Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Immunology, Endocrine and Metabolic Agents) - Volume 18, Issue 1, 2018

Background: In present decades, interest in tetrazole chemistry has been increasing rapidly because of its broad range of biological applications, primarily due to the role played by tetrazole in medicinal chemistry as this moiety offer a more complimentary pharmacokinetic profile and a metabolically stable substitute for carboxylic acid functionalities. The heterocyclic tetrazole moiety has admirable biological, pharmaceutical and clinical applications. Method: There are various approaches available for the synthesis of tetrazole derivatives which are reported in the present survey. The most versatile method for the synthesis of tetrazoles is [2+3] cycloaddition reaction between nitriles and azides. Observations: Among the family of nitrogen-containing heterocycles, tetrazole and its derivatives exhibit a large range of biological properties such as antibacterial, antifungal, anticancer, analgesic, anti-inflammatory, antidiabetic, anti-hyperlipidemic and antitubercular activities. The unique features of tetrazole, biological significance and applications are discussed in this review. Conclusion: The present investigation reviews the various synthetic approaches and different biological activity of substituted tetrazole derivatives. The rationale of this review was to pool literature work reported by researchers on tetrazole for their various biological activities and also reported current efforts made on tetrazole moiety.

Background: Insulin resistance is a frequent metabolic disorder in Polycystic Ovary Syndrome (PCOS). Moringa oleifera has been shown to increase insulin expression and decrease the degree of insulin in diabetes mellitus, therefore it is expected that Moringa oleifera could decrease insulin levels and increase folliculogenesis in PCOS. Objective: To prove the effect of Moringa oleifera leaf extract in various doses might decrease the insulin levels and increase folliculogenesis in female PCOS-insulin resistant rats. Methods: The three month old white rat of Wistar strain (Rattus norvegicus) 100-130 grams were divided into five groups (n=8) including normal control, PCOS-insulin resistance, PCOS-insulin resistance given metformin and PCOS-resistance insulin were given Moringa oleifera leaf extract in two doses. Then, the PCOS model-insulin resistance by injection of testosterone propionate for 28 days. After 14 days treatment, we analysed insulin levels and folliculogenesis. Results: The PCOS control group showed a significant increase in insulin levels compared to the normal control group. The insulin levels from group treatment with Moringa oleifera leaf extract of 250 mg/kgBW was significantly lower than the PCOS control group. Ovarian histology analysis found that the number and diameter of follicle of PCOS control group showed a significant decrease compared to normal control group. In addition, the treatment with metformin and leaf Moringa oleifera dose 250 mg/kgBW and 500 mg/kgBW showed significant increase of folliculogenesis compared to PCOS control group. Conclusions: Moringa oleifera could lowering the blood insulin levels, subsequently decreasing the androgen thus allowed the increasing of folliculogenesis in PCOS.

Background: Homeostasis of blood glucose concentration is a physiological phenomenon that is tightly regulated in humans and acts as a major cellular mechanism that decreases blood glucose during insulin-stimulated glucose transport. GLUT4 assumes a significant role in managing entire body glucose homeostasis. Recent research has found that overexpression of GLUT4 reduces glucose intolerance and diabetes. Interestingly, reduction of GLUT4 by inhibiting glucose transport has been found to have a powerful chemotherapeutic impact on myeloma. In order to further examine such interactions, a high-resolution crystal structure would be particularly useful. A homology model was produced for GLUT4 to screen for drug-like compounds and other docking complex connections. Conclusion: Our study provides further data for determining the role of GLUT controllers used to target glucose transport. Clarification of the three-dimensional structure of these transporters utilizing the steady, powerful and highly precise SWISS-MODEL protein structure prediction server will fundamentally help in the advancement of novel medications. The predicted model protein, GLUT4, demonstrated a comparable affinity for ATP and with inhibitor metformin binding motifs.

Background: The metabolic syndrome unites three pathologies of the person – obesity, arterial hypertension and diabetes. In recent years the progressing of such distribution covering from 2.5% to 3.8% of the population with increase twice each 10-15 years is noted. Even at maintenance of level of sugar at diabetes accumulation of the secondary metabolites breaking small vessels isn't excluded. At the same time many lifeendangering complications develop. Objective: To identify the possibilities of plasmapheresis in the prevention and treatment of complications of metabolic syndrome. Method: Analysis of the world literature data on complications of metabolic syndrome and methods of their treatment. Results: At metabolic syndrome the frequency of strokes and myocardial infarctions there is twice more often than in population. For 5-9 years the general life expectancy decreases. Disorders of microcirculation at diabetes lead to a retinopathy with total loss of sight, a nephropathy from the outcome in a renal failure, to polyneuropathy and diabetic foot syndrome with high risk of high level amputations of the lower extremities. At the same time medicamentous therapy is not able to prevent such complications and almost only way of removal of these pathological metabolites is therapeutic apheresis, mainly the plasmapheresis. Data from our own studies confirm the effectiveness of such tactics. Conclusion: Plasmapheresis has to be applied not only to the correction of already critical conditions, but also to their prevention.

Background and Aims: To our knowledge, no study has investigated neither how Moringa leaf extract modulates the immune system in normal nor diabetic subjects. Materials and Methods: Diabetes was induced by a single intraperitoneal dose of alloxan (150 mg/kg). A dose of 100 mg/kg of MO extract was orally administered to diabetic treated mice. The profile of glucose and insulin was evaluated. The activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione enzymes was determined. Liver function was monitored by measuring levels of alkaline phosphatase, glutamine pyruvate transaminase, and glutamic oxaloacetic transaminase. The percentage of single-or double-positive cells of each of CD8+/CD4+, CD117+/Sca-1+, Sca-1+/CD34+, CD11b+/Ly6-G+, CD11c+/CD11b+, and CD34+/CD117+ was investigated by flow cytometry in the peripheral blood. Results: MO promotes the activity of both CD4+ and CD8+ T cells in diabetic treated mice that may occur through the Sca-1+CD117+ stem cell factors. Administration of MO leaf extract enhanced the percentage of the endothelial progenitors (CD34+CD117+) and mature endothelial cells (CD34+CD117-). Moringa also increased the percentage of blood-derived circulating angiogenic cells (Sca-1+/CD34+). Discussion and Conclusions: This study shed light for the first time on how MO affects different immune cells; the knowledge gained may help to overcome diabetes and its complications.

Background: Despite its key role in the treatment, major abdominal surgery has been indicated as a cause of a metabolic, neuroendocrine and immunological response. Several studies have demonstrated that the magnitude of this postoperative Systemic Inflammatory Response (SIR) is directly associated with the development of complications after colorectal surgery. Objective: The aim of the present study was to investigate the association between preoperative administration of corticosteroids and overall survival, disease free survival rates and anastomotic leakage in colorectal cancer patients treated with surgery. Methods: A retrospective review of prospectively collected data was performed of 354 patients with colorectal cancer who had undergone curative resection between June 2012 and December 2016, at the Surgical Oncology Unit, University Hospital of Messina. Results: A total of 249 patients matched the inclusion criteria and were included in this study. A total of 159 patients in stages I and II with negative lymph vascular invasion were included in the ‘N- group’ while 90 patients from stage III with positive lymph vascular invasion were included in ‘N+ group’. The OS and DFS in N+ group showed a better 5-years OS (88,46% vs. 81,25%) and DFS (73% vs. 78,1%) rates for patients who have been given preoperative corticosteroids, but the Log-Rank test did not reach statistical significance. Also in the N- group, the Kaplan-Meier curves showed better 5-years OS (97% vs. 87,4%) and DFS (91,4% vs. 88,7%) rates for patients who have been given preoperative corticosteroids, but the Log-Rank test did not reach statistical significance. Moreover, the preoperative administration of corticosteroids did not modify the frequency of anastomotic leakage. Conclusion: This study has demonstrated that preoperative corticosteroids administration improves outcomes following colorectal surgery probably as a result of attenuating the SIR. Our results thus do not support avoiding low-dose preoperative corticosteroids in colorectal surgery. Nevertheless, further work is warranted to validate the influence of preoperative corticosteroids in colorectal surgery.

Background: This research was performed to investigate the effects of prostaglandins on the sexual functions of albino male rats. The effects of prostaglandins on LH, FSH, testosterone secretion and semen quality of the male rats were investigated. PGE1 induced a significant decline in the level of LH, FSH and testosterone levels. PGE1 also induced significant decline in the testis, epididymal and seminal vesicle weights. Conclusion: Furthermore, PGE1 caused significant reduction in sperm count, and significant decline in the viable and malformed sperm percent. However, PGF2α did not affect these parameters.

Background: Chronic and non-communicable diseases such as non-alcoholic fatty liver diseases, non-alcoholic steatohepatitis, obesity, diabetes, cardiovascular dysfunctions, renal insufficiency, alcoholism and other inflammation disorders often lead to severe organ damage. Fibrosis, on the contrary, is a complex phenomenon that may turn into critical conditions if not treated properly. Several biochemical pathways and signaling molecules, for instance, TGF-β, ECM, MMPs, Collagens, MAPK, AP-1, SMAD and NF-ΚB are responsible for the pathophysiology. In addition to these, inflammatory and pro-inflammatory cytokines are also blamed to be responsible in catalyzing fibrogenesis. Methods: The information was basically searched using PubMed, Google Scholar and Science Direct and put all together to correlate fibrosis pathophysiology. Only recent publications were targeted to show protective roles of Resveratrol in animal studies and human subjects. Findings: There is no effective treatment tactic available for curing fibrosis since multiple factors are associated with its progression; hence, it remains a big question to be answered by current healthcare associates. However, cell-based therapies have been showing quite effective approaches and are being suggested to counter fibrotic conditions. It is, however, highly expensive and complicated procedure and unfortunately, the availability of the strategy is limited worldwide. On the other hand, Resveratrol, a naturally occurring polyphenol which is largely being investigated in various animal models, cell cultures and human trials and thereby found highly potential in preventing measure against fibrosis. Conclusion: Our current study, therefore, tries to establish some molecular pathways which are responsible for the progression of pro-fibrogenesis and fibrosis. Our findings would also explore the possible inhibitory role of Resveratrol alongside fibrosis.

Background: Lactoferrin is a multifunctional protein found in breast milk. We previously reported the anti-obesity effects of enteric-coated lactoferrin (eLF). Objective: As the previous study included some subjects with high Body Mass Index (BMI) or low-Density Lipoprotein cholesterol (LDL-Cho), we investigated the antiobesity effect of lactoferrin excluding those subjects. Method: We conducted a subgroup analysis of a previous report excluding subjects with BMI ≥ 30 and/or hyper-LDL cholesterolemia. Results: Of the total 26 subjects in the previous study, 7 in the eLF group and 6 in the placebo group match the above criteria. The subgroup analysis revealed a significant decrease in visceral fat in the eLF group at week 8 compared with that at week 0 (-10.2 cm2, P < 0.01); no differences were observed in the placebo group. The mean visceral fat was also lower in the eLF group at week 8 compared with the placebo group (-16.2 cm2, P < 0.01). A significant decrease in BMI was observed in the eLF group at week 8 (-0.38 kg/m2, P < 0.05) compared with that at week 0. No differences were observed in the placebo group. The mean BMI was also lower in the eLF group at week 8 compared with that in the placebo group (-0.60 kg/m2, P < 0.05). Conclusion: eLF reduced visceral fat and BMI excluding subjects with obese and/or hyper- LDL cholesterolemia.