Table 1.
The Effect of Diosgenin on Markers Relevant to Lipid Metabolism
| Model | Diosgenin Dose | Duration | Effects on the Plasma Lipid Profile and Transcription Factors | Pharmacological Effect | Reference |
|---|---|---|---|---|---|
| HFDA Male SDB rats | Protodioscin (0.5 mg/kg/d); intraperitoneal injection | 15–28 days | TC↓,LDL↓,HDL↓,HDL/LDL↑ | Inhibited HMG-CoA reductase on endoplasmic reticulum | [37] |
| HFD SPFC Male SD rats | 0.15, 0.3 g/kg/d; intragastrically | 4 or 8 weeks | FTC↓,TTC↓, TC↓, TG↓, LDL-C↓ NPC1L1↓, ABCG5↑, ABCG8↑, LXR-α↓ |
Ameliorated hepatic steatosis and decreased the villi height and tunica mucosa thickness; Reduced cholesterol absorption; Increased cholesterol excretion | [21] |
| HCDD Male Wistar rats | 0.5g/100g orally | 4 weeks | TC↓, TG↓, HDL-C↑, LDL-C↓ | Reduced Cholesterol absorption in the intestine and/or increased Cholesterol excretion from the liver; Increased bile acid and Cholesterol excretions | [44] |
| STZE Male Wistar rats | 40 mg/kg b.w. orally | 45 days | TC↓, TG↓, Phospholipids↓, FFA↓, HMGR↓ | Decreased cholesterol synthesis | [52] |
| HFD+ STZ Male SD rats | 40, 80 mg/kg b.w. orally | 14 days | TC↓, TG↓, SOD↑, GPX↑, GSH↑, TBARS↓, PPARγ↑, PPARα↑ | Promoted pre-adipocytes differentiate; Antioxidation modulating oxidative stress | [68] |
| HFD Male SD rats | 22.1, 44.2, 88.4 mg/kg/d orally | 6 weeks | TC↓, TG↓,LDL-C↓, GSH-PX↑, NOS ↑, MDA↓, SOD↑, LPL↑, HL↑ | Antioxidation and modulating oxidative stress; Attenuated H2O2-induced cytotoxicity and increased the cell viability; Accelerated lipids metabolism; Decreased cholesterol absorption and increased biliary cholesterol secretion; | [74] |
| HFD Male C57 mice | In drinking water, 5 mg/L every 2 days | 4 weeks | PPARγ1↓, PPARγ2↓, MestF↓, MCP-1G↓, IL-6↓, ROS↓ | Ameliorated metabolic dysfunction; Inhibited adipocyte differentiation | [97] |
| Gestational diabetes-induced C57BL/KsJ+/+(wild type, homozygous) and C57BL/KsJdb/+(db/+, heterozygous) mice | Protocol 1: 10, 20 mg/kg b.w; Protocol 2: 20mg/kg intragastric tube | 4 weeks | TBARS↓, SOD↑, CAT↑, GSH↑, TC↓, TG↓, LDL↓, SREBP-1↓, FAS↓, SCD-1↓, ACC↓ | Antioxidation and regulation of oxidative stress; Inhibited the mRNA induction of lipogenic genes | [86] |
| HCD Male SD rats | 0.1%, 0.5% diet orally | 6 weeks | ALT↓, AST↓, TC↓, HDL-C↑, HDL/TC↑, GSH-Px↑, SOD↑, TBARS↓ | Liver protective effect; Antioxidation and regulation of oxidative stress; protection against lymphocyte DNA damage in both unstressed and stressed cells; Inhibited pancreatic lipase activity | [71] |
| HFD Male KK-Ay/Ta Jcl mice (obese diabetic model) | 0.5%, 2.0% fenugreek orally | 4 weeks | TG↓, SREBP-1↓, FAS↓, SCD-1↓, ACC↓, LXR↓ | Inhibited the mRNA induction of lipogenic genes; Inhibited hepatic steatosis | [53] |
| HFD KK-Ay/Ta Jcl mice (obese diabetic model) | 0.5%, 2% fenugreek orally | 4 weeks | aP2↑, LPL↑, Glut4↑, PPARγ1↑, MCP-1↓, TNF-α↓, adiponectin↑ | Enhanced insulin sensitivity; Promoted adipocyte differentiation and inhibited obesity-related inflammation | [72] |
| HCD Male New Zealand White rabbits | 50 g/kg 50 mesh-size, 50 g/kg nanoscale Dioscorea pseudojaponica orally | 8 weeks | TC↓, TG↓, AMPK↑, ACC↑ | Prevented lipid accumulation within liver tissue; Accelerated lipid catabolism | [54] |
| Semipurified-diet + 0.1% cholesterol female cynomolgus macaques | 1% die orally | 3 weeks | TC↓, TG↓, | Increased cholesterol excretion | [38] |
| Male apoE KO mice | 1% (w/w) orally | 8 weeks | TC↓, FC↓, CE↓, ABCA1↑, miR-19b ↓ | Enhanced macrophage cholesterol efflux; Inhibited macrophage cholesterol accumulation; accelerated RCT and improves plasma lipid profile; Inhibited aortic lipid deposition and atherogenesis | [63] |
| HFD Male SD rats | 0.5%, 1% (w/w) orally | 16 weeks | HDL↑, LDL↓, TG↓, ALT↓, pAMPK↑, pACC↑, AMPK↑, ACC↑,SREBP1-c↓, LXRα↓ | Increased AMPK and ACC phosphorylation; accelerated lipid catabolism | [91] |
| 45% kcal-fat content male Wistar rats | 20, 40, 80 mg/kg for mice and 15, 30, 60 mg/kg for rats orally | 8 weeks | AST↓,ALT↓,TG↓,TC↓,FFA↓,SREBP-1c↓,CPT↑,FAS↓,SCD↓,FoxO1↑,ATGL↑,SOD↑,MDA↓,GSH↑,SIRT1↑ | Improved hepatic lipid metabolism; decreased triacylglycerol accumulation | [87] |
| HepG2 cells; THP-1 monocytic cells | Protodioscin, pseudoprotodioscin, methylprotodioscin(5μm, 10μm, 25μm) | 24h; 48h | ABCA1↑, SREBP-1↓, SREBP-2↓, LXRα↓,PCSK9↓,FAS↓,ACC↓, LDLR↑ | Inhibited cholesterol triglycerides synthesis; accelerated RCT and improved plasma lipid profile; | [64] |
| Human THP-1 monocytic cells; HepG2 cells | Methyl protodioscin(100μm) | 24h | SREBP1c↓,SREBP2↓,miR-33a/b↓, ABCA1↑,HMGCR↑,FAS↓, ACC↓, LXRα↓ | Inhibited cholesterol triglycerides synthesis | [45] |
| C57BL/6 male mice; Wistar male rats | Acute experiment: 28, 56, 84 mg/kg/d; chronic test: 20, 40, 60mg/kg/d; intragastrically | Acute experiment: 2 weeks; chronic test: 12 weeks | AST↓,ALT↓,TG↓,TC↓,SOD↑,MDA↓,GSH↑,GSH-Px↑, GSR↑,TnF-α↓,IL-6↓, p38↓,pERK↓, pJNK↓,CYP2E1↓,PPARα↑,CPT↑,MCAD↑ | Reduced the oxidative stress,Inflammatory cytokine production, apoptosis and liver steatosis | [70] |
| HFD C57BL/6J male mice | 50, 100 dioscin mg/kg/d intragastrically | 7 weeks | SREBP-1c↓, FAS↓, GLUT4↓, pAMPK↑, pACC↑, p38↓, pERK↓ | Inhibited cholesterol triglycerides synthesis; Increased AMPK and ACC phosphorylation; | [57] |
| SW480 cell | 6.21 μg/mL | 24h; 48h | ACC↓,FAS↓,PPARγ↑, LDLR↑ | Inhibited the mRNA induction of lipogenic genes; decreased cholesterol absorption | [88] |
| HFD Male SD rats | 150, 300 mg/kg/d, intragastrically | 8 weeks | TC↓, TG↓, LDL-C↓, HDL-C↑, SRB1↑, CES-1↑, CYP7A1↑, FXR↓ | Accelerated hepatic RCT; enhanced cholesterol elimination | [49] |
| 1% (1g/100g) |
Abbreviations: AHFD, High-fat diet-fed; BSD, Sprague–Dawley; CSPF, specific-pathogen-free; DHCD, high-cholesterol diet; ESTZ, Streptozotocin-Induced; FMest, mesoderm specific transcript; GMCP-1, monocyte chemoattractant protein.