Novel promising reproductive and metabolic effects of Cicer arietinum L. extract on letrozole induced polycystic ovary syndrome in rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Chickpea was used in both greek and indian traditional medicine for hormonal related conditions as menstrual induction, acceleration of parturation, treatment of retained placenta and stimulation of lactation. Chickpea (Cicer arietinum) sprout isoflavone isolates exhibited reasonable estrogenic activities. Isoflavones, a subtype of phytoestrogens, are plant derivatives with moderate estrogenic activity that tend to have protective effects on hormonal and metabolic abnormalities of women with polycystic ovary syndrome (PCOS). AIM OF THE STUDY: In this study, we investigated the effect of UPLC/ESI-MS characterized Cicer arietinum L. seeds ethanol extract (CSE) on ovarian hormones, oxidative response and ovarian histological changes on induced PCOS rat model. MATERIALS AND METHODS: Thirty-five rats were divided into five groups including negative control, PCOS, and treatment groups. PCOS was induced using letrozole (1 mg/kg) daily orally for 21 days. Each treatment group was treated with one of the following for 28 days after induction of PCOS: clomiphene citrate (1 mg/kg), and CSE at 250 and 500 mg/kg. Ovaries and uteri were excised, weighed and their sections were used for quantitative real-time reverse transcriptase polymerase chain reaction, antioxidant assays and histomorphometric study of the ovaries. The antioxidant assays, histopathological examination, hormonal and metabolic profiles, and Cyp11a1(steroidogenic enzyme) mRNA expression were measured. RESULTS: In all treatment groups, ovarian weight was significantly decreased despite having no significant effect on uterine weight. Histomorphometric study in the treatment groups revealed a significant decrease in the number and diameter of cystic follicles, a significant increase in granulosa cell thickness while, thickness of theca cells was significantly decreased when compared to PCOS. Hormone levels, metabolic profile and antioxidant status were improved in the treatment groups. Moreover, Cyp11a1 mRNA expression was significantly downregulated in the treatment groups compared to PCOS. CONCLUSIONS: In the current study, CSE enhanced the reproductive and metabolic disorders which were associated with PCOS induction. For the first time, we have highlighted the effect of CSE in treating PCOS and its associated manifestations.

Benzyl isothiocyanates modulate inflammation, oxidative stress, and apoptosis via Nrf2/HO-1 and NF-κB signaling pathways on indomethacin-induced gastric injury in rats.

The present study investigated the gastroprotective activity of benzyl isothiocyanates (BITC) on indomethacin (IND)-induced gastric injury in a rat model and explicated the possible involved biochemical, cellular, and molecular mechanisms. The rat model with gastric ulcers was established by a single oral dose of IND (30 mg per kg b.wt). BITC (0.75 and 1.5 mg kg-1) and esomeprazole (20 mg per kg b.wt) were orally administered for 3 weeks to rats before the induction of gastric injury. Compared with the IND group, BITC could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. BITC significantly preserved the antioxidants (glutathione GSH, superoxide dismutase SOD), nitric oxide (NO), and prostaglandin E2 (PGE2) contents, while decreasing the gastric mucosal malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and myeloperoxidase (MPO) contents. Moreover, BITC remarkably upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NAD(P)H : quinone oxidoreductase (NQO1). In addition, BITC activates the expression of heat shock protein 70 (HSP-70) and downregulated the expression of nuclear factor-κB (NF-κB) and caspase-3 to promote gastric mucosal cell survival. To the best of our knowledge, this study is the first published report to implicate the suppression of inflammation, oxidative stress, and Nrf2 signaling pathway as a potential mechanism for the gastroprotective activity of BITC.

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: promising activity without the risk of hepatic adverse effect.

BACKGROUND: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. METHODS: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). RESULTS: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. CONCLUSION: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk.

Evaluation of the effect of methotrexate on the hippocampus, cerebellum, liver, and kidneys of adult male albino rat: Histopathological, immunohistochemical and biochemical studies.

Methotrexate (MTX) has been used for treatment of autoimmune diseases, inflammatory disorders as rheumatic arthritis, and different types of cancers. However, it has shown adverse effects on vital organs. The current study was conducted to investigate the toxic effect of MTX on the hippocampus, cerebellum, liver and kidneys of adult male albino rats. MTX was injected weekly at 5 mg/kg body weight via I/P injection for 6 weeks. At the end of the experiment, histopathological, immunohistochemical and biochemical evaluation were performed on the hippocampus, cerebellum, liver, and kidney tissues of the sacrificed rats. We observed that methotrexate induced neural tissue damage in the hippocampus and cerebellum, degeneration of hepatocytes, congestion of the central vein and blood sinusoids of the liver, distortion in the renal corpuscles and necrosis of the renal tubule. Immunohistochemical findings revealed strong positive expression of Caspase-3, PCNA and GFAP. Biochemical studies revealed significant elevation in the serum levels of AST and ALT, in addition to high serum concentrations of creatinine and urea. Also, MTX injection increased MDA, while it decreased GSH, SOD and AChE levels. We conclude the ability of MTX to induce oxidative stress that results into apoptosis and tissue injury, leading to neurotoxicity, hepatotoxicity, and nephrotoxicity.

Innovative application of helium-neon laser: enhancing the germination of Adansonia digitata and evaluating the hepatoprotective activities in mice.

The laser pretreatment of seed is drawing pronounced attention from the scientific community for its positive impact in boosting germination, seedling , and growth of plants. In this study, the laser pretreatment of Adansonia digitata (A. digitata) seeds was evaluated. Eight laser treatments were conducted at different powers, 10, 20, 40, and 80 mW, with the two-time interval for each power at 2 and 4 min. The outcomes indicated that the most efficient irradiation was 10 mW/2 min which induces the highest germination rate and polyphenolic contents for seeds. Based on these results, the animal experimental design was processed to assess the hepatoprotective activity of A. digitata extracts obtained through the optimum laser preillumination to enhance the resistance of liver damage in mice. The total phenol and flavonoid contents and the antioxidant properties of the methanolic extracts were estimated in vitro. The CCl4 was used to induce hepatotoxicity in mice. The animals were divided into five groups. The sera of the treated animals were used for the determination of transaminases, and the liver homogenates were used for the determination of antioxidant status, and further liver tissues were subjected to verify the anti-apoptotic effect of A. digitata methanolic extract. The in vivo results showed that the methanolic extract exposed to laser treatment at 10 mW/2 min provided better hepatoprotective capacity than the other treatments. Administration of A. digitata extract not only offered a significant decrease in liver enzyme activity but also markedly improved the antioxidant status and reduced the apoptotic progression induced by CCl4 toxicity in liver tissue.