Exploring the Therapeutic Potential of Natural Products in Polycystic Ovarian Syndrome (PCOS): A Mini-Review of Lipid Profile, Blood Glucose, and Ovarian Histological Improvements.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that is characterized by fluid-filled sacs in the ovaries and various symptoms, including high androgen levels, endometrial irregularities, and cysts. Although the main cause of PCOS remains unknown, it has been linked to genetic, endocrine, and metabolic factors, and there are several treatment options, including lifestyle modifications, medications, and surgery. Natural products such as medicinal plants and fruits are being explored as potential treatments for PCOS because of their bioactive compounds with pharmacological effects related to antioxidant, antimicrobial, anticancer, and antidiabetic properties. Some of these compounds improve insulin sensitivity, reduce inflammation, and enhance glucose metabolism, thereby benefiting patients with PCOS. This mini-review examined the effects of natural products on PCOS, including their effects on ovarian histological changes, blood glucose, sex hormones, and lipid profiles, based on animal and human studies. This study suggests that the use of natural products as complementary medicines can be a promising resource for the development of effective therapeutics for PCOS; however, further research is needed to fully understand their benefits.

Potential Roles of microRNAs for Assessing Cardiovascular Risk in Pre-Eclampsia-Exposed Postpartum Women and Offspring.

Pre-eclampsia, which is part of the spectrum of hypertensive pregnancy disorders, poses a significant health burden, contributing to maternal and infant morbidity and mortality. Pre-eclampsia is widely associated with persistent adverse effects on the cardiovascular health of women with a history of pre-eclampsia. Additionally, there is increasing evidence demonstrating that offspring of pre-eclamptic pregnancies have altered cardiac structure and function, as well as different vascular physiology due to the decrease in endothelial function. Therefore, early detection of the likelihood of developing pre-eclampsia-associated cardiovascular diseases is vital, as this could facilitate the undertaking of the necessary clinical measures to avoid disease progression. The utilisation of microRNAs as biomarkers is currently on the rise as microRNAs have been found to play important roles in regulating various physiological and pathophysiological processes. In regard to pre-eclampsia, recent studies have shown that the expression of microRNAs is altered in postpartum women and their offspring who have been exposed to pre-eclampsia, and that these alterations may persist for several years. This review, therefore, addresses changes in microRNA expression found in postpartum women and offspring exposed to pre-eclampsia, their involvement in cardiovascular disease, and the potential role of microRNAs to be used as predictive tools and therapeutic targets in future cardiovascular disease research.

Nicotine Impairs the Anti-Contractile Function of Perivascular Adipose Tissue by Inhibiting the PPARγ-Adiponectin-AdipoR1 Axis.

Nicotine is an addictive compound found in cigarette smoke that leads to vascular dysfunction and cardiovascular diseases. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the underlying vasculature through the production of adipokines, such as adiponectin, which acts on adiponectin receptors 1 (adipoR1) to cause vasorelaxation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates adiponectin gene expression and PVAT development. This study aimed to determine the effect of nicotine on the anti-contractile function of PVAT via the PPARγ-adiponectin-adipoR1 axis. Male Sprague Dawley rats were divided into a control group (given normal saline), a nicotine group (given 0.8 mg/kg of nicotine), and a nicotine + PPARγ agonist group (given nicotine and 5 mg/kg of telmisartan). Thoracic aorta PVAT was harvested after 21 days of treatment. The results showed that nicotine reduced the anti-contractile effect of PVAT on the underlying thoracic aorta. Nicotine also decreased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. Treatment with telmisartan restored the anti-contractile effect of PVAT and increased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. In conclusion, nicotine attenuates the anti-contractile function of PVAT through inhibition of the PPARγ-adiponectin-adipoR1 axis.

MicroRNAs in Endometriosis: Insights into Inflammation and Progesterone Resistance.

Endometriosis, a non-malignant gynecological disorder influenced by estrogen, involves the growth of endometrial tissue outside the uterus. Its development includes processes such as inflammation, progesterone resistance, angiogenesis, and cell proliferation. Epigenetic factors, particularly the dysregulation of microRNAs (miRNAs), have emerged as key factors in these mechanisms in endometriosis. This review aims to unveil the intricate molecular processes that control inflammation, progesterone resistance, and miRNA functions in endometriosis. In addition, it provides a comprehensive overview of the current understanding regarding the involvement of miRNAs in the inflammatory aspects of this condition. This synthesis encompasses research investigating the molecular underpinnings of inflammation, along with the biogenesis and roles of miRNAs in endometriosis. Furthermore, it examines human studies and functional analyses to establish the intricate connection between miRNAs, inflammation, and progesterone resistance in the context of endometriosis. The results highlight the significant impact of dysregulated miRNAs on the inflammatory pathways and hormonal imbalances characteristic of endometriosis. Consequently, miRNAs hold promise as potential non-invasive biomarkers and targeted therapeutic agents aimed at addressing inflammation and enhancing the response to progesterone treatment in individuals with endometriosis.

A Review of the Potential Health Benefits of Nigella sativa on Obesity and Its Associated Complications.

Obesity has become a worldwide epidemic and its prevalence continues to increase at an alarming rate. It is considered a major risk factor for the development of several comorbidities, including type 2 diabetes, stroke, other cardiovascular diseases and even cancer. Conventional treatments for obesity, such as dietary interventions, exercise and pharmacotherapy, have proven to have limited effectiveness and are often associated with undesirable side effects. Therefore, there is a growing interest in exploring alternative therapeutic approaches. Nigella sativa (NS), a medicinal plant with multiple pharmacological properties, has gained attention due to its potential role in the treatment of obesity and its associated complications. The aim of this review is therefore to assess the effects of NS on obesity and its complications and to provide insights into the underlying mechanisms. From this review, NS appears to play a complementary or supportive role in the treatment of obesity and its complications. However, future studies are needed to verify the efficacy of NS in the treatment of obesity and its complications and to prove its safety so that it can be introduced in patients with obesity.

Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review.

The homeobox A10 (HOXA10) gene is known to be related to endometriosis; however, due to a lack of knowledge/evidence in the pathogenesis of endometriosis, the mechanisms that link HOXA10 to endometriosis still need to be clarified. This review addresses the difference in the expression of the HOXA10 gene in endometriotic women versus non-endometriotic women across populations by country and discusses its influences on women's fertility. An organized search of electronic databases was conducted in Scopus, ScienceDirect, PubMed, and Web of Science. The keywords used were (HOXA10 OR "homeobox A10" OR PL OR HOX1 OR HOX1H OR HOX1.8) AND ("gene expression") AND (endometriosis). The initial search resulted in 623 articles, 10 of which were included in this review. All ten papers included in this study were rated fair in terms of the quality of the studies conducted. The expression of the HOXA10 gene was found to be downregulated in most studies. However, one study provided evidence of the downregulation and upregulation of HOXA10 gene expression due to the localization of endometriotic lesions. Measuring the expression of the HOXA10 gene in women is clinically essential to predicting endometriosis, endometrial receptivity, and the development of pinopodes in the endometrium during the luteal phase.

Hyperandrogenism and Its Possible Effects on Endometrial Receptivity: A Review.

Endometrial receptivity is a state of the endometrium defined by its readiness for embryo implantation. When the receptivity of the endometrium is impaired due to hyperandrogenism or androgen excess, this condition can lead to pregnancy loss or infertility. Hyperandrogenism encompasses a wide range of clinical manifestations, including polycystic ovary syndrome (PCOS), idiopathic hirsutism, hirsutism and hyperandrogaenemia, non-classical congenital adrenal hyperplasia, hyperandrogenism, insulin resistance, acanthosis nigricans (HAIR-AN), ovarian or adrenal androgen-secreting neoplasms, Cushing's syndrome, and hyperprolactinaemia. Recurrent miscarriages have been shown to be closely related to elevated testosterone levels, which alter the endometrial milieu so that it is less favourable for embryo implantation. There are mechanisms for endometrial receptivity that are affected by excess androgen. The HOXA gene, aVß3 integrin, CDK signalling pathway, MECA-79, and MAGEA-11 were the genes and proteins affect endometrial receptivity in the presence of a hyperandrogenic state. In this review, we would like to explore the other manifestations of androgen excess focusing on causes other than PCOS and learn possible mechanisms of endometrial receptivity behind androgen excess leading to pregnancy loss or infertility.

Phytofabrication of Selenium Nanoparticles with Moringa oleifera (MO-SeNPs) and Exploring Its Antioxidant and Antidiabetic Potential.

The advancement in nanotechnology is the trigger for exploring the synthesis of selenium nanoparticles and their use in biomedicine. Therefore, this study aims to synthesize selenium nanoparticles using M. oleifera as a reducing agent and evaluate their antioxidant and antidiabetic potential. Our result demonstrated a change in the color of the mixture from yellow to red, and UV-Vis spectrometry of the suspension solution confirmed the formation of MO-SeNPs with a single absorbance peak in the range of 240-560 nm wavelength. FTIR analysis revealed several bioactive compounds, such as phenols and amines, that could possibly be responsible for the reduction and stabilization of the MO-SeNPs. FESEM + EDX analysis revealed that the amorphous MO-SeNPs are of high purity, have a spherical shape, and have a size of 20-250 nm in diameter, as determined by HRTEM. MO-SeNPs also exhibit the highest DPPH scavenging activity of 84% at 1000 µg/mL with an IC50 of 454.1 µg/mL and noteworthy reducing ability by reducing power assay. Furthermore, MO-SeNPs showed promising antidiabetic properties with dose-dependent inhibition of α-amylase (26.7% to 44.53%) and α-glucosidase enzyme (4.73% to 19.26%). Hence, these results demonstrated that M. oleifera plant extract possesses the potential to reduce selenium ions to SeNPs under optimized conditions with notable antioxidant and antidiabetic activities.

Alcohol Dependence Modulates Amygdalar mTORC2 and PKCε Expression in a Rodent Model.

Multiple alcohol use disorder (AUD)-related behavioral alterations are governed by protein kinase C epsilon (PKCε), particularly in the amygdala. Protein kinase C (PKC) is readily phosphorylated at Ser729 before activation by the mTORC2 protein complex. In keeping with this, the current study was conducted to assess the variations in mTORC2 and PKCε during different ethanol exposure stages. The following groups of rats were employed: control, acute, chronic, ethanol withdrawal (EW), and EW + ethanol (EtOH). Ethanol-containing and non-ethanol-containing modified liquid diets (MLDs) were administered for 27 days. On day 28, either saline or ethanol (2.5 g/kg, 20% v/v) was intraperitoneally administered, followed by bilateral amygdala extraction. PKCε mRNA levels were noticeably increased in the amygdala of the EW + EtOH and EW groups. Following chronic ethanol consumption, the stress-activated map kinase-interacting protein 1 (Sin1) gene expression was markedly decreased. In the EW, EW + EtOH, and chronic ethanol groups, there was a profound increase in the protein expression of mTOR, Sin1, PKCε, and phosphorylated PKCε (Ser729). The PKCε gene and protein expressions showed a statistically significant moderate association, according to a correlation analysis. Our results suggest that an elevated PKCε protein expression in the amygdala during EW and EW + EtOH occurred at the transcriptional level. However, an elevation in the PKCε protein expression, but not its mRNA, after chronic ethanol intake warrants further investigation to fully understand the signaling pathways during different episodes of AUD.

From Teeth to Therapy: A Review of Therapeutic Potential within the Secretome of Stem Cells from Human Exfoliated Deciduous Teeth.

Stem cells derived from human exfoliated deciduous teeth (SHED) have emerged as an alternative stem cell source for cell therapy and regenerative medicine because they are readily available, pose fewer ethical concerns, and have low immunogenicity and tumourigenicity. SHED offer a number of advantages over other dental stem cells, including a high proliferation rate with the potential to differentiate into multiple developmental lineages. The therapeutic effects of SHED are mediated by multiple mechanisms, including immunomodulation, angiogenesis, neurogenesis, osteogenesis, and adipogenesis. In recent years, there is ample evidence that the mechanism of action of SHED is mainly due to its paracrine action, releasing a wide range of soluble factors such as cytokines, chemokines, and trophic factors (also known as 'secretome') into the local tissue microenvironment to promote tissue survival and recovery. This review provides an overview of the secretome derived from SHED and highlights the bioactive molecules involved in tissue regeneration and their potential applications in regenerative medicine.

Beneficial Effects of Probiotics on Benign Gynaecological Disorders: A Review.

Probiotics are live microorganisms that confer beneficial effects on human health when an adequate dose is administered. Recently, the use of probiotics has gained tremendous interest from the public due to its promising effects in the management of various reproductive diseases. However, the review of probiotics' benefits on benign gynaecological disorders, including vaginal infections, polycystic ovary syndrome (PCOS) and endometriosis, remains scarce. Therefore, this review is built on current knowledge on the beneficial effects of probiotics against selected benign gynaecological disorders. Recent findings point out that probiotics' supplementation in different clinical and in vivo models showed promising health effects and results in the amelioration of disease symptoms. Thus, in this review, we showed the findings of both studies performed in clinical settings and animal studies. However, current information, solely based on clinical trials or animal studies, is inadequate in communicating the excellent findings on the beneficial effects of probiotics on human health. Therefore, future clinical intervention studies are required to further elucidate the evidence of the benefits of probiotics benefits regarding these gynaecological disorders.

Protective Role of Kelulut Honey against Toxicity Effects of Polystyrene Microplastics on Morphology, Hormones, and Sex Steroid Receptor Expression in the Uterus of Rats.

BACKGROUND: Microplastics (MPs) are an emerging global pollutant. Previous studies have revealed that chronic exposure to MPs can affect animal and human reproductive health, particularly by impairing the reproductive system's normal functions, which may increase the risk of infertility in both males and females. Kelulut honey (KH), an excellent source of antioxidants, has been used to counteract the disruptive effects of Polystyrene microplastics (PS-MPs) in the rat uterus. Thus, this study aimed to investigate the potential protective effects of Kelulut honey against PS-MPs-induced uterine toxicity in pubertal rats. METHODS: Prepubertal female Sprague Dawley rats were divided into four groups (n = 8): (i) normal control group (NC: treated with deionized water), MPs-exposed group (M: exposed to PS-MPs at 2.5 mg/kg), (iii) Kelulut honey group (DM: pretreated with 1200 mg/kg of KH 30 minutes before they were administered with PS-MPs at 2.5 mg/kg), and (iv) Kelulut honey control group (DC: only treated with KH at 2.5 mg/kg). The rats were treated orally once daily for six consecutive weeks. RESULTS: Uterine abnormalities in PS-MPs-exposed rats were significantly improved after concurrent treatment with Kelulut honey. Morphology improvement was observed and luminal epithelial cells seemed thicker with more goblet cells, glandular cells had a more regular and circular shape, stromal cell increased in size, interstitial gaps between stromal cells expanded, and the myometrium layer was thicker. Kelulut honey treatment also effectively normalized the suppressive effect of PS-MPs on the expression and distribution of sex steroid receptors (ERα and ERß), as well as the level of serum gonadotropin (LH and FSH) and sex steroid (estradiol and progesterone) hormones. CONCLUSION: Kelulut honey can protect the female reproductive system against the disruptive effects of PS-MPs. The phytochemical properties of Kelulut honey might be responsible for these beneficial benefits. However, future studies are warranted to identify the mechanisms involved.

Modulation of vulvovaginal atrophy (VVA) by Gelam honey in bilateral oophorectomized rats.

Introduction: Vulvovaginal atrophy (VVA) is a common condition in post-menopausal women. Symptoms of VVA include dyspareunia, vaginal dryness, vaginal and/or vulvar itching, burning and soreness, dysuria and vaginal bleeding accompanying sexual activity. These symptoms are physiological responses to hypoestrogenicity, inducing atrophy of the vagina epithelia and sudden reduction in mucous production. Prevailing therapy for VVA is hormone replacement therapy (HRT), notably estrogen, progesterone or a combination of the two. However, using HRT is associated with an increased incidence of breast and endometrial cancer, venous thromboembolism in the lungs and legs, stroke and cardiovascular complications. Methods: This study evaluated Malaysian Gelam honey as a nutraceutical alternative to estrogen HRT (ERT) in alleviating VVA. A total of 24 female 8-weekold Sprague Dawley rats underwent bilateral oophorectomy. A minimum of 14 days elapsed from the time of surgery and administration of the first dose of Gelam honey to allow the female hormones to subside to a stable baseline and complete recovery from surgery. Vaginal tissues were harvested following a 2-week administration of Gelam honey, the harvested vagina tissue underwent immunohistochemistry (IHC) analysis for protein localization and qPCR for mRNA expression analysis. Results: Results indicated that Gelam honey administration had increased the localization of Aqp1, Aqp5, CFTR and Muc1 proteins in vaginal tissue compared to the menopause group. The effect of Gelam honey on the protein expressions is summarized as Aqp1>CFTR>Aqp5>Muc1. Discussion: Gene expression analysis reveals Gelam honey had no effect on Aqp1 and CFTR genes. Gelam honey had up-regulated Aqp5 gene expression. However, its expression was lower than in the ERT+Ovx group. Additionally, Gelam honey up-regulated Muc1 in the vagina, with an expression level higher than those observed either in the ERT+Ovx or SC groups. Gelam honey exhibits a weak estrogenic effect on the genes and proteins responsible for regulating water in the vaginal tissue (Aqp1, Aqp5 and CFTR). In contrast, Gelam honey exhibits a strong estrogenic ability in influencing gene and protein expression for the sialic acid Muc1. Muc1 is associated with mucous production at the vaginal epithelial layer. In conclusion, the protein and gene expression changes in the vagina by Gelam honey had reduced the occurrence of vaginal atrophy in surgically-induced menopause models.

HOXA10 DNA Methylation Level in the Endometrium Women with Endometriosis: A Systematic Review.

Endometriosis is an inflammatory chronic systemic disease resulting in pelvic pain and infertility. However, despite a high prevalence of endometriosis, disease identification is still insufficient, and a high percentage of misdiagnosing was observed. Hence, a comprehensive study needs to be done to improve our understanding of the pathogenesis of endometriosis. Aberrant hypermethylation of HOXA10 has been reported to play a role in endometriosis. Thus, a comprehensive literature search was conducted to identify the DNA methylation level of HOXA10 among endometriosis patients across populations. The literature search was done using PubMed, Scopus, EBSCOhost, and Science Direct applying (HOXA10 OR "homeobox A10" OR "HOXA-10" OR HOX1) AND ("DNA methylation" OR methylation) AND (endometriosis OR endometrioma) as keywords. From 491 retrieved studies, five original articles investigating the DNA methylation level of HOXA10 from endometrium tissues among endometriosis women were included. All five included studies were classified as high-quality studies. High HOXA10 DNA methylation level was observed in the endometrium tissue of women with endometriosis in all the included studies. The secretory phase was identified as the best sampling time for HOXA10 DNA methylation study in endometriosis, and the most studied DNA methylation site is the promoter region of the HOXA10. However, more studies are needed to expose the HOXA10 mechanism in the pathogenesis of endometriosis.

Endometrial Heparin-Binding Epidermal Growth Factor Gene Expression and Hormone Level Changes in Implantation Window of Obese Women with Polycystic Ovarian Syndrome.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder amongst reproductive-age women, and 61% to 76% of women with PCOS are obese. Obese women with PCOS are usually burdened with infertility problems due to implantation failure. Thus, progesterone treatment is usually used to improve implantation rates. Although Hb-EGF expression is actively involved in endometrial receptivity and implantation, the data on heparin-binding epidermal growth factor (Hb-EGF) expression following progesterone therapy in obese women with PCOS are still lacking. OBJECTIVE: To investigate the changes in serum follicle-stimulating hormone (FSH), luteinising hormone (LH), dehydroepiandrosterone sulphate (DHEA), progesterone and oestradiol levels and Hb-EGF expression in obese women with PCOS during the implantation window following progesterone therapy. METHOD: A total of 40 participants aged 18-40 years old were recruited following the provision of written consent. The participants were divided into the obese PCOS, normal-weight PCOS, obese fertile and normal-weight fertile groups. First blood collection was done before ovulation. Then, daily oral micronised progesterone (Utrogestan 200 mg) was given to the PCOS group for 10 days. The treatment was followed by a second blood collection and endometrial tissue sampling by using a Pipelle de Cornier catheter. In the fertile group, ovulation was confirmed by using ultrasound, and a second blood sample was collected on days 7 to 9 postovulation. The serum levels of FSH, LH, DHEA, progesterone and oestradiol were measured in all participants. Wilcoxon signed-rank test was used to compare FSH, LH, DHEA, progesterone and oestradiol levels during pre- and postovulation. Mann-Whitney test was performed to compare FSH, LH, DHEA, progesterone and oestradiol levels between two groups: (1) the PCOS group and the fertile group, (2) the obese PCOS group and the non-obese PCOS group and (3) the obese group and the non-obese fertile group. RESULT: Serum FSH levels were lower in obese women in their follicular phase than in women with normal weight regardless of their PCOS status, whereas serum LH/FSH ratios and DHEA levels were higher in women with PCOS than in women without PCOS. However, endometrial Hb-EGF expression was lower in the obese PCOS group than in the normal-weight PCOS group. CONCLUSIONS: Different patterns of hormonal levels and Hb-EGF expression levels were seen between the studied groups. However, further in vitro and in vivo studies are needed to investigate the mechanism underlying the changes in FSH, LH/FSH ratio, DHEA and Hb-EGF expression in PCOS after progesterone treatment.

Kelulut Honey Regulates Sex Steroid Receptors in a Polycystic Ovary Syndrome Rat Model.

Reproductive and metabolic anomalies in polycystic ovary syndrome (PCOS) have been associated with the dysregulation of sex steroid receptors. Kelulut honey (KH) has been shown to be beneficial in PCOS-induced rats by regulating folliculogenesis and the oestrus cycle. However, no study has been conducted to evaluate KH's effect on sex steroid receptors in PCOS. Therefore, the current study examined the effects of KH, metformin, or clomiphene alone and in combination on the mRNA expression and protein distribution of androgen receptor (AR), oestrogen receptor α (ERα), oestrogen receptor ß (ERß), and progesterone receptor (PR) in PCOS-induced rats. The study used female Sprague-Dawley rats, which were treated orally with 1 mg/kg/day of letrozole for 21 days to develop PCOS. PCOS-induced rats were then divided and treated orally for 35 days with KH, metformin, clomiphene, KH + metformin, KH+ clomiphene and distilled water. In this study, we observed aberrant AR, ERα, ERß and PR expression in PCOS-induced rats compared with the normal control rats. The effects of KH treatment were comparable with clomiphene and metformin in normalizing the expression of AR, ERα, and ERß mRNA. However, KH, clomiphene and metformin did not affect PR mRNA expression and protein distribution. Hence, this study confirms the aberrant expression of sex steroid receptors in PCOS and demonstrates that KH treatment could normalise the sex steroid receptors profile. The findings provide a basis for future clinical trials to utilize KH as a regulator of sex steroid receptors in patients with PCOS.

Potential health benefits of Nigella sativa on diabetes mellitus and its complications: A review from laboratory studies to clinical trials.

This review aims to gather and summarize up-to-date information on the potential health benefits of Nigella sativa (NS) on diabetes mellitus (DM) and its complications from different animal models, clinical trials and in vitro studies. DM is one of the most prevalent metabolic disorders resulting from chronic hyperglycaemia due to problems in insulin secretion, insulin action or both. It affects people regardless of age, gender and race. The main consequence of DM development is the metabolic dysregulation of glucose homeostasis. Current treatments for DM include pharmacological therapy, insulin and diabetic therapy targeting ß cells. Some of these therapeutic approaches are promising; however, their safety and effectiveness remain elusive. Since ancient times, medicinal plants have been used and proven effective against diseases. These plants are believed to be effective and benefit physiological and pathological processes, as they can be used to prevent, reduce or treat multiple diseases. Nigella sativa Linn. is an annual indigenous herbaceous plant belonging to Ranunculaceae, the buttercup family. NS exhibits multifactorial activities; it could ameliorate oxidative, inflammatory, apoptotic and insulinotropic effects and inhibit carbohydrate digestive enzymes. Thus, this review demonstrates the therapeutic potential of NS that could be used as a complement or adjuvant for the management of DM and its complications. However, future research should be able to replicate and fill in the gaps of the study conducted to introduce NS safely to patients with DM.

Kelulut Honey Ameliorates Oestrus Cycle, Hormonal Profiles, and Oxidative Stress in Letrozole-Induced Polycystic Ovary Syndrome Rats.

Kelulut honey (KH) has been proven to have excellent antioxidative and anti-inflammatory properties with unique physicochemical characteristics. Therefore, we investigated the isolated and combined effects of KH, metformin, or clomiphene in alleviating oxidative stress and reproductive and metabolic abnormalities in polycystic ovary syndrome (PCOS). Female Sprague-Dawley (SD) rats were given 1 mg/kg/day of letrozole for 21 days to induce PCOS. PCOS rats were then divided into six treatment groups: untreated, metformin (500 mg/kg/day), clomiphene (2 mg/kg/day), KH (1 g/kg/day), combined KH (1 g/kg/day) and metformin (500 mg/kg/day), and combined KH (1 g/kg/day) and clomiphene (2 mg/kg/day). All treatments were administered orally for 35 days. The physicochemical characteristics of KH were assessed through hydroxymethylfurfural, free acidity, diastase number, moisture content, sugar profile, metals, and mineral compounds. Additionally, we determined the semivolatile organic compounds present in KH through gas chromatography-mass spectrometry (GC/MS) analysis. KH and its combination with metformin or clomiphene were shown to improve the oestrus cycle, hormonal profile, and oxidative stress in PCOS rats. However, KH did not reduce the fasting blood glucose, insulin, and body weight gain in PCOS rats. These findings may provide a basis for future studies to discover the potential use of KH as a complementary treatment for women with PCOS.

Kelulut Honey Improves Folliculogenesis, Steroidogenic, and Aromatase Enzyme Profiles and Ovarian Histomorphology in Letrozole-Induced Polycystic Ovary Syndrome Rats.

Polycystic ovary syndrome (PCOS) has been linked to aberrant folliculogenesis and abnormalities in the aromatase enzyme (Cyp19a1) and the steroidogenic enzyme, 17-alpha-hydroxylase (Cyp17a1) expression. It has been demonstrated that Kelulut honey (KH) improves both female and male reproductive system anomalies in animal studies. Here, we examined the effects of isolated and combined KH, metformin, and clomiphene in improving folliculogenesis, aromatase, and steroidogenic enzyme profiles and ovarian histomorphology in letrozole-induced PCOS rats. Letrozole (1 mg/kg/day) was administered to female Sprague-Dawley (SD) rats for 21 days to induce PCOS. PCOS rats were subsequently divided into six experimental groups: untreated, treatment with metformin (500 mg/kg/day), clomiphene (2 mg/kg/day), KH (1 g/kg/day), combined KH (1 g/kg/day) and metformin (500 mg/kg/day), and combined KH (1 g/kg/day) and clomiphene (2 mg/kg/day). All treatments were given orally for 35 days. We found that KH was comparable with clomiphene and metformin in improving the expression of Cyp17a1 and Cyp19a1, apart from enhancing folliculogenesis both histologically and through the expression of folliculogenesis-related genes. Besides, the combination of KH with clomiphene was the most effective treatment in improving the ovarian histomorphology of PCOS rats. The effectiveness of KH in restoring altered folliculogenesis, steroidogenic, and aromatase enzyme profiles in PCOS warrants a future clinical trial to validate its therapeutic effect clinically.

Exposure to Microplastics during Early Developmental Stage: Review of Current Evidence.

In the last few decades, microplastics (MPs) have been among the emerging environmental pollutants that have received serious attention from scientists and the general population due to their wide range of potentially harmful effects on living organisms. MPs may originate from primary sources (micro-sized plastics manufactured on purpose) and secondary sources (breakdown of large plastic items through physical, chemical, and biological processes). Consequently, serious concerns are escalating because MPs can be easily disseminated and contaminate environments, including terrestrial, air, groundwater, marine, and freshwater systems. Furthermore, an exposure to even low doses of MPs during the early developmental stage may induce long-term health effects, even later in life. Accordingly, this study aims to gather the current evidence regarding the effects of MPs exposure on vital body systems, including the digestive, reproductive, central nervous, immune, and circulatory systems, during the early developmental stage. In addition, this study provides essential information about the possible emergence of various diseases later in life (i.e., adulthood).