crocin and Diabetes-Mellitus--Type-2

Crocus sativus L. (saffron, Iridaceae) has been traditionally used for thousands of years as herbal medicine for many diseases, including type-2 diabetes mellitus (T2DM), especially in Sri Lanka. Systematic reviews and meta-analysis on C. sativus for T2DM value traditional knowledge about this species.. To assess the effectiveness of C. sativus powdered plant, hydroethanolic extract and crocin in reducing fasting blood sugar (FBG), glycated hemoglobin (HbA1c), blood pressure, and other metabolic parameters in patients with T2DM.. Systematic review and meta-analysis based on searches in PubMed, Embase, and Cochrane, including all randomized clinical trials (RCTs) published before January 2, 2023. Two independent reviewers extracted the data and assessed the risks of bias. The effects of C. sativus and crocin were assessed on glycemic, metabolic, and blood pressure parameters. Weighted (WMD) or standardized (SMD) mean differences (before-after) and 95% confidence intervals (95%CI) of the outcomes were extracted or estimated and meta-analyses were conducted using RevMan 5.4 (Cochrane Collaboration). This protocol was registered in PROSPERO (#CRD42023390073).. Fifteen of 29 studies were included. Saffron powdered plant decreased AST (WMD -1.19, 95%CI -2.24, -0.13), but increased BMI (WMD 0.56, 95%CI 0.07, 1.05); saffron extract decreased HbA1c (WMD -0.35, 95%CI -0.65, -0.06), FBG (WMD -26.90, 95%CI -38.87, -14.93), creatinine (WMD -0.12, 95%CI -0.19, -0.05), and total cholesterol (WMD -9.29, 95%CI -18.25, -0.33); and crocin decreased HbA1c (WMD -0.43, 95%CI -0.66, -0.20), FBG (WMD -14.10, 95%CI -22.91, -5.30), and systolic blood pressure (WMD -8.18, 95%CI -12.75, -3.61), but increased creatinine levels (WMD 0.24, 95%CI 0.17, 0.32). Of the 15 included studies, 14 had a moderate risk of bias, and one study had a low risk of bias.. C. sativus (saffron) powdered plant, extract, and crocin have potential as an adjunct treatment for T2DM, improving control of metabolic and clinical parameters. However, C. sativus extract seems to be superior because it was effective in more parameters and did not induce adverse effects. Since many studies were at moderate risk of bias, further high-quality research is needed to firmly establish the clinical efficacy of this plant.

Topics: Biological Products; Creatinine; Crocus; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans

The purpose of this study was to evaluate the effect of Saffron and its active ingredient, crocin, as a natural antioxidant in the treatment of type II diabetes.. A total of 150 uncontrolled type 2 (non-insulin-dependent) diabetic patients were selected based on inclusion criteria, randomly divided into three groups (crocin, saffron and placebo) for three months' clinical trial. Fasting blood glucose (FBS), insulin level, glycosylated hemoglobin (HbA1c), lipid profile, kidney and liver function tests were performed before and three months after the study. The patients were followed every two weeks for possible clinical side effects.. Our results showed that after three months of treatment with crocin and saffron, FBS reduction was significant in all groups (P-value < 0.05). In addition, reduction of HbA1c was significant in the crocin and saffron groups compared to placebo group. Comparison between groups showed that treatment with crocin and saffron led to a significant reduction in HbA1c than placebo, and FBS level significantly reduced only in crocin compared to saffron and placebo groups. In addition, changes in lipid profile were not significant in any of the three groups. Also, there was no significant difference in liver and liver parameters in all three groups. Inter-group comparison of insulin levels showed significant difference only between the saffron and placebo groups.. Crocin can be effective in controlling the level of FBS and HbA1c in patients with type 2 diabetes.

Topics: Carotenoids; Crocus; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Lipids

Diabetic nephropathy (DN) is one of the most important complications of type 2 diabetes (T2DM). Oxidative stress and inflammatory cytokines play an essential role in the development and progression of DN. Despite adopting appropriate therapies, many patients with DN progress to end-stage renal disease (ESRD). Therefore, exploring innovative strategies for better management of DN is crucial. Crocin, a natural compound found in saffron, has profound antioxidant, antifibrotic and anti-inflammatory properties. This study aimed to evaluate the therapeutic effects of crocin in attenuation of the progression of DN.. In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients with T2DM and microalbuminuria were randomly assigned to receive either crocin (15 mg/day) or a placebo for 90 days. Eventually, 40 patients completed the study: 21 patients in the crocin group and 19 in the placebo group. The primary outcome was a change in urine Albumin-to-Creatinine Ratio (uACR) from baseline to the end of the treatment period. We also evaluated metabolic, anthropometric, and biochemical parameters as the secondary outcomes.. The results of the present study showed that uACR increased in both groups, but the increment was not significantly higher in the crocin group compared with the placebo. Serum levels of transforming growth factor-β (TGF-β) decreased in the crocin group and increased in the placebo group, but none of these changes was significant. Crocin significantly reduced triglyceride (TG) as an important metabolic parameter (P-Value = 0.03).. This study has shown that crocin may be a safe and potential adjunct to conventional therapies for DN patients but because of our limitations such as short duration of the treatment period, and prescribing low doses of crocin, we could not achieve the significant level.

Topics: Albumins; Antioxidants; Carotenoids; Creatinine; Cytokines; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Transforming Growth Factor beta; Transforming Growth Factors; Triglycerides

Inflammation and oxidative stress is a risk factor for the development of long-term consequences in patients with type 2 diabetes mellitus (T2DM). This study was designed to investigate the effects of crocin consumption on oxidative stress and inflammatory markers in patients with T2DM. In this clinical trial with a parallel-group design, 50 patients with T2DM were randomly assigned to either the crocin or the placebo group. The crocin group received 15 mg crocin twice daily, whereas the placebo group received corresponding placebos. At baseline and the end of week 12, serum high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-ɑ (TNF-ɑ), nuclear factor-κB (NF-κB), and malondialdehyde (MDA) were measured. Compared with placebo group, crocin reduced hs-CRP (-1.03 vs. 1.42, p = .007), TNF-ɑ (-0.8 vs. 0.28, p = .009), and NF-κB (-0.39 vs. 0.01, p = .047) after 12 weeks intervention; these improvements were also significant in comparison with the baseline values. Plasma IL-6 decreased significantly in the crocin group at the end of week 12 compared to baseline (p = .037), whereas no significant change was observed in the placebo group. Plasma concentration of MDA did not change within and between groups after intervention. This study indicates that daily administration of 30 mg crocin supplement to patients with T2DM reduces the concentrations of hs-CRP, TNF-ɑ, and NF-κB which are involved in the pathogenesis of complications of T2DM.

Topics: Biomarkers; Carotenoids; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Inflammation; Oxidative Stress

Present study investigated the effect of continued training (CT) and interval training (IT) with crocin (C) supplementation on mitochondrial biogenesis and redox-sensitive transcription factors in liver tissue of type 2 diabetes (T2D) rats. Forty-eight high fat diet and streptozotocin- induced diabetic rats (mean age: 20 weeks, mean weight: 360.12 ± 12.11 g) were randomly divided into six groups including: (1) sham (Sh), (2) CT, (3) IT, (4) C (25 mg/kg/day), (5) CT + C, and (6) IT + C. IT and CT were performed 8 weeks for five sessions per week on treadmill with 80-85% and 50-55% of maximum speed running respectively. IT, CT and C decreased AP1 and increased LCAD (

Topics: Animals; Carotenoids; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Supplements; Liver; NF-kappa B; Organelle Biogenesis; Oxidation-Reduction; Rats; Sirtuin 1; Streptozocin; Transcription Factors

Quercetin and crocin are the main active constituents of Eucommia and Gardenia species, respectively. This study was conducted to explore the effects of quercetin and crocin on fat reduction and renal fibrosis and the relationship of these compounds with autophagy. First, a model of high-fat diet- and streptozotocin-induced type 2 diabetes was established and then subjected model animals to 8 weeks of metformin, quercetin and crocin gavage. Then, a high glucose-induced rat mesangial cells (RMCs) model was established, and these cells were cocultured with quercetin and crocin. The results showed that quercetin and crocin can decrease fasting blood glucose levels, reduce fat accumulation in the liver, alleviate renal fibrosis, and reduce blood lipid levels. Quercetin and crocin increased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels in the liver and decreased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels in the kidneys. Moreover, quercetin and crocin inhibited the excessive proliferation of RMCs induced by high-glucose (HG) conditions, decreased autophagy-related protein (LC3, Atg5, Beclin-1 and p-AMPK) levels, and decreased TGF-β1 expression. Importantly, cotreatment with quercetin and crocin had a more significant effect than treatment with either compound alone. These results suggest that combined administration of quercetin and crocin can more significantly reduce blood glucose/lipid levels and improve renal fibrosis than administration of either compound alone and that AMPK-dependent autophagy might be involved in this process.

Topics: Animals; Autophagy; Blood Glucose; Carotenoids; Cell Proliferation; Cholesterol; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Hypoglycemic Agents; Kidney; Lipid Metabolism; Liver; Male; Obesity; Protective Agents; Quercetin; Rats, Sprague-Dawley

Amylin (hIAPP) amyloid formation plays an important role in the pathogenesis of type 2 diabetes (T2D), which makes it a promising therapeutic target for T2D. In this study, we established a screening tool for identifying chemicals affecting hIAPP amyloid formation based on a reported genetic tool, which constantly tracks protein aggregates in Saccharomyces cerevisiae. In order to obtain the hIAPP with better aggregation ability, the gene of hIAPP was tandemly ligated to create 1×, 2×, 4× or 6×-hIAPP expressing strains. By measuring the cell density and fluorescence intensity of green fluorescent protein (GFP) regulated by the aggregation status of hIAPP, it was found that four intramolecular ligated hIAPP (4×hIAPP) could form obvious amyloids with mild toxicity. The validity and reliability of the screening tool were verified by testing six reported hIAPP inhibitors, including curcumin, epigallocatechin gallate and so on. Combined with surface plasmon resonance (SPR) and the screening tool, which could be a screening system for hIAPP inhibitors, we found that crocin specifically binds to hIAPP and acts inhibit amyloid formation of hIAPP. The effect of crocin was further confirmed by Thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM) analysis. Thus, a screening system for hIAPP amyloid inhibitors and a new mechanism of crocin on anti-T2D were obtained as a result of this study.

Topics: Carotenoids; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Humans; Hypoglycemic Agents; Islet Amyloid Polypeptide; Protein Aggregation, Pathological

This study aimed to investigate the effect of crocin consumption, high-intensity interval training (HIIT), and low-intensity continuous training (LICT) and their interactive effect on the gene expression of Mfn2 and Drp1 in the skeletal muscle and serum glucose and insulin indices in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic rats. Fifty-six adult rats were divided into eight groups of seven subjects: crocin consumption, HIIT, LICT, HIIT with crocin, LICT with crocin, diabetic control, healthy control, and sham (placebo). At the end of the course (5 months), metabolic indices were measured. Moreover, the Mfn2 and Drp1 gene expression levels in all groups were measured using RT-PCR. The statistical analysis showed that in the exercise training (HIIT and LICT) and the crocin consumption groups, the glucose and insulin indices significantly improved (p = .005). Moreover, in these groups, the levels of gene expression of Mfn2 and Drp1 significantly increased and decreased, respectively (p = .001). Exercise training and crocin consumption appear to, either in combination or individually, have a beneficial effect on mitochondrial dynamics and diabetes by improving the mitochondrial fusion and fission indices (Mfn2 and Drp1), and by modifying the insulin resistance index and glucose homeostasis. PRACTICAL APPLICATIONS: Mfn2 and Drp1, as the main regulators of the mitochondrial fusion and fission, play an important role in maintaining mitochondrial dynamics and type 2 diabetes. Thus, the regulation of mitochondrial dynamics is an intricate process that retains the balance between mitochondrial fission and fusion, and any disturbance in this balance can lead to mitochondrial-associated diseases including insulin resistance and T2D. There is evidence that herbal antioxidants Including crocin and exercise training help improve the mitochondrial activity and insulin sensitivity in T2D. Considering the importance of the two Drp1 and Mfn1 genes in the mitochondrial dynamic pathway and coding the proteins that play a key role in relation to T2D, this study primarily examined the interactive effects of endurance training (HIIT and LICT) along with crocin consumption on the expression the genes mentioned above; the results obtained in this study can provide a new approach to the treatment of HFD + STZ-induced diabetic rats.

Topics: Animals; Carotenoids; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Endurance Training; Gene Expression; Glucose; GTP Phosphohydrolases; Humans; Insulin; Mitochondrial Proteins; Muscle, Skeletal; Rats

Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity, type 2 diabetes and other metabolic disorders worldwide. Crocin is a carotenoid compound possessing various pharmacological activities. In the present study, we aimed to investigate the effect on fatty liver under diabetic and obese condition and to examine the possible role of AMP-activated protein kinase (AMPK) signaling.. db/db mice were administrated with crocin and injected with LV-shAMPK or its negative control lentivirus. Metabolic dysfunction, lipogenesis and fatty acid-oxidation in liver were evaluated.. In db/db mice, we found that oral administration of crocin significantly upregulated the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in liver. Crocin reduced liver weight, serum levels of alanine aminotransferase, alanine aminotransferase, and liver triglyceride content, and attenuated morphological injury of liver in db/db mice. Crocin inhibited the mRNA expression of lipogenesis-associated genes, including sterol regulatory element binding protein-1c, peroxisome proliferator-activated receptor γ, fatty acid synthase, stearoyl-CoA desaturase 1, and diacylglycerol acyltransferase 1, and increased the mRNA expression of genes involved in the regulation of β-oxidation of fatty acids, including PPARα, acyl-CoA oxidase 1, carnitine palmitoyltransferase 1, and 3-hydroxy-3-methylglutaryl-CoA synthase 2. Moreover, treatment of crocin resulted in a amelioration of general metabolic disorder, as evidenced by decreased fasting blood glucose, reduced serum levels of insulin, triglyceride, total cholesterol, and non-esterified fatty acid, and improved glucose intolerance. Crocin-induced protective effects against fatty liver and metabolic disorder were significantly blocked by lentivirus-mediated downregulation of AMPK.. The results suggest that crocin can inhibit lipogenesis and promote β-oxidation of fatty acids through activation of AMPK, leading to improvement of fatty liver and metabolic dysfunction. Therefore, crocin may be a potential promising option for the clinical treatment for NAFLD and associated metabolic diseases.

Topics: Acyl-CoA Oxidase; Alanine Transaminase; AMP-Activated Protein Kinases; Animals; Anti-Obesity Agents; Aspartate Aminotransferases; Carnitine O-Palmitoyltransferase; Carotenoids; Diabetes Mellitus, Type 2; Diacylglycerol O-Acyltransferase; Disease Models, Animal; Fatty Acid Synthases; Gene Expression Regulation; Hydroxymethylglutaryl-CoA Synthase; Hypoglycemic Agents; Lipogenesis; Liver; Male; Mice; Mice, Transgenic; Non-alcoholic Fatty Liver Disease; PPAR alpha; PPAR gamma; Signal Transduction; Stearoyl-CoA Desaturase; Sterol Regulatory Element Binding Protein 1; Treatment Outcome; Triglycerides

Hyperglycemia is the main risk factor for microvascular complications in type 2 diabetes. Crocin and voluntary exercise have anti-hyperglycemic effects in diabetes. In this research, we evaluated the effects of crocin and voluntary exercise alone or combined on glycemia control and heart level of VEGF-A.. Animals were divided into eight groups as: control (con), diabetes (Dia), crocin (Cro), voluntary exercise (Exe), crocin and voluntary exercise (Cro-Exe), diabetic-crocin (Dia-Cro), diabetic-voluntary exercise (Dia-Exe), diabetic-crocin-voluntary exercise (Dia-Cro-Exe). Type 2 diabetes was induced by a high-fat diet (4 weeks) and injection of streptozotocin (STZ) (i.p, 35 mg/kg). Animals received oral administration of crocin (50 mg/kg) or performed voluntary exercise alone or together for 8 weeks. Oral glucose tolerance test (OGTT) was performed on overnight fasted control, diabetic and treated rats after 8 weeks of treatment. Then, serum insulin and heart VEGF-A protein levels were measured.. Crocin combined with voluntary exercise significantly decreased blood glucose levels (p < 0.001) and insulin resistance (HOMA-IR) (p < 0.001) compared to diabetic group. VEGF-A level was significantly (p < 0.01) lower in Dia group compared to control group. The combination of crocin and voluntary exercise significantly enhanced VEGF-A protein levels in Dia-Cro-Exe and Cro-Exe group compared to diabetic and control groups, respectively; p < 0.001 and p < 0.05.. Crocin combined with voluntary exercise improved insulin resistance (HOMA-IR) and reduced glucose levels in diabetic rats. Since both crocin and voluntary exercise can increase VEGF-A protein expression in heart tissue, they probably are able to increase angiogenesis in diabetic animals.

Topics: Animals; Biomarkers; Carotenoids; Combined Modality Therapy; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Glucose; Glucose Tolerance Test; Heart; Insulin Resistance; Male; Physical Conditioning, Animal; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A

The aim of this study is to scrutinize the effects of crocin on obesity and type-2 diabetes, with an approach that takes oxidative stress and inflammatory parameters into account.. The experimental obesity model was created by utilizing a 10-week-long high-fat diet (HFD). An experimental type-2 diabetes model was created by injecting multiple low-dose streptozocin (STZ) injections into rats that were fed with the HFD. The treatment groups were administered a daily crocin dose of 150 mg/kg for 6 weeks via gavage.. Findings of the study demonstrated that crocin could be effective in relieving the symptoms of obesity and diabetes (hyperinsulinemia, hyperleptinemia, insulin resistance, and weight gain). It was determined that crocin lowered the plasma TNF-α and IL-1β levels and the pancreas tissue TNF-α and IFN-γ levels, which were increased due to diabetes, and reduced the inflammation in diabetic rats. Similarly, it was found that oxidative stress, which increased due to the progress of diabetes, was reduced in crocin treatment group.. Crocin could contribute to the development of phytotherapeutic approaches in the treatment of obesity, diabetes, and diabesity (obesity-induced diabetes), which is promising as the abovementioned incidences have increased considerably in today's world.

Topics: Animals; Carotenoids; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Obesity; Rats

Background Oxidative stress plays a critical role in the pathogenesis and progression of type 2 diabetes and diabetic-associated cardiovascular complications. This study investigated the impact of crocin combined with voluntary exercise on heart oxidative stress indicator in high-fat diet-induced type 2 diabetic rats. Materials and methods Rats were divided into four groups: diabetes, diabetic-crocin, diabetic-voluntary exercise, diabetic-crocin-voluntary exercise. Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (intraperitoneally, 35 mg/kg). Animals received crocin orally (50 mg/kg); voluntary exercise was performed alone or combined with crocin treatment for 8 weeks. Finally, malondialdehyde (MDA), activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured spectrophotometrically. Results Treatment of diabetic rats with crocin and exercise significantly decreased the levels of MDA (p < 0.001) and increased the activity of SOD, GPx, and CAT compared with the untreated diabetic group. In addition, combination of exercise and crocin amplified their effect on antioxidant levels in the heart tissue of type 2 diabetic rats. Conclusion We suggest that a combination of crocin with voluntary exercise treatment may cause more beneficial effects in antioxidant defense system of heart tissues than the use of crocin or voluntary exercise alone.

Topics: Animals; Antioxidants; Carotenoids; Catalase; Combined Modality Therapy; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diet, High-Fat; Exercise Therapy; Glutathione Peroxidase; Lipid Peroxidation; Male; Malondialdehyde; Myocardium; Oxidative Stress; Rats, Wistar; Streptozocin; Superoxide Dismutase

Crocin is the only water soluble carotenoid in nature, and it has a known powerful antioxidant activity. The aim of this work was to investigate the hypoglycemic and hypolipidemic effects of crocin in streptozotocin (STZ)-induced type 2 diabetic rats. Neonatal male Wistar rats (2-5 days old) were randomly divided into five groups. Three groups were intraperitoneally injected with STZ (90 mg/kg body weight). Among them, two groups were treated with intraperitoneal injection of crocin (50 or 100 mg/kg), and the third group was treated with vehicle only. Two control groups were also considered, and one of them was treated with crocin. After 5 months, their blood and urine samples were collected, and the animals were sacrified. The results indicate a significant lower body weight (P < 0.001) and abnormal parameters in the diabetic rats compared with the normal group. An administration of both doses of crocin significantly decreased the levels of serum glucose, advanced glycation end products, triglyceride, total cholesterol, and low-density lipoprotein and increased the high-density lipoprotein in the diabetic rats. The treatments were also effective in decreasing HbA1c and microalbuminuria, as well as homeostatic model assessment for insulin resistance as a measure of insulin resistance in the diabetic rats.

Topics: Albuminuria; Animals; Animals, Newborn; Blood Glucose; Body Weight; Carotenoids; Cholesterol; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycation End Products, Advanced; Hypoglycemic Agents; Insulin Resistance; Lipoproteins, HDL; Lipoproteins, LDL; Male; Random Allocation; Rats; Rats, Wistar; Streptozocin; Triglycerides

Diabetic neuropathy is one of the most frequent complications of diabetes. Despite some studies, the exact mechanism of glucose neurotoxicity has not been fully elucidated. Increased reactive oxygen species (ROS) has proposed as a possible mechanism. Crocus sativus L. (saffron) has been known as a source of antioxidants. Therefore, neuroprotective effect of saffron extract, its active component crocin and gamma-glutamylcysteinylglycine (GSH) was studied in glucose-induced neurotoxicity, using PC12 cells as a suitable in vitro model of diabetic neuropathy. Cell viability was quantitated by MTT assay. ROS was measured using DCF-DA by flow cytometry analysis. The result showed that glucose (13.5 and 27 mg/ml) reduced the cell viability of PC12 cells after 4 days. Saffron extract (5 and 25 mg/ml), crocin (10 and 50 muM) and GSH (10 muM) could decrease this toxicity. Glucose toxicity was consistent with increased ROS production which reduced by saffron, crocin and GSH pretreatment. These results suggest saffron and its carotenoid crocin could be potentially useful in diabetic neuropathy treatment.

Topics: Animals; Antioxidants; Carotenoids; Cell Survival; Crocus; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dipeptides; Disease Models, Animal; Glucose; Humans; Neuroprotective Agents; Oxidative Stress; PC12 Cells; Plant Extracts; Rats; Reactive Oxygen Species