Table 1.
Selected studies on animal models and their outcomes in terms of inflammation, DM2, and NAFLD.
| Study | Group | Inflammation, NAFLD, DM2 Induction | Intervention | Duration | Outcomes |
|---|---|---|---|---|---|
| Choi et al. [78] | 110 C57BL/6 mice | Steatosis, steatohepatitis, and liver fibrosis induced by choline-deficient, L-amino-acid-defined, high-fat diet with 0.1% methionine | Modafinil in doses 10, 50, or 100 mg/kg | 20 weeks | Used diet and TAA lead to KCa2.3, KCa3.1, upregulation, and downregulation of catalase in liver tissues Modafinil can reverse KCa2.3, KCa3.1, collagen, and α-smooth muscle actin upregulation and downregulation of catalase, and leads to a decline in the inflammatory response, collagen deposition, and α-smooth muscle actin expression |
| 75 C57BL/6 male mice | Hepatitis and fibrosis induced by TAA in dose 100 mg/kg intraperitoneally 3 times per week | Modafinil in doses 10, 50, or 100 mg/kg | 16 weeks | ||
| Zhao et al. [80] | 50 male Wistar rats | Liver fibrosis induced by carbon tetrachloride CCl4 subcutaneous injections and high-lipid/low-protein diet for 8 weeks | DHC administration in doses 0.5 or 1.0 g/kg | 8 weeks | TGF-β1 and the expression of Gremlin mRNA and protein were higher than in the control group Expression of BMP-7 mRNA and protein lower than in the control group Improvement in liver fibrosis, Decrease in TGF-β1 and the mRNA and protein expression of Gremlin in DHC groups |
| Weng et al. [81] | 483 Sprague Dawley rats (205 in the CCL4 group and 278 in the DMN group) | Liver fibrosis induced by subcutaneous injection of CCl4 or intraperitoneal injection of DMN | IFN-γ administration (in different doses: 1.67 MU/kg daily, 5 MU/kg daily, and 15 MU/kg daily) | 8 weeks for the CCL4 group 4 weeks for the DMN group |
IFN-γ administration decreased the HSCs activation and is effective in reducing liver fibrosis The results of IFN-γ are dose-dependent (better results are achieved with a higher dose) |
| Tang et al. [91] | 40 male C57BL/6 mice | 6-week methionine choline-deficient diet to establish NASH | 2 weeks administration of CTSB inhibitor (CA-074 methyl ester) | 6 weeks | Higher expression of CTSB and caspase-1 than in the normal diet group Possible regulation of caspase-1 levels by CTSB CTSB inhibition results in a decline in IL-1β and IL-18 levels and downregulation of NLRP3 inflammasome in KCs |
| Benrick et al. [108] | 18 IL-6−/− mice and 18 wild-type mice | High-fat diet to induce weight gain | Access to running wheels and lack of this access | 4 weeks | IL-6 contributes to the exercise-associated increase in insulin sensitivity A high-fat diet without running led to impairing insulin sensitivity; in contrast, running was a preventive factor in conditions of insulin sensitivity in wild-type but not in IL-6−/− mice |
| Huang et al. [117] | C57BL/6 mice and a mice insulinoma immortalized β-cell line MIN6 | Diabetes induced by streptozotocin in dose 40 mg/kg intraperitoneal for five days or high-fat and high-sucrose diet | AAV8 to induce expression of Kindlin-2 | 12 weeks | Insufficiency of Kindlin-2 leads to exacerbating diabetes, promotes β-cell inflammation and dysfunction induced by a high-fat diet Overexpression of Kindlin-2 improves insulin secretion and ameliorates diabetes induced by streptozotocin In vitro model of high-glucose-induced β-cell dysfunction revealed that overexpression of Kindlin-2 leads to decreased expression of proinflammatory cytokines and NLRP3 inflammasome in β cells |
| Jiang et al. [120] | Mouse islet β-TC-6 cells | PCB118 (5, 10, and 20 nmol/L) | 48 or 72 h | NLRP3 inflammasome signaling pathways in β cells are important in diabetes development | |
| Abderrazak et al. [121] | 12 ApoE2.Ki female mice | Chronic high-fat diet | Arglabin 2.5 ng/g twice a day in intraperitoneal injection | 13 weeks | Inhibition of NLRP3 caused by arglabin leads to a decrease in inflammation and apoptosis in pancreatic β cells |
| Yang et al. [122] | 24 diabetes-prone C57BLKS/J-Leprdb/Leprdb (db/db) male mice and 24 wild-type male mice | WMW in different doses (4800, 9600, and 19,200 mg/kg) | 4 weeks | Compared with the control group diabetic mice had higher protein expression levels of NLRP3 inflammasome components NLRP3 and caspase-1 (P20) than wild-type mice WMW decreases caspase-12, increases Bcl-2 expression, and decreases the upregulated production of IL-1β,IL-18,MCP-1α, and macrophage-specific surface glycoprotein F4/80 in diabetic mice |
|
| Sharma et al. [138] | 36 male Wistar rats | NAFLD induced by 12 weeks high-fat diet | Berbamine (50 or 150 mg per kg) | 12 weeks + 28 days | Improvements in liver function, liver index, and liver image due to berbamine administration Inducing the SIRT1/LKB1/AMPK pathway leads to protection against hepatic lipid metabolic disorders |
| Zhou et al. [158] | Mice with maternal overnutrition | Obesity and NAFLD induced by high-fat diet + diethylnitrosamine (intraperitoneally 20–25 μg/g and 50 μg/L in drinking water at age 21 days) | 90 μg to 120 μg aspirin per day | 12 weeks | Improvement in insulin/Akt signaling, activation of AMPK signaling, inhibition of Wnt-signaling and MAPK signaling leads to improvements in glucose intolerance, weight gain, and liver fat accumulation in female mice |
Abbreviations: AMPK, 5′-adenosine monophosphate (AMP)-activated protein kinase; Akt, protein kinase B; Bcl-2, B-cell leukemia 2; BMP-7, bone morphogenetic protein-7; CCL4, carbon tetrachloride; CTSB, Cathepsin B; DHC, Danshao Huaxian capsule, DMN, dimethylnitrosamine; HSCs, hepatic stellate cells; IL, interleukin; KCs, Kupfer cells; MAPK, mitogen-activated protein kinases; MCP-1α, monocyte chemoattractant protein-1α; NLRP3, NOD-like receptor protein 3; SIRT1, sirtuin 1; LKB1, liver kinase B1; TAA, thioacetamide; TGF-β1, transforming growth factor beta 1; WMW, Wu–Mei–Wan.