Testosterone in the pathogenesis of tuberculosis

Tuberculosis is a leading cause of death from infectious diseases worldwide with more than 1.5 million deaths occurring annually. Males have been known to be more susceptible to tuberculosis than females. Sex hormones could be an important factor governing this gender bias. Here, we discuss the evidence that testosterone may be a crucial factor in male susceptibility to tuberculosis considering that testosterone impairs important factors which have a significant bearing on the outcome of tuberculosis. We also discuss possible underlying mechanisms through which testosterone modulates the immune response that is necessary for host resistance to tuberculosis. We discuss various models that have helped to uncover the role of testosterone in the outcome of infection by M. tuberculosis. Studying the role of testosterone on the various components that constitute the immune response to the disease have provided valuable insights into the sexual dichotomy observed in male bias in tuberculosis morbidity.

Resistin and visfatin: ‘connecting threads’ of immunity, energy modulations and male reproduction

Adipokines, mostly produced by white adipose tissues, have been established to be endocrine factors which are also essential in energy homeostasis. More recently, their contribution in fertility regulation has been recommended. Resistin as well as visfatin are unique adipocyte-derived signaling chemicals whose expressions enhance in advanced obesity and are implicated in insulin resistance as well as type-2 diabetes. They are also found to be immune modulators and may participate in aggravating inflammatory responses which may partly explain obesity-mediated systemic inflammation. They are yet much less explored adipokines with potential to regulate metabolic rate, immune homeostasis as well as fertility. These adipokines are shown to be expressed in the hypothalamus in an area in charge of energy balance. Evidence suggest that they can potentially affect the hypothalamo-pituitary-gonadal (HPG) axis thereby modulating reproductive functions. They are also found to be expressed highly by the testes. In rodents, resistin and visfatin may positively modulate Leydig cell number and steroidogenesis. Additionally, visfatin exists in the human spermatozoa and may play role in the sperm maturation. However, reports on the impact of resistin and visfatin on human male fertility are inconsistent. In this article, we review the available literature on the role resistin and visfatin on male reproduction and integrate the mechanisms to discuss if they act as sensor for body energy dyshomeostatis and modulate male reproductive functions as per the metabolic status.

Chemerin and male reproduction: ‘a tangled rope’ connecting metabolism and inflammation

Adipokines are peptides produced mainly by the fat tissue adipocytes and their levels are sensitive to alterations in metabolic state. While there is little known about the impact of adipokines on male reproductive control, both animal-based experimental data and clinical research suggest that they can influence numerous male fertility indices. Chemerin is a newly found adipokine which is generally recognized as a chemoattractant and chemokine. Chemerin has been correlated with inflammatory reactions and metabolic imbalances, as seen in various metabolic syndromes. A sex dimorphic chemerin expression pattern has also been shown with greater levels in men in comparison to women. Chemerin can thus be offered as a potential new candidate in the connection among metabolic disorders, inflammation and male reproduction. The present article explores the multidimensional metabolic and inflammatory roles of chemerin and discusses its impact upon the male reproduction.

Orexins: the ‘multitasking’ neuropeptides in the energy metabolism and immune regulation of male reproduction

Orexins are hypothalamus-derived neuropeptides with versatile functions. The most explored domains of orexins’ functions are their influence on the central nervous system (CNS) implicated in the regulation of sleep/wakefulness cycle, food intake behavior, energy homeostasis, and cognitive processes. Orexins reportedly bear two isoforms, orexin-A (OXA) and orexin-B (OXB), that act via their specific G protein-coupled receptor (GPCR), OX1R and OX2R. These peptides also play vital roles in various other peripheral organs where they regulate metabolism, neuroendocrine functions, blood pressure, as well as reproductive functions. Interestingly orexins also exhibit immuno-regulatory, anti-inflammatory properties and facilitate the mechanism of obesity resistance. Recent research has also shed light on significant role of orexins, in particular orexin A, in regulating reproductive functions in male since the Leydig cells, Sertoli cells, germ cells in various stages of the development, and even the epididymis and penis, manifest the OXA receptor. It will be intriguing to explore the properties of the orexins in reversing obesity, downregulation of inflammatory responses and mediation of male reproductive functions. The present article thus reviews these multitudinous properties of orexins and comprehends the possible connection among the behavioral, metabolic, anti-inflammatory functions of orexins with their roles in male reproduction.

Lactobacillus casei and Bifidobacterium bifidum reduces postprandial hyperglycaemia, inhibits α-glucosidase activity and improve histology of pancreatic islets in streptozotocin induced diabetic rats

Lactobacillus and Bifidobacteria are generally accredited as potential anti-diabetic agents, but the mechanism of action is still not clear. This study aimed to investigate the result of administration of Lactobacillus casei and Bifidobacterium bifidum on α-glucosidase enzyme, postprandial blood glucose level, and histological changes that occur in the pancreatic β-cells in streptozotocin (STZ (50 mg/kg body weight)) induced diabetic rats. The experimental diabetic rats were treated with a single dose of L. casei and B. bifidum alone and combination for 28 days. The diabetic animals of a positive control group were treated with the standard hypoglycaemic drug, acarbose (10mg/kg body weight). Maltose and starch tolerance tests were performed. Treatment demonstrated significant hypoglycemic activity, lower postprandial blood glucose levels induced by maltose and starch loading in diabetic rats. The results demonstrated that L. casei and B. bifidum had α-glucosidase inhibitory activity and can reduce blood glucose level observed from the maltose and starch tolerance test. Histological analysis showed treatment prevented the function of pancreatic islets and regenerate degenerated cells.

Leptin in Energy homeostasis, Male reproduction, and Immune regulation

Discovery of leptin has changed the view of adipose tissue from energy storehouse to active neuroendocrine and immune organ. Adipokineleptin is a16 kDa amino acid protein, encoded by LEP gene, secreted by adipose tissue, and acts through leptin receptor which is a cytokine receptor. Leptin is a central regulator of energy homeostasis by regulating food intake, appetite, satiety and basal metabolism. Leptin acts at each level of hypothalamus pituitary gonadal axis (HPG) and has a key role in initiation, progression of pubertal events and sexual maturation. Leptin acts directly at testicular level and affects the spermatogenesis, sperm quality and capacitation thus have important role in male reproduction and fertility. Leptin receptors are present on every cell involved in innate and adaptive immunity and regulate the functions of these cells. Leptin acts as common link between energy homeostasis, reproduction, stress responses and immune system by modulating common complex neuronal circuits. Leptin is implicated in pathogenesis of multiple disorders like obesity, type 2 diabetes mellitus, Systemic Lupus Erythematosis, osteoarthritis, rheumatoid arthritis, male infertility and other chronic inflammatory disorders. Therapies based on modulating the functions of leptin can be the key area of research in future for treatment of these chronic disorders.

An economic and efficient synthesis of acid-labile glycerol based β-thiopropionate esters for potential application in drug delivery

Acid labile linkers have been used widely for various biomedical applications with preferential applications in drug delivery. In this report, we have synthesized, glycerol based b-thiopropionate esters having an acid-labile β-thiopropionate linker with Michael addition reaction between hydrophobic thiol and hydrophilic tri-glycerol diacrylate. The solvent free reaction and purification by simply solvent extraction instead of any sophisticated chromatographic techniques provide an upper edge for their application in biomedical or other fields. These β-thiopropionate esters can potentially be used for the delivery and release of hydrophobic drugs at acidic sites particularly in cancer cells.

Assessing the antimycobacterial activity of the bioactive fractions of the Indian medicinal plant – Justicia adhatoda L.

Justicia adhatoda L. is an Indian medicinal plant traditionally used to treat respiratory ailments in Ayurvedic and Unani medicines.  It is widespread in the Indian subcontinent. The plant leaves are known to have broad range of pharmacological activities including analgesic, anti-inflammatory, antispasmodic and antibacterial properties. Some studies have highlighted the antimicrobial effects of its major bioactive components like vasicine and vasicinone However, not much work has been done to explore the enormous benefits that the bioactive components might hold. Hence, in the present study, we explored the plant for its potential as an effective anti- mycobacterial agent. We aim to investigate the antimycobacterial effect of J. adhatoda L. plant leaf extracts on Mycobacterium smegmatis and Mycobacterium bovis (BCG) and identify, and isolate th bioactive component(s) for the plant leaf extract. The isolated components were also analyzed further for their antimycobacterial activity in synergy with Isoniazid. The leaves of J. adhatoda L. were powdered and extracted with ethanol, water, ethyl acetate, and hexane and antimycobacterial activity was assessed by MABA. The ethanol extract showed >96% and 98% reduction in colony-forming units (CFU) at 100µg/ml on Mycobacterium smegmatis and Mycobacterium bovis (BCG) respectively. Active phytoconstituent from ethanol extract was isolated and further fractionated via Prep-TLC. They were bioassayed against M. smegmatis and M. bovis (BCG) to study cytotoxicity, synergy, and external damage on the bacteria. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were carried out on treated bacilli to observe the external and internal cellular damage. The isolated fractions showed strong anti-mycobacterial activity, with low cytotoxicity and synergism when used with isoniazid. When subjected to electron microscopy, the fractions were found to adversely affect the cell wall and membrane of BCG, causing cytoplasmic leakage. Our study demonstrated that the active fractions isolated from J. adhatoda L. could be evaluated further for potentially effective anti-mycobacterial agents.

Phytochemical and in vitro analysis of Bornetella oligospora extract as alpha-Glucosidase inhibitor

One of the first-line therapy of diabetes mellitus is alpha-glucosidase inhibitors. Due to side effects caused by synthetic drugs and limited sources, various studies have been conducted on herbal plants and macroalgae consisting of bioactive compounds with alpha-glucosidase inhibitory activity. This study examines the alpha-glucosidase inhibitory activity and phytochemical compounds in ethyl acetate and ethanol extract of Bornetella oligospora, an abundant green alga in eastern Indonesia. The result showed that ethanol and ethyl acetate extract of Bornetella oligospora contained phytochemical components such as flavonoid, glycoside, triterpenoid, and steroid. The thin layer chromatography test showed ethanol extract have five spots with Rf 0.545, 0.527, 0.5, 0.473, and 0.154, while the ethyl acetate extract has two spots with Rf 0.58 and 0.64. The alpha-glucosidase inhibition assay showed IC50 values of the ethanol extract was 11.702 ug/mL and ethyl acetate extract was 95.384 ug/mL. In conclusion, Bornetella oligospora extract has the potential as an antidiabetic agent.

Published in Chemical Biology Letters

Siswanto, M. A., Paramita, R. I., Fadilah, F., & Poerwaningsih, E. H. (2021). Phytochemical and in vitro analysis of Bornetella oligospora extract as alpha-Glucosidase inhibitor. Chemical Biology Letters, 8(1), 40–44. https://pubs.thesciencein.org/journal/index.php/cbl/article/view/120

Beneficial impacts of Astaxanthin on Biomarkers of Antioxidant status and oxidative damage in Rats exposed to Ambient air

Effect of astaxanthin from Haematococcus pluvialis on lipid peroxidation and oxidative stress induced by ambient air exposure was studied. Wistar albino rats were exposed to ambient air was administered with astaxanthin in doses varying between 0.5 to 2% of food intake. Various biological parameters like ALT, AST, ALP, malondialdehyde, hydrogen peroxide, superoxide dismutase, catalase and glutathione reductase, were estimated biochemically and the expression of Nrf2 and glutathione peroxidase genes were estimated by reverse transcriptase PCR. Plasma ALT, AST, ALP, MDA and the activity of antioxidant enzymes; SOD, GRd, catalase were found increased significantly in ambient air exposed rats. Ambient air exposure decreased the levels of glutathione, non protein thiols and GPx expression whereas total thiols and expression of Nrf2 increased. However the concurrent administration of astaxanthin was found to reverse these changes in a dose dependent manner. The results of this study revealed the ability of astaxanthin to alleviate liver toxicity and oxidative stress induced by ambient air exposure and points to the possibility of developing astaxanthin as a dietary supplement that reduce the ill effect of toxic chemicals from ambient air.

Published in: Chemical Biology Letters

Johnson, J. P., Renganthan, S., Menon, A., & Pillai, R. G. (2021). Beneficial impacts of Astaxanthin on Biomarkers of Antioxidant status and oxidative damage in Rats exposed to Ambient air. Chemical Biology Letters, 8(1), 1–9. https://pubs.thesciencein.org/journal/index.php/cbl/article/view/158