorders and obesity [ 227 , 228 , 229 , 230 , 231 , 232 , 233 ]. According to data obtained from cell culture studies, ginsenosides have great potential to be used for the treatment cardiovascular diseases, hypercholesterolemia, and some types of cancer [ 234 , 235 , 236 , 237 ].…”

Section: Resultsmentioning

confidence: 99%

Comparison between the Biological Active Compounds in Plants with Adaptogenic Properties (Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus and Panax ginseng)

Todorova

Ivanov

Ivanova

2021

Plants

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Background: In the 1960s, research into plant adaptogens began. Plants with adaptogenic properties have rich phytochemical compositions and have been used by humanity since ancient times. However, it is not still clear whether the adaptogenic properties are because of specific compounds or because of the whole plant extracts. The aim of this review is to compare the bioactive compounds in the different parts of these plants. Methods: The search strategy was based on studies related to the isolation of bioactive compounds from Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus, and Panax ginseng. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Results: This review includes data from 259 articles. The phytochemicals isolated from Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus, and Panax ginseng were described and classified in several categories. Conclusions: Plant species have always played an important role in drug discovery because their effectiveness is based on the hundreds of years of experience with folk medicine in different nations. In our view, there is great potential in the near future for some of the phytochemicals found in these plants species to become pharmaceutical agents.

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Section: Resultsmentioning

confidence: 99%

Comparison between the Biological Active Compounds in Plants with Adaptogenic Properties (Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus and Panax ginseng)

Todorova

Ivanov

Ivanova

2021

Plants

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“…Mouse primary hepatocytes (MPHs) were isolated and cultured in RPMI-1640 medium with 10% fetal bovine serum, 0.1 mg/ml streptomycin, and 100 units/ml penicillin as described above. (Liang et al, 2021b;Yang et al, 2020). After 24 h of incubation, the hepatocytes were treated with 10 mM APAP for an additional 24 h.…”

Section: Cell Protocolsmentioning

confidence: 99%

“…A 96-well plate was used as a culture tool for MPHs, and the concentration of 5 × 104/ml was repeated every five wells. After 6 h of cell incubation, a new culture base was formed, that is, configure various concentrations of ginsenoside Rc were configured, and the culture time was 24 h. The medium was removed and the culture was transferred to 100 μl of new medium containing CCK-8 (1640 medium and CCK-8 solution in a ratio of 10:1) for incubation, and then the OD value was measured at 450 nm (Liang et al, 2021b;Yang et al, 2020).…”

Section: Cck-8 Assaymentioning

confidence: 99%

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Ginsenoside Rc, as an FXR activator, alleviates acetaminophen-induced hepatotoxicity via relieving inflammation and oxidative stress

Zhong

Chen²,

Pan³

et al. 2022

Front. Pharmacol.

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Acetaminophen (APAP) intake leads to excessive NAPQI deposition, stimulating inflammatory and oxidative stress and causing fatal liver injury. However, the detailed molecular mechanism involved is unknown, and effective therapeutic approaches remain insufficient. In this study, we discovered that treatment with ginsenoside Rc can prevent the inflammatory response caused by APAP and oxidative stress in mouse primary hepatocytes (MPHs), along with the corresponding changes in related genes. Additionally, Ginsenoside Rc effectively alleviates APAP-induced cellular apoptosis and NAPQI accumulation in MPHs. In vivo, Ginsenoside Rc administration remarkably attenuates APAP-induced hepatotoxicity, repairing liver damage and improving survival. Moreover, Ginsenoside Rc treatment modulates genes involved in APAP metabolism, leading to a decrease in NAPQI and resulting in the alleviation of fatal oxidative stress and inflammatory response after APAP exposure, along with the expression of their related indicators. Furthermore, our RNA-seq and molecular docking analysis implies that FXR expression and FXR transcriptional activity are stimulated by Ginsenoside Rc treatment. Notably, due to the lack of FXR in mice and MPHs, ginsenoside Rc can no longer play its original protective role against hepatotoxicity and cell damage caused by APAP, and it is difficult to improve the corresponding survival rate and prevent hepatic apoptosis, NAPQI generation, fatal oxidative stress, and the inflammatory response induced by APAP and the expression of related genes. In summary, our results indicate that Ginsenoside Rc could act as an effective FXR activator and effectively regulate FXR-induced antioxidant stress and eliminate inflammation while also having an anti-apoptotic function.

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“…Hence, the SIRT6 knockout mice experienced disruption in fatty acid metabolism [111]. A novel SIRT6 activator, namely ginsenoside Rc, has been identified and ameliorated high fat diet-induced mitochondrial stress, oxidative stress, and inflammatory damage in mice [112].…”

Section: Fatty Acidsmentioning

confidence: 99%

A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer’s Disease, Aging, Cancer, Inflammation, and Diabetes

Akter

Afrose

Rahman³

et al. 2021

IJMS

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Natural products have long been used as drugs to treat a wide array of human diseases. The lead compounds discovered from natural sources are used as novel templates for developing more potent and safer drugs. Natural products produce biological activity by binding with biological macromolecules, since natural products complement the protein-binding sites and natural product–protein interactions are already optimized in nature. Sirtuin 6 (SIRT6) is an NAD+ dependent histone deacetylase enzyme and a unique Sirtuin family member. It plays a crucial role in different molecular pathways linked to DNA repair, tumorigenesis, glycolysis, gluconeogenesis, neurodegeneration, cardiac hypertrophic responses, etc. Thus, it has emerged as an exciting target of several diseases such as cancer, neurodegenerative diseases, aging, diabetes, metabolic disorder, and heart disease. Recent studies have shown that natural compounds can act as modulators of SIRT6. In the current review, a list of natural products, their sources, and their mechanisms of SIRT6 activity modulation has been compiled. The potential application of these naturally occurring SIRT6 modulators in the amelioration of major human diseases such as Alzheimer’s disease, aging, diabetes, inflammation, and cancer has also been delineated. Natural products such as isoquercetin, luteolin, and cyanidin act as SIRT6 activators, whereas vitexin, catechin, scutellarin, fucoidan, etc. work as SIRT6 inhibitors. It is noteworthy to mention that quercetin acts as both SIRT6 activator and inhibitor depending on its concentration used. Although none of them were found as highly selective and potent modulators of SIRT6, they could serve as the starting point for developing selective and highly potent scaffolds for SIRT6.

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Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD

Cited by 12 publications

References 35 publications

Comparison between the Biological Active Compounds in Plants with Adaptogenic Properties (Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus and Panax ginseng)

Comparison between the Biological Active Compounds in Plants with Adaptogenic Properties (Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus and Panax ginseng)

Ginsenoside Rc, as an FXR activator, alleviates acetaminophen-induced hepatotoxicity via relieving inflammation and oxidative stress

A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer’s Disease, Aging, Cancer, Inflammation, and Diabetes

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