Phytomedicinal therapeutics for male infertility: critical insights and scientific updates.

Infertility is a significant cause of anxiety, depression, and social stigma among couples and families. In such cases, male reproductive factors contribute widely to the extent of 20-70%. Male infertility is a multifactorial disease with several complications contributing to its diagnosis. Although its management encompasses both modern and traditional medicine arenas, the first line of treatment, adopted by most males, focuses on the reasonably successful medicinal plant-based conventional therapies. Phyto-therapeutics, which relies on active ingredients from traditionally known herbs, influences sexual behavior and male fertility factors. The potency of these phyto-actives depends on their preparation methods and forms of consumption, including decoctions, extracts, semi-purified compounds, etc., as inferred from in vitro and in vivo (laboratory animal models and human) studies. The mechanisms of action therein involve the testosterone pathway for stimulation of spermatogenesis, reduction of oxidative stress, inhibition of inflammation, activation of signaling pathways in the testes [extracellular-regulated kinase (ERK)/protein kinase B(PKB)/transformation of growth factor-beta 1(TGF-ß1)/nuclear factor kappa-light-chain-enhancer of activated B cells NF-kB signaling pathways] and mediation of sexual behavior. This review critically focuses on the medicinal plants and their potent actives, along with the biochemical and molecular mechanisms that modulate vital pathways associated with the successful management of male infertility. Such intrinsic knowledge will significantly further studies on medicinal plants that improve male reproductive health.

Role of TGF-ß signalling in PCOS associated focal segmental glomerulosclerosis.

Research on polycystic ovarian syndrome (PCOS) remains intense due to its evolving impact on metabolism, reproduction and cardiovascular function. Changes in metabolic pathways can also significantly impact renal function including the development of Focal Segmental Glomerulosclerosis (FSGS), one of the most highly investigated renal diseases. In FSGS, scarring of the glomerulus vascular tuft damages the kidneys. Onset of FSGS may either be congenital or due to other disorders that affect the metabolism and normal kidney function. Both PCOS and FSGS appear to be associated with Transforming Growth Factor-ß (TGF-ß) signalling. Over-expression of TGF-ß may be due to the activation of the thrombospondin 1 (TSP1) gene, which increases the probability of developing renal disorders. Higher androgen levels in PCOS may also cause podocyte damage thus directly impacting development of FSGS. This article reviews the role of TGF-ß's in PCOS and FSGS and explores the inter-relationship between these two disorders.

Anti-inflammatory and wound healing potential of a clove oil emulsion.

Emulsion formulations of essential oils are of major interest due to their relative biosafety, biocompatibility and good pharmacological potential. Their structural constituents (oil and water phase) facilitate ready solubilization of incorporated hydrophilic/lipophilic actives for their targeted delivery. In the present study, m5S cells were tested for their viability at various concentrations of clove oil and an alkyl polyglucoside emulsifier, viz., Montanov 202™. Thereafter, good cell viable concentrations of oil (10 %) and emulsifier (4%) were used at their optimised ratio (1:0.4) to formulate an oil in water emulsion using phase inversion technique followed by ultrasonication for particle size reduction. Gas chromatography-mass spectrometry (GC-MS) analysis of clove oil revealed eugenol (76.11 %) and eugenyl acetate (12.41 %) as major constituents. The formulated clove oil emulsion was then characterised with respect to its size, zeta potential, microscopic and thermal analysis and the presence of liquid crystals were observed in the same. It was further studied for its anti-inflammatory potential in female Wistar rats wherein topical treatment with the emulsion inhibited paw swelling induced by carrageenan model by 40-60% over 30-180 min compared to untreated animals. Similarly, the emulsion's wound healing potential was also significant with respect to wounds induced by both incision (wound breaking strength of 338.91 ±â€¯5.02 g) and excision (95 % wound contraction by 16th day) model in these animals, with a re-epithelization period of 10.67 ±â€¯1.67 days and results being comparable with diclofenac gel and neomycin cream (positive controls). Histopathology of the skin sections showed accelerated healing with early granular tissue and collagen formation in emulsion treated animals. It is hence envisaged that this clove oil emulsion can substitute chemical based topical products for anti-inflammatory and wound healing applications due to its biological constituents as well as because of the presence of liquid crystals in its formulation.

Formulation and characterization of a Helianthus annuus - alkyl polyglucoside emulsion cream for topical applications.

BACKGROUND: Green formulations with herbal oils and natural nonionic emulsifiers project several advantages, like favorable viscosity profiles, for use as topical applicants. Their inherent constituents also protect the skin against free radical damage and lipid peroxidation. They may hence serve as alternatives for synthetic chemical-based formulations. OBJECTIVE: Formulation and characterization of Helianthus annuus-alkyl polyglucoside cream for topical application has been attempted. Its inherent sun protection factor has been measured and compared with a similar commercial formulation. It is well known that the internal network of liquid crystals of such emulsifiers can store depot water to maintain moisturization for long time, thus bestowing beneficial dermatological effects. METHODS: Physicochemical characterization of the oil was done. The formulation process for the cream was optimized for reduced particle size with respect to ultrasonication conditions. It was characterized extensively; its inherent sun protection factor was measured and compared with a similar commercial cream. RESULTS: The cream was smooth, creamy, and showed non-Newtonian thixotropic behavior and good shear-thinning features with an SPF of 6.3 that compared favorably with a similar commercial cream. CONCLUSIONS: The cream may serve as a good topical applicant and also help in skin hydration due to the inherent nature of the emulsifier. It may protect against UV radiations due to the antioxidant and anti-inflammatory nature of the natural oil constituents. It may be used as a low-SPF formulation.

Combination effects of sorafenib with PI3K inhibitors under hypoxia in colorectal cancer.

AIM: This study reports the influence of hypoxia on response of colorectal cancer cells to anticancer effects of sorafenib in combination with PI3K inhibitors GDC-0941 and BEZ-235. MATERIALS AND METHODS: All hypoxic exposures were carried out at 1% O2/5% CO2. Antiproliferation activity was evaluated by 48 hours propidium iodide and 14 days clonogenic assay. Protein levels were evaluated by fluorescence ELISA. Metabolites lactate and glucose were evaluated biochemically. RESULTS: In the 48-hour proliferation assay, sorafenib acted synergistically with GDC-0941 but not with BEZ-235. In long-term colony-forming assays, both GDC-0941 and BEZ-235 were shown to potentiate the antiproliferative activity of sorafenib. At the molecular level, the synergism is mediated through inhibition of pAKT, pS6, p4EBP1, pERK, cyclin D1, and Bcl-2. No change in hypoxia-inducible factor-1α (HIF-1α) levels was observed in cells treated with the combination of compounds under hypoxia. A significant reduction in glucose uptake and lactate release was observed in cells treated with the combination of compounds under normoxia and hypoxia. CONCLUSION: Combinations of sorafenib with PI3K inhibitors BEZ-235 and GDC-0941 are efficacious under hypoxia. Thus, these anticancer combinations have a potential to overcome the hypoxia-mediated resistance mechanisms to antiproliferative agents in cancer therapy.

Anticancer activity of Ophiobolin A, isolated from the endophytic fungus Bipolaris setariae.

The present work describes the anticancer activity of Ophiobolin A isolated from the endophytic fungus Bipolaris setariae. Ophiobolin A was isolated using preparative HPLC and its structure was confirmed by HRMS, (1)H NMR, (13)C NMR, COSY, DEPT, HSQC and HMBC. It inhibited solid and haematological cancer cell proliferation with IC50 of 0.4-4.3 µM. In comparison, IC50 against normal cells was 20.9 µM. It was found to inhibit the phosphorylation of S6 (IC50 = 1.9 ± 0.2 µM), ERK (IC50 = 0.28 ± 0.02 µM) and RB (IC50 = 1.42 ± 0.1 µM), the effector proteins of PI3K/mTOR, Ras/Raf/ERK and CDK/RB pathways, respectively. It induced apoptosis and inhibited cell cycle progression in MDA-MB-231 cancer cells with concomitant inhibition of signalling proteins. Thus, this study reveals that anticancer activity of Ophiobolin A is associated with simultaneous inhibition of multiple oncogenic signalling pathways namely PI3K/mTOR, Ras/Raf/ERK and CDK/RB.

Combating drug resistant pathogenic bacteria isolated from clinical infections, with silver oxide nanoparticles.

The antibiogram study of methicillin resistant Staphylococcus aureus isolates revealed 100% resistance to vancomycin, bacitracin, erythromycin, ciprofloxacin and nalidixic acid. Eight isolates (53.3%) showed resistance to co-trimoxazole and one isolate to rifampicin, which was the drug of choice. An effort was made to evaluate the antimethicillin resistant Staphylococcus aureus activity of silver oxide (Ag2O) nanoparticles synthesized from Aspergillus terreus VIT 2013. Production of Ag2O nanoparticles was confirmed by color change of fungal filtrate and UV light absorption at 450 nm. X-ray diffraction pattern showed 2θ values at 27, 32, 38 and 57°, which corresponded to the cubic structure of Ag2O nanocrystals. Fourier transform infrared spectroscopy indicated the presence of primary amine, carbonyl group, NO2 and silver, revealing protein mediated nanoparticle production. The scanning electron microscope image showed freely dispersed Ag2O nanoparticles. The nanoparticles were active against all methicillin resistant isolates and hence can be used as antibacterial agents against drug resistant bacteria.

Structure-function studies on non-synonymous SNPs of chemokine receptor gene implicated in cardiovascular disease: a computational approach.

Among non-communicable diseases, cardiovascular disease (CVD) is claimed to be the leading cause of death worldwide. The chemokine (C-C Motif) receptor 5 (CCR5) gene has a strong association with the development of CVD and may culminate in myocardial infarction. In this study, its potential variations have been determined using molecular dynamics approach. Single nucleotide polymorphisms (SNPs) are the predominant mutations and their deleterious effects were initially screened using prediction tools. Further, for the 75 % of deleterious non-synonymous SNPs predicted in common by the above tools, root mean square deviation (RMSD) and stability residues were determined using SWISS-PDB viewer and SRide server respectively. Accordingly, four point mutations L55Q, V131F, R223W, and G301R which had RMSD ≥2.0 Å were selected and trajectory analyses were performed. In common, all trajectory analyses reported no similarities between native and mutants. Combined mutational analysis comparing all the mutants together with the native also showed significant and similar changes. Thus we conclude that the above four mutations are the potential targets of CCR5 and may lead to CVD.

Profiling deleterious non-synonymous SNPs of smoker's gene CYP1A1.

CYP1A1 gene belongs to the cytochrome P450 family and is known better as smokers' gene due to its hyperactivation as a consequence of long term smoking. The expression of CYP1A1 induces polycyclic aromatic hydrocarbon production in the lungs, which when over expressed, is known to cause smoking related diseases, such as cardiovascular pathologies, cancer, and diabetes. Single nucleotide polymorphisms (SNPs) are the simplest form of genetic variations that occur at a higher frequency, and are denoted as synonymous and non-synonymous SNPs on the basis of their effects on the amino acids. This study adopts a systematic in silico approach to predict the deleterious SNPs that are associated with disease conditions. It is inferred that four SNPs are highly deleterious, among which the SNP with rs17861094 is commonly predicted to be harmful by all tools. Hydrophobic (isoleucine) to hydrophilic (serine) amino acid variation was observed in the candidate gene. Hence, this investigation aims to characterize a candidate gene from 159 SNPs of CYP1A1.

Anthropometric parameter-based assessment for cardiovascular disease predisposition among young Indians.

AIM: To assess the predisposition for cardiovascular diseases among young Asian Indians by anthropometric data analysis. METHODS: One hundred and thirty males and 329 females aged between 15 and 26 years, attending health care check-ups at VIT University, were included in this study. Their body mass index, systolic and diastolic blood pressure, waist circumference, waist-to-hip ratio, pulse rate and pressure, along with mean arterial pressure, were measured and the data analyzed as per World Health Organization guidelines. RESULTS: Based on the analysis, 54% of the male population was found to be predisposed to cardiovascular disease. Of these, approximately 40% were at highest possible risk, with greater than threshold values of body mass index, waist circumference and waist-to-hip ratio. Females were found to have lower risk. Both genders showed significant correlation (P < 0.0001) between body mass index and waist circumference. Waist-to-hip ratio correlated significantly only in males with the former index whereas it correlated significantly with waist circumference in both genders. Receiver operating curve analysis, when performed, showed optimal sensitivity and specificity for body mass index and waist circumference. CONCLUSION: The above results indicate that seeds of cardiovascular disease may have been sown at a young age in Asian Indian populations. Interventional measures are advised to prevent accelerated atherosclerosis leading to premature cardiovascular disease.