Isolation and characterization of anti-diabetic component (bioactivity-guided fractionation) from Ocimum sanctum L. (Lamiaceae) aerial part

ObjectiveTo isolate and characterize antidiabetic component (bioactivity-guided fractionation) from hydro alcoholic extract of Ocimum sanctum (O. sanctum) aerial part.MethodsTen fractions (F1 - F10) were isolated from hydro alcoholic extract of O. sanctum aerial part by column chromatography. All the fractions F1 to F10 were screened for antidiabetic activity in alloxan induced diabetic rats by estimating serum glucose level and lipid parameters. The isolated bioactive component was elucidated on the basis of extensive spectroscopic (UV, IR, MS, ¹H and ¹³C NMR) data analysis.ResultsThe bioactive fraction (F5) was found to be potent antidiabetic by ameliorating glucose and lipid parameters (total cholesterol, triglycerides, low and high density lipoprotein cholesterol). The extensive spectroscopic data analysis reveals that, the isolated bioactive compound elucidated as tetracyclic triterpenoid [16-Hydroxy-4,4,10,13-tetramethyl-17-(4-methyl-pentyl)-hexadecahydro-cyclopenta[a]phenanthren-3-one].ConclusionsOur present study concluded that, tetracyclic triterpenoid isolated from aerial part of O. sanctum has a great anti-diabetic potential.     

A Test of Highly Optimized Tolerance Reveals Fragile Cell-Cycle Mechanisms Are Molecular Targets in Clinical Cancer Trials

Robustness, a long-recognized property of living systems, allows function in the face of uncertainty while fragility, i.e., extreme sensitivity, can potentially lead to catastrophic failure following seemingly innocuous perturbations. Carlson and Doyle hypothesized that highly-evolved networks, e.g., those involved in cell-cycle regulation, can be resistant to some perturbations while highly sensitive to others. The “robust yet fragile” duality of networks has been termed Highly Optimized Tolerance (HOT) and has been the basis of new lines of inquiry in computational and experimental biology. In this study, we tested the working hypothesis that cell-cycle control architectures obey the HOT paradigm. Three cell-cycle models were analyzed using monte-carlo sensitivity analysis. Overall state sensitivity coefficients, which quantify the robustness or fragility of a given mechanism, were calculated using a monte-carlo strategy with three different numerical techniques along with multiple parameter perturbation strategies to control for possible numerical and sampling artifacts. Approximately 65% of the mechanisms in the G1/S restriction point were responsible for 95% of the sensitivity, conversely, the G2-DNA damage checkpoint showed a much stronger dependence on a few mechanisms; ∼32% or 13 of 40 mechanisms accounted for 95% of the sensitivity. Our analysis predicted that CDC25 and cyclin E mechanisms were strongly implicated in G1/S malfunctions, while fragility in the G2/M checkpoint was predicted to be associated with the regulation of the cyclin B-CDK1 complex. Analysis of a third model containing both G1/S and G2/M checkpoint logic, predicted in addition to mechanisms already mentioned, that translation and programmed proteolysis were also key fragile subsystems. Comparison of the predicted fragile mechanisms with literature and current preclinical and clinical trials suggested a strong correlation between efficacy and fragility. Thus, when taken together, these results support the working hypothesis that cell-cycle control architectures are HOT networks and establish the mathematical estimation and subsequent therapeutic exploitation of fragile mechanisms as a novel strategy for anti-cancer lead generation.     

Gastroprotective effect of standardized extract of Amukkara choornam on experimental gastric ulcer in rats

Amukkara choornam ethanolic extract (ACE) was investigated for phytochemical screening, content of total phenolics and flavonoids, in vitro radical scavenging activity (RSA), quantification of various antiulcer marker compounds (i.e., eugenol, piperine, trans-caryophyllene, and withaferine A) by a validated HPTLC method, and evaluated for its in vivo gastroprotective ability against ethanol (EtOH)-induced and pylorus ligation (PL)-induced ulcer models in rats. Phytochemical screening revealed the presence of flavonoids, saponins, phenols, bitter principles, and steroids. Total phenolic and flavonoid content was found to be 61.12 ± 0.72 mg GAE/g of ACE and 24.06 ± 1.07 mg RE/g of ACE, respectively; this was found to be very high in plant extracts showing very good antioxidant and antiulcerogenic effect. RSA of ACE appeared significantly (p < 0.05) lower than that of ascorbic acid (AA), but higher than that of ranitidine (RAN). In vivo the pretreatment of rats with RAN (100 mg/kg) and 50, 100, and 200 mg/kg doses of ACE significantly reduced the ulcer index in a dose-dependant manner in both the models by blocking lipid peroxidation and by significant increases in superoxide dismutase and catalase activity. But rats treated with AA (200 mg/kg) did not have any effect on the ulcer induced by EtOH or PL as it has very good in vitro and in vivo antioxidant activity. HPTLC analysis showed the presence of 0.198 ± 0.01 μg/g, 0.754 ± 0.06 mg/g, 3.50 ± 0.04, and 0.854 ± 0.04 μg/g of eugenol, piperine, trans-caryophyllene, and withaferine A per gram of Amukkara choornam (AC). So the antiulcerogenic activity of ACE might be due to a possible synergistic antioxidant, supported by the holistic approach of polyherbal formulations, i.e., systematism, multi-target and multi-channel owing to their complex chemical constituents and antihistaminic-like effects.     

Intracoronary glycoprotein IIb/IIIa inhibitor infusion via a perfusion coronary catheter to decrease thrombus burden: Results from the ClearWay™ Multicenter Registry

ObjectivesThis multicenter registry aimed to assess the ClearWay? (CW) perfusion catheter in reduction of thrombus burden and improvement of the coronary flow during percutaneous coronary intervention (PCI).BackgroundThe presence or development of thrombus during PCI is associated with poor prognosis.MethodsThe utility of the CW perfusion catheter was assessed in patients who presented with intracoronary thrombus and were subjected to PCI. Data were collected by online survey from 15 US sites. Angiographic assessment of the coronary thrombus burden and the coronary flow after intracoronary infusion of glycoprotein (GP) IIb/IIIa inhibitors via the CW catheter was evaluated at baseline, immediately after infusion, and at the end of the procedure. The cohort included 102 patients; 71.6% presented with ST-elevation myocardial infarction (MI), 21.6% with non-ST-elevation MI, 5.9% with stable angina pectoris, and 2.9% with silent ischemia. The mean cohort age was 59.9 ± 14.5 years and comprised mostly of men (72.5%).ResultsGP IIb/IIIa inhibitors were infused via the CW catheter on average 1.1 ± 0.3 times, with a mean pressure of 4.2 ± 2.7 atm and a mean infusion time of 55 ± 55 s. Following the infusion, Thrombolysis In Myocardial Infarction (TIMI) flow improved by 1° in 71 patients (69.6%) and by 2° in 51 patients (50%), while visible thrombus was reduced by 52% (p < 0.001). In the final angiogram, TIMI flow was restored in 90.2% and clearance of a visible thrombus was obtained in 91.8% of the lesions.ConclusionIntracoronary infusion of GP IIb/IIIa inhibitors via the perfusion CW catheter is associated with significant reduction in thrombus burden and with improvement of the coronary flow in patients presenting or developing thrombus burden during PCI.     

In vitro and in vivo evaluation of the anticarcinogenic and cancer chemopreventive potential of a flavonoid-rich fraction from a traditional Indian herb Selaginella bryopteris

Prevention of cancer through nutritional intervention has gained significant recognition in recent years. Evidence revealed from mechanistic investigations coupled with molecular epidemiology show an inverse association of dietary flavonoids intake with cancer risk. The chemopreventive and anticarcinogenic potential of Selaginella bryopteris, a traditional Indian herb referred to as 'Sanjeevani' in the Ayurvedic system of medicine, was examined in the present study. Comprehensive in vitro and in vivo studies were conducted on the flavonoid-rich benzene fraction of the aqueous extract that demonstrated a significant cytoprotective activity. Biomarkers of chemoprevention such as proliferative index and status of cell-cycle regulatory proteins, antioxidant property, anti-inflammatory effect, reversal of stress-induced senescence and genoprotective effect were investigated in human and murine cell cultures. Chemopreventive potential was assessed in benzopyrene-induced lung carcinogenesis and 7,12-dimethyl benz(a)anthracene-mediated skin papillomagenesis test models. Inhibition of DNA fragmentation, unperturbed cell-cycle regulation, maintenance of intracellular antioxidant defence, anti-inflammatory activity, prevention of stress-induced senescence and genoprotective effects against methyl isocyanate carcinogenicity was observed. Medium-term anticarcinogenicity and two-stage skin papillomagenesis tests strongly substantiated our in vitro observations. Results from the present study provide evidence of anticarcinogenic and chemopreventive activities of S. bryopteris hitherto unreported and reaffirm the nutritional significance of flavonoids in cancer prevention.     

Role of <Emphasis Type="BoldItalic">Tumor Necrosis Factor-Alpha</Emphasis> (C-863A) Polymorphism in Pathogenesis of Inflammatory Bowel Disease in Northern India

Objective  

Inflammatory bowel diseases (IBDs), namely ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic and idiopathic inflammatory conditions of gastrointestinal tract that are immunologically mediated. Single nucleotide polymorphisms in cytokine genes have been reported to modulate inflammation. Therefore, we analyzed the association of pro/anti-inflammatory cytokine genes polymorphism with IBD susceptibility.     

A steroidal derivative from Trigonella foenum graecum L. that induces apoptosis in vitro and in vivo

Trigonella foenum graecum L. is a dietary herb used in traditional medicine system. In this study, we investigated the cytotoxicity, antitumor, antimetastatic and antiangiogenic effect of the steroidal compound, ethyl iso-allocholate isolated from T. foenum graecum L. seeds against A549 lung cancer cells in vitro and in vivo. Among all the isolated compounds, the ethyl iso-allocholate rendered the highest cytotoxicity potential. It showed least percentage cell viability in trypan blue assay and lowest nuclei count in hoechst staining. The caspase glo assay and western blot analysis showed the significant caspase 3 cleavage, indicating caspase dependent apoptosis. Consistent with the in vitro data, ethyl iso-allocholate showed highest percentage tumor growth inhibition i.e. 80 ± 5% in zebrafish, equivalent to doxorubicin. It significantly reduced angiogenesis to 5 ± 0.8% (**P < 0.01), compared to negative control group which was 60 ± 2%. The ethyl iso-allocholate showed 55 ± 3% inhibition in liver metastasis. To investigate the safety of the compounds on normal tissues, the percentage mortality was examined. The ethyl iso-allocholate showed zero percent mortality of zebrafish. These results indicate that the steroidal derivative isolated from T. foenum-graecum seeds induces caspase dependent apoptosis in cancer cells and reduces tumor growth, metastasis and angiogenesis in vivo, as well as it is safe on the normal tissues. The in vitro and in vivo anticancer studies suggest that the cytotoxic compound ethyl iso-allocholate has potential application in pharmaceutical industry.     

Prevalence of obesity in India: A systematic review

Recent studies have reported that globally, more than 1.9 billion adults are overweight and 650 million are obese. Approximately 2.8 million deaths are reported as a result of being overweight or obese. Due to the consumption of energy dense food (i.e. unhealthy food habits), sedentary life style, lack of health care services and financial support, the developing countries are facing high risk of obesity and their adverse consequences (i.e. diabetes, ischemic heart disease, etc). In India, more than 135 million individuals were affected by obesity. The prevalence of obesity in India varies due to age, gender, geographical environment, socio-economic status, etc. According to ICMR-INDIAB study 2015, prevalence rate of obesity and central obesity are varies from 11.8% to 31.3% and 16.9%–36.3% respectively. In India, abdominal obesity is one of the major risk factors for cardiovascular disease (CVDs). Various studies have shown that the prevalence of obesity among women were significantly higher as compared to men. Obesity is one of the main medical and financial burdens for the government. This problem of obesity can be preventable by spreading public awareness about obesity and its health consequences. Governmental agencies should promote the benefits of healthy life style, food habits and physical activity. The aim of this article is to report the prevalence of obesity in different regions of India and highlight the problem areas.     

Effect of plumbagin free alcohol extract of Plumbago zeylanica Linn. root on reproductive system of female Wistar rats

ObjectiveTo assess the effect of plumbagin-free alcohol extract (PFAE) of Plumbago zeylanica Linn. (Plumbaginaceae) (P. zeylanica) root, on female reproductive system and fertility of adult female wistar rats.MethodsAfter the oral acute toxicity study, the PFAE was administered at two dose levels to perform the estrous cycle study, anti-implantation and abortifacient activity and hormonal analysis. However, the estrogenic/antiestrogenic activity was evaluated at only one most effective dose.ResultsLD₅₀ cut-off was 5 000 mg/kg body weight. The extract exhibited significant anti-implantation and abortifacient activity at the tested dose levels (300 and 500 mg/kg, p.o.) (P<0.01). The extract dose-dependently decreased the levels of serum progesterone, follicle stimulating hormone and luteinizing hormone, while a dose-dependent increase was observed in the concentration of serum prolactin. The extract did not show any significant changes in structure and function of uterus when given alone, but when given along with ethinyl estradiol, it exhibited significant antiestrogenic activity in immature overiectomized female rats(P<0.001). Biochemical parameters in the serum/blood and haematological parameters did not show appreciable changes throughout and after the course of investigation. However, all the altered parameters returned to normalcy within 30 days following withdrawal of treatment.ConclusionsAll findings suggest that the antifertility activity of extract could possibly be through the changes in the implantation site, altered hormonal levels, prolonged estrous cycle and anti-estrogenic activity. Hence, the extract possesses reversible antifertility activity without adverse toxicity in female rats.