No abstract

In the last few years, kisspeptin-KISS1R signaling has appeared as a major regulator of the reproductive function in several vertebrate species. However, KISS1(encoding kisspeptin) and its putative receptor, KISS1R, are expressed in several other tissues. Adipose tissue, which secretes many peptides with diverse functions in normal physiology, expresses KISS1, which is modulated by gonadal steroids as well as by body nutritional status. Similarly, KISS1Rexpression is also found in adipose tissue, but the local role of kisspeptin in adipocyte function is currently unknown. Therefore, in the present study the effects of exogenous human kisspeptin-10 (KP10) were studied on three important adipokines, namely, adiponectin, leptin, and resistin in a set of four chair-restraint habituated intact adult male rhesus monkeys under; 1) normal fed conditions, 2) 24-h fasting conditions, and 3) 48-h fasting conditions. Plasma resistin and leptin levels decreased (p<0.01), whereas adiponectin levels increased (p<0.05) in fasted monkeys. Kisspeptin administration significantly increased (p<0.05) mean plasma adiponectin levels under fed and 24-h fasting conditions as compared to pretreatment or vehicle-treatment levels. A stimulatory effect was also observed on the 48-h fasting stimulated plasma adiponectin levels, but it lacked statistical significance. In contrast, no effect of kisspeptin was observed on mean plasma leptin and resistin levels. Thus, the present study demonstrated a stimulatory effect of peripheral kisspeptin administration on the plasma adiponectin levels under fed and 24-h fasting conditions in the adult male rhesus monkey. These findings, therefore, assign a novel role to kisspeptin, a regulator of adipocyte function in higher primate.

The gut microbiome is comprised of various types of bacteria, fungi, protozoa, and viruses naturally occurring in humans and animals as normal microflora. Gut microorganisms are typically host specific, and their number and type vary according to different host species and environment. Gut microbes contribute directly and/or indirectly to various physiological processes including immune modulation, regulation of various neurotransmitter, and hormones, as well as production of many antioxidants and metabolites. They also play a role as antibiotic, antiinflammatory, anti-diabetic, and anti-carcinogenic agents. Moreover, the ability of gut microbes to attenuate various systemic diseases like coronary heart disease, irritable bowel syndrome, metabolic diseases like diabetes mellitus, and infectious diseases like diarrhea has recently been reported. Current research findings have enough evidence to suggest that gut microbiome is a new organ system mainly due to the microorganisms' specific biochemical interaction with their hosts and their systemic integration into the host biology. Investigations into the potential ability of gut microbiome to influence metabolism inside their host via biochemical interaction with antibiotics and other drugs has recently been initiated. This chapter specifically focuses on the importance of gut microorganisms as a new organ system.

Kisspeptin-Kiss1R signalling in mammals has been implicated as an integral part of the reproductive cascade. Kisspeptinergic neurons upstream of GnRH neurons are involved in the activation of the hypothalamic GnRH pulse generator during pubertal onset. Thus, the major research focus has been on the central effects of kisspeptin. The demonstration of the presence of KissR expression in human testes suggests additional unknown actions of kisspeptin-KISS1R signalling at the distal component of the male reproductive axis. Here we explored the impact of kisspeptin at the testis in the adult male rhesus monkey. We employed the clamped monkey model to assess the intratesticular actions of kisspeptin. Plasma testosterone and LH levels were monitored in four adult male monkeys. The peripheral administration of human kisspeptin-10 (50 μg, iv bolus) caused a single LH pulse, which was followed by a robust increase in plasma testosterone levels sustained for at least 180 min. This response was abolished when kisspeptin was administered to GnRH receptor antagonist (acyline) pre-treated animals. However, kisspeptin administration significantly (P < 0.005) elevated hCG-stimulated testosterone levels in acyline pre-treated monkeys when compared with saline+ hCG treatment. These results revealed a novel peripheral facet of kisspeptin signalling.

Kisspeptin receptor and kisspeptin are localized in the testis of Old World and New World primates.

Background Traditional plant-based remedies prescribed to treat diabetes have shown promise in research-based setting. Current research was conducted to examine the antidiabetic and antioxidant effects of methanolic extract of a folk herbal plant Euphorbia helioscopia in a rat model of type 2 diabetes. Methods Diabetes was induced in male Wistar rats by administering 5% sucrose in drinking water and cafeteria diet for 8 weeks with subsequent nicotinamide and streptozotocin administration. Diabetic rats were then distributed into four individual groups (n = 8); Positive control (PC; no treatment), standard control (SC; Metformin @ 10 mg/kg bw), treatment 1 (EH1, E. helioscopia methanolic extract @200 mg/kg bw) and treatment 2 (EH2, E. helioscopia methanolic extract @400 mg/kg bw). After 21 days of treatments, the rats were decapitated for blood collection. Serum was evaluated for antidiabetic potential, antioxidant and lipid profile, thyroid hormone, amylin, leptin, and carbohydrate metabolic enzymes. Data were analyzed statistically by one-way analysis of variance (ANOVA). Results Serum levels of glucagon, glucose and C-peptide were significantly (P ≤ 0.05) decreased in EH1 (1915.33 ± 98.26a pg/ml, 122.59 ± 2.99a mg/dl, 277.59 ± 28.41a pg/ml respectively) and EH2 (1575.28 ± 56.46a pg/ml, 106.04 ± 5.21a mg/dl, 395.06 ± 42.55a pg/ml respectively) as compared to the PC (3135.78 ± 189.46bpg/ml, 191.24 ± 17.75bmg/dl, 671.70 ± 109.75b pg/ml respectively) group. A similar trend was observed in serum insulin levels in EH1 and EH2 groups. The plant’s methanolic extract effectively reduced the total oxidant status (TOS) and MDA levels in the diabetic rats and increased the total antioxidant capacity (TAC) along with an increased level of SOD, Catalase, Paraoxonase, and arylesterase. The plant extract also induced antihyperlipidemic activity and recovered the thyroid hormones, amylin, and leptin levels to normal. The activity of different carbohydrate metabolic enzymes like Pyruvate Kinase, Glucose 6 phosphate dehydrogenase, phosphofructokinase, and glucokinase has also been restored by the extract treatment. Conclusion Current study indicates the antioxidant and antidiabetic potential of E. helioscopia methanolic extract in normalizing the lipid profile, thyroid hormones, amylin, leptin, and carbohydrate metabolism in type 2 diabetic rat model.

In the literature archive, the intestinal microbiome is now considered as a discrete organ system. Despite living symbiotically with the human body, the gut microbiome is represented as potential drug targets because of its ability to modify the pharmacokinetics of orally administered drugs. Structural biology analysis indicates the existence of homology between transport proteins of microbial cells and membranes of enterocytes. It is speculated that structural similarity in the protein transporters may provoke an unwanted phenomenon of drug uptake by the gut microbiome present in the small intestine of the host. Considering this hypothesis, we analyzed the absorbance of orally administered caffeine by the gut microbiota in in vivo albino rat model through the RP-HPLC-UV approach. Microbiome absorbed the caffeine maximally at 2 hours and minimally at 5 hours post-drug administration following first-order absorption kinetics in a nonlinear way. Drug absorbance of microbial pellet and percent dose recovery was found significantly higher ( P ≤ .05) at 2 hours post-administration as compared to all other groups. As speculated, our findings advocated the phenomenon that the gut microbiome influences the absorption of caffeine molecules. Members of the gut microbiome exhibited grouped behavior following first-order absorption kinetics in a nonlinear pattern.

Purpose: To evaluate the effect of Ferula asafoetida (oleo gum resin powder) on sensory and motor functions retrieval on an induced sciatic nerve injury in a mouse model.Methods: A mechanical crush was inserted in the sciatic nerve of all the experimental mice after acclimatization. The mice were allocated to four groups; one normal chow group (control, n = 7) and three Ferula asafoetida chow groups (each n = 7) of different doses (50, 100 and 200 mg/kg). Muscle grip strength, muscle mass, and sciatic functional index were measured to evaluate the motor function regain, while sensory function regain was assessed by hot plate test. Oxidative stress and glycemic levels were measured by biochemical assays.Results: The findings of this study indicate that Ferula asafoetida 200 mg/kg has a highly significant (p≤ 0.001) ameliorating effect in terms of improved grip strength (77.7 ± 5.4 % for 200 mg/kg vs. 46 ± 5.1 % for control), reversal of SFI towards normal ( -34 ± 8.1 for 200 mg/kg group vs. –61 ± 6.1 for control), decrease in paw withdrawal latency (7.10 ± 0.06 s for 200 mg/kg group vs. 15 ± 0.5 s for control) on day 12 post-injury, as well as restoration of skeletal muscle mass towards normal. Interestingly, F. asafoetida chow 50 mg/kg and 100 mg/kg groups also impacted significant (p < 0.01) improvement in the ameliorative effect. However, the differences among all treatment groups in ameliorating recovery were not significant (p > 0.05). Moreover, comparatively improved (p < 0.0001) total antioxidant capacity along with reduced total oxidant status (p = 0.01) in the Ferula asafoetida chow (200 mg/kg) group, indicate the antioxidative effect of this plant. Furthermore, the treated mice (200 mg/kg) also expressedan improved glycemic level (p = 0.0005).Conclusion: Ferula asafoetida supplementation helps to accelerate both sensory and motor function retrieval following sciatic nerve injury. This  improvement is thought to be correlated with the antioxidant capacity of the plant. However, further investigations are required to identify the therapeutic principles responsible for the observed actions. Keywords: Sciatic nerve injury, Ferula asafoetida, Function recovery, Oxidative stress, Biochemical analysis