Table 3.
Beneficial effects of polyphenols on metabolic disorders not associated with a high-fat diet (HFD) or dextran sulfate sodium (DSS) in relation to the gut microbiota in murine models.
| Reference, Publication Year, Animal Model of the Disorder, Polyphenol(s), and Dosage | Major Physiological Issues Improved | Mode of Action | |
|---|---|---|---|
| Antioxidative and Anti-Inflammatory Action | Gut Microbiota Modulation | ||
| [66] 2019 Mice with fructose-induced NAFLD, loquat fruit extract rich in polyphenols including chlorogenic acid, cryptochlorogenic acid, and oleanolic acid, p.o. at 25 and 50 mg/kg/day for 8 weeks |
Prevented fructose-induced NAFLD with mitigation of abnormal body weight and improved lipid metabolism | Mitigated oxidative stress and inflammation; reduced the endotoxin content and improved fructose-induced breakage of the intestinal barrier | Maintained normal Firmicutes/Bacteroidetes ratio |
| [67] 2020 Mice with western diet-induced NAFLD, vine tea polyphenol extracted from Ampelopsis grossedentata, p.o. in drinking water (0.5, 1, and 2%) for 12 weeks |
Decreased the serum levels of cholesterol and triglycerides, and reduced the accumulation of hepatic lipid droplets | Activated Nrf2-mediated expression of hemeoxygenase-1 and quinone oxidoreductase, and reduced hepatic TBARS levels to prevent hepatic oxidative stress | Increased the relative abundance of Akkermansia, and reduced the Firmicutes/Bacteroidetes ratio |
| [68] 2021 Mice with alcohol-induced liver inflammation, Zhenjiang aromatic vinegar (a traditional fermented food in China) rich in polyphenols including catechin, p-hydroxybenzoic acid, and vanillic acid, p.o. at 200 and 800 mg/kg/day for 30 days; EtOH was given p.o. after 32 h, every day |
Protected against alcohol-induced liver injury | Inhibited oxidative stress (reduced the levels of ROS, iNOS, MDA, 4-HNE, and 8-OHdG) and LPS-mediated inflammation | Modulated the composition of the gut microbiota and improved gut immunity and intestinal homeostasis; decreased the Firmicutes/Bacteroidetes ratio |
| [69] 2021 Mice with alcoholic liver disease, ellagic acid, p.o. at 50 and 100 mg/kg/day for 4 weeks to mice that received 15% alcohol |
Alleviated alcohol-induced liver injury | Alleviated hepatic antioxidant activities (GSH-Px, CAT, MDA, SOD, and GSH), and proinflammatory cytokines levels (IL-6, IL-1β, and TNF-α) | Improved the alcohol-induced gut microbiota dysbiosis; restored the relative abundance of microbiota, such as Firmicutes, Verrucomicrobia, Actinobacteria, Bacteroidetes, and Proteobacteria at the phylum level |
| [70] 2021 Rats with LPS-induced liver disease, Aronia melanocarpa polyphenols containing anthocyanins, flavonols, and hydroxycinnamates, p.o. at 50, 100, and 200 mg/kg/day with LPS (p.o. at 200 μg/kg/day) for 4 weeks |
Alleviated the degree of LPS-induced liver disease | Alleviated LPS-induced oxidative stress in the liver (reduced ROS and increased GSH levels). | Modulated the composition of the gut microbiota and improved the intestinal barrier function. At the phylum level, the enrichment of Verrucomicrobia microflora was alleviated and the abundance of Actinobacteria was decreased |
| [71] 2021 Mice with L-carnitine-induced liver injury, chlorogenic acid, p.o. at 200 and 400 mg/kg/day for 12 weeks with 3% L-carnitine in drinking water |
Prevented L-carnitine-induced liver injury | Inhibited free radical production and improved the antioxidant defense system; inhibited the inflammatory reaction (i.e., IL-1, IL-6, TNF-α, and TNF-β levels). |
Inhibited the L-carnitine-induced increase in the abundance of Firmicutes and Proteobacteria, and promoted Bacteroidetes at the phylum level |
| [72] 2021 Mice with obesity and hepatic steatosis induced by a western diet (WD), low in fiber but high in fats and sugars, p.o. as the WD supplemented with 1% grape polyphenols rich in B-type proanthocyanidins |
Higher lean mass and lower fat mass, body weight, and hepatic steatosis | Reduced the intestinal oxidative stress | Increased the abundance of Akkermansia muciniphila, a gut microbe reported to increase energy expenditure |
| [73] 2018 Diabetic db/db mice, polyphenol-rich extract of Dendrobium loddigesi, p.o. at 50 and 100 mg/kg/day for 8 weeks |
Decreased blood glucose, LDL-C, and body weight | Inhibited oxidative stress (reduced MDA and increased SOD, CAT, and GSH) in liver and kidney, attenuated serum inflammatory markers (IL-6 and TNF-α) | Decreased the Firmicutes/Bacteroidetes ratio |
| [74] 2019 Mice exposed to PM2.5 by instillation, hydroxytyrosol, p.o. at 50 mg/kg/day for 4 weeks |
Alleviated PM2.5-induced visceral adiposity and insulin resistance | Inhibited PM2.5-induced oxidative stress-mediated activation of NF-κB | Enrichment of gut microbiota, and reduction of pathogenic bacteria |
| [75] 2020 Rats fed an obesogenic cafeteria diet, hesperidin (a citrus polyphenol), p.o. at 40 and 100 mg/kg/day for 8 weeks |
Decreased the total cholesterol, LDL-C, and free fatty acids; ameliorated blood pressure and insulin sensitivity, and decreased the markers of arterial stiffness and inflammation | Metabolomics revealed an improvement in lower excretion of inflammation- and oxidative stress-related metabolites | Excretion of higher amounts of microbe-derived metabolites, which positively correlated with the Bacteroidaceae family |
| [76] 2021 Spontaneously hypertensive rats, Litchi chinensis seed extract, rich in polyphenols, including procyanidins, cinnamtannins, and rutin, p.o. at 30 and 60 mg/kg/day for 10 weeks |
Reduced blood pressure and alleviated hypertension-induced renal damage | Attenuated oxidative stress and inflammation | Increased the relative abundance of Lactobacillus and production of SCFAs in the intestine |
| [77] 2021 Mice with doxorubicin (DOX)-induced heart failure, purified polyphenols from Arctium lappa L. including arctiin, dicaffeoyl succinoylquinic acid, and luteolin, p.o. at 50 and 150 mg/kg/day for 29 days; on day 22, 24, and 26, DOX was i.p. injected |
Reduced heart failure syndrome and reduced serum activities of casein kinase and lactate dehydrogenase | Alleviated serum oxidative stress and reduced serum levels of inflammatory indices (TNF-α and NO). | Increased the abundance of Lactobacillaceae, Muribaculaceae, and Ruminococcaceae and decreased the abundance of Proteobacteria, Enterobacteria, and Escherichia_Shigella; enhanced the abundance of bacteria producing SCFAs |
| [78] 2021 Mice with potassium oxonate-induced hyperuricemia, Camellia japonica bee pollen extract containing polyphenols including kaempferol, quercetin, and gallic acid, p.o. at 2 and 4 g/kg/day for 3 weeks; starting on the 15th day, mice received potassium oxonate for the following 7 days |
Reduced serum uric acid by inhibiting XOD activity and improved renal function | Increased antioxidant biomarkers, SOD activity, and GSH content, and decreased MDA content in the liver | Increased the abundance of Lactobacillus that has an anti-hyperuricemia effect; decreased the Firmicutes/Bacteroidetes ratio |
p.o., per os; NAFLD, nonalcoholic fatty liver disease; PM2.5, particulate matter (≤2.5 μm); NF-κB, nuclear factor-κB; LDL-C, low-density lipoprotein-cholesterol; Nrf2, nuclear factor (erythroid-derived 2)-like 2; TBARS, thiobarbituric acid reactive substances; ROS, reactive oxygen species; iNOS, inducible nitric oxide synthase; MDA, malondialdehyde; 4-HNE, 4-hydroxy-2-nonenal; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; LPS, lipopolysaccharide; GSH, glutathione; TNF-α, tumor necrosis factor-α; NO, nitric oxide; SCFAs, short-chain fatty acids; XOD, xanthine oxidase; SOD, superoxide dismutase; IL-6, interleukin-6; IL-1β, interleukin-1β; TNF-β, tumor necrosis factor-β.