Table 1.
UA in animal disease models.
| Disease | UA | Delivery | Model | Outcome | References |
|---|---|---|---|---|---|
| CVD | 60 mg/kg body weight | IP | Dahl salt-sensitive rat model | ↓ HTN, BG, and TC; ↑ GPx and SOD | [20] |
| CVD | 85 mg/kg body weight | subq IP | Windsor rats | against ISO-induced MI, ↓ CK-MB, LDH, LDL, TG, and FFA | [57] |
| CVD | 85 mg/kg body weight | subq IP | Windsor rats | ↑ Bcl-2, Bcl-xl and ↓ of Bax, caspase-3, -8, and -9, cytochrome c, TNF-alpha, and FAS. ↓ lipid peroxidation markers and ↑ antioxidant enzymes and non-antioxidant enzymes in the plasma and heart tissue of ISO-induced MI | [58] |
| CVD | 50 mg/kg | oral gavage | STZ-Diabetic mice | ↓ aortic damage, RAGE, P22, and NFĸB | [59] |
| CVD | 0.05% | HFD | LDLR-KO mice | ↓atherosclerotic plaque size and weight gain | [19] |
| CVD | 0.20% | HFD | STZ-treated LDLR-KO, mice | ↓ atherosclerosis lesion formation, fewer infiltrating macrophages, ↓ BG, Alb/Crt ratio, inflammatory blood monocytes, ↑ low inflammatory blood monocytes | [60] |
| Diabetes | 0.05% | HFD | STZ-Diabetic mice | Protects pancreatic islet cells and ↑ insulin secretion | [61] |
| Diabetes | 5 mg/kg | HFD | C57BL/6J mice | UA combined with rosiglitazone ↓ whole BW gain, and can have profound responses to rosiglitazone or metformin. | [62] |
| Diabetes | 0.01% and 0.05% | AIN-76 semisynthetic diet | STZ/NA-Diabetic mice | Significant improved diabetic outcomes and stimulated T-lymphocytes in the thymus | [52] |
| Diabetes | 5 mg/kg | HFD | C57BL/6J mice | UA combined with rosiglitazone ↓ hepatic marker enzyme activities and ↓ lipid accumulation in liver | [63] |
| Kidney Disease | 0.01% | Standard rat chow | STZ-Diabetic mice | ↓ glomerular hypertrophy, collagen accumulation, and suppressed activation of STAT-3, ERK1/2, JNK and iNOS overexpression | [64] |
| Kidney Disease | 0.05%, 0.1% and 0.2% | 64 g starch, 23 g protein, 3.5 g fat, 5 g fiber, 1 vitamin mixture and 3 salt mixtures | STZ-Diabetic mice | ↑ kidney function ↓ flux through the renal polyol pathway, and ↓ AGEs formation in urine | [65] |
| Kidney Disease | 0.2% | Standard rat chow | STZ-Diabetic mice | ↓ UAE, renal oxidative stress, NF-KB activity, and P-selection expression | [66] |
| Kidney Disease | 25 and 50 mg/kg | oral gavage | ICR mice | UA prevents CCl4-induced nephrotoxicity, ROS, DNA damage, and proinflammatory markers | [37] |
| Kidney Disease | 2, 5, and 10 mg/kg | orally | Wistar albino rats | UA protected kidneys from gentamicin-induced damage | [67] |
| Kidney Disease | 0.2% in diet | Standard rat chow | Wistar rats | ↓ UAE, renal oxidative stress level, NF-κB activity, and P-selectin expression. | [42] |
| Liver Disease | 1–100 µM | Incubation medium | Human liver microsomes | UA regulation of cytochrome P450 shows hepatoprotective properties | [44] |
| Liver Disease | 50 mg/kg | IP | Wistar rats | Induced apoptosis in liver-damaging hepatic stellate cells while maintaining normal hepatocyte function | [45] |
| Liver Disease | 50 mg/kg | oral gavage | C57/BL6 WT mice | ↓ oxidative stress through activation of LKB1-AMPK signaling | [46] |
| Liver Disease | 25 and 50 mg/kg | intragastrically | ICR mice | ↓ CCl(4)-induced lipid peroxidation levels and depleted TAC levels in liver. ↓ CYP2E1, TNF-α, IL-1β and COX-2, JNK, p38 MAPK, ERK, and inactivation of NF-κB | [37] |
| Liver Disease | 1, 10, and 100 µg/mL | cell culture UA treatment | Albino Druckery rats | UA isolated from Eucalyptus tereticornis improved liver function measured by AST, ALT, and ↑ glutathione, α-tocopherol, and ascorbic acid | [38] |
| Liver Disease | 10, 20, and 40 mg/kg/day | intragastrically | Wistar albino rats | Pure UA improved liver function measured by AST, ALT, and ↑ glutathione, α-tocopherol, and ascorbic acid | [39] |
| Liver Disease | 0.125%, 0.25%, and 0.50% | HFD | Sprague-Dawley rats | Significantly reversed HFD-induced hepatic steatosis and liver injury | [43] |
| Liver Disease | 5, 20, and 80 µM | cell culture UA treatment | Cultured HepG2 cells | ↑ PPARα binding to its response element but did not directly bind PPARα in the liver hepatocyte cell line, HepG2 cells | [47] |
| Liver Disease | HepG2 (6.25, 12.5, and 25 µM) and HUVECs (5, 10, 20 µM) | cell culture UA treatment | HUVECs and HepG2 cells | ↓ inflammatory cytokine production induced by IL-6 in HepG2 cells | [48] |
| Liver Disease | 0.1 and 0.05% | AIN-76 semisynthetic diet | STZ/NA-Diabetic mice | ↓ FBG, TG, FFA, TC and VLDL, LDL. ↓ hepatic G6-P activity and ↑ glucokinase activity, the glucokinase/G6-P ratio, GLUT2 mRNA levels and glycogen content. ↑ aldose reductase activity, ↓ SDH | [52] |
| Metabolic Disease | 50 µM | cell culture UA treatment | C2C12 cells | Inhibited mTORC activation by leucine through suppression of mTOR lysosomal localization | [55] |
| Metabolic Disease | 250 mg/kg | IP | Sprague-Dawley rats | UA sustained exercise-induced mTORC1 activity | [56] |
| Metabolic Disease | 40 mg/kg body weight | IP | C57Bl/6 mice | ↑ muscle mass by inhibiting skeletal muscle atrophy and improved metabolic outcomes | [50] |
| Metabolic Disease | 0.5 g/kg | HFD | STZ-Diabetic mice | ↓ blood glucose, TC, FFA, TG, and improved liver function | [41] |
| Metabolic Disease | 125 nM, 250 nM, 500 nM and 1 µM | cell culture UA treatment | CHO/hIR cells | Inhibition of PTP1B ↓ blood glucose. PTP1B is a phosphatase inhibitor of insulin-mediated signaling. | [68] |
| Neuro. Disease | 5, 10, and 15 µM | cell culture UA treatment | Sprague-Dawley rats | ↓ free radical generation in primary rat hippocampus neurons in response to kainite | [69] |
| Neuro. Disease | 10 mg/kg/day | oral gavage | Kunming strain mice | ↑ activity of antioxidant enzymes, SOD, CAT, GPx, and GR and ↓ general lipid peroxidation in the brain | [70] |
| Neuro. Disease | 10 mg/kg/day | oral gavage | Kunming strain mice | ↓ AGEs, ROS, PCO levels, and down-regulated iNOS, COX-2, and various inflammatory cytokines mediated through NFκB, all found in the prefrontal cortex of the brain | [71] |
| Neuro. Disease | 10 or 20 mg/kg/day | oral gavage | C57BL/6J | improved cognitive deficits attributed to ↓ COX2, iNOS, TNFα and various inflammatory interleukins mediated through p38/NFκB signaling pathways | [72] |
| Neuro. Disease | 10 mg/kg/day | oral gavage | C57BL/6J | improves cognitive impairments by inhibiting ER stress and NFκB signaling pathway, restoring insulin signaling and the mTOR pathway | [73] |
| Neuro. Disease | 50 or 100 µM | cell culture UA treatment | CHO-CD36 and primary microglia cells | Potential treatment for Alzheimer’s Disease due to ↓ amyloid β binding to CD36 | [74] |
| Neuro. Disease | 25 and 50 mg/kg | IP | SD rats | ↓ oxidative stress attenuating EBI after SAH | [75] |
| Neuro. Disease | 130 mg/kg | IP | Nrf2−/− and WT rats | Protects brain from ischemic injury through activation of NRF2 pathway | [76] |
| Neuro. Disease | 100 nM | cell culture UA treatment | Patients with parkin or LRRK2 mutations | ↑ activity of the mitochondrial respiratory chain and displayed drug-like dose-response curves for Parkinson’s Disease | [77] |
| Obesity, Diabetes | 0.05% | HFD | C57Bl/6 mice | improved glucose tolerance and wt maintenance while ↓ lipid accumulation in liver | [42] |
| Obesity | 0.05% | Drinking Water | C57Bl/6 mice | ↓ visceral adiposity, total BW, BG, and lipid | [49] |
| Obesity | 0.14% and 0.27% | HFD | C57Bl/6 mice | ↑ muscle mass, skeletal muscle glucose uptake, and BAT resulting in ↓ obesity, hepatic steatosis, and improved glucose tolerance | [40] |
| Obesity | 2.5 to 10 µM | cell culture UA treatment | 3T3-L1 mouse embryo fibroblasts | Attenuated adipogenesis through the LKB1/AMPK pathway | [53] |
| Obesity | 25, 50, and 100 µM | cell culture UA treatment | Sprague-Dawley rats | Anti-obesity mechanism by stimulating lipolysis by upregulation of ATGL in primary rat adipocytes | [54] |
| Obesity | Cynomorri extract, 100–360 mg/kg body weight | HFD | C57Bl/6 mice | ↓ wgt gain likely to ↑ energy expenditure based on observed mitochondrial uncoupling in skeletal muscle | [51] |