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Effects of Testosterone on the Expression of Connexin 26 and Connexin 43 in the Uterus of Rats During Early Pregnancy

Kamal DAM, Ibrahim SF, Mokhtar MH

In Vivo, 2020 7 2;34(4):1863-1870.
PMID: 32606156 DOI: 10.21873/invivo.11981

BACKGROUND/AIM: It was hypothesized that testosterone could affect the distribution and expression of connexin 26 and connexin 43 in the uterus. Thus, the effects of testosterone on these parameters in the uterus during the uterine receptivity period were investigated.
MATERIALS AND METHODS: Intact pregnant rats were administered 1 mg/kg/day testosterone alone or in combination with flutamide, finasteride or anastrozole, subcutaneously on day-1 of pregnancy till day 3. The rats were sacrificed at day 4 of pregnancy, which was considered as the uterine receptivity period for determining the expression and distribution of connexin 26 and connexion 43 by immunohistochemistry and quantitative polymerase chain reaction, respectively.
RESULTS: Treatment with 1 mg/kg/day testosterone increased connexin 26 and decreased connexin 43 mRNA expression and protein distribution in the uterus of early pregnancy rats.
CONCLUSION: Changes in the uterine connexin 26 and connexin 43 expression by testosterone could disrupt embryo implantation, resulting in early pregnancy loss.
Fulltext Beneficial Effects of Green Tea Catechins on Female Reproductive Disorders: A Review

Kamal DAM, Salamt N, Zaid SSM, Mokhtar MH

Molecules, 2021 May 03;26(9).
PMID: 34063635 DOI: 10.3390/molecules26092675

Tea is one of the most widely consumed beverages worldwide after water, and green tea accounts for 20% of the total tea consumption. The health benefits of green tea are attributed to its natural antioxidants, namely, catechins, which are phenolic compounds with diverse beneficial effects on human health. The beneficial effects of green tea and its major bioactive component, (-)-epigallocatechin-3-gallate (EGCG), on health include high antioxidative, osteoprotective, neuroprotective, anti-cancer, anti-hyperlipidemia and anti-diabetic effects. However, the review of green tea's benefits on female reproductive disorders, including polycystic ovary syndrome (PCOS), endometriosis and dysmenorrhea, remains scarce. Thus, this review summarises current knowledge on the beneficial effects of green tea catechins on selected female reproductive disorders. Green tea or its derivative, EGCG, improves endometriosis mainly through anti-angiogenic, anti-fibrotic, anti-proliferative and proapoptotic mechanisms. Moreover, green tea enhances ovulation and reduces cyst formation in PCOS while improving generalised hyperalgesia, and reduces plasma corticosterone levels and uterine contractility in dysmenorrhea. However, information on clinical trials is inadequate for translating excellent findings on green tea benefits in animal endometriosis models. Thus, future clinical intervention studies are needed to provide clear evidence of the green tea benefits with regard to these diseases.
Fulltext Kelulut Honey Regulates Sex Steroid Receptors in a Polycystic Ovary Syndrome Rat Model

Kamal DAM, Ibrahim SF, Ugusman A, Mokhtar MH

Int J Mol Sci, 2022 Nov 25;23(23).
PMID: 36499085 DOI: 10.3390/ijms232314757

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 β (ERβ), 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, ERβ 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 ERβ 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.
Fulltext Potential Health Benefits of Curcumin on Female Reproductive Disorders: A Review

Kamal DAM, Salamt N, Yusuf ANM, Kashim MIAM, Mokhtar MH

Nutrients, 2021 Sep 07;13(9).
PMID: 34579002 DOI: 10.3390/nu13093126

Curcumin is one of the main polyphenolic compounds in the turmeric rhizome. It possesses antioxidant, anti-inflammatory, anti-cancer, anti-arthritis, anti-asthmatic, anti-microbial, anti-viral and anti-fungal properties. This review aims to provide an overview of the potential health benefits of curcumin to treat female reproductive disorders, including polycystic ovary syndrome (PCOS), ovarian failure and endometriosis. Comprehensive information on curcumin was retrieved from electronic databases, which were MEDLINE via EBSCOhost, Scopus and Google Scholar. The available evidence showed that curcumin reduced the high level of androgen in PCOS. Studies in rodents suggest that curcumin resulted in the disappearance of cysts and the appearance of healthy follicles and corpora lutea. Furthermore, animal studies showed curcumin improved the overall function of the ovary in ovarian diseases and reversed the disturbance in oxidative stress parameters. Meanwhile, in vitro and in vivo studies reported the positive effects of curcumin in alleviating endometriosis through anti-inflammatory, anti-proliferative, anti-angiogenic and pro-apoptotic mechanisms. Thus, curcumin possesses various effects on PCOS, ovarian diseases and endometriosis. Some studies found considerable therapeutic effects, whereas others found no effect. However, none of the investigations found curcumin to be harmful. Curcumin clinical trials in endometriosis and ovarian illness are still scarce; thus, future studies need to be conducted to confirm the safety and efficacy of curcumin before it could be offered as a complementary therapy agent.
Fulltext Kelulut Honey Improves Folliculogenesis, Steroidogenic, and Aromatase Enzyme Profiles and Ovarian Histomorphology in Letrozole-Induced Polycystic Ovary Syndrome Rats

Kamal DAM, Ibrahim SF, Ugusman A, Zaid SSM, Mokhtar MH

Nutrients, 2022 Oct 18;14(20).
PMID: 36297046 DOI: 10.3390/nu14204364

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

Adam SH, Abu IF, Kamal DAM, Febriza A, Kashim MIAM, Mokhtar MH

Plants (Basel), 2023 Sep 08;12(18).
PMID: 37765374 DOI: 10.3390/plants12183210

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.