Effect of monosodium glutamate on serum sex hormones and uterine histology in female rats along with its molecular docking and in-silico toxicity.

Monosodium glutamate (MSG) is commonly used worldwide as a food flavour enhancer by the food industry. The current study investigated the in vivo toxic effects of MSG on the uterus in adult female Sprague Dawley rats and in vitro using MCF-7 and MDA-MB-231 cells, computational toxicity and molecular docking. The average levels of progesterone and oestrogen in the MSG-treated animals significantly altered. Besides, the average uterine lumen area (µm2) was smaller than the control group. MSG showed high-affinity binding to acetylcholine receptors and disrupted the normal nerve signal with a predicted LD50 of 4500 mg/kg. MSG also demonstrated good binding affinity to human oestrogen receptors beta and some other proteins that have an oxidative stress role in the female reproductive organs. Therefore, a precaution should be taken when utilising this compound, especially for females under the risk factor of hormonal abnormality.

Acute and sub-chronic toxicological evaluation of Averrhoa carambola leaves in Sprague Dawley rats.

Averrhoa carambola is a species of tree native to tropical Southeast Asia. It possesses antioxidant and anti-hyperlipidemia effects and has traditionally been used to treat a variety of ailments. However, the presence of oxalic acid in its fruits might restrict its consumption by individuals suffering from kidney disease, and caramboxin can cause neurotoxicity. In this study, we evaluated the acute and sub-chronic toxicity of the methanolic extract of A. carambola leaves (MEAC) in male and female rats. In the acute study, female rats were given a single oral dose of 5000 mg/kg of MEAC and closely examined for distinct indications of toxic effects during the first 4 h, periodically for 48 h, and daily thereafter for 14 days. Rats of both sexes were employed in the sub-chronic investigation for the 28-day repeated dose oral toxicity study. Results of the acute study revealed the safety of MEAC up to a dose of 5000 mg/kg where the rats did not show changes or signs of toxicity. In the sub-chronic toxicity study, MEAC (250, 500, and 1000 mg/kg) administration did not affect the body weight, food, and water consumption, motor coordination, behavior, or mental alertness in the treated rats. In addition, no variations in hematological or biochemical markers were found in MEAC-treated rats. In conclusion, these findings pinpoint the safety of MEAC at doses up to 5000 mg/kg. The leaves of A. carambola could be safely consumed by people with kidney disease to treat other ailments.

Therapeutic Potential of Certain Terpenoids as Anticancer Agents: A Scoping Review.

Cancer is a life-threatening disease and is considered to be among the leading causes of death worldwide. Chemoresistance, severe toxicity, relapse and metastasis are the major obstacles in cancer therapy. Therefore, introducing new therapeutic agents for cancer remains a priority to increase the range of effective treatments. Terpenoids, a large group of secondary metabolites, are derived from plant sources and are composed of several isoprene units. The high diversity of terpenoids has drawn attention to their potential anticancer and pharmacological activities. Some terpenoids exhibit an anticancer effect by triggering various stages of cancer progression, for example, suppressing the early stage of tumorigenesis via induction of cell cycle arrest, inhibiting cancer cell differentiation and activating apoptosis. At the late stage of cancer development, certain terpenoids are able to inhibit angiogenesis and metastasis via modulation of different intracellular signaling pathways. Significant progress in the identification of the mechanism of action and signaling pathways through which terpenoids exert their anticancer effects has been highlighted. Hence, in this review, the anticancer activities of twenty-five terpenoids are discussed in detail. In addition, this review provides insights on the current clinical trials and future directions towards the development of certain terpenoids as potential anticancer agents.

Ameliorative Effect of Thymoquinone-Loaded PLGA Nanoparticles on Chronic Lung Injury Induced by Repetitive Intratracheal Instillation of Lipopolysaccharide in Rats.

Thymoquinone (TQ), the active constituent of Nigella sativa, possesses several benefits in traditional and modern medicines. This study examined the effect of a single dose of Nano-TQ on chronic lung injury induced by repetitive intratracheal installation of lipopolysaccharide (LPS). Rats received LPS twice weekly for 8 weeks via intratracheal installation and a single dose of TQ-PLGA NPs on the day after the last dose of LPS. Six rats from each group were sacrificed after 8 and 10 weeks, and samples were collected for analysis. Repetitive intratracheal installation of LPS caused histopathological alterations, including partial or complete obstruction of the alveoli, interstitial edema, mild fibroblastic proliferation, fibrous strands besides lymphocytes and plasma infiltrations, suffered fetalization, bronchiectasis, hypertrophied arterioles, and others. Investigation of the ultrastructure revealed prominent necrotic pneumocytes with destructed chromatin and remnant of necrotic debris in the narrowing alveolar lumen in LPS-induced rats. TQ-PLGA NPs effectively ameliorated LPS-induced histopathological and ultrastructural alterations in the lung of rats. In addition, TQ-PLGA NPs significantly alleviated serum levels of IL-10 and TGF-ß1 in LPS-induced rats. In conclusion, TQ-PLGA NPs prevented inflammation and tissue injury in the lungs of rats challenged with repetitive intratracheal installation of LPS. Therefore, TQ-PLGA NPs represent a promising candidate for the prevention of lung injury induced by LPS, pending further studies to determine its safety and exact protective mechanism.

Effect and Mechanism of Ganoderma lucidum Spores on Alleviation of Diabetic Cardiomyopathy in a Pilot in vivo Study.

BACKGROUND: Ganoderma lucidum spores (GLS) exhibit disease prevention properties, but no study has been carried out on the anti-diabetic cardiomyopathy property of GLS. The aim of this study was to evaluate the hyperglycemia-mediated cardiomyopathy protection and mechanisms of GLS in streptozotocin (STZ)induced diabetic rats. METHODS: Male SD rats were randomly divided into three groups. Two groups were given STZ (50 mg/kg, i.p.) treatment and when their fasting plasma glucose was above 16.7 mmol/L, among them, one group was given placebo, as diabetic group, and another group was given GLS (300 mg/kg) treatment. The group without STZ treatment was given placebo as a control group. The experiment lasted 70 days. The histology of myocardium and biomarkers of antioxidants, myocardial injury, pro-inflammatory cytokines, pro-apoptotic proteins and phosphorylation of key proteins in PI3K/AKT pathway were assessed. RESULTS: Biochemical analysis showed that GLS treatment significantly reduced the blood glucose (-20.3%) and triglyceride (-20.4%) levels compared to diabetic group without treatment. GLS treatment decreased the content of MDA (-25.6%) and activity of lactate dehydrogenase (-18.9%) but increased the activity of GSH-Px (65.4%). Western blot analysis showed that GLS treatment reduced the expression of both alpha-smooth muscle actin and brain natriuretic peptide. Histological analysis on the cardiac tissue micrographs showed that GLS treatment reduced collagen fibrosis and glycogen reactivity in myocardium. Both Western blot and immunohistochemistry analyses showed that GLS treatment decreased the expression levels of pro-inflammatory factors (cytokines IL-1ß, and TNF-α) as well as apoptosis regulatory proteins (Bax, caspase-3 and -9), but increased Bcl-2. Moreover, GLS treatment significantly increased the phosphorylation of key proteins involved in PI3K/AKT pathway, eg, p-AKT p-PI3K and mTOR. CONCLUSION: The results indicated that GLS treatment alleviates diabetic cardiomyopathy by reducing hyperglycemia, oxidative stress, inflammation, apoptosis and further attenuating the fibrosis and myocardial dysfunction induced by STZ through stimulation of the PI3K/Akt/mTOR signaling pathway.

Associated Targets of the Antioxidant Cardioprotection of Ganoderma lucidum in Diabetic Cardiomyopathy by Using Open Targets Platform: A Systematic Review.

Even with substantial advances in cardiovascular therapy, the morbidity and mortality rates of diabetic cardiomyopathy (DCM) continually increase. Hence, a feasible therapeutic approach is urgently needed. Objectives. This work is aimed at systemically reviewing literature and addressing cell targets in DCM through the possible cardioprotection of G. lucidum through its antioxidant effects by using the Open Targets Platform (OTP) website. Methods. The OTP website version of 19.11 was accessed in December 2019 to identify the studies in DCM involving G. lucidum. Results. Among the 157 cell targets associated with DCM, the mammalian target of rapamycin (mTOR) was shared by all evidence, drug, and text mining data with 0.08 score association. mTOR also had the highest score association 0.1 with autophagy in DCM. Among the 1731 studies of indexed PubMed articles on G. lucidum published between 1985 and 2019, 33 addressed the antioxidant effects of G. lucidum and its molecular signal pathways involving oxidative stress and therefore were included in the current work. Conclusion. mTOR is one of the targets by DCM and can be inhibited by the antioxidative properties of G. lucidum directly via scavenging radicals and indirectly via modulating mTOR signal pathways such as Wnt signaling pathway, Erk1/2 signaling, and NF-κB pathways.

Class 1 Integrons in Clinical Multi Drug Resistance E. coli, Sana'a Hospitals, Yemen.

BACKGROUND AND OBJECTIVES: The occurrence of multi-drug resistance (MDR) Escherichia coli is one responsible for raised mortality and morbidity and was reported as major health problem. Class 1 integrons has crucial role in distributing antibiotic resistance genes among bacteria. Present work was aimed to determine the prevalence of class 1 integrons and its association with antibiotic resistance in MDR E. coli isolated from patient's body fluid and tissues from 6 health centers in Sana'a, Yemen. MATERIALS AND METHODS: A cross-sectional study a total of 198 E. coli from patients diagnosed with infection that had been referred to 6 hospitals and medical diagnostic from July, 2017 to August, 2017 in Sana'a, Yemen. Susceptibility of E. coli isolates to 15 antibiotics using the disc diffusion method. Conventional polymerase chain reaction was used for detection of class 1 of integrons in 100 randomly selected MDR E. coli. RESULTS: Overall 174 (87.9%) of 198 E. coli isolates were MDR. Class 1 integrons were detected in 67% of the randomly selected 100 of 198 MDR E. coli. A significant range (p<0.05-p<0.0001) was identified between presence of class 1 integrons and resistance to ceftriaxone, aztreonam, cefepime, amoxicillin-clavulanic acid, cefotoxime, cefepime-clavulanic acid, ceftazidime-clavulanic acid, ciprofloxacin, ceftazidime, norfloxacin and trimethoprim-sulfamethoxazole, while no significant difference were identified between integron class 1 and resistance to gentamicin, amikacin, nitrofurantoin and imipenem. CONCLUSION: High MDR E. coli isolates were detected in this study, among them the prevalence of class 1 integrons is the most common. The significant association between class 1 integrons and resistance to common prescribed antibiotics in hospitals in Sana'a, Yemen.