As the hub of systemic metabolism, the liver is prone to lipid metabolism disorders in hyperlipidemic and obese states, which directly promote the progression of NAFLD (Mato et al., 2019). Studies have shown that ginseng improves lipid homeostasis through the following mechanisms (Figure 2). Significantly reduces triglyceride (TG), total cholesterol (TC), free fatty acids (FFAs), lipid droplets (LDs), low density lipoprotein (LDL), low density lipoprotein cholesterol (LDL-C), LDL-C to high density lipoprotein cholesterol (HDL-C) ratio (LDL-C/HDL-C) in the liver and serum (Guo et al., 2023; Liang et al., 2021; Meng et al., 2023; Xu et al., 2018). In addition evidence of pathologic improvement showed that model animals raised with ginseng had lighter liver weights and body weights, more aligned hepatocytes, fewer vacuoles, and less steatosis (Meng et al., 2023). Analysis of FFAs using molecular networking showed that RG fed thoroughbred riding horses reduced pro-inflammatory FFAs (C12:0, dodecanoic acid; C14:0, myristric acid; C18:1, oleic acid; C18:2, linoleic acid) (Kwak et al., 2024). The above studies demonstrated some intuitive manifestations of the hypolipidemic properties of ginseng and its functional components.

Aged ginseng reduced appetite and decreased the body’s lipid intake at the source (Chung et al., 2016). Ginseng water-soluble dietary fiber (GWDF) upregulated glucagon-like peptide 1, peptide YY, cholecystokinin and serum gastric hunger hormone levels. It increased satiety, promoted digestion, delayed gastric emptying, decreased food intake and affected glucolipid metabolism in male SD rats (Hua et al., 2021). Aged ginseng and ginsenosides acted as modulators and significantly reversed abnormally high leptin levels. Restores leptin’s appetite-suppressing function by reducing leptin resistance (Chung et al., 2016; Liang et al., 2021).

HDL-C and apolipoprotein A4 (apoA4) have a role in transporting cholesterol from peripheral tissues to the liver for removal. Ginseng and its functional components promotes reverse cholesterol transport into the liver and accelerates cholesterol breakdown and excretion by up-regulating HDL-C and apoA4 (Kim et al., 2018; Park et al., 2018; Xuan et al., 2015). Microsomal triglyceride transfer protein is a lipid transfer protein necessary for the synthesis of very low density lipoprotein in hepatocytes, and its synthesis is upregulated in response to increased TG. Fermented ginseng (FG) and non-fermented ginseng reduces very low density lipoprotein secretion and alleviates hepatic TG accumulation by inhibiting MTP expression (Park et al., 2018). Monascus ruber fermented ginseng (MFG) inhibits FXR receptor, increases cholesterol 7α-hydroxylase (CYP7A1) expression, and promotes bile acid synthesis. Rb₁ directly promotes CYP7A1 activity, accelerating the conversion of cholesterol to bile acids and promoting cholesterol excretion (Li et al., 2020; Zhao et al., 2021).

On the one hand, hepatic nascent fatty acid (FA) are esterified to TG and will be stored as LDs in hepatocytes or secreted in other forms into the bloodstream, and on the other hand, it is directly metabolised by the β-oxidation pathway (Badmus et al., 2022). Therefore, an increase in nutrients delivered to the liver and FA synthesis, a decrease in FA oxidation and lipid output will result in an excessive accumulation of fat in the liver (Badmus et al., 2022). Ginseng and its functional components are a potent modulator of lipid metabolism (Figure 2).

Ginseng and its functional components plays a key role in reducing FA synthesis by directly inhibiting the expression of lipid synthesis genes such as SREBP-1 gene (isoforms SREBP-1a and SREBP-1c), fatty acid synthase (FAS) gene, stearoyl-coenzyme A desaturase-1 (SCD-1) gene and acetyl-coenzyme A carboxylase (ACC, ACC-1 and ACC-2 subtypes) 1 (Choi N. et al., 2019; Park et al., 2018; Wang et al., 2021). AMPK is a key sensor of cellular energy status. Rg₁ significantly increased AMPK phosphorylation and restored hepatic lipid homeostasis (Xiao et al., 2019). CK and Rg₃ inhibited downstream ACC-1 expression and reduced hepatic lipogenesis by activating AMPK phosphorylation (Kim et al., 2013; Lee et al., 2012). In addition, Rb₁ and ginseng diol saponin (GDS) significantly inhibited SREBP-1c activity upon activation of AMPK, reducing the activation of downstream targets FAS and SCD-1 (Mi et al., 2024; Shen et al., 2013). GSO, Rh₁ and Rg₂ block de novo lipogenesis by directly blocking carbohydrate responsive element-binding protein (ChREBP) nuclear translocation and the synthesis of ACC, SCD-1, and FAS. In addition, wild ginseng cambial meristematic cells (WGCM) inhibits DNL by directly reducing the synthesis of the key enzymes ACC, SCD-1, and FAS (Kim et al., 2018; Lee et al., 2016; Wang et al., 2021). Lipocalin is an insulin-sensitive adipocyte-specific cytokine that inhibits de novo lipogenesis. Aged ginseng inhibited de novo lipogenesis and delayed NAFLD progression by upregulating lipocalin expression (Chung et al., 2016).

RG reduced the expression of hepatic lipid metabolism-related factors liver X receptors (LXR) α and LXRβ. This process regulates intracellular cholesterol and lipid homeostasis and reduces pro-inflammatory factor production. (Jeong et al., 2018). 20(S)-PPT and GF₂ regulated the LXRα by inhibiting the transcription of the adipogenic genes SREBP-1c and FAS to reduce adipogenesis (Kim K. et al., 2024; Oh et al., 2015). Rb₁, MFG and Rg₃ blocked the SREBP-2/3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) pathway, while Rg₃ directly inhibited the expression of the downstream gene HMGCR (Lee et al., 2012; Li et al., 2020; Zhao et al., 2021). The above processes contribute to the inactivation of key pathways of cholesterol synthesis and reduce cholesterol biosynthesis. GDS targets fat-specific protein, a key protein in lipid droplet synthesis, to reduce its expression and significantly decrease the area of hepatocyte LDs, thereby reducing fat storage (Mi et al., 2024).

During FA oxidation, ginseng and its functional components maintains hepatic lipid homeostasis by stimulating the transcription of PPAR α and PPAR-γ response genes (Liang et al., 2021; Xuan et al., 2015). In addition ginseng and its functional components also synergizes with carnitine palmitoyl transferase (CPT) to accomplish FA oxidation. Examples include the transport and oxidation of acyl-CoA from the cytoplasm to the mitochondrial matrix, and FA oxidation processes involving acyl-CoA synthetase and ester oxygenase (Choi S. Y. et al., 2019; Kim et al., 2013; Mi et al., 2024). One study further found that GSO, Rc and Rd promote PPAR-α-mediated FA oxidation by increasing the expression of sirtuins (SIRT) 1 or SIRT6 proteins (Cui et al., 2023; Kim et al., 2018; Yang Z. et al., 2023). GSO and Rb₁ synergistically regulated PPAR-α-mediated FAO by activating peroxisome proliferators-activated receptor γ co-activator α (PGC-1α) (Kim et al., 2018; Shen et al., 2013). STAT5 promotes the binding of PPAR-γ to PPAR response elements and regulates downstream genes related to adipogenesis, lipid metabolism and glucose homeostasis. However, Rg₃ blocked STAT5 and PPAR-γ associated target adipogenesis and inhibited the adipogenic process in 3T3-L1 cells (Lee et al., 2017). Fermentation of red ginseng with C. militaris (FRG) reduced adipogenesis and lipid uptake by decreasing the expression of acyl-CoA synthetase long-chain and FA translocase (Choi S. Y. et al., 2019). Bioinformatic experiments and cellular experiments validated that Rf downregulated the methylation level of the DNMT3L gene and reversed the aberrant expression of the adipogenesis-related gene ANXA2 (Chen et al., 2022).

The core pathologic features of NASH and NAFLD encompass lipotoxicity-mediated hepatocellular injury and a chronic inflammatory cascade response. Controlling inflammation is one of the fundamental strategies for treatment (Wiering and Tacke, 2023). In this study, we systematically revealed the molecular mechanisms by which ginseng and its functional components modulate inflammatory signaling networks through multiple targets (Figure 3).

Lipotoxic substances induce hepatocyte damage, leading to abnormal release of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and lactate dehydrogenase as a diagnostic indicator of the early stages of the disease. Ginseng and its functional components reduces serum levels of damage markers and this effect is directly related to hepatocyte protection (Kim M. Y. et al., 2024; Xuan et al., 2015). In addition, ginseng and its functional components inhibited the production of various inflammatory factors, such as tumor necrosis factor α (TNF-α), interleukin (IL) 6, IL-1β, IL-18, IL-10, IgA, arginase 1, and C-C motif chemokine ligand (CCL) 2. It also reduced the recruitment and activation of immune cells and improved the inflammatory microenvironment (Kim M. Y. et al., 2024; Wang et al., 2021; Zhao et al., 2021).

Lipid overaccumulation leads to aberrant activation of mammalian target of rapamycin C1, causing macrophage 1 polarisation and elevating levels of CCL2, CCL5, IL-1β, IL-6, inducible nitric oxide sythase and TNF-α. FRG reduced the levels of CCL2, CCL5, IL-1β, IL-6, inducible nitric oxide sythase and TNF-α by inhibiting aberrant activation of mTORC1, which reverses macrophage 1 type to macrophage 2 type polarization. It also increases the levels of the macrophage 2 markers CD163 and IL-10, achieving an anti-inflammatory-promoting repair dynamic balance (Choi S. Y. et al., 2019). RG significantly increased natural killer cells counts in otsuka long-evans tokushima fatty rats, improving their immunity (Hong et al., 2013). In addition, RG reduced the phosphorylation of p38 mitogen-activated protein kinase and decreased the secretion of the inflammatory cytokine IL-1β (Kim et al., 2019). RG attenuates downstream hepatic injury and inflammation by inhibiting the FA binding protein4/c-Jun N-terminal kinase (JNK) pathway and reduces the production of ALT, AST, TNF-α, IL-1β, IL-12a, IL-12b, and IL-17a (Jeong et al., 2018).

In the LXRs regulatory module, GF₂ enhances the binding capacity of co-inhibitory factors to LXRα. Reduction of LXRα transcriptional activity improves intracellular lipid homeostasis and correspondingly reduces the number of immune cells and pro-inflammatory factors infiltrating the liver (Kim K. et al., 2024). The body assembles and activates nod-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome after sensing lipotoxic danger signals, which in turn induces the maturation of cysteine-containing aspartate-specific protease (Caspase) 1 and catalyses the production of pro-inflammatory cytokines IL-18 and IL-1β (Mridha et al., 2017; Yu et al., 2022). Ginseng and its functional components modulated NLRP3 inflammasome-mediated inflammation by blocking the activation of NLRP3 inflammasome and Caspase-1 (Kim M. Y. et al., 2024; Xu et al., 2018). Ginsenosides, Rg₁ and Rd reduced the expression of pro-inflammatory factors by directly inhibiting the activation of NF-κB, which is an important nuclear transcriptional regulator of pro-inflammatory genes (Cui et al., 2023; Liang et al., 2021; Xiao et al., 2019; Xu et al., 2018). GDS inhibits nuclear translocation of NF-κB and downregulates transcription of key inflammatory factor genes through activation of AMPK/PPAR-γ (Mi et al., 2024). Another study found that Rc and Rd regulate the production of inflammatory factors TNF-α, IL-6 and IL-1β by increasing SIRT6 protein expression (Cui et al., 2023; Yang Z. et al., 2023). Rg₁ specifically upregulates activating transcription factor (ATF) 3/acyl-coenzyme A oxidase (ACOX) 2 to alleviate NAFLD, and how Rg₁ regulates NAFLD through these two genes is unknown (Gu et al., 2021). Leukocyte expression of active the MMP9 gene enhanced its ability to infiltrate during the inflammatory process, and Rf regulation of NAFLD inflammation may be related to the MMP9 gene (Chen et al., 2022).

The occurrence of OS in the body indicates that the antioxidant system scavenges ROS at a slower rate than the rate of ROS production, which is an important factor in liver injury and NAFLD progression (Kumar et al., 2021). The tricarboxylic acid cycle transfers the generated NADH and FADH2 to oxygen via the electron transport chain, which generates large amounts of ATP and promotes ROS production (Chen et al., 2020). In addition non-electron transport chain sources of ROS, especially the compensatory acceleration of β-oxidation due to hepatic steatosis, appear to generate more ROS and cause OS (Clare et al., 2022). Ginseng improves OS by intervening in the following targets (Figure 3).

Rg₁, WGCM, Rh₁ and Rg₂ reduced abnormally elevated levels of ROS and malondialdehyde (MDA) and increased the vigour of antioxidants such as superoxide dismutase (SOD), catalase, glutamate dehydrogenase and glutathione (Hou et al., 2022; Lee et al., 2016; Wang et al., 2021). Further studies revealed that GDS supplementation activated AMPK and further activated the nuclear factor-erythroid 2 related factor 2/heme oxygenase 1 signalling pathway, elevating the level of SOD and enhancing the antioxidant capacity of hepatocytes (Mi et al., 2024). Rg₁ elevated nuclear FOXO1 protein levels and subsequently targeted to increase SOD and CAT expression and decrease MDA levels (Qi et al., 2020).

Rd repairs abnormal mitochondrial morphology, ameliorates REDOX disorder, and reduces ROS generation due to electron leakage from ETC (Cui et al., 2023). WGCM elevated the levels of mitochondrial biogenesis related factors, such as PGC-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A, which inhibited mitochondrial OS and promoted mitochondrial biogenesis (Lee et al., 2016). SIRT6 protein attenuated the mitochondrial stress and ameliorated redox deficits in the organism, and ginseng Rc and Rd improved OS status in normal mice better than in SIRT6-deficient mice (Cui et al., 2023; Yang Z. et al., 2023). Rg₁ attenuated OS injury-induced cellular senescence and mitigated hepatic OS by improving biological processes such as cellular matrix composition, membrane receptors, and cellular responses to the outside (Hou et al., 2022). GBCK25 inhibited cytochrome P450 2E1 expression and blocked the lipid peroxidation chain reaction, while down-regulating JNK phosphorylation and attenuating OS-associated cell injury (Choi N. et al., 2019).

The accumulation of large amounts of FFAs in fatty liver promotes the production of lipotoxic substances causing ER structural disruption and decrease in number, and ERS occurs in hepatocytes in order to restore homeostasis of the internal environment (Lebeaupin et al., 2018; Lei et al., 2023). During this process, the ER will trigger the unfolded protein response (UPR) to restore the protein homeostasis of the ER, and if the ERS remains at a high level for a long period of time, the terminal UPR programme will trigger cell death (Senft and Ronai, 2015; Zhang et al., 2022). Lipotoxicity induced ERS-OS interaction network constitutes the core pathology axis. We outline the evidence that ginseng intervention in NAFLD is associated with ERS and discuss possible points of intervention (Figure 3).

ERS and OS are both adaptive responses to NAFLD in the early stages of the body, and become damaging factors when they exceed a certain limit, and they form a two-way positive feedback between them. Rg₁ was found to achieve synergistic hepatoprotection through dual regulation of ERS-OS cross-talk (Xu et al., 2018). Furthermore, Rg₁ significantly reduced OS-induced ERS marker levels, suah as CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), glucose-regulated protein78 (GRP78) and Caspase-12. It also attenuated NLRP3 inflammasome-mediated associated inflammation. Binding of the ER chaperone protein GRP78 to unfolded or misfolded proteins will activate ERS sensors, including inositol-requiring enzyme 1α, PRKR-like ER kinase, and ATF6, which are the initiators of the major signalling cascade of the UPR and the survival mechanism of the ERS (Xu et al., 2018). UPR promotes restoration of ER homeostasis, but failure of restoration induces increased synthesis of pro-apoptotic proteins and triggers cell death. Mc₁ reduced the expression levels of GRP78 and CHOP proteins, which inhibited ERS and UPR activation, and Mc₁ has not been found to ameliorate ERS through activation of the AMPK signalling pathway (Roh et al., 2020).

Hepatocyte death (apoptosis, pyroptosis, impaired autophagy) and fibrosis are key components of NAFLD progression to NASH (Shojaie et al., 2020). Hepatic injury factors such as fat deposition, inflammation, OS and ERS are involved in the pathological changes and accelerate the process of hepatocyte death and fibrosis. Ginseng significantly ameliorates a variety of cell death and aging-related pathological processes through the following multi-targeted mechanisms (Figure 4).

Upon stimulation of the organism from internal or external factors, pro-Caspase-3, the common downstream effector part of multiple apoptotic pathways, will be cleaved to the activator Caspase-3 and activate the cascade reaction of apoptosis (McComb et al., 2019). FRG, Rg₁ and Mc₁ significantly downregulated the expression levels of pro-apoptotic proteins Bcl-2-associated X (Bax) and Caspase-3, while up-regulating the expression levels of anti-apoptotic proteins B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL) to reduce hepatocyte apoptosis (Choi S. Y. et al., 2019; Li G. et al., 2022; Roh et al., 2020). Supplementation of Mc₁ lowered reduced CHOP and Bax activity. This process avoids prolonged high levels of ERS, which activates apoptosis induced by the terminal UPR program (Roh et al., 2020). Rg₁ reduces sphingosine-1-phosphate cleavage by inhibiting sphingosine-1-phosphate lyase 1. Enhanced sphingosine-1-phosphate/p-AKT survival signaling in the liver and promoted hepatocyte survival (Li G. et al., 2022). GBCK25 reduced FFAs-induced steatotic apoptosis in hepatocytes by inhibiting the activation of the JNK pathway (Choi N. et al., 2019). Activation of the NLRP3 inflammasome promotes pro-Caspase-1 cleavage and activation. Activated Caspase-1 promotes both the maturation and release of IL-1β and IL-18, as well as being involved in the process of cellular pyroptosis. Panaxydol inhibited NLRP3 inflammatory vesicle activation (ASC oligomerization) and synthesis of lactate dehydrogenase (LDH), a marker of cellular cell death. The reduction of Caspase-1 activity and LDH content reversed the Caspase-1-dependent pathway of cellular cell death (Kim M. Y. et al., 2024). Lipophagy is the interaction of LC3 protein on the autophagosome membrane with envelope proteins on LDs to encapsulate LDs in autophagosomes for degradation. Abnormal lipophagy or degradation of autophagosomes (generation of p62 protein) will cause cell death. Rb₁ and Rb₂ increased autophagic vesicle survival by increasing LC3 protein and decreasing p62 protein content. Rb₂ accelerated LD degradation by activating AMPK/SIRT1, upregulating LC3 protein and decreasing p62 protein (Huang et al., 2017; Meng et al., 2023). Rb₁ enhances the transcription of transcription factor EB nuclear translocation and its downstream lysosome-associated genes by inhibiting miR-128. This resulted in increased lysosomal degradation of autophagic lipids and alleviated palmitic acid-induced autophagic flux block (Meng et al., 2023).

Additionally it has been proposed that although ginseng lowered Bax levels, it also elevated Bcl-2 during modeling of the disease. Because the Bax/Bcl-2 changes during treatment were slight, it is possible that the improvement in the course of Rg₁ treatment for NAFLD was not cell death (Qi et al., 2020). In addition, impaired autophagy and free radical attack on mitochondria both contribute to cellular senescence. Rg₁-treated mitochondria showed reduced swelling and vacuolization, more intact cytoplasmic matrix, and restoration of cellular autophagy. The expression of the key signals tumor protein P53, senescence-associated β-galactosidase, the nuclear damage marker phospho-histone H2A.X, and cyclin-dependent kinase inhibitor (CDKN) 1A/CDKN2A was decreased in the early stage of senescence (Hou et al., 2022; Qi et al., 2020). Validated by bioinformatic experiments and cellular experiments, Rf was found to inhibit aging-related phenotypes by affecting the BAZ1A gene (Chen et al., 2022). Hepatocyte injury or necrosis activates the body to repair damaged cells, and it causes hepatic fibroproliferation when repair persists. Panaxydol, Rg₁, Rh₁ and Rg₂ was found to be effective in reducing the size of fibrotic areas, the number of inflammatory foci in the periportal and pericentric areas. Decreased the levels of liver fibrosis markers collagen (COL) 1, COL3, lysyl oxidas, tissue inhibitor of metalloproteinase 1 (TIMP1), α-smooth muscle actin, transforming growth factor β and hypoxia-inducible factor 1α (Kim M. Y. et al., 2024; Wang et al., 2021; Xu et al., 2018). In addition, Rk₃ reduced the expression of hypoxia-inducible factor 1α, COL1 and hepatic TIMP1 through activation of the PI3K/AKT signaling pathway, and attenuated COL deposition and fibrosis in hepatocytes (Guo et al., 2023). FRG, Rg₁, Rh₁ and Rg₂ inhibit high CCL2 expression. Reduced hepatic fibrosis and even cirrhosis formation by blocking CCL2 hepatic stellate cell activation (Choi S. Y. et al., 2019; Qi et al., 2020; Wang et al., 2021). Rg₁ promotes the expression of downstream negative regulators of hepatic fibrosis and increases extracellular matrix degradation by regulating the epidermal growth factor receptor/STAT1 axis (Hou et al., 2022).

As a hub of systemic metabolic regulation, hepatic lipotoxicity injury (inflammation/OS/ERS) triggers systemic IR through multiple cascade reactions, which is manifested by (1) decreased glucose disposal in non-hepatic tissues (including adipose tissues and muscles). (2) dysregulation of lipolysis leading to aberrant lipid release. (3) impaired hepatic glycogen storage, which causes metabolic abnormalities and exacerbates systemic IR (Sakurai et al., 2021). In this study, we systematically elucidated the action network of ginseng in ameliorating disorders of glucolipid metabolism through multi-target synergism (Figure 5).

Ginseng and its functional components reduced fasting blood glucose (FBG) levels, fasting insulin and homeostatic model assessment for insulin resistance index (HOMA-IR) in animals of NAFLD disease model and improved glucose homeostasis, glucose tolerance and insulin tolerance in the organism (Cui et al., 2023; Kim K. et al., 2024; Li et al., 2022d). JNK elevates levels of TNF-α and IL-6 during obesity-driven macrophage activation, subsequently triggering IR. Mc₁ inhibited the above process. In addition Mc₁ restored insulin receptor substrate 1 tyrosine phosphorylation levels and increased insulin sensitivity in the process of driving down JNK phosphorylation levels (Roh et al., 2020). In regulating glucose metabolic activities, aged ginseng activates glucose uptake and utilization by decreasing insulin, FBG levels and increasing glucokinase expression. It also inhibits the synthesis of pyruvate, FAs and cholesterol by inhibiting malic enzyme and glucose-6-phosphate dehydrogenase enzyme activities (Chung et al., 2016). In addition both Rc and aged ginseng reduce the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. This process reduces gluconeogenesis, decreases the body’s blood glucose level and improves glucose intolerance (Chung et al., 2016; Yang Z. et al., 2023). Rb₁ improvement of IR and glucose tolerance is partially dependent on lipocalin. Specifically, it improves systemic glucose metabolism, insulin homeostasis, FA oxidation, and hepatic insulin sensitivity after activation of AMPK using lipocalin (Li et al., 2022d).

The microbial community in the human gastrointestinal tract has been shown to be involved in a variety of physiopathological processes in the gut, and a unique gut microbiome signature exists for NAFLD (Aron-Wisnewsky et al., 2020; Vallianou et al., 2021). The intestinal microecological disorder of NAFLD is characterized by the imbalance of “flora-intestinal-hepatic axis”, and the present study systematically reveals that ginseng can improve the metabolic abnormalities by regulating the homeostasis of intestinal flora in a multi-dimensional way (Figure 5) (Hsu and Schnabl, 2023).

High-fat diets increases intestinal permeability and exposes the liver to endotoxins, and a disturbed gut microbiota also disrupts the intestinal vascular barrier, enhancing intestinal permeability and bacterial lipopolysaccharide leakage into the circulation (Kobayashi et al., 2022; Mouries et al., 2019). Ginsenosides treatment increased the tight junction proteins ZO-1 and occludin levels in a dose-dependent manner, attenuating microecological dysregulation-mediated intestinal leakage and metabolic endotoxaemia (Liang et al., 2021). Qualitative and quantitative abnormalities of the gut microbiota are involved in the pathogenesis of NAFLD and NASH and promote hepatic lipogenesis and fibrosis (Hu et al., 2020; Kolodziejczyk et al., 2019). The study show that GWDF significantly increased the abundances of biomarkers such as L. salivarius, L. hamsteri (SDFL200), B. pseudolongum, L. helveticus, and R. bromii (SDFH800), and show a significant prebiotic effect. MFG and Rk₃ selectively promoted colonisation by the probiotic bacteria Akkermansiaceae and Prevotella_9 and reduce the relative abundance of Muribaculaceae (Guo et al., 2023; Hua et al., 2021; Zhao et al., 2021). GWDF, ginsenosides, MFG and Rk₃ had the effect of decreasing the Firmicutes and Bacteroidetes ratio, increasing the concentration of fecal short-chain FA, the abundance and diversity of intestinal flora species, and ameliorating the imbalance of gut microbiota induced by high-fat diets (Guo et al., 2023; Hua et al., 2021; Liang et al., 2021; Zhao et al., 2021). The above results demonstrated that ginseng has a three-in-one action model of “flora reconstruction, barrier repair and metabolic regulation”.