IMPACT OF AGRO CLIMATIC AND SOCIO-ECONOMIC VARIABILITY ON THE NUTRITIONAL STATUS OF INHABITANTS In THE GARHWAL HIMALAYAS

The Garhwal Himalayas are a part of a unique ecosystem, with sharp agro-climatic variations within a very small geographical area (53,485 km²). The varied agro-climatic situations result in different cropping systems and socio-economic lifestyles that could likely affect the nutritional status of the people living in this region. This article will attempt to explore the impact of these variables (namely, age, family size, education, income, calorie and protein intake, land holding, number of animals, and wheat production) on the body mass index (BMI) of the population residing in the Garhwal Hills. A total of 1,030 subjects were studied from the three agro-climatic zones (406 from the high hills, 292 from the mid hills, and 332 from the low hills). It has been found that the people living in the high hills are the most undernourished, as the lowest percentage of people (52.6 per cent) with an acceptable BMI and the highest percentage of people in the severely malnourished category (11.1 per cent) are found here. People living in urban areas have a better nutritional status. Correlation studies show that the nutritional status of the population improves with age, literacy levels, and small family size. In some cases, calorie and protein intake have a positive impact on the health of the people, whereas size of land holding, number of animals, and income of the family do not have any significant influence on nutritional status.     

Design and synthesis of some acridine‐piperazine hybrids for the improvement of cognitive dysfunction

A novel series of hybrid molecules ( 5a–5m ) was designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against cognitive dysfunction. Heterocyclic moieties acridine and piperazine were conjugated with suitable linkers in a single scaffold, and the structures of the target compounds were confirmed by IR, ¹H NMR, ¹³C NMR, and LC‐MS analysis. The pharmacological activity of synthesized compounds was evaluated using behavioral models of amnesia viz. step‐down passive avoidance and elevated plus maze at a dose 0.5 mg/kg as compared to standard rivastigmine. In vitro acetylcholinesterase (AChE) inhibition studies using brain homogenate of mice as the enzyme source revealed that most of the compounds exhibited a significant ability to inhibit the enzyme cholinesterase with compound 5c being the most potent (IC₅₀ 0.33 μm ). Biochemical estimation of oxidative stress markers viz. plasma nitrite, thiobarbituric acid reactive substances, catalase, superoxide dismutase, and glutathione has been carried out using the respective assays to see the effect of the synthesized compounds on the scopolamine‐induced oxidative damage. The molecular docking studies indicated the binding mode of the compounds to the catalytic site, peripheral site, and mid‐gorge of AChE simultaneously. The calculated absorption, distribution, metabolism and excretion properties ensured the drug‐likeness of the target compounds. The synthesized compounds were found to be potential cognitive enhancers, which were able to interfere with the scopolamine‐induced oxidative stress also.     

4‐Substituted thieno[2,3‐d]pyrimidines as potent antibacterial agents: Rational design,microwave‐assisted synthesis,biological evaluation and molecular docking studies

In an attempt to discover a new class of antibacterial agents with improved efficacy and to overcome the drug‐resistant problems, some novel 4‐substituted thieno[2,3‐d]pyrimidines have been synthesized via microwave‐assisted methodology and evaluated for their in vitro antibacterial activity against various pathogenic bacterial strains. Compounds 12 b and 13 c showed the promising inhibitory potencies against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli with MICs ranging from 2 to 10 μg/ml. Compound 13 c was also found to be highly potent against methicillin‐resistant S. aureus (MRSA) with MIC value of 4 μg/ml. Docking simulation studies have been performed to unravel the mode of action and association study indicate the binding of potent compounds with DHPS enzyme. In silico ADME studies suggest the drug‐like characteristics of the potent compounds.     

Troxerutin attenuates diet‐induced oxidative stress,impairment of mitochondrial biogenesis and respiratory chain complexes in mice heart

Mitochondrial abnormality is thought to play a key role in cardiac disease originating from the metabolic syndrome (MS). We evaluated the effect of troxerutin (TX), a semi‐synthetic derivative of the natural bioflavanoid rutin, on the respiratory chain complex activity, oxidative stress, mitochondrial biogenesis and dynamics in heart of high fat, high fructose diet (HFFD) ‐induced mouse model of MS. Adult male Mus musculus mice of body weight 25‐30 g were fed either control diet or HFFD for 60 days. Mice from each dietary regimen were divided into two groups on the 16th day and were treated or untreated with TX (150 mg/kg body weight [bw], per oral) for the next 45 days. At the end of experimental period, respiratory chain complex activity, uncoupling proteins (UCP)‐2 and ‐3, mtDNA content, mitochondrial biogenesis and dynamics, oxidative stress markers and reactive oxygen species (ROS) generation were analyzed. Reduced mtDNA abundance with alterations in the expression of genes related to mitochondrial biogenesis and fission and fusion processes were observed in HFFD‐fed mice. Disorganized and smaller mitochondria, reduction in complexes I, III and IV activities (by about 55%) and protein levels of UCP‐2 (52%) and UCP‐3 (46%) were noted in these mice. TX administration suppressed oxidative stress, improved the oxidative capacity and biogenesis and restored fission/fusion imbalance in the cardiac mitochondria of HFFD‐fed mice. TX protects the myocardium by modulating the putative molecules of mitochondrial biogenesis and dynamics and by its anti‐oxidant function in a mouse model of MS.     

Protective effect of fenugreek (Trigonella foenum graecum) seeds in experimental ethanol toxicity

The study investigates the effect of aqueous extract of fenugreek seeds (Trigonella foenum graecum) on lipid peroxidation and antioxidant status in experimental ethanol toxicity in rats. The ability of the seed extract to prevent iron-induced lipid peroxidation in vitro was also investigated. Ethanol feeding for 60 days resulted in significant increases in the activities of serum aspartate transaminase, alanine transaminase and alkaline phosphatase. The levels of serum lipid hydroperoxides and thiobarbituric acid reactive substances in liver and brain were also significantly elevated. Significantly lower activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione reductase were observed in liver and brain accompanied by depletion in glutathione, ascorbic acid and alpha-tocopherol concentrations. Activity of Ca(2+) ATPase in brain was significantly lowered. Simultaneous administration of aqueous extract of fenugreek seeds with ethanol prevented the enzymatic leakage and the rise in lipid peroxidation and enhanced the antioxidant potential. The seeds exhibited appreciable antioxidant property in vitro which was comparable with that of reduced glutathione and alpha-tocopherol. Further, histopathological examination of liver and brain revealed that, aqueous extract of fenugreek seeds could offer a significant protection against ethanol toxicity.     

High‐throughput Screening for Identification of Inhibitors of EpCAM‐Dependent Growth of Hepatocellular Carcinoma Cells

The cancer stem cell marker, EpCAM, is an important indicator of Wnt/β‐catenin signaling activation and a functional component of hepatocellular tumor‐initiating cells. A high‐throughput screening assay was developed to identify inhibitors of EpCAM‐dependent growth of hepatocellular carcinoma (HCC) cells. EpCAM(+) and EpCAM(?) HCC cell lines were assessed for differential sensitivity to a Wnt/β‐catenin pathway inhibitor. Libraries comprising 22 668 pure compounds and 107 741 crude or partially purified natural product extracts were tested, and 12 pure compounds and 67 natural product extracts were identified for further study. Three active compounds and the positive control were further characterized in terms of effects on EpCAM expression. Treatment of EpCAM(+) Hep3B cells resulted in loss of EpCAM expression as assessed by flow cytometry. This reduction was incomplete (most cells continued to express EpCAM), but resulted in generation of cell populations expressing lower levels of EpCAM. Sublethal concentrations (~IC₅₀) reduced median EpCAM expression to 28% of control after 1 day and 19% of control after 2 days. Reduction in EpCAM expression preceded growth inhibition suggesting that a threshold of EpCAM expression may be required for growth of EpCAM‐dependent cells. The identification of compounds with a variety of possible molecular targets suggests a likelihood of multiple mechanisms for modulation of EpCAM‐dependent cell growth.     

Efficacy of Desmodium gangeticum extract and its fractions against experimental visceral leishmaniasis

Crude ethanolic extract of Indian medicinal plant, Desmodium gangeticum (A001) and its three fractions-hexane (F002), n-butanol (F003) and aqueous (F004) were evaluated chemoprophylactically and chemotherapeutically against experimental visceral leishmaniasis in hamsters. Ethanolic extract showed 41.2+/-5.3% inhibition of parasite multiplication when administered at a dose of 250 mg/kgx2 on day -7 and +7 of Leishmania donovani challenge. Its n-butanol fraction exhibited better efficacy than the ethanolic extract to the tune of 66.7+/-6.1% inhibition when administered at similar dose schedule. But the other two fractions failed to exert any action prophylactically. F003 also imparted significant (P<0.001) non-specific resistance to peritoneal macrophages against Leishmania infection. F003 also showed moderate antileishmanial activity when tested against established infection of Leishmania donovani in hamsters but the rest three fractions failed to show any significant inhibition of parasite multiplication. These findings revealed that this plant has potential prophylactic and therapeutic efficacy against Leishmania infection and warrants detailed investigations on its possible immunopotentiatory actions.     

Evaluation of protective effects of diosmin (a citrus flavonoid) in chemical-induced urolithiasis in experimental rats

Context There have not been any conclusive studies of the effects of diosmin, a modified flavanone glycoside obtained from Teucrium gnaphalodes L’Her (Lamiaceae), on urolithiasis.

Objective To evaluate anti-urolithiatic effects of diosmin in ammonium chloride and ethylene glycol-induced renal stone in experimental animals.

Materials and methods Thirty Sprague-Dawley were divided into five groups (n=6) receiving the following treatments, respectively, p.o. for 15 consecutive days: distilled water, 0.75% v/v ethylene glycol?+?2% w/v ammonium chloride, 0.75% v/v ethylene glycol?+?2% w/v ammonium chloride?+?cystone® 750?mg/kg, 0.75% v/v ethylene glycol?+?2% w/v ammonium chloride?+?diosmin 10?mg/kg or 0.75% v/v ethylene glycol?+?2% w/v ammonium chloride?+?diosmin 20?mg/kg. Different biomarkers of urolithiasis in urine and serum were evaluated and histopathological examination of kidney was done.

Results Animals treated with diosmin (both 10 and 20?mg/kg) had significantly (p?<?0.005) decreased in kidney weight, urinary pH, total urinary protein, urinary calcium, phosphorus, serum potassium, sodium, magnesium, creatinine, uric acid and blood urea nitrogen levels and significantly (p?<?0.005) increased in urinary volume, urinary magnesium, potassium, sodium, creatinine, uric acid and serum calcium levels in comparison to animals treated with ethylene glycol and ammonium chloride. However, results were better with diosmin 20?mg/kg in comparison to the control group.

Conclusion Diosmin (10 and 20?mg/kg) has very good anti-urolithiatic activity similar to the standard drug cystone®.