Serum leptin correlates in fertile and idiopathic infertile Yemeni males: a comparative cross-sectional study.

This comparative cross-sectional study aimed to evaluate the relationship between serum leptin and testosterone, FSH, LH, PRL and semen quality in fertile and idiopathic infertile Yemeni men. A total of 30 infertile males with unknown causes and 30 age-matched healthy fertile males were enrolled in this study. The body mass index (BMI) and waist circumference (WC) were measured. Semen samples were analyzed according to the WHO manual for semen analysis. Serum samples were tested for hormones. Subjects were then divided into subgroups and compared based on their main seminal findings. The WC, serum leptin, PRL, FSH and LH levels were significantly higher (p < 0.05) in the infertile subjects than in the fertile group. Serum leptin demonstrated a significant positive correlation (p < 0.01) with body weight, BMI and WC in fertile males and a significant negative correlation (p < 0.01) with testosterone in fertile and infertile males. Similarly, a significant positive correlation was found between serum leptin and FSH (p < 0.01) and LH (p < 0.05) levels in the infertile subjects. The findings showed that non-obstructive azoospermic (NOA) patients have significant (p < 0.05) high levels of serum leptin, FSH, and LH. These findings may support the possibility of a direct peripheral negative effect of leptin on testicular steroidogenesis independent of the suggested indirect effect, and it could directly impact spermatogenesis without inhibiting testosterone production. This effect was accompanied by increasing serum PRL levels. Furthermore, serum leptin and gonadotropins were found to be increased in the idiopathic NOA group. The present study provided valuable insights into the fertile and idiopathic infertile Yemeni males and could establish an important foundation for future andrological-related studies such as investigating the relationship between leptin and other hormones; and infertility-related genetic and epigenetic factors.

The impact of SARS-CoV-2 treatment on the cardiovascular system: an updated review.

The coronavirus disease-2019 (COVID-19) pandemic has become a major global health problem. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and exhibits pulmonary and extrapulmonary effects, including cardiovascular involvement. There are several attempts to identify drugs that could treat COVID-19. Moreover, many patients infected with COVID-19 have underlying diseases, particularly cardiovascular diseases. These patients are more likely to develop severe illnesses and would require optimized treatment strategies. The current study gathered information from various databases, including relevant studies, reviews, trials, or meta-analyses until April 2022 to identify the impact of SARS-CoV-2 treatment on the cardiovascular system. Studies have shown that the prognosis of patients with underlying cardiovascular disease is worsened by COVID-19, with some COVID-19 medications interfering with the cardiovascular system. The COVID-19 treatment strategy should consider many factors and parameters to avoid medication-induced cardiac injury, mainly in elderly patients. Therefore, this article provides a synthesis of evidence on the impact of different COVID-19 medications on the cardiovascular system and related disease conditions.

Chemical composition, antiproliferative and antioxidant attributes of ethanolic extract of resinous sediment from Etlingera elatior (Jack. ) inflorescence

The ethanolic extract of resinous sediment (EERS) of Etlingera elatior young inflorescence was examined for its anticancer effect and potential antioxidant activity. The anticancer effect of the EERS was evaluated on four human cancer cell lines, HCT 116, HT-29, Hela, and MCF-7, using the MTT assay. GC-MS analysis showed that the main components found in the EERS were nonyl cyclopropane (4.44%), 1-tetradecane (3.66%), cyclotetradecane (2.41%), cyclododecane (1.92%), and 1-decene (1.72%). The antioxidant activity was determined through different methods. High amounts of TPC and TFC in the EERS were found. Moderate antioxidant capacity of the EERS was detected by DPPH and ABTS assays, with EC50 values of 44.19 and 56.61 µg/mL and a high FRAP value of 281.79 nmol Fe+2 equivalent/mg extract. In the MTT assay, the EERS showed potent anticancer activity, with IC50 values of 19.82, 37.001, 50.49, and 53.29 µg/mL against HT-29, HCT 116, Hela, and MCF-7 tumour cell lines, respectively. Moreover, the results were comparable to or less potent than the standard reference drug, 5-fluorouracil. The results showed that the EERS of Etlingera elatior inflorescence contained a high amount of polyphenols and flavonoids, which may to the selective antiproliferative effects towards colon cancer in vitro

Proapoptotic and Antiangiogenic Activities of Arctium Lappa L. on Breast Cancer Cell Lines.

In this study, the bioactivity-guided fractionation was conducted on the aerial parts of Arctium lappa L. and then the extracts were tested in vitro on breast cancer (MCF-7), colorectal cancer (HCT-116), and normal cells (EA.hy926). The n-hexane fraction (EHX) of the ethanolic extract showed strong activity against both MCF-7 and EA.hy926 cell lines (IC50 values: 14.08 ± 3.64 and 27.25 ± 3.45 µg/mL, respectively). The proapoptotic activity of EHX was assessed using MCF-7. Morphological alterations were visualized using Hoechst staining and a transmission electron microscope. Cancer cell signal transduction pathways were investigated, and EHX significantly upregulated p53, TGF-ß, and NF-κB. Furthermore, EHX was found to disrupt the metastatic cascade of breast cancer cells by the inhibition of cell proliferation, migration, invasion, and colonization. The antiangiogenic activity of EHX fraction showed potent inhibition of rat aorta microvessels with IC50 value: 4.34 ± 1.64 µg/mL. This result was supported by the downregulation of VEGF-A expression up to 54%. Over 20 compounds were identified in EHX using GC-MS, of which stigmasterol, ß-sitosterol, and 3-O-acetyllupeol are the major active compounds. Phytochemical analysis of EHX showed higher phenolic and flavonoid contents with a substantial antioxidant activity. In conclusion, this work demonstrated that A. lappa has valuable anticancer activity and antiangiogenic properties that might be useful in breast cancer therapy.

Comparative proteomic analysis of different stages of breast cancer tissues using ultra high performance liquid chromatography tandem mass spectrometer.

BACKGROUND: Breast cancer is the fifth most prevalent cause of death among women worldwide. It is also one of the most common types of cancer among Malaysian women. This study aimed to characterize and differentiate the proteomics profiles of different stages of breast cancer and its matched adjacent normal tissues in Malaysian breast cancer patients. Also, this study aimed to construct a pertinent protein pathway involved in each stage of cancer. METHODS: In total, 80 samples of tumor and matched adjacent normal tissues were collected from breast cancer patients at Seberang Jaya Hospital (SJH) and Kepala Batas Hospital (KBH), both in Penang, Malaysia. The protein expression profiles of breast cancer and normal tissues were mapped by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The Gel-Eluted Liquid Fractionation Entrapment Electrophoresis (GELFREE) Technology System was used for the separation and fractionation of extracted proteins, which also were analyzed to maximize protein detection. The protein fractions were then analyzed by tandem mass spectrometry (LC-MS/MS) analysis using LC/MS LTQ-Orbitrap Fusion and Elite. This study identified the proteins contained within the tissue samples using de novo sequencing and database matching via PEAKS software. We performed two different pathway analyses, DAVID and STRING, in the sets of proteins from stage 2 and stage 3 breast cancer samples. The lists of molecules were generated by the REACTOME-FI plugin, part of the CYTOSCAPE tool, and linker nodes were added in order to generate a connected network. Then, pathway enrichment was obtained, and a graphical model was created to depict the participation of the input proteins as well as the linker nodes. RESULTS: This study identified 12 proteins that were detected in stage 2 tumor tissues, and 17 proteins that were detected in stage 3 tumor tissues, related to their normal counterparts. It also identified some proteins that were present in stage 2 but not stage 3 and vice versa. Based on these results, this study clarified unique proteins pathways involved in carcinogenesis within stage 2 and stage 3 breast cancers. CONCLUSIONS: This study provided some useful insights about the proteins associated with breast cancer carcinogenesis and could establish an important foundation for future cancer-related discoveries using differential proteomics profiling. Beyond protein identification, this study considered the interaction, function, network, signaling pathway, and protein pathway involved in each profile. These results suggest that knowledge of protein expression, especially in stage 2 and stage 3 breast cancer, can provide important clues that may enable the discovery of novel biomarkers in carcinogenesis.

Safety assessment of the ethanolic extract of Gongronema latifolium Benth. leaves: a 90-day oral toxicity study in Sprague Dawley rats.

BACKGROUND: The leaves of Gongronema latifolium Benth. have long been recognized traditionally as a remedy for a variety of ailments in Africa. This study was conducted to evaluate the safety profile of the ethanolic extract of G. latifolium (GLES) leaves through a repeated dose 90-day oral toxicity study in male and female of Sprague Dawley rats. METHODS: GLES was orally administered at doses of 250, 500 and 1000 mg/kg/day consecutively for 90 days. RESULTS: No behavioral or physiological changes and mortality were observed. GLES did not have a marked impact on general hematological parameters and did not precipitate nephrotoxicity. However, compared to the control, serum triglycerides, total cholesterol and low-density lipoprotein levels were lower and white adipose tissue paired retroperitoneal fat depots were depleted in male rats treated with GLES3 by the end of the experiment. The liver was significantly enlarged in GLES-treated rats of both sexes. Negative gender-specific alterations were observed with the highest dose. Adverse risk was evident in the female rats mainly due to marked body weight gain and cerebrum weight reduction. CONCLUSION: Further research is needed to reach more specific conclusions about to the safety of ingesting high doses of GLES for long periods of time.

The phytochemical and anti-inflammatory studies of Dillenia suffruticosa leaves.

The Dillenia suffruticosa leaves (Dilleniaceae), a folk medicine recommended in Southeast Asia for treating inflammation, were phytochemically studied for the first time and assessed for suppression of λ-carrageenan-induced paw oedema in rats. The crude methanolic extract orally administered at 5,000 mg/kg, displayed no toxicity and at 250 to 1,000 mg/kg significantly suppressed the paw oedema. Two-isolated triterpenoids, betulinic acid (1) and koetjapic acid (2) orally administered at 50 mg/kg, significantly reduced the paw oedema, (p < 0.001) and (p < 0.005) at the fourth h onwards to 47.36% ± 2.23 and 53.43% ± 7.09, respectively, from 95.90% ± 6.88 oedema induced by λ-carrageenan alone. 1 and the isolated flavonoids of vitexin (3), tiliroside (4), and kaempferol (5), displayed moderately more of cyclooxygenase (COX)-2 than COX-1 enzyme inhibition, whereas 2 was slightly more inhibition of COX-1. The in silico molecular docking studies provided support to the in vitro COX studies that the isolated compounds formed H-bonding with the amino acid residues at the COX-2 catalytic sites. The triterpenoids were bound to the peroxidase, possibly inhibiting the peroxidase reaction, whereas the flavonoids interacted more at the cyclooxygenase, resembling celecoxib, therefore providing evidences that these compounds were responsible for the anti-inflammatory properties of D. suffruticosa.

Vasorelaxant activities and the underlying pharmacological mechanisms of Gynura procumbens Merr. leaf extracts on rat thoracic aorta.

Previous studies have investigated the cardiovascular activity of Gynura procumbens Merr. single-solvent extracts. The objective of this study was to evaluate the in vitro vasorelaxant properties and the underlying pharmacological mechanisms of serial extracts and fractions of Gynura procumbens (GP). The leaves of GP were serially extracted with petroleum ether, chloroform, methanol and water using the maceration method. Suspended aortic ring preparations were pre-contracted with phenylephrine (PE 1 µM), followed by cumulative addition of GP extracts (0.25-3 mg/mL). The petroleum ether extract (GPPE) was the most potent among the four extracts. Pre-incubation of endothelium-intact aorta with atropine (1 µM), indomethacin (10 µM), methylene blue (10 µM), propranolol (1 µM) and potassium channel blockers such as TEA (1 µM), glibenclamide (10 µM), 4-aminopyridine (1 µM) and barium chloride (10 mM) had no effect on GPPE-induced vasorelaxation. The vasorelaxant effect of GPPE was partly diminished by pretreatment of aortic rings preparations with L-NAME (10 µM) and even more so in endothelium-denuded aortic rings, indicating a minimal involvement of endothelium-dependent pathway in GPPE-induced vasorelaxation. The calcium-induced vasocontractions were antagonized significantly and concentration-dependently by GPPE in calcium free and high potassium medium. These results illustrate that Ca2+ antagonizing actions of GPPE in rat isolated aorta are comparable to that of verapamil and may be mainly responsible for its vasodilation effect. The antioxidant activity of GPPE supports its vasorelaxant effect by attenuating the production of deleterious free radicals and reactive oxygen species in the vasculature.

Adipocytokine Regulation and Antiangiogenic Activity Underlie the Molecular Mechanisms of Therapeutic Effects of Phyllanthus niruri against Non-Alcoholic Fatty Liver Disease.

The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague⁻Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.

Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague-Dawley Rats.

Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.

Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark.

Alstonia scholaris has been used by traditional medicine practitioners since the medieval ages for the treatment of diseases. The aim of this research was to evaluate the acute and sub-acute oral toxicity of its methanolic extract. The acute toxicity test was conducted using Sprague Dawley (SD) rats. The methanolic extract of Alstonia scholaris stem bark (ASME) was administrated in a single dose of 2000 mg/kg via oral gavage; and the animals were observed for any behavioral changes or mortality. In the sub-acute toxicity study, SD rats received three doses of ASME (250, 500 and 1000 mg/kg) for 28 days via oral gavage. During these 28 days of treatment, the rats were observed weekly for toxicity symptoms. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, Alstonia scholaris was found to be non-toxic at a dose of 2000 mg/kg b.w. In the sub-acute toxicity study, significant variations in body weight, hematological and biochemical parameters were observed in the experimental groups at the dose of 500 and 1000 mg/kg with the death of two female rats being recorded at the highest dose (1000 mg/kg b.w.). Histopathological studies revealed slight degeneration (lesion) and centrilobular necrosis in the liver, which was most expressed in the highest-dose group. These results demonstrate that, while a single dose and short term oral intake of Alstonia scholaris bark extract caused no toxicity up to a dose of 2000 mg/kg b.w., toxic effects manifested in the long term treatment at the highest dose (500 and 1000 mg/kg). The long-term toxic effect was found to be associated with alterations in hematological compositions and end-organ damage to the liver. Thus, prolonged use of high doses of ASME orally should be discouraged and lower doses encouraged.

Effect of extraction solvents and plant parts used on the antihyperlipidemic and antioxidant effects of Garcinia atroviridis: a comparative study.

BACKGROUND: Garcinia atroviridis is a seasonal fruit plant found in many parts of South East Asia. The fruit rind is used in cooking and traditionally consumed for various reasons, including to lower blood cholesterol. A comparative study was undertaken to investigate the influence of extraction solvents and plant parts used on the lipid-lowering and antioxidant activities of Garcinia atroviridis. RESULTS: Aqueous extracts showed better antihyperlipidemic activity than the methanol extracts. Aqueous extract of ripe fruit showed the most potent antihyperlipidemic activity, comparable to that of atorvastatin. It significantly reduced the total cholesterol (P < 0.05), triglycerides (P < 0.01), low-density lipoprotein (P < 0.01), very-low-density lipoprotein (P < 0.01) and atherogenic index (P < 0.01). In contrast, antioxidant activities of methanol extracts of all parts of G. atroviridis were higher than their respective aqueous extracts, whereby the stem and leaves extracts showed better antioxidant activities than the fruits. CONCLUSION: Aqueous and methanol extracts of G. atroviridis showed higher antihyperlipidemic and antioxidant effects, respectively. Total phenolic and flavonoid contents showed significant correlations with antioxidant but not with antihyperlipidemic activities, indicating the involvement of other compounds. Contrary to the traditional belief, the present findings suggest that the fruit has higher antihyperlipidemic potential than the fruit rind.