Mohammad Kaleem Ahmad

Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males

OBJECTIVE To investigate the impact of Withania somnifera roots on semen profile, oxidative biomarkers, and reproductive hormone levels of infertile men. DESIGN Prospective study. SETTING Departments of Biochemistry and Urology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India. PATIENT(S) Seventy-five normal healthy fertile men (control subjects) and 75 men undergoing infertility screening. INTERVENTION(S) High-performance liquid chromatography assay procedure for quantization of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma were estimated by standard spectrophotometric procedures. Estimation of T, LH, FSH, and PRL in blood serum by RIA methods. MAIN OUTCOME MEASURES(S) Before and after the treatment, seminal plasma biochemical parameters, antioxidant vitamins, and serum T, LH, FSH, and PRL levels were measured. RESULT(S) Withania somnifera inhibited lipid peroxidation and protein carbonyl content and improved sperm count and motility. Treatment of infertile men recovered the seminal plasma levels of antioxidant enzymes and vitamins A, C, and E and corrected fructose. Moreover, treatment also significantly increased serum T and LH and reduced the levels of FSH and PRL. CONCLUSION(S) The treatment with W. somnifera effectively reduced oxidative stress, as assessed by decreased levels of various oxidants and improved level of diverse antioxidants. Moreover, the levels of T, LH, FSH and PRL, good indicators of semen quality, were also reversed in infertile subjects after treatment with the herbal preparation.

Withania somnifera Improves Semen Quality in Stress-Related Male Fertility

Stress has been reported to be a causative factor for male infertility. Withania somnifera has been documented in Ayurveda and Unani medicine system for its stress-combating properties. However, limited scientific literature is available on this aspect of W. somnifera. We undertook the present study to understand the role of stress in male infertility, and to test the ability of W. somnifera to combat stress and treat male infertility. We selected normozoospermic but infertile individuals (N = 60), further categorized in three groups: normozoospermic heavy smokers (N = 20), normozoospermics under psychological stress (N = 20) and normozoospermics with infertility of unknown etiology (N = 20). Normozoospermic fertile men (N = 60) were recruited as controls. The subjects were given root powder of W. somnifera at a rate of 5 g/day for 3 months. Measuring various biochemical and stress parameters before and after treatment, suggested a definite role of stress in male infertility and the ability of W. somnifera to treat stress-related infertility. Treatment resulted in a decrease in stress, improved the level of anti-oxidants and improved overall semen quality in a significant number of individuals. The treatment resulted in pregnancy in the partners of 14% of the patients.

Mucuna pruriens Reduces Stress and Improves the Quality of Semen in Infertile Men

The present investigation was undertaken to assess the role of Mucuna pruriens in infertile men who were under psychological stress. Study included 60 subjects who were undergoing infertility screening and were found to be suffering from psychological stress, assessed on the basis of a questionnaire and elevated serum cortisol levels. Age-matched 60 healthy men having normal semen parameters and who had previously initiated at least one pregnancy were included as controls. Infertile subjects were administered with M. pruriens seed powder (5 g day−1) orally. For carrying out morphological and biochemical analysis, semen samples were collected twice, first before starting treatment and second after 3 months of treatment. The results demonstrated decreased sperm count and motility in subjects who were under psychological stress. Moreover, serum cortisol and seminal plasma lipid peroxide levels were also found elevated along with decreased seminal plasma glutathione (GSH) and ascorbic acid contents and reduced superoxide dismutase (SOD) and catalase activity. Treatment with M. pruriens significantly ameliorated psychological stress and seminal plasma lipid peroxide levels along with improved sperm count and motility. Treatment also restored the levels of SOD, catalase, GSH and ascorbic acid in seminal plasma of infertile men. On the basis of results of the present study, it may be concluded that M. pruriens not only reactivates the anti-oxidant defense system of infertile men but it also helps in the management of stress and improves semen quality.

Mucuna pruriens improves male fertility by its action on the hypothalamus-pituitary-gonadal axis.

OBJECTIVE To understand the mechanism of action of Mucuna pruriens in the treatment of male infertility. DESIGN Prospective study. SETTING Departments of Biochemistry, Urology, and Obstetrics and Gynecology, C.S.M. Medical University, Lucknow, India. PATIENT(S) Seventy-five normal healthy fertile men (controls) and 75 men undergoing infertility screening. INTERVENTION(S) High-performance liquid chromatography assay for quantitation of dopa, adrenaline, and noradrenaline in seminal plasma and blood. Estimation by RIA of hormonal parameters in blood plasma, namely T, LH, FSH, and PRL. MAIN OUTCOME MEASURE(S) Before and after treatment, serum T, LH, FSH, PRL, dopamine, adrenaline, and noradrenaline in seminal and blood plasma were measured. RESULT(S) Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment. CONCLUSION(S) Treatment with M. pruriens regulates steroidogenesis and improves semen quality in infertile men.

Interaction of silver nanoparticles with Escherichia coli and their cell envelope biomolecules

The antibacterial effect of AgNPs was investigated by determining MIC/MBC and growth kinetics assay. The lowest MIC/MBC was found to be in the range of 11.25–22.5 µg ml−1. The growth kinetics curve shows that 25 µg ml−1 AgNPs strongly inhibits the bacterial growth. Confocal laser scanning electron microscopy (CLSM) shows that as the concentration of NPs increases, reduction in the number of cells was observed and at 50 µg ml−1 of NPs, 100% death was noticed. Scanning electron microscopy (SEM) shows cells were severely damaged with pits, multiple depressions, and indentation on cell surface and original rod shape has swollen into bigger size. High resolution‐transmission electron microscopic (HR‐TEM) micrograph shows that cells were severely ruptured. The damaged cells showed either localized or complete separation of the cell membrane. The NPs that anchor onto cell surface and penetrating the cells may cause membrane damage, which could result in cell lysis. The interaction of AgNPs to membrane biomolecules; lipopolysaccharide (LPS) and L‐α‐phosphatidyl‐ethanolamine (PE) were investigated by attenuated total reflectance–fourier transform infrared (ATR–FTIR) spectroscopy. LPS and PE showed IR spectral changes after AgNPs exposure. The O‐antigen part of LPS was responsible for interaction of NPs through hydrogen bonding. The phosphodiester bond of PE was broken by AgNPs, forming phosphate monoesters and resulting in the highly disordered alkyl chain. The AgNPs‐induced structural changes in phospholipid may lead to the loss of amphiphilic properties, destruction of the membrane and cell leaking. The biomolecular changes in bacterial cell envelope revealed by ATR–FTIR provide a deeper understanding of cytotoxicity of AgNPs.

1H NMR spectroscopic studies on human seminal plasma: A probative discriminant function analysis classification model

Traditional seminal fluid-based clinical descriptors used to predict infertility and sub-fertility have shortcomings, including lack of insight into the underlying pathology. These methods are also time-consuming and labor-intensive. To address these limitations, (1)H nuclear magnetic resonance (NMR) spectroscopy was used to identify and classify signature biomarkers. Semen samples collected from 60 healthy, fertile men and from 125 infertile (normozoospermic and oligozoospermic) patients. Lactate, alanine, choline, citrate, glycerophosphocholine (GPC), glutamine, tyrosine, histidine, phenylalanine, and uridine were measured by (1)H NMR spectroscopy. The sperm concentration, motility, lipid peroxidation, and total protein were evaluated with standard laboratory methods in the same samples. NMR-quantified metabolites and clinical laboratory data were analyzed, separately, through linear multivariate discriminant function analysis (DFA) to determine the signature descriptors for each group. DFA reveals that alanine, citrate, GPC, tyrosine, and phenylalanine can be used to determine infertility. DFA-based classification demonstrated high accuracy (92.4% by NMR and 94.1% by clinical laboratory method) in differentiating healthy controls from infertile patients. This statistical analysis was also able to accurately classify normozoospermic to oligozoospermic samples (92.9% by NMR and 92.6% by clinical laboratory method). In conclusion, (1)H NMR-based metabolic screening appears to be a promising, rapid, and non-invasive approach to probing infertility that has similar sensitivity and specificity to the tedious laboratory method.

A proton NMR study of the effect of Mucuna pruriens on seminal plasma metabolites of infertile males

The objective of this study was to employ proton nuclear magnetic resonance ((1)H NMR) spectroscopy to evaluate the impact of Mucuna pruriens seeds on the metabolic profile of seminal plasma of infertile patients. A total of 180 infertile patients were administered M. pruriens seed powder for a period of three months. Age-matched healthy men comprised the control (n=50) group in the study. Lactate, alanine, choline, citrate, glycerophosphocholine (GPC), glutamine, tyrosine, histidine, phenylalanine, and uridine were measured in seminal plasma by (1)H NMR spectroscopy. To evaluate the degree of infertility and extent of hormonal imbalance induced by this milieu, separate sperm concentration, motility, lipid peroxide in seminal plasma and LH, FSH, T, and PRL hormone concentration in serum were measured using standard laboratory methods and RIA, respectively, in the same subjects. M. pruriens therapy rectifies the perturbed alanine, citrate, GPC, histidine and phenylalanine content in seminal plasma and improves the semen quality of post-treated infertile men with compared to pre-treated. Concomitantly, clinical variables in seminal plasma and blood serum were also improved over post therapy in infertile men. On the basis of these observations, it may be proposed that M. pruriens seed powder not only reactivates the enzymatic activity of metabolic pathways and energy metabolism but also rejuvenates the harmonic balance of male reproductive hormones in infertile men. These findings open more opportunities for infertility treatment and management by improving semen quality.

Efficacy of Withania somnifera on seminal plasma metabolites of infertile males: a proton NMR study at 800 MHz.

ETHNOPHARMACOLOGICAL RELEVANCE Traditional Indian systems of medicine use roots of Withania somnifera for impotence, infertility treatment, stress, and the aging process. Although Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress, the molecular mechanism is not clear. AIM OF THE STUDY Our study uses high-resolution Nuclear Magnetic Resonance (NMR) spectroscopy to explore the scientific basis to reveal the pre- and post-treatment efficacy of Withania somnifera on seminal plasma of infertile men-which remains unexplored to date. MATERIALS AND METHODS A total of 180 infertile male patients were administered Withania somnifera root powder at the rate of 5 g/d for a 3-month period. The study included age-matched, healthy men as a control (n=50) group. Proton NMR spectroscopy was used to measure lactate, alanine, glutamate, glutamine, citrate, lysine, choline, glycerophosphocholine (GPC), glycine, tyrosine, histidine, phenylalanine, and uridine in all seminal plasma samples. To appraise infertility levels, we also measured sperm concentration, motility, lipid peroxide, and hormonal perturbation. RESULTS Withania somnifera therapy repairs the disturbed concentrations of lactate, alanine, citrate, GPC, histidine, and phenylalanine in seminal plasma and recovers the quality of semen of post-treated compared to pre-treated infertile men. Serum biochemistry was also improved over post-therapy in infertile men. Our findings reveal that Withania somnifera not only reboots enzymatic activity of metabolic pathways and energy metabolism but also invigorates the harmonic balance of seminal plasma metabolites and reproductive hormones in infertile men. CONCLUSION The results suggest that Withania somnifera may be used as an empirical therapy for clinical management and treatment of infertility.

Drug Targets for Cancer Treatment: An Overview

Cancer is one of the major causes of the death worldwide.Malignant cells display metabolic changes, when compared to normal cells, because of both genetic and epigenetic alterations. Number of drugs being used for the cancer treatment follows different mechanisms of action. Therapeutic strategies include targeting of drugs at specific genes or proteins/enzymes found in cancer cells or the internal tissueenvironment which contributes to growth and survival of these cells. Targeted therapy is often used along with chemotherapy and other treatments to restrict the growth and spread of cancer cells. During the past few decades, targeted therapy has emerged as a promising approach for the development of selective anticancer agents. There is a class of targeted therapy drugs called angiogenesis inhibitors which focus on blocking the development of new blood vesselsin tumor tissues. In addition, anticancer drugs also include DNA intercalators, DNA synthesis inhibitors, transcription regulators, enzyme inhibitors etc. This review focuses on major classes of anticancer drug targets and their therapeutic importance.

Association of TNF-α (-238 and -308) promoter polymorphisms with susceptibility of oral squamous cell carcinoma in North Indian population

BACKGROUND The pro-inflammatory cytokines play an essential role in immune response and are involved in a variety of inflammatory and infectious disease. Tumor necrosis factor alpha (TNF-α) gene polymorphism has been a potential determinant of susceptibility to various types of cancer. OBJECTIVE To evaluate the association of TNF-α gene promoter (-238) G/A and (-308) G/A polymorphisms with the susceptibility of OSCC patients in North Indian population. METHODS A total 272 patients with OSCC and 185 healthy volunteers were genotypes for the TNF-α (-238) G/A and (-308) G/A gene polymorphism. Genotypes were identified by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). Genotype frequencies were evaluated by Chi-square test and Odds ratio (OR) relative risk. RESULTS TNF-α (-238) G/A polymorphism was significantly associated with OSCC patients as compared to healthy volunteers (GG vs. GA: OR=0.3500, 95% CI=0.1289-09502; p=0.036; G vs. A: OR=0.3589 1.477, 95% CI=0.1335-0.9652; p=0.0386). No significant association was found in TNF-α (-308) G/A gene polymorphism with OSCC patients and controls. CONCLUSIONS We conclude that the TNF-α (-238) G/A polymorphism was significantly associated with OSCC however TNF-α (-308) G/A polymorphism was not associated in OSCC patients.