Diacerein mitigates endocrine and cardio-metabolic disruptions in experimental PCOS mice model by modulating AdipoR1/ PON 1.

BACKGROUND: This study aimed to explore the impact of Diacerein (DIC) on endocrine and cardio-metabolic changes in polycystic ovarian syndrome (PCOS) mouse model. METHODS: A total of 18 adult female mice (Parkes strain), aged 4-5 weeks, were randomly assigned to three groups, each comprising 6 animals, as follows: Group I (control), received normal diet and normal saline as vehicle for 51 days; Group II received Letrozole (LET; 6 mg/kg bw) for 21 days to induce PCOS; Group III received LET, followed by daily oral gavage administration of DIC (35 mg/kg bw) for 30 days. RESULTS: This study indicates that treatment with LET resulted in PCOS with characteristics such as polycystic ovaries, elevated testosterone, weight gain, visceral adiposity, high levels of insulin as well as fasting blood glucose in addition to insulin resistance, improper handling of ovarian lipids, atherogenic dyslipidemia, impaired Na + /K + -ATPase activity and serum, cardiac, and ovarian oxidative stress. Serum/ovarian adiponectin levels were lowered in LET-treated mice. In mice treated with LET, we also discovered a reduction in cardiac and serum paraoxonase 1 (PON1). Interestingly, DIC restored ovarian andcardio-metabolic abnormalities in LET-induced PCOS mice. DIC prevented the endocrine and cardio-metabolic changes brought on by letrozole-induced PCOS in mice. CONCLUSION: The ameliorative effects of DIC on letrozole-induced PCOS with concurrent oxidative stress, abdominal fat deposition, cardiac and ovarian substrate mishandling, glucometabolic dysfunction, and adiponectin/PON1 activation support the idea that DIC perhaps, restore compromised endocrine and cardio-metabolic regulators in PCOS.

Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome.

Introduction: Polycystic Ovary syndrome (PCOS) affects the health of many women around theworld. Apart from fundamental metabolic problems connected to PCOS, focus of our study is on the role of quercetin on genes relevant to steroidogenesis and folliculogenesis. Methods: Eighteen mature parkes strain mice (4-5 weeks old) weighing18-21 g were randomly divided into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kgbw) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days. Results: In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH ratio, decreased estrogen level and decline in expression of Kitl, Bmp1, Cyp11a1, Cyp19a1, Ar, lhr, Fshr and Esr1 in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in cholesterol, triglycerides, testosterone, vascular endothelial growth factor VEGF and insulin levels. All these changes were reversed after the administration of quercetin in PCOS mice. Discussion: Quercetin treatment reversed the molecular, functional and morphological abnormalities brought on due to letrozole in pathological and physiological setting, particularly the issues of reproduction connected to PCOS. Quercetin doesn't act locally only but it acts systematically as it works on Pituitary (LH/FSH)- Ovary (gonad hormones) axis. the Side effects of Quercetin have to be targeted in future researches. Quercetin may act as a promising candidate for medical management of human PCOS.

Low-dose spironolactone combats dyslipidemia and hepatic inflammation by modulating PCSK9 in rat model of polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women and it is associated with overt metabolic derangement. Circulating lipids are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9) which blocks low density lipoprotein (LDL) receptors especially in the liver. The liver is highly vulnerable in dyslipidemia as lipid accumulation leads to progression of non-alcoholic fatty liver disease (NAFLD). An array of scientific endeavours hold that low-dose spironolactone (LDS) is beneficial as intervention for PCOS traits, but this claim is yet to be fully elucidated. The aim of this study was to investigate the effect of LDS on dyslipidemia and hepatic inflammation in rats with letrozole (LET)-induced PCOS and to assess the possible involvement of PCSK9 in these effects. Eighteen female Wistar rats were randomly assigned into 3 groups. The control group received vehicle (distilled water; p.o.), LET-treated group received letrozole (1 mg/kg; p.o.), LET+LDS-treated group received LET plus LDS (0.25 mg/kg, p.o.) for 21 days. Exposure to LET increased body and hepatic weights, plasma and hepatic total cholesterol (TC), TC/HDL, LDL, interleukin-6, MDA, PCSK9, ovarian degenerated follicles and hepatic NLRP3 intensity, reduced GSH and normal ovarian follicles. Interestingly, LDS averted dyslipidemia, NLRP3-dependent hepatic inflammation and ovarian PCOS traits. It is evident herein that LDS ameliorates PCOS traits and combats dyslipidemia and hepatic inflammation in PCOS by a PCSK9-dependent mechanism.

Chlorogenic Acid Restores Ovarian Functions in Mice with Letrozole-Induced Polycystic Ovarian Syndrome Via Modulation of Adiponectin Receptor.

Around the world, polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic condition that typically affects 6-20% of females. Our study's major goal was to examine how chlorogenic acid (CGA) affected mice with endocrine and metabolic problems brought on by letrozole-induced PCOS. Group I served as the control for 81 days; Group II was given Letrozole (LETZ) orally at a dose of 6 mg/kg bw for 21 days to induce PCOS; Group III was given LETZ (6 mg/kg) for 21 days, followed by treatment with CGA (50 mg/kg bw daily) for 60 days. The study indicated that LETZ-treated mice displayed symptoms of PCOS, such as dyslipidemia, hyperinsulinemia, elevated testosterone, increases in inflammatory markers and malonaldehyde, and a decline in antioxidants (Ar, lhr, fshr, and esr2) in the ovaries. These alterations were affected when the mice were given CGA and were associated with reduced levels of adiponectin. Adiponectin showed interactions with hub genes, namely MLX interacting protein like (MLXIPL), peroxisome proliferator-activated receptor gamma Coactivator 1- alpha (PPARGC1), peroxisome proliferator-activated receptor gamma (Pparg), and adiponectin receptor 1 (Adipor1). Lastly, the gene ontology of adiponectin revealed that adiponectin was highly involved in biological processes. The findings from our research suggest that adiponectin has direct impacts on metabolic and endocrine facets of PCOS.

Chitosan Nanoparticles: A Versatile Platform for Biomedical Applications.

Chitosan is a biodegradable and biocompatible natural polymer that has been extensively explored in recent decades. The Food and Drug Administration has approved chitosan for wound treatment and nutritional use. Furthermore, chitosan has paved the way for advancements in different biomedical applications including as a nanocarrier and tissue-engineering scaffold. Its antibacterial, antioxidant, and haemostatic properties make it an excellent option for wound dressings. Because of its hydrophilic nature, chitosan is an ideal starting material for biocompatible and biodegradable hydrogels. To suit specific application demands, chitosan can be combined with fillers, such as hydroxyapatite, to modify the mechanical characteristics of pH-sensitive hydrogels. Furthermore, the cationic characteristics of chitosan have made it a popular choice for gene delivery and cancer therapy. Thus, the use of chitosan nanoparticles in developing novel drug delivery systems has received special attention. This review aims to provide an overview of chitosan-based nanoparticles, focusing on their versatile properties and different applications in biomedical sciences and engineering.

Vitamin C mitigates hematological and biochemical alterations caused by di(2-ethylhexyl) phthalate toxicity in female albino mice, Mus musculus.

Di(2-ethylhexyl) phthalate (DEHP) is ubiquitous environmental contaminant and identified as endocrine-disrupting chemical (EDC), present in plastics as plasticizer. Due to its versatile use, human exposure level reaches to danger limit. The main focus of our study is to see the effect of vitamin C on hematological and biochemical alterations caused by Di(2-ethylhexyl) Phthalate toxicity in female albino mice, Mus musculus. It is found to cause defects of the liver, kidney, and lungs. Its anti-androgenic nature brings the main focus on its toxicity associated with reproductive and endocrine system. In this experimental study, 18 young female Swiss albino mice, Mus musculus, were used and divided into 3 groups of 6 animals each as control (corn oil vehicle), DEHP group (100 mg/kg body weight dissolved in corn oil), and DEHP + vitamin-C group (100 mg/kg body weight each, dissolved in corn oil and double distilled water, respectively) for 90 days. In this research, serum metabolites were evaluated to study the effect of DEHP on glucose, total protein, and lipid profile along with some hematological, enzymological, and oxidative stress parameters. Simultaneously, we compared the effectiveness of vitamin-C against DEHP toxicity to mitigate the serum homeostasis disturbance. In present study, we observed, in DEHP-treated animals, glucose, triglycerides, very-low-density lipoprotein (VLDL), total protein, alkaline phosphatase (ALP), acid phosphatase (ACP), and alanine aminotransferase (ALT) levels increased remarkably, whereas total cholesterol, high-density lipoproteins (HDL), aspartate aminotransferase (AST), total RBC count, total WBC count, and hemoglobin (Hb) level significantly decreased as compared to control group. In addition, we noticed there was a decrease in superoxide dismutase (SOD) and increase in levels of lipid peroxidation (MDA) and interleukin-6 (IL-6) in DEHP treatment group as compared to control group. The results indicated vitamin C had a better improving effect against DEHP toxicity on balancing metabolic abnormalities and inflammation-related comorbidities.

Turmeric extract alleviates endocrine-metabolic disturbances in letrozole-induced PCOS by increasing adiponectin circulation: A comparison with Metformin.

One of the most common causes of female infertility is polycystic ovarian syndrome, which affects 6-21% of the population. Regrettably, the currently available treatments are mostly symptomatic and ineffective. As a result, safer options are needed now more than ever. In a letrozole PCOS albino mouse model, the current study compares the therapeutic advantages of Turmeric extract (Curcuma longa) to metformin. Adiponectin is a circulating protein generated by adipocytes that has been linked to metabolic diseases (MDs) in an inverse relationship. The effects of Turmeric Extract (Curcuma Longa) in contrast to Metformin, as well as the involvement of adiponectin in endocrine-metabolic abnormalities in experimentally induced PCOS mice model, were studied in this study. Letrozole (6 mg/kg) was administered orally (p.o) for 21 days to induce PCOS, followed by a dose of Turmeric Extract (Curcuma longa) (175 mg/kg and p.o) and Metformin (150 mg/kg) for 30 days, both with normal saline water (0.9%) as the carrier. The findings revealed that LET-treated mice displayed PCOS-like characteristics, such as higher LH levels, increased body weight growth, and ovarian morphology with numerous cysts, increase in fasting blood glucose, lipid profile, plasma lipid peroxidation (MDA) and IL-6, as well as a decrease in serum Progesterone, Estrogen, FSH, SOD and GSH levels in the ovary. These changes were linked to lower levels of circulating adiponectin and were reversed when treated Turmeric extract. By altering circulating androgen-adiponectin balance, the data implies that Turmeric extract alleviates endocrine-metabolic abnormalities and inflammation-related comorbidities associated with LET-induced PCOS.