Relation between insulin resistance and plasma concentrations of lipid hydroperoxides, carotenoids, and tocopherols

BACKGROUND: It is not known whether total circulating lipid hydroperoxides are increased in insulin-resistant individuals and whether this correlates with depletion of liposoluble antioxidant vitamins that are consumed during lipid peroxidation. OBJECTIVE: The goal of this study was to define the relation between resistance to insulin-mediated glucose disposal and plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins in healthy volunteers. DESIGN: Insulin-mediated glucose disposal was determined in 36 healthy, nondiabetic volunteers by measuring their steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a 180-min constant infusion of octreotide, insulin, and glucose. In addition, fasting plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins were determined by using the FOX 2 assay and liquid chromatography. RESULTS: Statistically significant direct relations were observed between SSPG and mean arterial blood pressure (r = 0.44, P: = 0.008) and plasma lipid hydroperoxide concentrations (r = 0.42, P: = 0.01), whereas significant inverse correlations were found between SSPG and alpha-carotene (r = -0.58, P: = 0.0002), beta-carotene (r = -0.49, P: = 0.004), lutein (r = -0.35, P: = 0.04), alpha-tocopherol (r = -0. 36, P: = 0.04), and delta-tocopherol (r = -0.45, P: = 0.007). CONCLUSIONS: Variations in insulin-mediated glucose disposal in healthy individuals are significantly related to plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins. These findings suggest that total plasma lipid peroxidation is increased in insulin-resistant individuals at an early, preclinical stage, ie, well before the development of glucose intolerance and type 2 diabetes.     

Exploring the anticancer activities of novel bioactive compounds derived from endophytic fungi: mechanisms of action,current challenges and future perspectives

Cancer is the second leading cause of death all around the world. The natural compounds derived from the endophytic flora of fungi are possible solutions to cancer treatment because they are safe for health, cost-effective, biocompatible and have fewer toxicity issues. The active ingredients in endophytic fungi that are responsible for anti-cancer activities are alkaloids, terpenoids, glycosides, saponin, peptides, steroids, phenols, quinones, and flavonoids. This review highlights the anti-cancer activities of entophytic fungus against human papillary thyroid carcinoma (IHH4), human pancreatic (PANC-1), ovarian (OVCAR-3), hepatic (HepG2), lung (A-549), human lymphoma (U937), human skin carcinoma (A431), breast (MCF-7), and Kaposi’s sarcoma. The emerging evidence suggested that bioactive compounds isolated from endophytic fungi showed their anti-cancer activities by revealing the disturbance of the microtubule network caused by increased levels of Bax and Bcl-2 proteins that triggers cell cycle arrest at the G2-M phase, by inhibiting the DNA replication via binding with topoisomerase II, by regulating the activity of extracellular signal-regulated kinase and NF-kB, by evaluating the levels of p21, p27, and cyclins B/D1/E that led to cell death by apoptosis and cell cycle arrest. This review will assist readers in better comprehending bioactive chemicals and the beneficial interaction between the fungal endophytes and medicinal plants.     

Mentha: A genus rich in vital nutra‐pharmaceuticals—A review

The genus Mentha comprises several aromatic species, which are cultivated world‐over due to their distinct aroma and commercial value. In addition to traditional food flavoring uses, Mentha are well recognized for their folk medicinal uses, especially to treat cold, fever, and digestive and cardiovascular disorders. A number of biological activities such as antioxidant, antimicrobial, biopesticidal, antitumor, anticancer, antiviral, antiallergic, antiinflammatory, antihypertensive, and urease inhibitory activity have been ascribed to Mentha. The traditional pharmacological attributes of Mentha herbs can be linked to the occurrence of bioactive phytochemicals such as terpenoids, alcohols, rosmarinic acid, and antioxidant phenolics among others. A rich source of bioactives, different species of Mentha, can be explored as a promising candidate for the development of nutra‐pharmaceuticals. This review covers the nutritional, phytochemical, and traditional medicinal aspects and multiple biological activities of some commonly available species of Mentha so as to explore their potential applications for nutra‐pharmaceutical and cosmo‐nutraceutical industry. Detailed chemical profile and pharmaceutical attributes of various Mentha essential oils are also covered. Moreover, based on computational analysis, quantitative chemical component–antioxidant activity relationship model is reviewed to predict and correlate structure–activity relationship of potential bioactives in selected Mentha essential oils leading to discovery and developmenmt of novel natural drugs.     

Phase I trial of fludarabine and paclitaxel in non-Hodgkin's lymphoma

Fludarabine is an active agent in low-grade non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Paclitaxel is also active in patients with refractory lymphoma, and preclinical data suggest an additive effect with fludarabine in vitro. We performed a phase I trial of fludarabine (25 mg/m² d 1–3) plus a 3-h infusion of paclitaxel (125, 150, or 175 mg/m²) on d 3 every 28 d in 13 patients with non-Hodgkin’s lymphoma. The paclitaxel dose was escalated in cohorts of 3–4 patients using standard phase I design schema. Dose-limiting toxicity was defined as febrile neutropenia, platelet nadir less than 50,000/μL, or grade 3–4 nonhematologic toxicity. Thirteen patients were accrued to the study, 8 of these 13 patients (62%) had received prior chemotherapy. At the 125-, 150-, and 175-mg/m² dose levels of paclitaxel, dose-limiting toxicity occurred in 1/4, 0/4, and 0/4 patients, respectively. The single patient with dose-limiting toxicity had febrile neutropenia. Partial response occurred in two of eight patients with low-grade lymphoma and none of five patients with other types of lymphoma. A paclitaxel dose of 175 mg/m² given as a 3-h infusion on d 3 in conjunction with fludarabine (25 mg/m² d 1–3 every 4 wk) is a well-tolerated regimen for non-Hodgkin’s lymphoma. Further study will be required in order to determine whether the fludarabine-paclitaxel is more active than fludarabine alone in patients with low-grade lymphoma and chronic lymphocytic leukemia.