Table 1.
In vitro and in vivo studies on the anti-diabetic potential of saffron.
| In vitro/Animal trials/Dosage | Results | References |
|---|---|---|
| Effect of Saffron Extract and Crocin on PC12 cells. | It decreased the cell viability of PC12 after 4 days and increased the glucose-induced toxicity in PC12 cells mediated by ROS production partly. | Mousavi et al 35 |
| Different effects of Crocus sativus. | It can inhibit the growth of numerous cancer cells and have antidiabetic, antimicrobial, and α-glucosidase inhibitory activity. | Wali et al 34 |
| The action of Crocin on microglial cells | Crocin decreases microglial activation after traumatic brain injury and can prevent oxidative stress. | Yang et al 36 |
| Role of saffron on glucose rate in skeletal muscle cells | Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK, ACC, and MAPKs. It can also induce (dependent on time- and dose) the increase of AMPK phosphorylation in C2C12 cells. | Kang et al 6 |
| Saffron impacts on GLUT4/AMPK | Saffron can stimulate AMPK and GLUT4 via redox-mediated mechanisms. It also has been shown that the more dosage of saffron causes more glucose uptake. Saffron intensely stimulates phosphorylation in AMPK and GLUT4 cell lines. | Dehghan et al 31 |
| Adult male Sprague-Dawley rats divided into 4 groups: normal control group (G1) received distilled water for 4 weeks and 3 groups injected with STZ (50 mg/kg, IP (intra-peritoneal)) received distilled water (G2), sitagliptin (10 mg/kg, orally) (G3) and crocin extract of saffron (10 mg/kg, orally) (G4) for 4 weeks. | Crocin and sitagliptin prevented blood sugar spikes. Crocin and sitagliptin significantly reduced serum glucose (Crocin was more effective than sitagliptin). serum glucagon and suppressed pancreatic caspase-3 and CD68 expression. Also, body weight and serum insulin increased after 4 weeks of treatment. | Samaha et al 37 |
| Adult male Wistar rats (weight 150-200 g) divided into 6 groups: normal control group (G1) received distilled water(1 ml) and 5 groups injected with STZ (60 mg/kg, ip) received orally distilled water(1 ml), Hydroethanolic extracts of tepal (250 mg/kg/day), stigma (50 mg/kg/day), leaf (250 mg/kg/day) of crocus and glibenclamide (2 mg/kg/day) (G6) for 21 days. | The glibenclamide and Hydroethanolic extract of tepals, stigmas, and leaves decreased blood glucose levels, plasma total cholesterol, plasma triglycerides, and plasma creatinine in the treated diabetic rats compared with the untreated. Also, glibenclamide and Hydroethanolic significantly can protect rats against weight loss. | Ouahhoud et al 38 |
| Adult male Albino mice (25-30 g each) divided into 4 groups: control (G1), saffron(G2), untreated diabetic group(G3), and diabetic rats that received aqueous saffron extract (ASE) (80 mg/kg BW) (G4) for 45 days. | The saffron aqueous extract was significantly reduced the blood glucose levels of the treated diabetic group (G4). Also, the untreated diabetic group (G3) exhibited significantly increased serum glucose. | Nassar et al 39 |
| Adult male Wistar rats (Weight 225 ± 25 g) divided into 5 groups: normal control group (G1) received normal saline(1 ml) for 21 days and 4 groups injected with STZ (60 mg/kg, ip) received ethanolic extract of saffron stigma extract (SSE) 25 mg/kg (G2) and 100 mg/kg (G3), Normal saline(1 ml) (G4), glibenclamide (0.6 mg/kg) (G5). | Significant reduction in serum glucose, MDA level, G6Pase, and glucokinase gene (GK) expression after treatment with SSE (especially in high dose). SSE in specified doses increased β cell counts results in an increased level of insulin. | Motamedrad et al 40 |
| Adult male C57BL/6 mice were divided into 3 groups (n = 10): Healthy mice(G1), untreated diabetic mice(G2), treated diabetic mice that received The hydroalcoholic extract of saffron (500 mg/kg, orally) (G3) for 3 weeks. | The hydroalcoholic extract of saffron was significantly reduced the blood glucose, triglyceride, and cholesterol levels of diabetic mice(G3). | Faridi et al 41 |
| Male Wistar rats (weight = 309.91 ± 29.68) divided into 5 groups: normal control group (G1) received citrate buffer solution for 2 weeks, diabetic control group (G2), diabetic aerobic exercise group (G3), treated diabetic group (G4), and treated aerobic exercise group (G5). Treated rats received daily 25 mg/kg hydro extract of saffron for 2 weeks. | glucose and cholesterol Serum levels were significantly decreased in diabetic rats that were used saffron extract along with aerobic exercise compared to the diabetic control and normal control groups. However, no change was seen in free fatty acids, serum triglycerides, insulin, and insulin resistance in any group. | Iraji et al 42 |
| male Sprague–Dawley rats(250 g) divided into 2 groups: A) 5 groups injected with STZ (55 mg/kg, ip): 1) control, 2) training, 3) extract treatment, 4) training + extract treatment 5) treated with metformin 100 mg/kg B) non-diabetic group: 1) control, 2) training, 3) extract treatment 4) training + extract Treated rats received a hydroalcoholic extract of saffron at 40 mg/kg daily for 6 weeks. |
Significant reduction in serum glucose, insulin resistance, HbA1c39, triglyceride, LDL, and VLDL levels in treated rats compared to untreated after 6 weeks. | Dehghan et al 31 |
| Adult male Sprague-Dawley rats (200-220 g) divided into 9 groups: one normal control group received 0.9% saline and 8 groups injected with STZ (60 mg/kg, ip) received the hydroalcoholic extract of jujube (25 mg/kg (G1), 100 mg/kg (G2)), hydroalcoholic extract of saffron (G3, G4), hydroalcoholic extract of barberry (25 mg/kg (G5), 100 mg/kg (G6)), quercetin (15 mg/kg, ip) (G7), 0.9% saline (G8) for 14 days. | That serum levels of triglyceride, VLDL, and FBS decreased and adiponectin level increased significantly in all treated groups. In conclusion, Jujube could increase significantly HDL-C but other plant extracts did not affect cholesterol. | Hemmati et al 43 |
| Female Wistar albino rats(150-200 g) divided into 3 groups: one normal control group (G1) injected 1 ml sodium citrate buffer intraperitoneally and received normal saline (5 ml/kg) and 2 groups injected with STZ (60 mg/kg, IP) that also received normal saline (5 ml/kg) (G2) and crocin extract of saffron dissolved in normal saline (20 mg/kg/day) (G3) for 21 days. | Significant reduction in MDA level, XO activities, and elevated GSH contents in the treated diabetic group (G3). Also, crocin slightly decreased the high level of plasma Cr and BUN. | Altinoz et al 44 |
| Neonatal male Wistar rats were randomly divided into five groups: the control group (G1), the control group that received a higher dose of crocin (G3), and 3 groups injected with STZ (90 mg/kg, IP). One control diabetic group(G3) and two treated diabetic groups received crocin that was extracted from saffron (50 mg/kg (G4) and 100 mg/kg (G5)) for 5 months. | Significant reduction in serum glucose, AGE, HBA1c, LDL, TG, fasting insulin levels, and a significant increase in HDL level in rats treated with crocin compare with the untreated group was seen. But no significant difference was observed between the two doses of crocin. | Shirali et al 29 |
| Male Wistar rats divided into 5 groups: one normal control group received normal saline (G1) and 4 groups injected with STZ (55 mg/kg, IP) received normal saline (G2), crocin at doses of 15 mg/kg (G3), 30 mg/kg (G4) and 60 mg/kg (G5) for 6 weeks. |
After 6 weeks, the serum glucose level of G4 and G5 decreased but G3 serum glucose levels had no change. TBARS levels in the liver and kidney significantly decreased at the dose of 30 and 60 mg/kg compared with the diabetic control group (G2) and the total thiol concentration of liver increased in the treated diabetic group (G3, G4, G5) compare with the control group, but the total thiol concentration of kidney didn’t change. | Rajaei et al 45 |
| 35 male albino rats of Sprague-Dawley strain were divided into five groups: Normal control group (G1), diabetic control group (G2) and treated diabetic groups received orally saffron at levels of 200 mg/kg (G3), 400 mg/kg (G4), and 600 mg/kg (G5) for 4 weeks. |
body weight and serum insulin level in all treated diabetic groups significantly increased while significantly reduced blood glucose levels as well as the improvement in lipid profile and liver (ALT, AST, ALP) and kidney (BUN, UA, Cr) functions compared to the positive control group. | Elgazar et al 46 |
| 30 male Wistar rats divided into 5 groups One negative control group fed on a normal laboratory diet and 4 groups injected with STZ (40 mg/kg, IP) were fed a High fat (HF) diet as the positive control (G2), a High-fat diet enriched with pure saffron (S) at a level of 0.08% (G3), a high-fat diet enriched with rye bread (RB) (G4), a high-fat diet with rye bread fortified with 0.12% saffron (RB + S) (G5) for 5 weeks. |
significant reduction in TBARS concentration, TG, FBG levels after S(G3), RB(G4), S + RB(G5) treatment. Also, incorporation of S, RB, or RB + S into the HF diet led to significantly increased blood insulin levels in comparison to the control STZ-induced rats. | Bajerska et al 47 |
| Male adult Wistar rats divided into 11 groups: two healthy control groups received physiological saline (G1) and 10% DMSO in physiological saline (G2) And 9 groups injected with alloxan (125 mg/kg, IP) received physiological saline (G3), 10% DMSO in physiological saline (G4), saffron extract at the dose of 80 mg/kg (G5) and 240 mg/kg (G6), crocin of saffron at the dose of 50 mg/kg (G7) and 150 mg/kg (G8), safranal (an organic compound isolated from saffron) of saffron at the dose of 0.25 ml/kg (G9) and 0.5 ml/kg (G10), glibenclamide (G11) respectively for 6 weeks. | Compare with control diabetic rats there was a significant reduction in blood glucose and blood HbA1c levels and significant elevation of the blood insulin level of the diabetic rats that received saffron extract, crocin, safranal, and glibenclamide. Also, crocin, safranal, and glibenclamide did not have any significant effects on the blood SGOT, SGPT, and creatinine levels in diabetic rats. | Kianbakht and Hajiaghaee 48 |
| Male Wistar rats were accidentally separated into four groups including control, normal treated, diabetic, and diabetic treated. control and diabetic groups were handled by crocin (the chemical primarily responsible for the color of saffron.) 40 mg/kg/day for 8 weeks. The animals were victimized to delete liver tissues. | However, crocin markedly decreases blood glucose in the diabetic-treated group, STZ infusion markedly enhanced blood glucose. In the diabetic group, crocin markedly, decrease MDA and nitrate amount but enhanced CAT and SOD enzyme activity. | Yaribeygi et al 49 |
| Rats were separated into Control, Diabetes, Safranal, and Metformin groups. STZ was administered at the first. Low doses mixture of chemicals containing metformin and Safranal were imported after verification of diabetes on days 3 and carried on for 37 days. Memory and acquisition tested by using MWM on days 40-45 | Safranal and metformin had no traces, whereas their low dose mixture remedy markedly decreases STZ contained hyperglycemia. | Delkhosh-Kasmaie et al 50 |
| rats were divided into the following groups: control, untreated diabetic, and three saffron extract-treated diabetic groups. Diabetes was induced by STZ in rats. Saffron was administered 3 days after STZ administration and carried on a total of 4 weeks. | in the saffron-treated diabetic group saffron markedly reduced blood glucose, triglycerides, nitric oxide, total lipids, malondialdehyde, cholesterol levels and increase the glutathione level, superoxide dismutase, and catalase activities. The outcomes accredit using saffron as a cure against diabetes mellitus and its vascular problems. | Samarghandian et al 51 |
| Animals were separated into the following groups: control, diabetes, diabetic-crocin, diabetic-voluntary exercise, diabetic-crocin-voluntary exercise. Type 2 diabetes is enforced for 4 weeks by a high-fat diet and with the infusion of STZ. Animals received crocin orally and the voluntary exercise administrated together or alone for 8 weeks. | the levels of p53 in pancreas tissue of diabetics were markedly high. exercise and have anti-apoptotic effects on type 2 diabetic rats. crocin could decrease the blood glucose, p53 expression, and HbA1c levels in the diabetic-crocin group. | Ghorbanzadeh et al 52 |
| The rats were separated into three groups and remedied with CR and Met for 8 weeks. as such given 100 mg/kg of Met was dissolved in the physiological saline once per day for the whole of the test. | In the CR group the levels of insulin serum, HDL, cholesterol (which are also indicators of hypoglycemic functions), and pyruvate kinase increased. | Qiu et al 53 |
| Wistar rats were divided into control, type-1 diabetes induction, negative controls. Crocin dispensed for 4 weeks daily basis. and the prosperous induction of diabetes confirmed 14 days after STZ Prescription. | Diabetes disrupts the balance of oxidation-antioxidation, while crocin improved the antioxidant situation in the liver by affecting SOD1 gene expression and restitution of SOD and TAC levels. | Margaritis et al 54 |
| Fertilized embryos of zebrafish accumulated at 3 HPF and treated with CRC. The total level of embryo glucose was measured at 48 h post-treatment. | Crocin can increase the expression of insulin, phosphoenolpyruvate, and carboxykinase (a key gene involved with glucose metabolism). and reduces the level of zebrafish embryo glucose. | Kakouri et al 55 |
| Male Wistar rats were separated randomly into the following groups: normal, normal-treated, diabetic, and diabetic-treated groups. Diabetes received a single dose of STZ. every day the treated groups received crocin for 8 weeks. | Crocin Strengthened the anti-oxidant defense system by enhancing the effect of both SOD and catalase and recover OS by reducing MDA manufacture in pancreatic cells. Uncontrolled hyperglycemia did not change the GLT amount in non-treated rats and decreased the level of nitrate markedly. | Yaribeygi et al 56 |
| the type-2 diabetes model created by low-dose STZ into rats fed with the HFD. The treatment groups received a daily crocin for 6 weeks. | crocin could be effective in creating hyperleptinemia, hyperinsulinemia, insulin resistance, and weight gain. Also, the oxidative stress, which is enhanced due to the progress of diabetes reduced in the crocin treatment group. | Hazman et al 57 |
| Wistar albino rats were randomly divided into 5 groups to find diabetic Encephalopathy (one of the serious complications in diabetic patients) in STZ Induced Experimental Diabetes Mellitus. | findings showed that saffron extraction decreased the risk of hyperglycemia and hyperlipidemia and also reduce the oxidative stress in diabetic encephalopathy rats. | Samarghandian et al 58 |
| The rats were divided into 3 groups: saffron group, physiologic serum group, and the normal group. Daily injection of hydromethanolic extract of saffron was performed for 2 weeks. | the level of insulin in the test group markedly was enhanced and serum glucose markedly reduced. These results indicate that saffron extract has hypolipidemic and hypoglycemic effects on wholesome rats. | Arasteh et al 5 |
| Rats were separated into 6 groups of 10 animals: Control (C) Group, Sham + Streptozotocin (STZ) Group, Pinealectomy (PX) Group, PX + STZ Group, PX + Crocin (PX + Cr) Group, PX + STZ + Cr Group. Daily crocin treatment intraperitoneally for 15 days (50 mg/kg) | crocin significantly reduced serum BUN and Cr levels in the PX + STZ + Cr group. crocin treatment improved DN progression in addition to impaired histopathological, biochemical, immunohistochemical and parameters. It reduced TGF-β1 and suppressed oxidative stress. |
Keelo et al 59 |
| 40 diabetic Sprague Dawley male mice were selected with an average age of 4 weeks. Rats were divided into 5 groups including control, normal, damask rose petal, saffron petal, and saffron with damask rose petal groups. The study lasted 9 weeks, during which time 3 ml of herbal tea was given to rats by oral gavage. |
In the saffron petal group, decreased TG, HBA1C, and IGF-1 were observed. Also, FBS, HDL, and LDL were decreased compared to the control group. | Majidi et al 60 |