Table 1.
The roles of SIRT1 agonists in endocrine and metabolic diseases.
| Compound | Molecular formula | Molecular weight | Model | Vitro/Vivo | Dosage and Administration | Effects | Reference |
|---|---|---|---|---|---|---|---|
| Res | C14H12O3 | 228.24 | Obesity rats models | Rats | AIN93G supplemented with 2 g/kg or 4 g/kg diet, 12 weeks | Res reduces adipocyte browning and fat loss, and improves other metabolic phenotypes, including hyperglycemia and hyperlipidemia in mice, which are mediated through SIRT1. | 54 |
| Res | C14H12O3 | 228.24 | Yeast polysaccharide and potassium oxonate induced hyperuricemia model in C57BL/6 mice | C57BL/6 female mice | 20 or 40 mg/kg, intragastrically, 0, 7, 14, 21 and 28day |
SIRT1 and its activator, Res, have clear anti-hyperuricemia functions in this mouse model, which possible mechanism is the activation of ABCG2 in the ileum through the PGC-1α/PPARγ pathway. | 91 |
| Res | C14H12O3 | 228.24 | Dehydroepiandrosterone-induced polycystic ovary syndrome rats | Rats | 20 or 40 mg/kg, intraperitoneal injection, 28day | Res combined therapy may improve the weight gain, hormone profile, and ovarian follicular cell architecture by inducing antioxidant and anti-inflammatory systems via SIRT1 and AMPK activation in polycystic ovary syndrome. | 126 |
| Res | C14H12O3 | 228.24 | Obesity model and nicotinamide-streptozotocin-high fat diet induced mild type 2 diabetes rats | Rats | 60 ng/kg min, infusion into the lumen of the duodenum, 50 min | Res reverses a 3d high fat diet-induced reduction in duodenal-mucosal Sirt1 protein levels while also enhancing insulin sensitivity and lowering hepatic glucose production. | 17 |
| Res | C14H12O3 | 228.24 | Particle-induced osteolysis (PIO) animal | C57BL/6 female mice | 60 mg/kg, intragastrically, 2 weeks. | Res inhibits endoplasmic reticulum stress and reduces polyethylene particle - induced osteoclast differentiation and osteolysis. | 144 |
| SRT3025 | C31H31N5O2S2 | 569.74 | Apolipoprotein E-deficient mouse of atherosclerosis | C57BL/6J mice | 3.18 g/kg diet, 12 weeks | SRT3025 can reduce plasma cholesterol levels, inflammation and atherosclerosis, and increase LDL receptor (Ldlr) and proprotein convertase subtilisin/kexin type 9 (Pcsk9) accumulation in the liver. | 183 |
| SRT3025 | C31H31N5O2S2 | 569.74 | Ovariectomy (OVX)-induced bone loss | C57BL/6J mice | 50 and 100 mg/kg/day, Oral administration, 6 weeks. | Treatment with SRT3025 decreased bone sclerostin expression and increased cortical periosteal mineralizing surface and serum propeptide of type I procollagen, a bone formation marker. | 197 |
| SRT3025 | C31H31N5O2S2 | 569.74 | Streptozotocin (STZ)-induced diabetes | Male CD1 mice | 3.18 g/kg, milled in chow, 20 weeks. | Treatment with SRT3025 diminished their glucagon secretion and proliferative activity in association with a reduction in the alpha cell associated transcription factor, Aristaless Related Homeobox (Arx) | 198 |
| SRT3025 | C31H31N5O2S2 | 569.74 | Advanced oxidation protein products (AOPPs) induce osteoporosis. | C57Bl/6 mice | 50 mg/kg, in drinking water, 16 weeks. | SRT3025 inhibits the expression of sclerosclerin in bone cells by activating SIRT1, and reduced the resorptive activity and formation activity of bone tissue, thereby alleviating age-related bone loss | 200 |
| SRT3025 | C31H31N5O2S2 | 569.74 | Diabetes mouse | Old male db/db mouse | 3.18 g/kg, milled in chow, 12 weeks. | While reducing hyperglycaemia and promoting beta cell expansion, enhancing the activity of SIRT1 facilitates a phenotypic change in a db/db mouse model of diabetes to one that more closely resembles the physiological state of torpor or hibernation. | 238 |
| Nicotinic acid | C6H5NO2 | 123.11 | Hyperlipidemia and atherosclerosis mice | LDL receptor knockout mice | 50, 250, or 1000 mg/kg, milled in chow, 8 weeks. | Nicotinic acid reduces total cholesterol, cholesterol esters, plasma triglycerides, atherosclerotic lesion size, lipid area, and aortic macrophage infiltration. | 239 |
| ginsenoside Rb2 | C53H90O22 | 1079.27 | Nonalcoholic fatty liver disease (NAFLD) and glucose tolerance model | C57BL/KsJ-Lepdb (db/db) mice | 10 mg/kg/day, intraperitoneal injection, 4 weeks. | Rb2 alleviates hepatic lipid accumulation by restoring autophagy via the induction of sirt1 and activation of AMPK, and resultes in improved NAFLD and glucose tolerance. | 174 |
| Melatonin | C13H16N2O2 | 232.282 | Apolipoprotein E-deficient mice (ApoE-/-) | C57BL/6 male mice and ApoE-/- male mice | 10 mg/kg/day, dissolved in 1% ethanol and then diluted in tap water, 9 weeks | Melatonin treatment improves serum biochemical markers and hepatic morphological impairment and inhibited oxidative stress through its antioxidant properties and also by SIRT1 upregulation. | 175 |
| Melatonin | C13H16N2O2 | 232.282 | Polycystic ovary syndrome (PCOS) and premature ovarian failure (POF) mice | ICR(CD-1) mice Liver Microsomes (Female) | 15 mg/kg/day, intraperitoneal injection, 2 days | Melatonin suppresses FOXO1 via the PI3K-AKT axis, improves granulosa cell resistance to oxidative stress, and abolishes the autophagic response, from genes expression to the formation of autophagic vacuoles. | 217 |
| Melatonin | C13H16N2O2 | 232.282 | chronic stress mice | Female BALB/c mice | 20 mg/kg/day, intraperitoneal injection, 28 days | Melatonin alleviates chronic stress-induced oxidative meiosis defects in mouse MII oocytes by regulating SIRT1 and autophagy | 61 |
| SRT1720 | C25H24ClN7OS | 506.02236 | Type 2 diabetic mice | Male C57BL/KsJ db/db mice | 50 mg/kg/day, gavage,10 weeks. | SRT1720 inhibits the expression of HF1 α, GLUT1 and SNAIL by activating SIRT1, and alleviates and prevents diabetic induced renal fibrosis | 211 |
| SRT1720 | C25H24ClN7OS | 506.02236 | High-fat diet mice | Adult female Kunming mice | 50 mg/kg/day, intraperitoneal injection, 6 weeks. | SRT1720 may improve the follicle pool reserve in high-fat diet-induced obese female mice via activating SIRT1 signaling and suppressing mTOR signaling, thus extending the ovarian lifespan. | 212 |
| Metformin (MF) | C₄HN₅ | 129.164 | polycystic ovary syndrome (PCOS) rats | Female rats | 300 mg/kg/day, subcutaneous injection, 4 weeks. | MF can improve the reproductive and endocrine functions of rats with PCOS via the AMPKα-SIRT1 pathway. | 128 |
| Quercetin | CHO7 | 302.236 | Letrozole-induced Polycystic ovary syndrome (PCOS) mice | Female Wistar rats | 100 mg/kg/day, intragastric administration, 30 days. | Treatment with quercetin improves the PCOS related disturbances in estrous cycle, lipid profile, serum levels of testosterone, estradiol and progesterone, and insulin resistance. Besides, the expression levels of AMPK and SIRT-1 in ovarian tissue are upregulated in the rats which received quercetin. Quercetin also reverses the PCOS-induced alteration in adipose tissue levels of adiponectin, visfatin, and resistin. | 129 |