Antioxidant Properties of Trianthema Portulacastrum and Protection Against Ionizing Radiation-Induced Liver Damage Ex vivo.

Antioxidants in fruits and vegetables protect cells against radiation induced damage. Trianthema portulacastrum is used as vegetables from ancient time. The effects of T. Portulacastrum ethanolic extracts against γ-radiation induced liver tissue damage ex vivo were evaluated in this study. Antioxidant phytochemicals present in T. Portulacastrum includes flavonoids [3.3 ± 0.15 to 10 ± 0.16 mg catethin equivalent (CE)/g fresh weight (fw)], ascorbic acid (0.15 ± 0.03 to 0.21 ± 0.03 mg/g fw), glutathione s-transferase (GST) (1.57 ± 0.06 to 3.59 ± 0.05 nmole/mg fw/min), superoxide dismutase (SOD) (1.6 ± 0.03 to 1.79 ± 0.04 U/min), peroxidase (3.26 ± 0.18 to 6.38 ± 0.03 U/g fw) and catalase (0.51 ± 0.03 to 2.84 ± 0.15 mg H2O2 decomposed/g fw/min). Total phenolic content varied from 122.9 ± 8.7 to 302.8 ± 15.7 mg gallic acid equivalent/g extract, and flavonoid content varied from 316.7 ± 33.3 to 800.7 ± 28.9 CE mg/g extract. The IC50 value of Nitric oxide (NO•) scavenging activity of extracts varies from 208.7 to 387.4 µg/ ml. Pre-treatment with the T. portulacastrum extracts mitigated the 4-Gy gamma(γ) radiation-induced oxidative stress related parameters in hepatic tissue such as TBARS, catalase, nitrite, Glutathione reductase (GR), SOD and GST in dose dependent manner. The ethanolic extract of the stem from T. Portulacastrum demonstrated highest protection in comparison to leaf and whole plant extracts. This study demonstrated the hepatoprotective efficacy of T. portulacastrum extracts against γ-radiation in ex-vivo condition was possibly due to its potential antioxidant properties of phenolic and flavonoids present in extracts.

Rational approaches of drug design for the development of selective estrogen receptor modulators (SERMs), implicated in breast cancer.

Drug discovery and development have gained momentum due to the rational drug design by engaging computational tools and bioinformatics methodologies. Bioisosteric replacements and hybrid molecular approaches are the other inventive processes, used by medicinal chemists for the desired modifications of leads for clinical drug candidates. SERMs, ought to produce inhibitory activity in breast, uterus and agonist activity in other tissues, are beneficial for estrogen-like actions. ER subtypes α and ß are hormone dependent modulators of intracellular signaling and gene expression, and development of ER selective ligands could be an effective approach for treatment of breast cancer. This report has critically investigated the possible designing considerations of SERMs, their in silico interactions, and potent pharmacophore generation approaches viz. indole, restricted benzothiophene [3, 2-b] indole, carborane, xanthendione, combretastatin A-4, organometallic heterocycles, OBHS-SAHA hybrids, benzopyranones, tetrahydroisoquinolines, Dig G derivatives and their specifications in drug design and development, to rationally improve the understanding in drug discovery. This also includes various strategies for the development of dual inhibitors for the management of antiestrogenic resistance.

Estrogen signaling: An emanating therapeutic target for breast cancer treatment.

Breast cancer, a most common malignancy in women, was known to be associated with steroid hormone estrogen. The discovery of estrogen receptor (ER) gave us not only a powerful predictive and prognostic marker, but also an efficient target for the treatment of hormone-dependent breast cancer with various estrogen ligands. ER consists of two subtypes i.e. ERα and ERß, that are mostly G-protein-coupled receptors and activated by estrogen, specially 17ß-estradiol. The activation is followed by translocation into the nucleus and binding with DNA to modulate activities of different genes. ERs can manage synthesis of RNA through genomic actions without directly binding to DNA. Receptors are tethered by protein-protein interactions to a transcription factor complex to communicate with DNA. Estrogens also exhibit nongenomic actions, a characteristic feature of steroid hormones, which are so rapid to be considered by the activation of RNA and translation. These are habitually related to stimulation of different protein kinase cascades. Majority of post-menopausal breast cancer is estrogen dependent, mostly potent biological estrogen (E2) for continuous growth and proliferation. Estrogen helps in regulating the differentiation and proliferation of normal breast epithelial cells. In this review we have investigated the important role of ER in development and progression of breast cancer, which is complicated by receptor's interaction with co-regulatory proteins, cross-talk with other signal transduction pathways and development of treatment strategies viz. selective estrogen receptor modulators (SERMs), selective estrogen receptor down regulators (SERDs), aromatase and sulphatase inhibitors.

Naphthalene, a versatile platform in medicinal chemistry: Sky-high perspective.

Naphthalene, a cytotoxic moiety, is an extensively explored aromatic conjugated system with applications in various pathophysiological conditions viz. anticancer, antimicrobial, anti-inflammatory, antiviral, antitubercular, antihypertensive, antidiabetic, anti-neurodegenerative, antipsychotic, anticonvulsant, antidepressant. Naphthalene epoxides and naphthoquinones are most reactive metabolites of naphthalene and are responsible for the covalent interaction with cysteine amino acid of cellular proteins for cytotoxic nature. Many naphthalene derived bioactive phytoconstituents are present in nature including podophyllotoxins (Etoposide, teniposide), bis-ANS 82, Rifampicin, Justiprocumin A, B, Patentiflorin A. The naphthalene-based molecules, viz. Naphyrone, tolnaftate, naftifine, nafcillin, terbinafine, propranolol, nabumetone, nafimidone, naproxen, duloxetine, lasofoxifene, bedaquiline etc. have also been approved by FDA and are being marketed as therapeutics. Thus, the naphthalene scaffold emerges as an important building block in drug discovery owing to its broad spectrum of biological activities through varying structural modifications. This review incorporates the pharmacological aspects of different types of chemically modified naphthalene-based molecules along with their activity profile. This compiled information may serve as a benchmark for the alteration of existing ligands to design novel potent molecules with lesser side effects.

Role of nitric oxide, angiogenic growth factors and biochemical analysis in preeclampsia.

Preeclampsia, a pregnancy-related hypertensive disorder, is one of the leading causes of fetal and maternal mortality and morbidity globally. Angiogenic growth factors, including vascular endothelial growth factor (VEGF) and placental growth factor (P1GF) are involved in the generation of new blood vessels required for placental development and physiological functions, while nitric oxide (NO) acts as vasodilator and also plays a role in angiogenesis. The objective of this study was to evaluate the role of NO, angiogenic growth factors (VEGF and PIGF) and other biochemical parameters in the development of preeclampsia among pregnant mothers. A complete clinical history, including anthropometric measurements and biochemical investigations, including renal function tests, liver function tests and lipid profile were performed among twenty preeclampsia patients aged 19 to 32 yrs. Results were compared with age-matched normotensive pregnant mothers. The body weight, body mass index (BMI), blood pressure, concentrations of urea, uric acid and triglyceride and activities of transaminase enzymes (aspartate transaminase, AST and alanine transaminase, ALT) in serum were significantly higher (p < 0.05) than normotensive subjects. Serum concentrations of VEGF, P1GF and NO were significantly decreased (p < 0.005) in preeclamptic patients. NO was found negatively correlated with body weight (r = -0.369, p < 0.05), systolic blood pressure (r = -0.822, p < 0.005), diastolic blood pressure (r = -0.714, p < 0.005) and was positively correlated with VEGF (r = 0.464, p < 0.005) and P1GF (r = 0.546, p < 0.005). VEGF and P1GF showed significant (p < 0.005) negative correlation with systolic and diastolic blood pressure and PIGF was significantly correlated with triglyceride (r = -0.379). However, no significant correlation was observed between the VEGF and P1GF. In conclusion, the results indicated that body weight, triglyceride, angiogenic growth factors and NO might associate with preeclampsia development.

Insulin resistance and metabolic profile in antipsychotic naïve schizophrenia patients.

OBJECTIVES: Several studies have suggested insulin resistance related to dyslipidemia and body weight in drug treated schizophrenia patients. Although, insulin resistance or impaired glucose tolerance is also reported in antipsychotic naïve schizophrenia patients, their relationship with dyslipidemic changes and body weight is not well established. The present study was undertaken to examine insulin resistance in antipsychotic naïve schizophrenia patients of this region and to evaluate any association between lipid parameters and body weight with their insulin resistance, if any. METHOD: Plasma glucose, total serum cholesterol and its LDL, HDL fractions, and serum insulin levels were measured from fasting blood samples of newly diagnosed, antipsychotic naïve schizophrenia patients (n=30) and matched control group (n=25) in a hospital based case control study. Homoeostatic model assessment (HOMA) was done to evaluate insulin resistance. RESULTS: Means of plasma glucose, total serum cholesterol and its LDL, HDL fractions did not vary significantly (p>0.05) between cases and control. Insulin resistance was significantly increased (p<0.05) in drug naïve cases. Multiple linear regression analyses did not show any association (p>0.05) between insulin resistance and lipid parameters. CONCLUSIONS: Newly diagnosed schizophrenia patients were more prone to insulin resistance in our study population. This was not associated with any dyslipidemic changes as the lipid parameters were not elevated in them compared to the healthy controls. It was not dyslipidemia, but some other common genetic or risk factors that might be responsible for the increased insulin resistance in antipsychotic naïve schizophrenia patients in our study population.