Autoimmune thyroid disorders and polycystic ovary syndrome: Tracing links through systematic review and meta-analysis.

Polycystic Ovary Syndrome (PCOS) and Autoimmune Thyroiditis (AIT) are two prevalent endocrine disorders affecting women, often coexisting within the same patient population. This meta-analysis aims to systematically assess and synthesize the existing body of literature to elucidate the intricate relationship between PCOS and AIT. A systematic literature search for relevant observational studies was conducted in electronic databases such as Web of Science, Google Scholar, PubMed, Cochrane, and Scopus until March 2023. All Statistical analyses were performed using CMA Software v3.7 in a random-effects network meta-analysis. In addition, sensitivity and meta-regression analyses were conducted to identify sources of Heterogeneity based on related risk factors. Our meta-analysis included eighteen studies with 3657 participants, which revealed significant differences between PCOS patients and control groups. In particular, a considerable association was detected between PCOS and the presence of AIT (OR = 2.38; 95% CI: 1.63-3.49; P< 0.001) and elevated levels of TSH (SMD = 0.24; 95% CI: 0.06-0.42; P= 0.01), anti-TPO (SMD = 0.36; 95% CI: 0.19-0.53; P< 0.001), anti-TG (SMD = 1.24; 95% CI: 0.37-2.10; P< 0.001), and other positive serum antibodies compared to the control groups. The findings from this meta-analysis may contribute to enhanced diagnostic strategies like complete thyroid function tests, more targeted interventions, and improved patient care for individuals presenting with both PCOS and AIT. Additionally, identifying commonalities between these conditions may pave the way for future research directions, guiding the development of novel therapeutic approaches that address the interconnected nature of PCOS and AIT.

Association of Free Radical Product and Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine disorder that primarily affects women of reproductive age. It is recognized as the leading cause of infertility due to anovulation. This research aims to evaluate the diagnostic potential of oxidative stress biomarkers, including advanced oxidation protein products (AOPP), malondialdehyde (MDA), uric acid (UA), and nitric oxide (NO), in identifying PCOS. METHODS: A literature search was conducted in the EMBASE, PubMed, Cochrane Library, and Scopus databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were employed to assess the correlation between free radical product and PCOS. Moreover, the presence of heterogeneity among the studies was assessed utilizing the I2 statistic and Cochran Q test. The methodological rigor of the incorporated studies was assessed through the application of the Newcastle-Ottawa Scale. Furthermore, the presence of publication bias was determined via Begg and Egger tests. RESULTS: This meta-analysis reviewed 38 observational studies, including 17,845 women. The results revealed a significant association between PCOS in women and alterations in free radical levels. The study revealed that the PCOS group had significantly higher levels of AOPP (SMD = 3.193; 95% CI, 2.86 to 3.25), UA (SMD = 0.68; 95% CI, 0.24 to 1.13), and MDA (SMD = 1.16; 95% CI, 0.77 to 1.56) compared to the healthy control group. Furthermore, the analysis found a significantly lower level of NO (SMD = (- 0.59); 95% CI, - 1.15 to - 0.03) in the PCOS patient. CONCLUSION: Screening of specific biomarkers associated with free radical products could provide valuable benefits in the prognosis and diagnosis of PCOS.

Comparison of the anti-inflammatory and antilipidemic activity of diosmin and saroglitazar in a model of nonalcoholic fatty liver induced by a high-fat diet in Wistar rats.

Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common liver-related metabolic disorder in the world, with a global prevalence of 25%. Compounds with anti-inflammatory, lipid-lowering, and insulin-sensitizing properties can be used for the prevention or treatment of NAFLD. Therefore, this study was conducted to investigate the effect of saroglitazar (a dual PPARα/γ agonist) and diosmin (a flavonoid) on non-alcoholic fatty liver induced by a high-fat diet (HFD) in Wistar rats. Materials and Methods: Forty male Wistar rats (6-8 weeks old) were fed an HFD to induce NAFLD. After 7 weeks, rats were divided into four groups: group1 was fed HFD, and the other groups received HFD+saroglitazar, HFD+diosmin, and HFD+ saroglitazar+diosmin. We examined body and liver weight, histopathology, serum levels of liver enzymes (ALT and AST), and lipid profiles (LDL-C and HDL-C) using the standard protocols. qRT-PCR was also used to examine the expression of PPARα, PPARγ, SREBP1c, FAS, ACC, CPT1α, and pro-inflammatory genes (IL6, TNFα, and TGFß). Results: Rats fed the HFD showed characteristics of NAFLD (pathologically and biochemically). Administration of saroglitazar and diosmin alone caused a significant decrease in the levels of PPARγ, SREBP1c, FAS, ACC, ALT, AST, LDL-C, and pro-inflammatory genes and a significant increase in PPARα, CPT1a, and HDL-C in comparison with the HF group (P<0.05). Their combined effect was more evident. Conclusion: Our results showed that diosmin, like saroglitazar, significantly ameliorated inflammatory and lipid profiles in HFD-induced NAFLD, suggesting that diosmin, as a natural compound, could be a suitable alternative to saroglitazar.

Circulating nesfatin-1 levels in women with polycystic ovary syndrome: A systematic review and meta-analysis.

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in females. Nesfatin-1 is a neuropeptide synthesized in the hypothalamus and other peripheral organs, and there are conflicting opinions about its correlation with PCOS. Objective: This study aims to investigate the correlation between nesfatin-1 and PCOS and evaluates the effectiveness of nesfatin-1 as a biomarker for the detection of PCOS in women. Materials and Methods: A systematic review and meta-analysis were conducted to identify pertinent articles from databases such as PubMed, Web of Science, Cochrane, EMBASE, Scopus, and Google Scholar. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using a random effects model to compare group outcomes. Additionally, meta-regression and subgroup analysis were performed to elucidate sources of heterogeneity. Results: The meta-analysis involved 12 studies with 1222 participants, and the findings revealed a significant relationship between PCOS and nesfatin-1 levels. The pooled (SMD = 0.54; 95% CI: 0.00-1.07; p = 0.04) indicated a significant difference between the evaluated groups. Moreover, a subgroup analysis showed that there was a substantial difference in nesfatin-1 levels among women with PCOS and higher homeostatic model assessment for insulin resistance ratio (SMD = 1.46; 95% CI: 0.92-2.00; p < 0.001). Conclusion: Our meta-analysis indicates an association between high nesfatin-1 levels and PCOS. This suggests a potential role of nesfatin-1 in the development of PCOS and proposes it as a potential diagnostic biomarker for the disease. However, further research is necessary to validate these findings.

The Effect of Lipopolysaccharide-Stimulated Adipose-Derived Mesenchymal Stem Cells on NAFLD Treatment in High-Fat Diet-Fed Rats.

Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are 2 common liver diseases that currently lack effective treatment options. Objectives: This study aimed to investigate the effect of lipopolysaccharide (LPS)-stimulated adipose-derived stem cells (ADSCs) on NAFLD treatment in an animal model. Methods: Male Wistar rats were fed a high-fat diet (HFD) to induce NAFLD for 7 weeks. The rats were then categorized into 3 groups: Mesenchymal stem cell (MSC), MSC + LPS, and fenofibrate (FENO) groups. Liver and body weight were measured, and the expression of genes involved in fatty acid biosynthesis, ß-oxidation, and inflammatory responses was assessed. Results: Lipopolysaccharide-stimulated ADSCs were more effective in regulating liver and body weight gain and reducing liver triglyceride (TG) levels compared to the other groups. Treatment with LPS-stimulated ADSCs effectively corrected liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and lipid factors, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) values, better than treatment with both FENO and MSCs. ADSCs + LPS treatment significantly decreased transforming growth factor ß (TGF-ß) and genes associated with inflammatory responses. Additionally, there was a significant reduction in reactive oxygen species (ROS) levels in the rats treated with ADSCs + LPS. Conclusions: Lipopolysaccharide-stimulated ADSCs showed potential in alleviating NAFLD by reducing inflammatory genes and ROS levels in HFD rats, demonstrating better results than treatment with ADSCs and FENO groups alone.

Hepatoprotective effects of gentisic acid through its anti-oxidant properties in nicotinamide-streptozotocin induced diabetic mice.

Objectives: Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that causes many complications. Liver failure is one of the complications of T2DM. Oxidative stress plays a major role in the development and progression of T2DM-induced liver injury. Gentisic acid (GA) is a metabolite of aspirin and also a phenolic compound found in natural sources that is a highly effective antioxidant and free radical scavenger. So, in this study, the potential preventive benefits of GA against liver damage induced by T2DM were explored. Materials and Methods: This study was conducted on 24 adult male mice. T2DM was induced by intraperitoneal injection of a single dose of streptozotocin (at a dose of 65 mg/kg), 15 min after the injection of nicotinamide (at a dose of 120 mg/kg). The grouping was as follows: 1) Normal Control Group; 2) Diabetic Control Group; 3) Positive Control Group: received metformin (150 mg/kg body weight daily) through gavage; 4) Treatment Group: received GA at the dose of 100 mg/kg body weight daily through gavage. Treatments continued for two weeks. Results: Two weeks of GA treatment in diabetic mice reduced fasting blood glucose, improved plasma levels of hepatic enzymes, and increased liver tissue antioxidant capacity. Histopathological examination revealed that GA administration reduced diabetes-induced liver damage. Furthermore, GA treatment led to the down-regulation of Kelch-like ECH-associated protein 1 (Keap1) and up-regulation of nuclear factor E2-related factor 2 (Nrf2). Conclusion: The results of this study showed that GA exerts hepatoprotective effects in STZ-induced T2DM mice.

The association between the dietary inflammatory index and gestational diabetes mellitus: A systematic review of observational studies.

BACKGROUND & AIMS: Unhealthy dietary habits contribute to low-grade chronic inflammation that is known to be associated with metabolic disorders and pregnancy complications such as gestational diabetes mellitus (GDM). The dietary inflammatory index (DII) is a scoring system for assessing the inflammatory potential of various nutrients and foods. This systematic review aims to investigate the current state of evidence on the association between DII and GDM in pregnant women. METHODS: PubMed, Scopus and Web of Science electronic databases were systematically searched for relevant English-language articles published up to February 2023. This study was developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (CRD42022382813). RESULTS: This review included seven studies (98,115 participants) from five countries. In total, two case-control studies have shown a positive association between DII and GDM. In contrast, three of five cohort studies found no association between dietary inflammatory potential and the risk of developing GDM. CONCLUSION: We found some controversial results due to the small number of studies, with major heterogeneity in research design and findings. Collectively, the current study does not support an association between the DII score and the risk of gestational diabetes. Further, longitudinal studies are needed to elucidate the association between dietary inflammatory potential and GDM.

The effects of rutin supplement on blood pressure markers, some serum antioxidant enzymes, and quality of life in patients with type 2 diabetes mellitus compared with placebo.

Background: This trial aimed to investigate the effects of rutin supplement in type 2 diabetes mellitus (T2DM) patients. Methods: In this trial with a double-blind and controlled design, fifty patients were randomly divided into intervention (n = 25) and control groups (n = 25) and were treated with 1 g of rutin or placebo for three months, respectively. At the baseline and end of the intervention, mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), systolic and diastolic blood pressure (SBP and DBP), serum levels of antioxidant enzymes, such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) and quality of life (QOL) parameters, were evaluated. Results: Rutin consumption caused a significant reduction in SBP, DBP, PP, MAP, and HR, with a significant increase in SOD, CAT, and GPx and some QOL parameters (emotional limitations, energy and freshness, mental health, social performance, and general health) compared with baseline (p for all <0.05). Also, the mean changes of emotional limitations, energy and freshness, mental health, and general health (unadjusted p for all <0.05) and GPX and SOD (adjusted p for all <0.05) were significantly higher in the rutin group compared with the placebo group. Although, in the supplement group compared with the placebo group, the mean changes of SBP, DBP, MAP, PP, and HR were significantly lower (adjusted p for all <0.05). Conclusion: Rutin consumption improved blood pressure, the levels of antioxidant enzymes, and QOL in patients with T2DM.

Gentisic acid ameliorates type 2 diabetes induced by Nicotinamide-Streptozotocin in male mice by attenuating pancreatic oxidative stress and inflammation through modulation of Nrf2 and NF-кB pathways.

AIMS: There is a close link between oxidative stress, inflammation, and type 2 diabetes mellitus (T2DM). Gentisic acid (GA) is a di-phenolic compound and an active metabolite of aspirin that possesses antioxidant and anti-inflammatory properties, but its potential anti-diabetic effects have not been evaluated so far. Therefore, this study aimed to evaluate GA's potential antidiabetic effects through the Nuclear Factor Erythroid 2-Related Factor (Nrf2) and Nuclear Factor Kappa Beta (NF-кB) signaling pathways. MATERIAL AND METHODS: In this study, T2DM induced by a single intraperitoneal injection of STZ (65 mg/kg B.W) after 15 min nicotinamide (120 mg/kg B.W) injection. After seven days of injections, fasting blood glucose (FBS) was measured. Seven days after FBS monitoring treatments started. Grouping and treatments were as follows: 1) Normal control group; NC, 2) Diabetic control group; DC, 3) Metformin group; MT (150 mg/kg B.W, daily), 4) Test group; GA (100 mg/kg B.W, daily). Treatments continued for 14 consecutive days. KEY FINDINGS: Diabetic mice treatment with GA significantly decreased FBS, improved plasma lipid profiles and pancreatic antioxidant status. GA modulated Nrf2 pathway by upregulation of Nrf2 protein, NAD(P)H: quinone oxidoreductase 1 (Nqo1), and p21, and downregulation of miR-200a, Kelch-like ECH-associated protein 1 (Keap1), and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2). Also, GA attenuated inflammation by upregulation of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and interleukin-10 (IL-10) and downregulation of miR-125b, NF-кB, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß). SIGNIFICANCE: GA attenuates T2DM, possibly by improving antioxidant status through the Nrf2 pathway and attenuation of inflammation.

Gentisic acid protects against diabetic nephropathy in Nicotinamide-Streptozotocin administered male mice by attenuating oxidative stress and inflammation: The role of miR-200a/Keap1/Nrf2 pathway, renin-angiotensin system (RAS) and NF-кB.

Oxidative stress and inflammation play a pivotal role in the pathogenesis of diabetic nephropathy (DN). Local renin-angiotensin systems (RAS) contribute to the pathogenesis and progression of DN by exacerbating oxidative stress and inflammation.Gentisic acid (GA), a phenolic compound and also a metabolite of aspirin, is reported to possess antioxidant and anti-inflammatory properties. However, the protective effects of GA against DN remain to be elucidated. Nicotinamide (120 mg/kg) and streptozotocin (65 mg/kg) were used to induce diabetes in male mice. Oral administration of GA once daily for 2 weeks (100 mg/kg) ameliorated diabetes-induced renal injury by reducing plasma creatinine, urea, blood urea nitrogen, and urinary albuminuria levels. Diabetic mice showed a significant increase in total oxidant status and malondialdehyde, along with decreased catalase, superoxide dismutase, and glutathione peroxidase in the kidney tissue, which was ameliorated in the GA-treated mice. Histopathological analysis showed that GA treatment reduced diabetes-induced renal injury. Furthermore, GA treatment was associated with the downregulation of miR-125b, nuclear factor kappa beta (NF-кB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and upregulation of interleukin-10 (IL-10), miR-200a, and nuclear factor erythroid 2-related factor 2 (Nrf2) in the renal tissue. GA treatment also downregulated angiotensin-converting enzyme 1 (ACE1), angiotensin II receptor 1 (AT1R), and NADPH oxidase 2 (NOX 2) and upregulated angiotensin-converting enzyme 2 (ACE2). In conclusion, the ameliorative effects of GA against DN may be attributed to its powerful antioxidant and anti-inflammatory properties through the downregulation of NF-кB, upregulation of Nrf2, and modulation of RAS in renal tissue.

Protective effects of crocin and gallic acid on the liver damage induced by methylglyoxal in male mice: role of inflammatory factors.

Aim: This study aims to evaluate whether biochemical alterations caused by methylglyoxal (MG), improves by the administration of gallic acid (GA), crocin (Cr), and metformin (MT) in the liver. Background: MG is produced naturally through various physiological processes, but high levels of MG cause inflammation in hepatocytes. Normal liver function is essential for maintaining glucose homeostasis. Gallic acid and crocin can reduce inflammation. Methods: This experiment was done in 5 weeks. 50 male NMRI mice were randomly divided into 5 groups (n=10): 1) Control, 2) MG (600 mg/Kg/d, p.o.), 3) MG+GA (30 mg/kg/day, p.o.), 4) MG+Cr (60 mg/kg/day, p.o.), 5) MG+MT (150 mg/kg/day, p.o.). After one week of habituation, MG was administered for four weeks. Gallic acid, crocin, and metformin were administered in the last two weeks. Biochemical and histologic evaluations were assessed after plasma collection and tissue sample preparation. Results: Gallic acid and crocin-received groups significantly reduced fasting blood glucose, total cholesterol, triglyceride levels, and elevated insulin sensitivity. Administration of MG exerted a marked increase in the levels of hepatic enzymes. Treatment with gallic acid, crocin, and metformin significantly decreased them. The altered levels of inflammatory factors in the diabetic group were significantly improved in the diabetic-treated groups. High levels of steatosis and red blood cells (RBCs) accumulation in the MG group markedly recovered in other treated mice. Conclusion: Harmful effects of accumulated MG in the liver of diabetic mice were effectively attenuated by using gallic acid and crocin.

Diabetic nephropathy induced by methylglyoxal: gallic acid regulates kidney microRNAs and glyoxalase1-Nrf2 in male mice.

BACKGROUND: Methylglyoxal (MG) has been reported to be a toxic by-product of glycolysis and intracellular stressor compound. This study investigated the effects of gallic acid (GA) against diabetic nephropathy (DN) induced by MG in male mice. METHODS: DN was induced by methylglyoxal (600 mg/kg/day, p.o.) treated for 28 consecutive days. The animals received GA (30 mg/kg/day, p.o.) and metformin (MT) (150 mg/kg/day, p.o.) for 7 consecutive days after diabetes induction. Biochemical assays, antioxidant evaluation, microRNAs associated with fibrosis, endoplasmic reticulum stress, and histopathological analysis were examined. RESULTS: MG increased malondialdehyde, albuminuria, Nrf2, miR-192 and miR-204 expression in diabetic groups and GA decreased them. Superoxide dismutase, catalase, glyoxalase1, and miR-29a expression decreased in diabetic groups and increased in treatment with GA. CONCLUSION: Our results revealed that GA has improved DN induced by MG via amelioration of biochemical indices, histopathological aspects, oxidative stress and microRNAs associated with endoplasmic reticulum stress and fibrosis.

Evaluation of the protective effects of berberine and berberine nanoparticle on insulin secretion and oxidative stress induced by carbon nanotubes in isolated mice islets of langerhans: an in vitro study.

The increasing use of single-walled carbon nanotubes (SWCNT) in various fields highlights the need to investigate the test toxicity of these nanoparticles in humans. Previous documents showed that SWCNT induced oxidative stress. Oxidative stress and reactive oxygen species (ROS) cause cell dysfunction and reduced insulin secretion. Therefore, this study aimed to investigate the effects of SWCNT on oxidative stress and insulin secretion of islets also evaluate the protective effects of berberine (BBR) and berberine nanoparticles (NP-BBR) as antioxidants on pancreatic ß-islets. Double emulsion with solvent evaporation was the technique used to prepare nanoparticles in this study. Islets were isolated and pretreated with various concentrations of BBR and NP-BBR and then treated with single dose of SWCNT (160 µg). The results of this study showed that SWCNT decreased cell viability based on MTT assay, reduced insulin secretion of islets, increased malondialdehyde (MDA) amounts, reactive oxygen species (ROS) levels, reduced glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities, whereas pretreatment of islets with low doses of BBR (5 and 15 µM) and NP-BBR (5 µM) significantly reversed all changes induced by SWCNT. These findings suggested that SWCNT might trigger other pathways involved in insulin secretion by activating the oxidative stress pathway in the pancreatic islets, reducing insulin secretion, consequently diabetes. BBR and NP-BBR as antioxidants were able to protect pancreatic ß-islets and prevent the progression of diabetes.

Crocin attenuates endoplasmic reticulum stress in methylglyoxal-induced diabetic nephropathy in male mice: MicroRNAs alterations and glyoxalase 1-Nrf2 signaling pathways.

Objectives: Accumulation of methylglyoxal (MGO) occurs in diabetes. MicroRNA-204 is an important intracellular marker in the diagnosis of endoplasmic reticulum stress. Crocin (Crn) has beneficial effects for diabetes, but the effect of Crn on MGO-induced diabetic nephropathy has not been investigated. The current research evaluated the effects of Crn and metformin (MET) on diabetic nephropathy induced by MGO in male mice. Materials and Methods: In this experimental study, 70 male NMRI mice were randomly divided into 7 groups: control, MGO (600 mg/Kg/d), MGO+Crn (15, 30, and 60 mg/kg/d), MGO+MET (150 mg/kg/d), and Crn60 (60 mg/kg/d). Methylglyoxal was gavaged for four weeks. After proving hyperglycemia, Cr and MET were administered orally in the last two weeks. Biochemical and antioxidant evaluations, microRNA expression, and histological evaluation were assessed. Results: The fasting blood glucose, urine albumin, blood urea nitrogen, plasma creatinine, malondialdehyde, Nrf2, miR-204, and miR-192 expression increased in the MGO group. These variables decreased in Crn-treated animals. The decreased levels of superoxide dismutase, catalase, glyoxalase 1, Glutathione, and miR-29a expression in the MGO group improved in the diabetic-treated mice. Histological alterations such as red blood cell accumulation, inflammation, glomerulus diameter changes, and proximal cell damage were also observed. Conclusion: Our study indicated that Crn and MET attenuated renal damage by inhibiting endoplasmic reticulum stress.

The Dietary Inflammatory Index is positively associated with cardiometabolic risk parameters in atherosclerosis patients.

Inflammation is implicated in the development and progression of a variety of cardiovascular diseases. We hypothesized that the Dietary Inflammatory Index (DII) is associated with anthropometric indices and metabolic parameters in Iranian atherosclerosis patients. The present cross-sectional study was conducted on 320 Iranian atherosclerosis patients. The DII was estimated using a valid and reliable 168-item food frequency questionnaire. Odds ratios and 95% confidence intervals were evaluated for anthropometric indices and metabolic parameters according to the DII score. Linear regression was used to estimate the relationship between DII scores with atherosclerosis-related dependent variables. According to the continuous score of DII, there was no significant association between DII and odds of obesity, total cholesterol/high-density lipoprotein cholesterol ratio, and aspartate aminotransferase/alanine aminotransferase ratio in all 3 models (P ≥ .05). In linear regression analysis, we found a significant association between DII score and fasting blood sugar, lipid profile (except for high-density lipoprotein cholesterol), liver enzymes (except for alkaline phosphatase), and serum sodium in adjusted models (P < .05). In this study, patients with atherosclerosis consuming a pro-inflammatory diet was positively associated with fasting blood sugar, lipid, and liver enzymes measures. Future studies with prospective and interventional designs are required to clarify the association between this dietary index and cardiovascular disease risk factors among patients with atherosclerosis.

Crocin ameliorates MicroRNAs-associated ER stress in type 2 diabetes induced by methylglyoxal.

Objectives: Methylglyoxal (MG) provokes endoplasmic reticulum (ER) stress in ß-cells and triggers pancreatic ß-cell dysfunction. Crocin has anti-diabetic properties. The present study investigated whether crocin prevented pancreas damages induced by MG. Materials and Methods: Diabetes was induced by MG administration (600 mg/kg/day, PO). On the fourteenth day, after proving hyperglycemia, crocin (15, 30, and 60 mg/kg) and metformin (MT) (150 mg/kg) were used for detoxification of MG until the end of the experiment. The animals were divided into 6 groups: 1) control, 2) diabetic by MG, 3) MG + crocin 15 mg/kg, 4) MG + crocin 30 mg/kg, 5) MG + crocin 60 mg/kg, and 6) MG + MT. The data were analyzed by one-way analysis of variance and significant differences were compared by Tukey and Bonferroni tests (P<0.05). Biochemical assays, antioxidant evaluation, and microRNAs expression associated with ER stress were assessed. Results: MG induced hyperglycemia, insulin resistance, and dyslipidemia (P<0.001). Crocin and MT significantly ameliorated ß-cell function through reduction of fasting blood glucose, malondialdehyde levels (P<0.001), and significant elevation of anti-oxidant enzyme activity accompanied by regulation of glutathione and glyoxalase1-Nrf2 in MG induced diabetic mice. Crocin and MT significantly down-regulated microRNAs 204, 216b, 192, and 29a expression (P<0.001). Crocin (60 mg/kg) (P<0.01) and MT (P<0.001) could improve diameter of pancreatic islets in MG treated mice. Conclusion: Crocin prevents the progression of diabetes through modulating ER stress-associated microRNAs and GLO1 activity with the helpful effects of glutathione and Nrf2.

Gallic Acid and Gallic Acid Nanoparticle Modulate Insulin Secretion Pancreatic ß-Islets against Silica Nanoparticle-Induced Oxidative Damage.

Due to the increasing use of silica nanoparticles (SiNPs), their possible toxic effects on human health have undoubtedly been considered. Previous studies proved that SiNPs induced oxidative stress. Reactive oxygen species (ROS) and oxidative stress disrupt cell function and decrease insulin secretion. Therefore, this study intended to assess the effects of SiNPs on oxidative stress and insulin secretion and also the protective effects of gallic acid (GA) and gallic acid nanoparticles (NP-GA) on pancreatic ß-islets. In this study, the mice islets were separated and pretreated with various concentrations of GA and NP-GA then treated with a single dose of SiNPs. The cell viability of islets examined by MTT assay and also the levels of ROS, malondialdehyde (MDA), glutathione (GSH); activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and insulin secretion were evaluated. The results of MTT assay showed that SiNPs reduced islet viability in a dose-dependent manner and also insulin secretion, induced the formation of ROS, augmented MDA amounts, and decreased GSH levels, SOD, GPx, and CAT activities. Furthermore, pretreatment of islets with GA and NP-GA significantly returned these alterations at low dose. These findings suggested that SiNPs induced oxidative stress in the pancreatic islets, which could be one of the reasons for the decrease in insulin secretion and inducing diabetes. This study also showed that low doses of GA and NP-GA boosted the antioxidant defense system in the pancreatic ß-islets, preventing oxidative stress and, consequently, the progression of diabetes.

Myricitrin and Its Solid Lipid Nanoparticle Increase Insulin Secretion and Content of Isolated Islets from the Pancreas of Male Mice

Abstract Glucose exposure induces toxic effects on the function of the pancreatic islets. Moreover, myricitrin as a flavonoid glycoside may have favorable effects on insulin secretion of Langerhans islets. The present study aimed to investigate the effect of Myricitrin and its solid lipid nanoparticles (SLN) on the insulin secretion as well as the content of isolated pancreatic islets from male mice. In this experimental study, Langerhans islets were separated from adult male NMRI mice using the collagenase method. The insulin secretion and content of islets were assessed in glucose-containing medium (2.8, 5.6, and 16.7mM). Further, islets treated were prepared by the administration of Myricitrin and its SLN (1, 3 and 10µM). Myricitrin 3µM, and SLN containing Myricitrin 3 and 10µM increased insulin secretion in medium containing glucose concentration 2.8mM. Accordingly, this variable increased in Myricitrin 3 and 10µM, SLN containing Myricitrin 1, 3, and 10µM utilization as well as glucose concentration 5.6mM. Afterward, the insulin secretion increased in medium containing 16.7mM glucose after the addition of Myricitrin and SLN containing Myricitrin 1, 3, and 10µM. Also, the insulin content increased in Myricitrin and SLN containing Myricitrin 1, 3, and 10µM administered groups in all medium containing glucose concentrations. Myricitrin and its SLN increased islets insulin secretion and content in low, moderate, and high glucose concentration mediums

The effects of gallic acid and metformin on male reproductive dysfunction in diabetic mice induced by methylglyoxal: An experimental study.

BACKGROUND: Diabetes mellitus is a disease that has reached a dangerous point. Today, nearly 500 million men and women around the world live with diabetes. Gallic acid (Gal) affects diabetes. OBJECTIVE: To evaluate the effects of Gal and metformin (met) on the levels of glucose, insulin, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sperm count, antioxidant status, and histological changes in the testes of diabetic mice induced by methylglyoxal (MGO). MATERIALS AND METHODS: In this experimental study, 50 male adult NMRI mice, weighting 25-30 gr, aged 3-4 months were randomly divided into five equal groups (n = 10/each). (i) Control (vehicle, normal saline), (ii) MGO (600 mg/kg/d) orally for 28 days, (iii) Gal (50 mg/kg/d), (iv) MGO+Gal, and (v) MGO+met (200 mg/kg/d). Gal and met were administered orally for 21 consecutive days after the induction of diabetes. Blood samples were taken at 24 hr after the latest doses of treatment. Histological assessment of the testis was done, and the epididymis sperm count was obtained. Antioxidant indices, glucose, insulin, LH, FSH, and testosterone levels were measured. RESULTS: In the MGO group compared to the control group, insulin, glucose (p = 0.001), LH (p = 0.04) and malondialdehyde (p = 0.001) were increased. However, the level of testosterone (p = 0.001), seminiferous tubule diameters, epithelial height, sperm count, superoxide dismutase activity (p = 0.02), and testis volume (p = 0.01) were decreased. The results indicated that Gal and met ameliorated the MGO effects. CONCLUSION: These findings suggested that the animals receiving MGO became diabetic. According to the results, Gal and met can effectively prevent MGO-induced diabetes. The effect of Gal was equivalent and sometimes better than metformin.