Table 1.
The effects and mechanisms of herbs and some natural products on fatty liver diseases.
| Herbs or Natural products | Model | Effects | Mechanisms | References |
|---|---|---|---|---|
| Rosmarinus officinalis Linn. | Orotic acid induced NAFLD model in rats | Reduced the levels of hepatic TG, TC, FFA and improved cell hypertrophy, vacuolation, and cell necrosis in the liver | ↑Phosphorylation of AMPK and ↓SREBP-1c cracking into the nucleus, following ↓FAS | (Wang et al., 2019) |
| Chinese Herbal Formula (CHF03, composition confidentiality) | HFD induced NAFLD model in mice; AML12 cells treated with palmitic acid in vitro | Reduced hepatic steatosis | ↓lipogenesis via down-regulating the expression of SREBF1, Fasn, and Acaca, ↓ lipid accumulation | (Cui et al., 2019) |
| Dachaihu Decoction (Bupleuri Radix, Scutellaria baicalensis Georgi, Pinellia ternate, Paeonia lactiflora, Citrus trifoliata, Rheum rhabarbarum, Zingiber officinale, Ziziphus jujuba Mill) | High-fat high-fructose diet induced NAFLD model in rats | Reduced the levels of elevated liver coefficient, serum TG, TC, LDL, AST, and ALT, blood glucose, plasma endotoxin, reduced TG, TNF-α, TGF-β, NF-κB, and TLR4 in liver tissues | ↓oxidative stress and inflammation | (Yang J.M. et al., 2019) |
| Leaves of Aloysia citrodora Paláu (syn. Lippia triphylla) | KK‐Ay mice | Improved hepatic lipid metabolism | via activating AMPK | (Zhang Y. et al., 2019) |
| Polygonatum kingianum | HFD induced NAFLD model in rats | ↓ALT, AST, TC, LDL in serum, and hepatic TC and TG | ↑mRNA expression of carnitine palmitoyl transferase-1 and ↓uncoupling protein-2 respectively, ↓caspase 9, caspase 3 and Bax expression in hepatocytes, ↑expression of Bcl-2 in hepatocytes and cytchrome c in mitochondria | (Yang X. X. et al., 2019) |
| Bangpungtongseong-san (Bofutsushosan) | HFD induced NAFLD model in C57BL/6J mice | Ameliorated dyslipidemia and hepatic steatosis, reduced body weight gain | Altered transcriptional changes in the liver, ↓mitochondrial oxidative phosphorylation-related genes in the liver, ↓hepatic fibrosis-related transcriptome. | (Choi et al., 2019) |
| Thymbra spicata L. extracts | endothelial cells in vitro | Ameliorated lipid accumulation, oxidative stress and inflammation, reduced hepatic steatosis | Preventing endothelium dysfunction | (Khalil et al., 2019) |
| Swertiamarin | fructose-fed mice | Lowed levels of serum glucose, TG, uric acid, ALT, AST, alleviation of hepatic ballooning degeneration and steatosis | ↓SREBP-1, FAS and acetyl-CoA carboxylase 1 (ACC1) in liver | (Yang Y. et al., 2019) |
| Si He Decoction (Zingiber officinale., Cyperus rotundus L., Lilium, Lindera aggregate, Salvia miltiorrhiza, Santalum album, Amomum villosum, Typha angustifolia L., Trogopterus xanthipes Milne) | HFD induced NAFLD model in rats | Improved liver pathological conditions | ↓expression level of TNF-alpha and IL-6, ↑visfatin, adiponectin, leptin and resistin, targeting adipokines | (Sun et al., 2019) |
| Modified Longdan Xiegan Tang (composed of Scutellaria baicalnsis Geprgi, Gardenia jasminoides, Adenophora capillaris, Akebia quinate, Plantago asiatica, Angelica sinensis, Rehmannia glutinosa, Alisma plantago-aquatica, Bupleurum gibraltaicum, and Glycyrrhiza uralensis) | Olanzapine-induced fatty liver in rats | ↓TG, cell vacuolar degeneration and Oil Red O-stained area | Regulating hepatic de novo lipogenesis and fatty acid β-oxidation-associated Gene expression mediated by SREBP-1c, PPAR-α and AMPK-α | (Ren et al., 2019) |
| LongShengZhi Capsule | apoE-Deficient Mice | Reduced atherosclerosis | ↓lipogenic and cholesterol synthetic genes while activating expression of triglyceride catabolism genes | (Ma et al., 2019) |
| Thymoquinone | Hypothyroidism with NAFLD rats | Reduced steatosis and lobular inflammation | ↑antioxidant CAT gene | (Ayuob et al., 2019) |
| Monomer Hairy Calycosin | NAFLD rats | Control the lipid peroxidation, and reduce the levels of serum TNF-alpha, IL-6, MDA and FFA, improve the steatosis and inflammation of liver tissue | ↓CYP2E1, ↓apoptosis of hepatocytes. | (Liu X. et al., 2019) |
| Hongqi Jiangzhi Formula (Astragali Radix, Red yeast rice, Nelumbinis Folium, Curcumae Longae Rhizoma, Lych Fructus, Magnoliae Officinals Cortex, Artemisiae Scopariae Herba) | HFD induced NAFLD model in rats | Reduced lipid accumulation | ↓the expression of NF-kappa B through TLR4 downstream signalling pathways | (Liang et al., 2019) |
| Jiang Zhi Granule (Herba Gynostemmatis, Folium Nelumbinis, Radix Salviae, Rhizoma Polygoni Cuspidati, and Herba Artemisiae Scopariae) | NAFLD in animal and PA-treated hepatocytes in vitro | Showed anti-steatotic effects | droplet degradation via autophagy though the mTOR signalling | (Zheng et al., 2018) |
| Curcumin | Steatotic hepatocyte model in vitro and NAFLD rat models | Improved lipid accumulation | Reversed the DNA methylation at the PPAR-alpha gene | (Li Y. Y. et al., 2018) |
| Samjunghwan Herbal Formula (Mori Fructus, Lycium chinensis Miller, Atractylodis Rhizoma) | HepG2 Cells and OLETF Rats | ↓Body weights, and visceral adipose tissue (VAT) weights, AST and ALT levels, | ↑HMGCOR, SREBP, and ACC, and ↓AMPK and LDLR gene expressions levels. | (Ansari et al., 2018) |
| Oxyresveratrol | NAFLD in mice | Ameliorated NAFLD | ↓LXR alpha agonists-mediated SREBP-1c induction and expression of the lipogenic genes, ↑mRNA of fatty acid beta-oxidation-related genes in hepatocytes; induced AMPK activation, helped inhibit SREBP-1c using compound C. | (Lee et al., 2018) |
| Sedum sarmentosum Bunge extract | Tilapia fatty liver model | Restored the changes to feed coefficient, immune capacity, and pathological characters | Altered expression of genes in the lipid metabolic process, metabolic process, and oxidation-reduction process. Our results suggest that disorders of the PPAR and p53 signaling pathways | (Huang et al., 2018) |
| Berberine and curcumin | HFD induced NAFLD model in rats | ↓LDL-c, ALT, AST, ALP, MDA, LSP | ↓SREBP-1c, pERK, TNF-alpha, and pJNK | (Feng et al., 2018) |
| Gegen Qinlian decoction (Pueraria lacei Craib, Scutellaria baicalensis Georgi, Coptis chinensis Franch., and Glycyrrhiza uralensis Fisch.) and resveratrol | Rat model of HFD-induced NAFLD | Restored lipid metabolism and inflammatory and histological abnormalities | Triggering the Sirt1 pathway | (Guo et al., 2017) |
| Gegenqinlian Decoction | Rat model of HFD-induced NAFLD and HepG2 | Suppress inflammation and regulate lipid | Improving PPAR-γ | (Wang Y. L. et al., 2015) |
| Lingguizhugan Decoction (Poria, Ramulus Cinnamomi, Rhizoma Atractylodis Macrocephalae, and Radix Glycyrrhizae) | Rat model of HFD-induced NAFLD | Attenuated phenotypic characteristics of NAFLD | By affecting insulin resistance and lipid metabolism related pathways (e.g., PI3K-Akt, AMPK); activating cholesterol secretio; increasing serum thyroid hormone levels, improving beta-oxidation (via modulation of TR beta 1 and CPT1A expression), metabolism and transport (through modulation of SREBP-1c, ACSL and ApoB100 expression) of fatty acid. | (Liu X. et al., 2017; Yang et al., 2017; Zhu et al., 2017) |
| Chinese herb extract, QSHX (Bupleurum falcatum, Salvia miltiorrhiza, rhubarb, lotus leaf, capillary Artemisia, rhizome polygoni cuspidate and gynostemma pentaphyllum) | High-fat and high-sugar diet-induced NAFLD in rat | ↓Body weight, liver index, and serum levels of AST, ALT and TG; and increased the serum level of adiponectin | Promoting the expression of HMW APN and DsbA-L, which may have been induced by inhibiting the activation and expression of FOXO1 in adipocytes | (Liu X. et al., 2017) |
| Qushi Huayu Decoction (Herba Artemisiae capillaris, Polygonum cuspidatum, Hypericum japonicum Thunb, Gardenia, and Rhizoma Curcumae Longae) | NAFLD rats | Attenuated phenotypic characteristics of NAFLD | ↑Hepatic anti-oxidative mechanism, ↓hepatic lipid synthesis, and promoted the regulatory T cell inducing microbiota in the gut. | (Feng et al., 2017) |
| Rhododendron oldhamii Maxim. leaf extract | HepG2 cells and HFD-fed mice | Improves fatty liver syndrome | Increasing lipid oxidation and decreasing the lipogenesis pathway | (Liu Y. L. et al., 2017) |
| Herbal Formula HT048 (Crataegus pinnatifida leaf and Citrus unshiu peel extracts.) | HFD-fed rats | Attenuates Diet-Induced Obesity | ↓Genes involved in lipogenesis, gluconeogenesis, and adipogenesis, ↑β–oxidation genes | (Lee Y. H. et al., 2016) |
| Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. | HFD-induced hyperlipidemic mice | ↓TC and TG in the livers | ↓CAT and sterol carrier protein2 (SCP2), ↑ the expression of lipid metabolism related genes-lipase member C (LIPC) and PPAR-γ | (Lu et al., 2016) |
| Daisaikoto (Bupleuri Radix, Scutellaria baicalensis Georgi, Pinellia ternate, Paeonia lactiflora, Citrus trifoliata, Rheum rhabarbarum, Zingiber officinale, Ziziphus jujuba Mill) | Diabetic fatty liver rats induced by a high-fat diet and streptozotocin (STZ) | Reversing dyslipidemia and insulin resistance | Regulating expressions of SIRT1 and NF-κB | (Qian et al., 2016) |
| Herb Formula KIOM2012H (Arctium lappa Linne, Glycyrrhiza uralensis Fischer, Magnolia officinalis Rehder & Wilson, Zingiber officinale Roscoe) | HFD-fed mice | Inhibited lipid accumulation | Gene expressions involved in lipogenesis and related regulators | (Park et al., 2015) |
| Hawthorn (Crataegus) leaf flavonoids | HFD-fed rats | Alleviated NAFLD | Enhancing the adiponectin/AMPK pathway | (Li et al., 2015) |
| Herbal SGR Formula (Semen Hoveniae extract, Ginkgo biloba extract, and Rosa roxburghii Tratt extract) | Acute ethanol-induced liver steatosis in mice | Inhibited acute ethanol-induced liver steatosis, ↓serum and hepatic TG level, and improved classic histopathological changes | ↓Protein expression of hepatic SREBP-1c and TNF-α and increased adiponectin, PPAR-α, and AMPK phosphorylation in the liver | (Qiu et al., 2015) |
| Nitraria retusa (Forssk.) Asch. ethanolic extract | db/db mice model | ↓Increases in body and fat mass weight, ↓TG and LDL-c levels | ↑Gene expression related to lipid homeostasis in liver, modulating the lipolysis-lipogenesis balance | (Zar Kalai et al., 2014) |
| 14-Deoxyandrographolide | Ethanol-induced hepatosteatosis in rats | Alleviate hepatosteatosis | ↑AMPK, ↓SREBP-1c, ACC, and FAS, ↑sirtuin I and depletion of malonyl-CoA, ↑fatty acid oxidation | (Mandal et al., 2014) |
| Total Alkaloids in Rubus aleaefolius Poir | Modified HFD-fed rats | ↓TG, TC, and LDL-C levels and ↑HDL-C level | ↓Expression of FAS, ACC, ↑carnitine palmitoyltransferase (CPT) | (Li Y. et al., 2014) |
| Lycium barbarum L. polysaccharide | HFD-fed mice | Improved body compositions and lipid metabolic profiles, ↓hepatic intracellular TG | ↓SREBP-1c, ↑AMPK activation | (Li W. et al., 2014) |
| Salacia oblonga Wall. ex Wight & Arn. root | fructose-induced fatty liver in rats | Diminished fructose-induced fatty liver | ↓SREBP-1/1c mRNA and nuclear protein | (Liu L. et al., 2013) |
| Chunggan extract (Artemisia capillaries Thunberg, Trionyx sinensis Wiegmann, Raphanus sativus Linne, tractylodes macrocephala Koidz, Poria cocos Wolf, Alisma orientalis (Sam.) Juzepczuk, Atractylodes chinensis Koidzumi, Salvia miltiorrhiza Bunge, Polyporus umbellatus Fries, Poncirus trifoliate Rafin, Amomum villosum Lour, Glycyrrhiza uralensis Fisch., Aucklandia lappa Decne.) | methionine- and choline-deficient (MCD) diet | ↓TG, AST, ALT, ALP, and total bilirubin | Anti-oxidative stress | (Park et al., 2013) |
| Celastrus orbiculatus Thunb. | HFD-induced NAFLD in guinea pigs | ↓TC, free cholesterol (FC), cholesterol ester (CE) and TG in liver | ↑mRNA abundance of cholesterol 7 alpha-hydroxylase A1 (CYP7A1) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). | (Zhang et al., 2013) |
| Oxymatrine | NAFLD rats fed with high fructose diet | ↓Body weight gain, liver weight, liver index, dyslipidemia, and TG, ↓liver lipid accumulation. | ↓ SREBF1 and ↑PPAR-α | (Shi et al., 2013) |
| Rhein | HFD-induced obese mice | ↓Body weight, particularly body fat content, improved insulin resistance, and ↓circulating cholesterol levels, ↓TG, reversed hepatic steatosis, and normalized ALT | Mediated negative energy balance, metabolic regulatory pathways, and immunomodulatory activities involved in hepatic steatosis | (Sheng et al., 2011) |
| Osthol | Alcohol-induced fatty liver in mice | Inhibit alcohol-induced fatty liver | Anti-oxidation and suppression of TNF-α production | (Sun et al., 2009) |
↑ means increase and up-regulate and ↓ means decrease and down-regulate.