Effect of Curcuma longa extract on reproduction function in mice and testosterone production in Leydig cells.

Curcuma longa, best known for its culinary application as the main constituent of curry powder, has shown potential impact on the reproductive system. This study aimed to investigate the efficacy of Curcuma longa extract (CLE) on Kidney-Yang deficiency mice induced by hydrocortisone and the possible roles in testosterone secretion in Leydig cells. We evaluated male sexual behaviour, reproductive organ weight, testosterone levels, and histological tissue changes in hydrocortisone-induced mice. CLE effectively reversed hydrocortisone-induced Kidney-Yang deficiency syndrome by improving sexual behaviour, testis and epididymis weight, testosterone levels and reducing pathological damage. Our in vitro study further indicated that CLE stimulated testosterone production via upregulating the mRNA and protein expression of steroidogenic enzymes in Leydig cells. It significantly improved H89-inhibited protein expression of StAR and cAMP-response element-binding (CREB), as well as melatonin-suppressed StAR protein expression. The data obtained from this study suggest that CLE could alleviate Kidney-Yang deficiency symptoms and stimulate testosterone production by upregulating the steroidogenic pathway. This research identifies CLE as a potential nutraceutical option for addressing testosterone deficiency diseases.

Testosterone Supplementation Promotes Estrogen Synthesis of Buffalo Cumulus Cells Surrounding In Vitro-Matured Oocytes.

Cumulus cells (CCs) synthesize estrogens that are essential for follicular development. However, the effects of androgen on estrogen production in buffalo CCs remain unknown. In the present study, the impacts of testosterone on estrogen synthesis of buffalo CCs surrounding in vitro-matured oocytes were investigated. The results showed that testosterone supplementation improved both the expression levels of estrogen synthesis-related genes (CYP11A1, CYP19A1, and 17ß-HSD) and the secretion levels of estradiol in buffalo CCs surrounding in vitro-matured oocytes. Furthermore, testosterone treatment enhanced the sensitivity of buffalo CCs surrounding in vitro-matured oocytes to follicle-stimulating hormone (FSH). This study indicated that testosterone supplementation promoted the estrogen synthesis of buffalo CCs surrounding in vitro-matured oocytes mainly through strengthening the responsiveness of CCs to FSH. The present study serves as a foundation of acquiring high-quality recipient oocytes for buffalo somatic cell nuclear transfer.

The relationship between hematologic malignancies on male hypogonadism: a scoping review.

INTRODUCTION: The associated symptoms of hypogonadism have been reported in patients with various types of cancer. However, the prevalence and significance of hypogonadism among certain hematologic malignancies have not been completely summarized in recent literature. OBJECTIVE: In this review we aimed to examine the current literature on hypogonadism in patients with hematologic malignancies, with emphasis on leukemias, lymphomas, and multiple myeloma (MM). METHODS: This review included relevant studies published before July 2023 that were retrieved through a search of PubMed using the keywords "hematologic cancer," "hematologic malignancy," blood cancer," "leukemia," "lymphoma," "hypogonadism," "multiple myeloma," and "testosterone." RESULTS: The search yielded 214 studies, of which 21 met the inclusion criteria. Commonly reported findings were that patients who had received hematopoietic stem cell therapy for acute lymphoblastic leukemia and acute myelogenous leukemia as children had laboratory-confirmed hypogonadism as adults. However, the impact of these diseases on hypogonadal symptoms was variable in these studies.Studies reporting on lymphoma and hypogonadism had mixed results, with some studies finding that the degree of cytotoxic chemotherapy was associated with hypogonadism, while others showed no correlation. Regardless, multiple studies found that hypogonadism secondary to lymphoma treatment and symptoms of hypogonadism had no apparent association.The most comprehensive assessment of the frequency of hypogonadism in an MM cohort found that 74% of 561 MM patients were classified as hypogonadal compared to 33% of patients in a control population. Testosterone supplementation was found to lower interleukin-6 levels, which could potentially help manage some of the adverse effects of MM, including decreased bone mineral density. CONCLUSION: There is a relationship between hematologic malignancies and hypogonadism, which is likely multifactorial. In this review we established that the most plausible factors are related to the secondary effects of gonadotoxic treatments and/or systemic inflammatory responses to the diseases.

Effects of testosterone and vitamin D on fall risk in pre-frail hypogonadal men: a factorial design RCT.

OBJECTIVE: To test whether transdermal testosterone at a dose of 75 mg per day and/or monthly 24'000 IU Vitamin D reduces the fall risk in pre-frail hypogonadal men aged 65 and older. DESIGN: 2 × 2 factorial design randomized controlled trial, follow up of 12 months. METHODS: Hypogonadism was defined as total testosterone <11.3 nmol/L and pre-frailty as ≥1 Fried- frailty criteria and/or being at risk for falling at the time of screening. The primary outcomes were number of fallers and the rate of falls, assessed prospectively. Secondary outcomes were appendicular lean mass (ALM), sit-to-stand, gait speed, and the short physical performance test battery. Analyses were adjusted for age, BMI, fall history and the respective baseline measurement. RESULTS: We aimed to recruit 168 men and stopped at 91 due to unexpected low recruitment rate (1266 men were pre-screened). Mean age was 72.2 years, serum total testosterone was 10.8 ± 3.0 nmol/l, and 20.9% had 25(OH)D levels below 20 ng/mL. Over 12 months, 37 participants had 72 falls. Neither the odds of falling nor the rate of falls were reduced by testosterone or by vitamin D. Testosterone improved ALM compared to no testosterone (0.21 kg/m2 [0.06, 0.37]), and improved gait speed (0.11 m/s, [0.03, 0.20]) compared to placebo. CONCLUSION: Transdermal testosterone did not reduce fall risk but improved ALM and gait speed in pre-frail older men. Monthly vitamin D supplementation had no benefit.

Activation of testosterone-androgen receptor mediates cerebrovascular protection by photobiomodulation treatment in photothrombosis-induced stroke rats.

RATIONALE: Numerous epidemiological studies have reported a link between low testosterone levels and an increased risk of cerebrovascular disease in men. However, there is ongoing controversy surrounding testosterone replacement therapy due to potential side effects. PBMT has been demonstrated to improve cerebrovascular function and promote testosterone synthesis in peripheral tissues. Despite this, the molecular mechanisms that could connect PBMT with testosterone and vascular function in the brain of photothrombosis (PT)-induced stroke rats remain largely unknown. METHODS: We measured behavioral performance, cerebral blood flow (CBF), vascular permeability, and the expression of vascular-associated and apoptotic proteins in PT-induced stroke rats treated with flutamide and seven consecutive days of PBM treatment (350 mW, 808 nM, 2 min/day). To gain further insights into the mechanism of PBM on testosterone synthesis, we used testosterone synthesis inhibitors to study their effects on bEND.3 cells. RESULTS: We showed that PT stroke caused a decrease in cerebrovascular testosterone concentration, which was significantly increased by 7-day PBMT (808 nm, 350 mW/cm2 , 42 J/cm2 ). Furthermore, PBMT significantly increased cerebral blood flow (CBF) and the expression of vascular-associated proteins, while inhibiting vascular permeability and reducing endothelial cell apoptosis. This ultimately mitigated behavioral deficits in PT stroke rats. Notably, treatment with the androgen receptor antagonist flutamide reversed the beneficial effects of PBMT. Cellular experiments confirmed that PBMT inhibited cell apoptosis and increased vascular-associated protein expression in brain endothelial cell line (bEnd.3) subjected to oxygen-glucose deprivation (OGD). However, these effects were inhibited by flutamide. Moreover, mechanistic studies revealed that PBMT-induced testosterone synthesis in bEnd.3 cells was partly mediated by 17ß-hydroxysteroid dehydrogenase 5 (17ß-HSD5). CONCLUSIONS: Our study provides evidence that PBMT attenuates cerebrovascular injury and behavioral deficits associated with testosterone/AR following ischemic stroke. Our findings suggest that PBMT may be a promising alternative approach for managing cerebrovascular diseases.

Salivary testosterone and cortisol response in acute stress modulated by seven sessions of mindfulness meditation in young males.

Stress is an established risk factor for negative health outcomes. Salivary cortisol and testosterone concentrations increase in response to acute psychosocial stress. It's crucial to reduce stress for health and well-being through evidence-based interventions. Body-mind interventions such as meditation and Tai Chi have shown reduced cortisol levels but mixed results in testosterone concentration after stress. To address this research gap, we conducted a pilot randomized controlled trial to examine the modulating effects of a short-term (seven 20-minute sessions) mindfulness meditation on testosterone and cortisol in response to acute stress. Using one form of mindfulness meditation - Integrative Body-Mind Training (IBMT) and an active control-relaxation training (RT), we assessed salivary cortisol and testosterone concentrations at three stages of stress intervention - rest, stress, and an additional 20-min IBMT or RT practice. We found increased cortisol and testosterone concentrations after acute stress in both groups, but testosterone rise was not associated with cortisol rise. Moreover, an additional practice immediately after stress produced higher testosterone concentrations in the IBMT group than the RT group, whereas cortisol concentration increased in the RT group than in the IBMT group at the same time point. These findings indicate that brief mindfulness intervention modulates a dual-hormone profile of testosterone and cortisol in response to acute stress presumably via the co-regulation of hypothalamus-pituitary-adrenal and hypothalamus-pituitary-testicular axes.

Multi-omics reveals the testosterone promotion effect mechanism of Cordyceps Sobolifera on Leydig cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sobolifera (CS) has been traditionally utilized as an ethnic remedy for various health conditions, including chronic kidney diseases, anti-fatigue interventions, and management of chronic inflammation. Notably, CS is recognized for its substantial content of bioactive compounds, among which nucleosides prominently feature as constituents with diverse therapeutic advantages. AIM OF THE STUDY: This study aims to investigate the effects of CS on testosterone secretion in Leydig cells and explore the underlying mechanism. MATERIALS AND METHODS: Leydig cells were isolated from rat testes to establish a primary rat Leydig cells model. Cell proliferation and testosterone secretion were assessed via the methyl-piperidino-pyrazole (MTT) assay and enzyme-linked immunosorbent assay (ELISA), respectively. Samples earmarked for RNA sequencing (RNA-Seq) analysis facilitated the identification of significantly differentially expressed genes (DEGs), and we conducted Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation and enrichment analyses. The veracity of our findings was validated through quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. RESULTS: The results showed that CS and guanosine could promote Leydig cell proliferation and bolster testosterone secretion. Our integrative analysis of metabolomics and transcriptomics has unveiled the potential mechanisms governing testosterone synthesis. Specifically, metabolomics has illuminated striking correlations within cholesterol metabolism, and bile secretion. Concurrently, transcriptomics has underscored the pivotal roles played by the cyclic adenosine monophosphate (cAMP) signaling pathway and steroid hormone biosynthesis. Furthermore, our investigation has demonstrated CS's aptitude in elevating the expression of proteins and genes. Notably, our findings have elucidated that these effects can be mitigated by protein kinase A (PKA) and adenylate cyclase (AC) specific inhibitors. CONCLUSION: This study delineates the cAMP-PKA pathways as plausible mechanisms underpinning the testosterone-enhancing properties of CS, with guanosine emerging as a fundamental bioactive constituent.

Testosterone regulates thymic remodeling by altering metabolic reprogramming in male rats.

The thymus is an energy-consuming organ, and its metabolism changes with atrophy. Testosterone regulates thymus remodeling (atrophy and regeneration). However, the characteristics of the energy metabolism during testosterone-mediated thymic atrophy and regeneration remain unclear. In this study, we demonstrated that testosterone ablation (implemented by immunocastration and surgical castration) induced global metabolic changes in the thymus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment for differential metabolites and metabolite set enrichment analysis for total metabolites revealed that testosterone ablation affected thymic glycolysis, glutamate metabolism, and fatty acid ß-oxidation. Testosterone ablation-induced thymic regeneration was accompanied by attenuated glycolysis and glutamate metabolism and changed fatty acid composition and content. Testosterone supplementation in immunocastrated and surgically castrated rats enhanced glutaminolysis, reduced the level of unsaturated fatty acids, enhanced the ß-oxidation of unsaturated fatty acids in the mitochondria, boosted the tricarboxylic acid (TCA) cycle, and accelerated thymic atrophy. Overall, these results imply that metabolic reprogramming is directly related to thymic remodeling.

Evaluation of Salvia hispanica as a Therapeutic Agent against Sodium Arsenic-Induced Testicular Toxicity in a Male Rats Model.

Chia seeds offer therapeutic properties that aid in the prevention of a variety of ailments, including cardiovascular disease, diabetes, obesity, and other risk factors. Arsenite, a common environmental chemical, has been identified as a reproductive toxin owing to its negative effects on male reproductive health. It has been shown to inhibit spermatogenesis and generate androgenic effects in men. The primary goal of this research was to look into the effect of Salvia hispanica on testicular toxicity caused by sodium arsenite in male rats. A set of 36 male albino rats was allocated to a negative control cohort. The individuals in this group were given a basic meal and orally given distilled water for a duration of 28 days. The other five groups were given a regular meal and received intra-peritoneal injections of sodium arsenite (NaAsO2) at a concentration of 4 mg/kg body weight that was diluted in a 0.9% NaCl solution. The injections were administered consecutively, with two doses given within a two-day period. Subsequently, the rats were categorized into several groups using the following classification: Group 2 consisted of a positive control cohort, in which the rats were given a typical baseline diet. Groups 3, 4, 5, and 6 were given a basic diet that included varying proportions of ground chia seeds, namely 5%, 10%, 15%, and 20% per 100 g of the diet. After the trial was completed, the rats were euthanized, and further biological examination was conducted. The measurements of the reproductive organs were documented and reported. The research assessed the following characteristics: sperm count, motility, progressive motility, and normal morphology. The research included examining serum sex hormones, namely luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. An evaluation of the activity of antioxidant enzymes was performed in the tissue of the testicles. There were statistically significant improvements in the sperm parameters, serum sex hormone levels, and the activity of antioxidant enzymes, such as GPX, SOD, and CAT, in the therapy groups. The levels of malondialdehyde (MDA) exhibited a noteworthy decrease (p ≤ 0.05) when compared to the positive control group. Salvia hispanica seeds have demonstrated a significant level of effectiveness in reducing sodium arsenite-induced testicular toxicity, which leads to the conclusion. The flavonoid content and antioxidant properties of Salvia hispanica seeds may be to blame for the observed behavior. These indicated characteristics may have therapeutic significance in treating testicular harm induced by arsenite exposure.

Emerging Role of Eruca sativa Mill. in Male Reproductive Health.

A growing interest has been drawn to the use of traditional medicinal plants for the treatment of human diseases and, in particular, infertility and reproductive toxicity associated with environmental factors. The Mediterranean basin area is a recognized source of plant species with therapeutic interest. In this frame, Eruca sativa (ES) is an annual edible plant and a member of the Brassicaceae family. A relatively large number of studies, focusing on the biological effects of the extract from the leaves of ES on in vitro and in vivo models of disease, have been published in recent years. The present narrative review aims to analyze the phytochemical constituents, traditional uses, possible pharmacological activities, and recognized effects of ES on male reproductive outcomes. Available investigations have revealed the presence of a number of compounds with antioxidant properties, such as polyphenols, glucosinolates, flavonoids, and carotenoids in extracts from ES. Based on the chemical and pharmacological characteristics of the aforementioned compounds, we show that ES has possible preventive properties and therapeutic uses, especially in the functional derangements of the male reproductive system.

Supplementation of L-glutamine enhanced mucosal immunity and improved hormonal status of combat-sport athletes.

BACKGROUND: Maintaining proper immune function and hormone status is important for athletes to avoid upper respiratory tract infection (URTI) and insufficient recovery, which is detrimental to sport performance and health. The aim of this study was to evaluate whether three-week supplementation of L-glutamine could benefit the mucosal immunity and hormonal status of combat-sport athletes as well as their rates of upper respiratory tract infection (URTI) and subjective feelings of well-being after intensive training. METHODS: Twenty-one combat-sport athletes from the National Taiwan University of Sport were recruited in this study. After intensive training, two groups of the participants were asked to consume powder form of 0.3 g/kg body weight of L-glutamine (GLU group) or maltodextrin (PLA group) with drinking water in a randomized design at the same time every day during 3 weeks. Saliva samples were collected to measure immunoglobulin A (IgA), nitric oxide (NO), testosterone (T) and cortisol (C) before and after three-week supplementation; moreover, Hooper's index questionnaires were completed for wellness assessment. The incidence and duration of URTI were recorded by using a health checklist throughout the entire study period. RESULTS: Supplementation of L-glutamine significantly enhanced the concentrations of IgA and NO in saliva; additionally, the incidence of URTI was significantly reduced. Regarding hormones, T concentration was significantly decreased in the PLA group, whereas C concentration was significantly increased, resulting in a significant decrease of T/C ratio. In contrast, the GLU group showed a significant increase of T/C ratio, while the mood scores of the Hooper's index questionnaire were higher in the PLA group. CONCLUSIONS: Three-week supplementation of L-glutamine after intensive training enhanced the mucosal immunity, improved hormonal status and reduced the rate of URTI of combat-sport athletes while feelings of well-being were also enhanced. Therefore, L-glutamine would be beneficial for the sports performance and recovery of athletes.

Recovery Effects of Nephelium lappaceum var. pallens (Hiern) Leenh. Extract on Testosterone-Induced Inhibition of Hair Growth in C57BL/6 Mice and Human Follicular Dermal Papilla Cells.

Although various hair health medicines have been developed and are used today, additional safe and effective natural hair growth therapies still need to be developed. Nephelium lappaceum var. pallens (Hiern) Leenh. extract (NLE) reportedly exhibits anticancer, antidiabetic, and antioxidant effects, which could be linked to androgenic processes; however, there are no reports of its effects on testosterone (TS)-inhibited hair growth. The present study investigated the effects of NLE on TS-induced inhibition of hair growth in C57BL/6 mice and human follicular dermal papilla cells. Oral administration of NLE restored hair growth that was suppressed following subcutaneous injection of TS more effectively than finasteride, a drug used for treating hair loss. Histological analysis demonstrated that oral NLE administration increased the number and diameter of hair follicles in the dorsal skin of C57BL/6 mice. In addition, western blot and immunofluorescence assays showed that the oral NLE administration restored TS-induced suppression of cyclin D1, proliferating cell nuclear antigen, and loricrin expression in the skin cells of the mice. Finally, TS suppression of cell proliferation in human follicular dermal papilla cells was significantly reversed by NLE pretreatment. The results suggest that NLE is a promising nutraceutical for hair growth because it promotes hair growth in androgenetic alopecia-like models.

In ovo injection of testosterone to yolk sac modulates early posthatching development and physiology of male chick in broilers.

The aim of this study was to investigate the effects of in ovo testosterone injection into the yolk sac of embryos on physiology and development of broiler chicks during the early posthatching period. A total of 1,010 hatching eggs were obtained from the Ross genotype. Trial design was conducted with a noninjected group (control) and injection groups in which 100 µL sesame oil, or 100 µL sesame oil + 0.50 µmol testosterone were injected into the yolk sac of the embryo on d 6 or d 12 of incubation. Testosterone hormone level was measured in the egg yolk and albumen at onset of incubation, in the yolk sac on d 19 of incubation and in the residual yolk sac at hatching. Weights of chick, yolk sac and organ, morphological traits (body length, lengths of bilateral traits and beak length), asymmetrical development of bilateral morphological traits and body mass index were measured at hatching and on d 7 after hatching. Testosterone, corticosterone and growth hormone levels were determined in blood plasma obtained from male chicks at hatching and on d 7 of chick age. Chick weight was not affected, plasma testosterone level and brain weight decreased, while body mass index, plasma corticosterone and growth hormone levels increased by administering 0.50 µmol testosterone on d 12 of embryonic age. However, plasma testosterone and growth hormone levels did not change, chick weight increased, while plasma corticosterone level and the chick body length decreased by administering 0.50 µmol testosterone on d 6 of embryonic age. A significant interaction between chick age and in ovo testosterone administration resulted in an increase in lung weight of chicks. In conclusion, this study found that in ovo testosterone administered at different embryonic ages due to age-specific effects of testosterone in the yolk sac of embryo modulates development related to physiological parameters of male broiler chicks during early posthatching period.

Zinc Ameliorates Tripterygium Glycosides-Induced Reproductive Impairment in Male Rats by Regulating Zinc Homeostasis and Expression of Oxidative Stress-Related Genes.

Tripterygium glycosides (TG) can seriously damage male reproductive function, and the reproductive system is difficult to restore after stopping the administration of TG in male rats. Zinc (Zn) is one of the most important trace elements in the human body and plays an important role in maintaining male fertility. The aim of this study was to investigate whether zinc supplementation could improve the testicular reproductive damage induced by TG toxicity in rats and to investigate its mechanism of action. The results showed that zinc sulfate (ZnSO4) could improve testicular tissue structure and semen parameters, promote testosterone synthesis, increase zinc-containing enzyme activity, increase zinc concentration in serum and testicular tissues, and maintain zinc homeostasis in male rats induced by TG toxicity. Zinc supplementation activated relevant signalling molecules in the KEAP1-NRF2/ARE pathway and alleviated TG-induced oxidative stress. Therefore, this study concluded that zinc supplementation could improve reproductive damage by regulating zinc homeostasis and the expression of genes related to oxidative stress.

Effect of Selenium and Zinc Supplementation on Reproductive Organs Following Postnatal Protein Malnutrition.

Protein diets are required for the normal development of the reproductive system and their inadequacy or deficiency might have hazardous functional complications during maturational and developmental stages. The study was carried out to evaluate the effect of selenium (Se) and zinc (Zn) supplementation on the male and female reproductive organs of rats with postnatal protein malnutrition. Male and female weanling rats were randomly assigned to six groups respectively. The adequate protein diet rats were fed with 16% casein diet while the protein malnourished diet (PMD) rats were fed with 5% casein diet. After the 8th week of feeding, Se (sodium selenite; Na2SeO3) and Zn (zinc sulfate; ZnSO4·7H2O) were supplemented for 3 weeks. The growth curve of body weights, lipid profile, testosterone and progesterone level, Na+-K+-ATPase activity, oxidative stress, and antioxidant status were evaluated. The results showed that PMD reduced the body weights of male and female rats. It also reduced the activities of catalase and glutathione peroxidase in the testes, but reductions in superoxide dismutase and glutathione-S-transferase activities, glutathione, vitamins C and E, testosterone, and progesterone levels were observed in both the testes and ovaries. Furthermore, PMD increased the nitric oxide level in both organs and altered the plasma lipid profiles in both sexes. Se and Zn supplementation, however, restored almost all the alterations observed in all the parameters analyzed. In conclusion, Se and Zn supplementation protects the male and female reproductive organs of rats against postnatal protein malnutrition.

Effects of vitamin D on sex steroids, luteinizing hormone, and testosterone to luteinizing hormone ratio in 307 infertile men.

OBJECTIVE: Vitamin D status has been associated with sex steroid production. The question is whether vitamin D supplementation has an impact on sex steroid production in infertile men with vitamin D insufficiency? DESIGN: A single-center, double-blinded, randomized clinical trial. Differences in sex steroids and reproductive hormones were predefined secondary outcomes, vitamin D status at baseline was a predefined subgroup and the primary outcome was differences in semen quality. METHODS: A total of 307 infertile men were included and randomized 1:1 to active or placebo treatment for 150 days. Men in the active group initially received an oral bolus of 300,000 IU cholecalciferol, followed by daily supplementation with 1400 IU cholecalciferol and 500 mg calcium. RESULTS: After intervention, no differences were found in serum concentrations of sex steroids, luteinizing hormone, testosterone/luteinizing hormone ratio or SHBG between the vitamin D and placebo group. However, in a predefined subgroup analysis of men with serum 25OHD ≤ 50 nmol/L, men treated with vitamin D had a significantly higher testosterone/luteinizing hormone ratio [4.2 (3.8-4.4) vs. 3.7 (3.4-4.0); p = 0.033] compared with placebo treatment. In men with vitamin D deficiency, the difference between groups was larger but not significant due to few men with serum 25OHD < 25 nmol/L. CONCLUSION: Vitamin D + calcium supplementation did not alter sex steroid production in infertile men. However, vitamin D insufficient men treated with vitamin D supplementation had a significantly higher testosterone/LH ratio compared with placebo-treated men, suggesting that optimal Leydig cell function are dependent on adequate vitamin D status.

Evaluation of Andrographis paniculata-supplemented Diet on the reproductive indices of Plasmodium berghei-infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The King of Bitters (Andrographis paniculata) is a plant used to cure a wide range of infectious diseases which includes malaria, fever and others. However, there is a paucity of scientific evidence of its effect on male reproductive indices during malaria treatment. AIM OF THE STUDY: The aim of this study is to evaluate the effect of supplemented diet on antiplasmodial, hematological and male reproductive indices in mice infected with Plasmodium berghei. MATERIALS AND METHODS: Aqueous extract of A. paniculata (King of Bitters, KGB) was prepared and the total phenol and flavonoid contents were determined. Forty-two mice, weighing 20-25 g, were distributed into 7 groups consisting of 6 mice each. The mice were innoculated with strain NK65 Plasmodium berghei (Chloroquine, CQ sensitive) and the parasitemia suppression was assessed. The mice were fed with the dietary supplementation of KGB at varying inclusions (2.5%, 5%, 7.5%, and 10%) and administered 10 mg/kg CQ (which served as the positive control) for 5 consecutive days after infection was established. The reactive malondialdeahyde (MDA), antioxidant [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH)] and the hematological (hemoglobin, packed cell volume and red blood cell) parameters in the infected mice were determined. The reproductive indices (serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sperm count, sperm motility, and sperm viability) and testis histopathology were also assessed. RESULT: The result revealed that KGB had a total phenol content of 32.55 mgGAE/g and total flavonoid content of 19.71 mgQUE/g. The infected mice treated with the dietary supplementation of KGB showed significantly decreased (p < 0.05) parasitaemia and MDA levels. Furthermore, the 7.5% dietary inclusion showed significant improvement in the antioxidant, hematological and reproductive indices as well as the restoration of testis morphology as seen in the histopathology plate of the infected mice treated with KGB. Hence, this study suggests that the KGB- supplemented diet (7.5%) may be a potential alternative and complementary therapy in the treatment of malaria infection and reproductive disorders.

The association of testosterone with sarcopenia and frailty in chronic liver disease.

BACKGROUND: Testosterone is an important anabolic hormone responsible for maintaining body composition and muscle mass and circulates mostly albumin-bound, or sex hormone binding globulin (SHBG)-bound or free in the plasma. Of these fractions, the latter is bioactive and exerts the androgenic effects on male population. Liver cirrhosis, the advanced stage of any chronic liver disease characterized by permanent distortions to the hepatic architecture, disrupts the hypothalamic-pituitary-gonadal axis, leading to diminished levels of free testosterone and hypogonadism. METHODS: We retrieved the PubMed database to provide a synopsis of testosterone's physiology and action and summarize the effect of sarcopenia in pre-cirrhotic and cirrhotic patients. Moreover, we scoped to provide insight into the relationship of testosterone levels with sarcopenia, frailty and survival in cirrhotic and non-cirrhotic population as well as to discuss the efficacy of exogenous testosterone supplementation on the anthropometric parameters and survival of those patients. RESULTS: Low testosterone levels have been associated with sarcopenia, reduced body lean mass, decreased bone mineral density and frailty, thus leading to increased morbidity and mortality especially among cirrhotic patients. Furthermore, exogenous testosterone administration significantly ameliorated body composition on patients with chronic hepatic disease, without significant adverse effects. However, the current literature does not suggest any significant effect on survival of those patients. Moreover, the long-term safety of testosterone use remains an open question. CONCLUSION: Low serum testosterone is strongly correlated with sarcopenia, frailty, higher rate of hepatic decompensation and mortality. Nonetheless, exogenous supplementation of testosterone did not ameliorate the liver-related outcomes and complications.

Estrogen and testosterone supplementation improves tendon healing and functional recovery after rotator cuff repair.

Failure of healing after rotator cuff repair (RCR) is common. The purpose of the current study was to evaluate the effect of systemic estrogen or testosterone supplementation on tendon healing after RCR. Seventy-two adult male mice were utilized for all experiments. The supraspinatus tendon was transected and repaired with 6-0 Prolene suture on the left shoulder of 51 animals. Mice were segregated into three groups postoperative: (1) vehicle group (VG; n = 18), (2) estrogen group (EST; n = 17), and (3) testosterone group (TST; n = 16). An unrepaired control group (unrepaired, n = 21) did not have surgery. Utilizing these animals, histological analysis, activity testing, biomechanical testing and RNA sequencing (RNA-seq) was performed. At 8 weeks post-RCR, TST, and EST supplementation improved the overall histologic structure of the repaired enthesis site. No differences in ultimate failure loads or stiffness were detected between VG, EST, and TST groups after biomechanical testing. RCR caused a reduction in wheel activity compared to unrepaired controls and supplementation with TST restored wheel activity. RNA-seq analysis indicated that estrogen and testosterone regulated different pathways associated with enthesis healing, including a suppression of inflammatory signaling. Supplementation with sex hormones improved the structure of the repaired tendon enthesis and significantly regulated expression of diverse pathways regulating multiple biological processes. Testosterone administration following RCR restored wheel activity without having a detrimental impact on biomechanical strength. Future human studies of sex hormone supplementation after RCR are warranted as supplementation in an animal model may improve tendon enthesis healing.