Ginsenoside CK ameliorates hepatic lipid accumulation via activating the LKB1/AMPK pathway in vitro and in vivo

Zhang, Jingjing; Ma, Xiaoxuan; Fan, Daidi

doi:10.1039/d1fo03026d

Cited by 33 publications

(23 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…First, in hepatocytes, Panax ginseng treatment suppressed NAFLD-induced cellular stress responses, such as oxidative stress [ 23 , 50 ], ER stress [ 35 , 47 ], and mitochondrial dysfunction [ 26 ]. In addition, the administration of Panax ginseng has beneficial effects on hepatic energy metabolism by activating AMP-activated protein kinase [ 22 , 29 , 56 , 58 ] but inhibiting the mammalian target of rapamycin complex 1 [ 37 ], resulting in the normalization of hepatic glucose [ 30 ] and lipid metabolism [ 32 , 33 , 34 , 41 ] in NAFLD. In the hepatic microenvironment, Panax ginseng reduced inflammatory responses by preventing activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), thereby suppressing gene and protein expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α [ 35 , 36 , 38 , 49 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…( A ) A graph of the risk in the bias of included studies. ( B ) A summary of the risk of bias in the included studies [ 7 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ].…”

Section: Figurementioning

confidence: 99%

“… The effect of Panax ginseng on the levels of liver injury markers in NAFLD-induced animals. Forest plots for comparison: ( A ) Alanine aminotransferase (ALT) levels [ 7 , 19 , 20 , 23 , 24 , 27 , 28 , 29 , 30 , 31 , 32 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 47 , 48 , 49 , 50 , 52 , 54 , 55 , 56 , 58 ]. ( B ) Aspartate aminotransferase (AST) levels [ 19 , 23 , 27 , 28 , 29 , 30 , 31 , 32 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 44 , 45 , 47 , 48 , 49 , 50 ...…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

The Efficacy of Panax ginseng for the Treatment of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

et al. 2023

View full text Add to dashboard Cite

Although tremendous research has reported the protective effects of natural compounds in nonalcoholic fatty liver disease (NAFLD), there is still no approved drug. This study aimed to examine the efficacy of Panax ginseng in NAFLD in preclinical studies. A total of 41 studies were identified by searching the PubMed, Web of Science, and Cochrane Library databases. The methodological quality was assessed by the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation. The standardized mean difference (SMD) with a 95% confidence interval was calculated, and the random effects model was used to examine overall efficacy or heterogeneity. The publication bias was analyzed by Egger’s test. The results showed that Panax ginseng treatment significantly reduced the systemic levels of alanine aminotransferase (SMD: −2.15 IU/L; p < 0.0001), aspartate aminotransferase (SMD: −2.86 IU/L; p < 0.0001), triglyceride (SMD: −2.86 mg/dL; p < 0.0001), total cholesterol (SMD: −1.69 mg/dL; p < 0.0001), low-density lipoprotein (SMD: −1.46 mg/dL; p < 0.0001), and fasting glucose (SMD: −1.45 mg/dL; p < 0.0001) while increasing high-density lipoprotein (SMD: 1.22 mg/dL; p = 0.0002) in NAFLD regardless of animal models or species. These findings may suggest that Panax ginseng is a promising therapeutic agent for NAFLD treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

The Efficacy of Panax ginseng for the Treatment of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The typical metabolization model of ginsenosides to compound K (CK) has been widely reported ( Figure 5 ), with enhanced anti-tumor, anti-inflammatory, and lipid-lowering effects ( Kim et al, 2013 ; Kim, 2018 ). At 50 μM, CK inhibits the growth of glioblastoma cells by upregulating caspase-3-, caspase-8-, caspase-9- and cAMP-dependent protein kinases ( Lee et al, 2017 ); At 20 μM, CK reduces hepatic lipid accumulation in human hepatocellular carcinoma cells by activating AMPK ( Zhang et al, 2022 ); CK attenuates macrophage inflammation and foam cell formation via autophagy induction and by modulating NF-κB, p38 and JNK/MAPK signaling ( Lu et al, 2020 ). The bioavailability of curcumin metabolites is dependent on the microbiota dependent ( Hassaninasab et al, 2011 ).…”

Section: Biotransformation Contributions To Mining the Active Substan...mentioning

confidence: 99%

Potential roles of gut microbes in biotransformation of natural products: An overview

et al. 2022

View full text Add to dashboard Cite

Natural products have been extensively applied in clinical practice, characterized by multi-component and multi-target, many pharmacodynamic substances, complex action mechanisms, and various physiological activities. For the oral administration of natural products, the gut microbiota and clinical efficacy are closely related, but this relationship remains unclear. Gut microbes play an important role in the transformation and utilization of natural products caused by the diversity of enzyme systems. Effective components such as flavonoids, alkaloids, lignans, and phenols cannot be metabolized directly through human digestive enzymes but can be transformed by enzymes produced by gut microorganisms and then utilized. Therefore, the focus is paid to the metabolism of natural products through the gut microbiota. In the present study, we systematically reviewed the studies about gut microbiota and their effect on the biotransformation of various components of natural products and highlighted the involved common bacteria, reaction types, pharmacological actions, and research methods. This study aims to provide theoretical support for the clinical application in the prevention and treatment of diseases and provide new ideas for studying natural products based on gut biotransformation.

show abstract

“…Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease with complex etiology and is considered one of the major causes of HCC development. Zhang et al ( Zhang J et al, 2022 ) observed that ginsenoside C-K reduced lipid deposition in HepG2 cells, attenuated lipid accumulation in serum and liver tissues, ameliorated liver inflammation and injury, regulated the expression of factors related to lipid synthesis and metabolism, activated the phosphorylation of LKB1 and AMPK, and intervened in the progression of NAFLD. In addition, Li et al ( Li et al, 2022a ) observed that GRg1 significantly downregulated the expression level of sphingosine-1-phosphate lyase 1 (SGPL1) and increased the expression levels of p-Akt and p-ERK1/2 in steatosis HHL 5 cells, exerting an anti-apoptotic effect on nonalcoholic fatty liver cells.…”

Section: Prevention Of Precancerous Lesions By the Active Ingredients...mentioning

confidence: 99%

Research progress of ginseng in the treatment of gastrointestinal cancers

Song²,

Shi³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Cancer has become one of the major causes of human death. Several anticancer drugs are available; howeve their use and efficacy are limited by the toxic side effects and drug resistance caused by their continuous application. Many natural products have antitumor effects with low toxicity and fewer adverse effects. Moreover, they play an important role in enhancing the cytotoxicity of chemotherapeutic agents, reducing toxic side effects, and reversing chemoresistance. Consequently, natural drugs are being applied as potential therapeutic options in the field of antitumor treatment. As natural medicinal plants, some components of ginseng have been shown to have excellent efficacy and a good safety profile for cancer treatment. The pharmacological activities and possible mechanisms of action of ginseng have been identified. Its broad range of pharmacological activities includes antitumor, antibacterial, anti-inflammatory, antioxidant, anti-stress, anti-fibrotic, central nervous system modulating, cardioprotective, and immune-enhancing effects. Numerous studies have also shown that throuth multiple pathways, ginseng and its active ingredients exert antitumor effects on gastrointestinal (GI) tract tumors, such as esophageal, gastric, colorectal, liver, and pancreatic cancers. Herein, we introduced the main components of ginseng, including ginsenosides, polysaccharides, and sterols, etc., and reviewed the mechanism of action and research progress of ginseng in the treatment of various GI tumors. Futhermore, the pathways of action of the main components of ginseng are discussed in depth to promote the clinical development and application of ginseng in the field of anti-GI tumors.

show abstract

Ginsenoside CK ameliorates hepatic lipid accumulation via activating the LKB1/AMPK pathway in vitro and in vivo

Abstract: Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease with complex etiology, which is considered as one of the main causes of hepatocellular carcinoma (HCC). The incidence of NAFLD...

Cited by 33 publications

References 44 publications

The Efficacy of Panax ginseng for the Treatment of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

The Efficacy of Panax ginseng for the Treatment of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

Potential roles of gut microbes in biotransformation of natural products: An overview

Research progress of ginseng in the treatment of gastrointestinal cancers

Contact Info

Product

Resources

About