Impact of supplementation with iron-folic acid (IFA) and vitamin D3 compared with IFA alone on haemoglobin levels in elderly people with mild-to-moderate anaemia: protocol for the double-blind, randomised, placebo-controlled Iron and vitamin D trial in Elderly Anemia (IDEA).

INTRODUCTION: Anaemia in the elderly is often difficult to treat with iron supplementation alone as prevalence of anaemia of chronic disease (ACD) alone or mixed with iron-deficiency anaemia (IDA) is high in this age group. Hepcidin remains high in ACD, preventing utilisation of iron for heme synthesis. Vitamin D3 has shown hepcidin suppression activity in both in vitro and in vivo studies. As there is no study assessing the effect of iron-folic acid (IFA) with vitamin D3 on haemoglobin levels in the elderly in India, we want to conduct this study to estimate the impact of supplementation of a therapeutic package of IFA and vitamin D3 on haemoglobin levels in the elderly with mild-to-moderate anaemia in comparison with IFA only. The study will also assess the impact of the proposed intervention on ferritin, hepcidin, 25-hydroxyvitamin D, C reactive protein (CRP) and parathyroid hormone (PTH) levels. METHODS AND ANALYSIS: This study is a community-based, double-blind, placebo-controlled, randomised trial. The study will be done in the Kalyani municipality area. Individuals aged ≥60 years with mild-to-moderate anaemia and normal vitamin D3 levels will be randomised into the intervention (IFA and vitamin D3 supplementation) group or the control group (IFA and olive oil as placebo). All medications will be self-administered. Follow-up will be done on a weekly basis for 12 weeks. The calculated sample size is 150 in each arm. Block randomisation will be done. The primary outcome is change in haemoglobin levels from baseline to 12 weeks. Secondary outcome is change in serum ferritin, 25-hydroxyvitamin D, hepcidin, CRP and PTH levels from baseline to 12 weeks. ETHICS AND DISSEMINATION: Ethical approval from the Institutional Ethics Committee of All India Institute of Medical Sciences Kalyani has been obtained (IEC/AIIMS/Kalyani/Meeting/2022/03). Written informed consent will be obtained from each study participant. The trial results will be reported through publication in a reputable journal and disseminated through health talks within the communities. TRIAL REGISTRATION NUMBER: CTRI/2022/05/042775. PROTOCOL VERSION: Version 1.0.

Diabetic Retinopathy Leading to Blindness- A Review.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes that damages the retina, leading to blindness. People with type 1 diabetes are at greater risk of developing DR than people with type 2 diabetes. Diabetic retinopathy may be divided into two primary categories: Proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR). There are multiple risk factors for the onset and progression of diabetic retinopathy, such as hypertension, obesity, smoking, duration of diabetes, and genetics. Numerous investigations have evaluated the levels of a wide range of inflammatory chemokines within DR patients' serum, vitreous, and aqueous fluids. In diabetic retinopathy, the vitreous fluid exhibited rises in angiogenic factors like platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF) or declines in antiangiogenic factors like pigment epithelium-derived factor (PEDF). For prevention of diabetic retinopathy, more physical activity as well as less sedentary behavior were linked to a reduced likelihood of DR. Supplementing with nutraceuticals containing vitamins (B1, B2, B6, B12, C, D, E, and l-methyl folate) and mineral (zinc) can help decrease or avoid an outbreak of DR. Only laser photocoagulation and Anti-vascular endothelial growth factor (Anti-VEGF) injections are advised as favorable therapies in severe retinopathy. When it comes to treating DR's VEGF levels, inflammation, oxidative stress, apoptosis, and angiogenesis, Traditional Chinese medicine (TCM) has an excellent future.

Combined effects of vermicompost and vermicompost leachate on the early growth of Meloidogyne incognita stressed Withania somnifera (L.) Dunal.

Roots of Withania somnifera, an important medicinal herb, are prone to the infection of Meloidogyne incognita (a root parasitic nematode). The infection lowers the quality and quantity of plant material and poses a challenge in crop cultivation and obtaining desirable yield. In the present study, in vitro inhibitory activity of vermicompost leachate (Vcom-L) was assessed against % hatch and survival of M. incognita in a 96 h assay. Then, Vcom-L was used as soil supplement in combination with vermicompost (Vcom) to evaluate their nematode inhibitory and stress alleviating effect in W. somnifera, in a pot experiment. Root galling intensity and growth performance of nematode-stressed W. somnifera raised from seeds pre-soaked in distilled water (DW), Vcom-L, vermicompost tea (Vcom-T) and different dilutions of Vcom-L were assessed. We observed 79% suppression of egg hatching and 89% juvenile (J2) mortality after 96 h compared to control, at 100% concentration of Vcom-L. Significant reduction in gall formation with increase in growth parameters of seedlings was observed after combined application of Vcom (60% or 100%) + Vcom-L and was evident as enhancement in seedling biomass and contents of chlorophyll and protein. However, proline, total phenolics and malondialdehyde (MDA) content declined significantly in these combinations compared to the control (0% Vcom). Activity of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidise (APX), guaiacol peroxidise (GPX) and glutathione reductase (GR) declined with Vcom as well as Vcom + Vcom-L and corresponded with decline in the accumulation of reactive oxygen species in leaves. Further, 1:5 and 1:10 dilutions of Vcom-L in combination with Vcom (60%) proved beneficial in mitigating the nematode-induced stress in W. somnifera. Present results showed the potential of Vcom and Vcom-L in standardised combination as an effective strategy in controlling the pathogenicity of M. incognita in medicinal plants such as W. somnifera.

A Comprehensive Review on Medicinal Herbs and Novel Formulations for the Prevention of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases reported in the aging population across the globe. About 46.8 million people are reported to have dementia, and AD is mainly responsible for dementia in aged people. Alzheimer's disease (AD) is thought to occur due to the accumulation of ß-amyloid (Aß) in the neocortex portion of the brain, nitric oxide mediated dysfunctioning of blood-brain barrier, reduced activity of serine racemase enzyme, cell cycle disturbances, damage of N-methyl-D-aspartate (NMDA) receptors and glutamatergic neurotransmission. Modern treatment methods target the pathways responsible for the disease. To date, solely symptomatic treatments exist for this disease, all making an attempt to counterbalance the neurotransmitter disturbance. Treatments able to prevent or at least effectively modifying the course of AD, referred to as 'disease-modifying' drugs, are still under extensive research. Effective treatments entail a better indulgence of the herbal bioactives by novel drug delivery systems. The herbal bioactive administered by novel drug delivery systems have proved beneficial in treating this disease. This review provides detailed information about the role of medicinal plants and their formulations in treating Alzheimer's disease which will be highly beneficial for the researchers working in this area.

Spontaneous Regression of Metastatic Lesions of Adenocarcinoma of the Gastro-Esophageal Junction.

Spontaneous regression of cancer is a rarely recognized entity in modern medicine. Historically, this was recognized and hypothesized that an infection causes immune activation, indirectly stimulating the body to destroy tumor cells. Similarly, immune-oncology has now become a major modality in the treatment of solid and some liquid malignancies. However, now with improved therapeutic modalities in the oncology world, one does not get to appreciate our own immune system's ability to fight cancer. We present a patient who had spontaneous regression of metastatic adenocarcinoma of the gastroesophageal junction (GEJ). The patient is a 58-year-old female who had presented with early satiety and dysphagia for which she underwent esophagogastroduodenoscopy which showed an esophageal mass and endoscopic ultrasounds (EUSs) confirmed adenocarcinoma of the GEJ with metastasis to the regional lymph nodes and left supraclavicular lymph nodes. The patient had refused to undergo any surgical, medical oncological, or holistic treatments. Interim disease monitoring positron emission tomography-computed tomography (PET-CT) showed resolution of the metastatic sites of gastroesophageal cancer with clinical improvement of her symptoms. She continues to have this distant regression of metastatic gastroesophageal cancer six months after the initial diagnosis. In literature, spontaneous cancer regression has been reported in melanoma, renal cell carcinoma, and basal cell carcinoma. To our knowledge, this is the first case reported of spontaneous regression of metastatic lesions involving adenocarcinoma of the GEJ with no medical or surgical intervention.

Effect of degree of milling and defatting on proximate composition, functional and texture characteristics of gluten-free muffin of bran of long-grain indica rice cultivars.

Effect of different degrees of milling (DoM: 2%, 4%, 6% and 8%) and defatting on the proximate composition, protein characteristics, functional properties of bran of long grain rice cultivars and texture characteristics of bran (RB) supplemented muffins were evaluated. Protein, ash content, redness and yellowness increased while fat content decreased for RB by extended DoM and defatting. A higher proportion of ß sheets, random coils, α-helix and ß-turns for all fractions of RB of both cultivars after defatting were also observed. Defatting and extended DoM both improved the essential amino acid content in RB. A higher level of prolamines (15-18 kDa) in RB and DF-RB of PUSA1121 than PR111 was observed. Muffins made from 2% DoM bran from PUSA1121 showed improved texture characteristics and achieved the highest score for sensory attributes. Therefore, DoM and defatting improved the proximate, protein profiling, and functionality of the different fraction of RB.

Dietary Tomato or Lycopene Do Not Reduce Castration-Resistant Prostate Cancer Progression in a Murine Model.

BACKGROUND: Dietary tomato products or lycopene protect against prostate carcinogenesis, but their impact on the emergence of castration-resistant prostate cancer (CRPC) is unknown. OBJECTIVE: We hypothesized that tomato or lycopene products would reduce the emergence of CRPC. METHODS: Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were castrated at 12-13 wk and the emergence of CRPC was monitored by ultrasound in each study. In Study 1, TRAMP mice (n = 80) were weaned onto an AIN-93G-based control diet (Con-L, n = 28), a 10% tomato powder diet (TP-L, 10% lyophilized w/w, n = 26), or a control diet followed by a tomato powder diet after castration (TP-Int1, n = 26). In Study 2, TRAMP mice (n = 85) were randomized onto a control diet with placebo beadlets (Con-Int, n = 29), a tomato diet with placebo beadlets (TP-Int2, n = 29), or a control diet with lycopene beadlets (Lyc-Int, n = 27) following castration (aged 12 wk). Tumor incidence and growth were monitored by ultrasound beginning at an age of 10 wk. Mice were euthanized 4 wk after tumor detection or aged 30 wk if no tumor was detected. Tissue weights were compared by ANOVA followed by Dunnett's test. Tumor volumes were compared using generalized linear mixed model regression. RESULTS: Ultrasound estimates for the in vivo tumor volume were strongly correlated with tumor weight at necropsy (R2 = 0.75 and 0.94, P <0.001 for both Studies 1 and 2, respectively). Dietary treatments after castration did not significantly impact cancer incidence, time to tumor detection, or final tumor weight. CONCLUSIONS: In contrast to studies of de novo carcinogenesis in multiple preclinical models, tomato components had no significant impact on the emergence of CRPC in the TRAMP model. It is possible that specific mutant subclones of prostate cancer may continue to show some antiproliferative response to tomato components, but further studies are needed to confirm this.

Novel allelic variation in the Phospholipase D alpha1 gene (OsPLDα1) of wild Oryza species implies to its low expression in rice bran.

Rice bran, a by-product after milling, is a rich source of phytonutrients like oryzanols, tocopherols, tocotrienols, phytosterols, and dietary fibers. Moreover, exceptional properties of the rice bran oil make it unparalleled to other vegetable oils. However, a lipolytic enzyme Phospholipase D alpha1 (OsPLDα1) causes rancidity and 'stale flavor' in the oil, and thus limits the rice bran usage for human consumption. To improve the rice bran quality, sequence based allele mining at OsPLDα1 locus (3.6 Kb) was performed across 48 accessions representing 11 wild Oryza species, 8 accessions of African cultivated rice, and 7 Oryza sativa cultivars. From comparative sequence analysis, 216 SNPs and 30 InDels were detected at the OsPLDα1 locus. Phylogenetic analysis revealed 20 OsPLDα1 cDNA variants which further translated into 12 protein variants. The O. officinalis protein variant, when compared to Nipponbare, showed maximum variability comprising 22 amino acid substitutions and absence of two peptides and two ß-sheets. Further, expression profiling indicated significant differences in transcript abundance within as well as between the OsPLDα1 variants. Also, a new OsPLDα1 transcript variant having third exon missing in it, Os01t0172400-06, has been revealed. An O. officinalis accession (IRGC101152) had lowest gene expression which suggests the presence of novel allele, named as OsPLDα1-1a (GenBank accession no. MF966931). The identified novel allele could be further deployed in the breeding programs to overcome rice bran rancidity in elite cultivars.

Effects of Supplementing the Usual Diet with a Daily Dose of Walnuts for Two Years on Metabolic Syndrome and Its Components in an Elderly Cohort.

Accumulating evidence links nut consumption with an improved risk of metabolic syndrome (MetS); however, long-term trials are lacking. We examined the effects of a daily dose of walnuts for two years on MetS in a large elderly cohort. A total of 698 healthy elderly participants were randomly assigned to either a walnut supplemented or a control diet. The participants in the walnut group were provided with packaged walnuts (1, 1.5, or 2 oz. or ~15% of energy) and asked to incorporate them into their daily habitual diet. The participants in the control group were asked to continue with their habitual diet and abstain from eating walnuts and other tree nuts. Intake of n-3 fatty acid supplements was not permitted in either group. Fasting blood chemistries, blood pressure, and anthropometric measurements were obtained at baseline and at the end of intervention. A total of 625 participants (67% women, mean age 69.1 y) completed this two-year study (90% retention rate). Triglycerides decreased in both walnut (-0.94 mg/dl) and control (-0.96 mg/dl) groups, with no significant between-group differences. There was a non-significant decrease in systolic and diastolic blood pressure in the walnut group (-1.30 and -0.71 mm Hg, respectively) and no change in the control group. Fasting blood glucose decreased by ~1 point in both the walnut and control groups. There were no significant between-group differences in the development or reversion of MetS. In conclusion, supplementing the diet of older adults with a daily dose of walnuts had no effect on MetS status or any of its components, although the walnut group tended to have lower blood pressure.

Role of Oropharyngeal Administration of Colostrum in Very Low Birth Weight Infants for Reducing Necrotizing Enterocolitis: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to study the role of oropharyngeal administration of colostrum (OAC) in very-low-birth-weight infants for reducing necrotizing enterocolitis (NEC). STUDY DESIGN: In this randomized controlled trial, 117 infants were enrolled, 59 were randomized to OAC group and 58 to routine care group. Infants with birth weight ≤ 1,250 g and/or gestational age ≤ 30 weeks were enrolled. Infants in OAC group received maternal colostrum (0.2 mL), 0.1 mL on either side, after 24 hours of postnatal life and were given every 2 hour for the next 72 hours irrespective of the enteral feeding status of the neonate. The primary outcome of the study was the incidence of NEC (stage 2 or 3). RESULTS: Baseline characteristics were comparable between the two groups. There was no significant reduction in the incidence of NEC in OAC group (0 [0%] vs. 3 [7.1%]; p = 0.11). There was significant reduction of 7 days of hospital stay in OAC group (34.2 ± 5.7 vs. 41.5 ± 6.7 days; p = 0.04).The incidence of early-onset sepsis, late-onset sepsis, blood culture positive sepsis, and ventilator-associated pneumonia were comparable between the two groups. CONCLUSION: OAC is safe and reduces the duration of hospital stay.

Multi-target-directed triazole derivatives as promising agents for the treatment of Alzheimer's disease.

A novel series of triazole-based compounds have been designed, synthesised and evaluated as multi-target-directed ligands (MTDLs) against Alzheimer disease (AD). The triazole-based compounds have been designed to target four major AD hallmarks that include Aß aggregation, metal-induced Aß aggregation, metal dys-homeostasis and oxidative stress. Among the synthesised compounds, 6n having o-CF3 group on the phenyl ring displayed most potent inhibitory activity (96.89% inhibition, IC50 = 8.065 ±â€¯0.129 µM) against Aß42 aggregation, compared to the reference compound curcumin (95.14% inhibition, IC50 = 6.385 ±â€¯0.009 µM). Compound 6n disassembled preformed Aß42 aggregates as effectively as curcumin. Furthermore, 6n displayed metal chelating ability and significantly inhibited Cu2+-induced Aß42 aggregation and disassembled preformed Cu2+-induced Aß42 aggregates. 6n successfully controlled the generation of the reactive oxygen species (ROS) by preventing the copper redox cycle. In addition, 6n did not display cytotoxicity and was able to inhibit toxicity induced by Aß42 aggregates in SH-SY5Y cells. The preferred binding regions and key interactions of 6n with Aß42 monomer and Aß42 protofibril structure was evaluated with molecular docking. Compound 6n binds preferably to the C-terminal region of Aß42 that play a critical role in Aß42 aggregation. The results of the present study highlight a novel triazole-based compound, 6n, as a promising MTDL against AD.

Bioinspired Small-Molecule Tools for the Imaging of Redox Biology.

The availability of electrons to biological systems underpins the mitochondrial electron transport chain (ETC) that powers living cells. It is little wonder, therefore, that the sufficiency of electron supply is critical to cellular health. Considering mitochondrial redox activity alone, a lack of oxygen (hypoxia) leads to impaired production of adenosine triphosphate (ATP), the major energy currency of the cell, whereas excess oxygen (hyperoxia) is associated with elevated production of reactive oxygen species (ROS) from the interaction of oxygen with electrons that have leaked from the ETC. Furthermore, the redox proteome, which describes the reversible and irreversible redox modifications of proteins, controls many aspects of biological structure and function. Indeed, many major diseases, including cancer and diabetes, are now termed "redox diseases", spurring much interest in the measurement and monitoring of redox states and redox-active species within biological systems. In this Account, we describe recent efforts to develop magnetic resonance (MR) and fluorescence imaging probes for studying redox biology. These two classes of molecular imaging tools have proved to be invaluable in supplementing the structural information that is traditionally provided by MRI and fluorescence microscopy, respectively, with highly sensitive chemical information. Importantly, the study of biological redox processes requires sensors that operate at biologically relevant reduction potentials, which can be achieved by the use of bioinspired redox-sensitive groups. Since oxidation-reduction reactions are so crucial to modulating cellular function and yet also have the potential to damage cellular structures, biological systems have developed highly sophisticated ways to regulate and sense redox changes. There is therefore a plethora of diverse chemical structures in cells with biologically relevant reduction potentials, from transition metals to organic molecules to proteins. These chemical groups can be harnessed in the development of exogenous molecular imaging agents that are well-tuned to biological redox events. To date, small-molecule redox-sensitive tools for oxidative stress and hypoxia have been inspired from four classes of cellular regulators. The redox-sensitive groups found in redox cofactors, such as flavins and nicotinamides, can be used as reversible switches in both fluorescent and MR probes. Enzyme substrates that undergo redox processing within the cell can be modified to provide fluorescence or MR readout while maintaining their selectivity. Redox-active first-row transition metals are central to biological homeostasis, and their marked electronic and magnetic changes upon oxidation/reduction have been used to develop MR sensors. Finally, redox-sensitive amino acids, particularly cysteine, can be utilized in both fluorescent and MR sensors.

Physical Inaccessibility of a Resistant Starch Shifts Mouse Gut Microbiota to Butyrogenic Firmicutes.

SCOPE: Resistant starch (RS) is utilized by Gram-negative Bacteroidetes through a starch utilization system (Sus), which requires physical attachment of the bacteria to the substrate. Gram-positive Firmicutes, which include butyrate producers, utilize RS by other mechanisms, such as amylosomes and secreted amylases/glucoamylases. It has been previously shown that fabricated RS [alginate-based starch-entrapped microspheres (SM)] increases butyrate in in vitro human fecal fermentation and was slow fermenting. It has been hypothesized that in vivo SM would disfavor Bacteroidetes and promote Firmicutes, leading to an increase in butyrate production. METHODS AND RESULTS: A C57BL/6J mouse model is used to test type 2 RS (RS2, raw potato) and SM for SCFAs and fecal microbial community structure. Feeding SM for 2 weeks results in 2.4 times higher mol% butyrate in the mouse distal gut than RS2. SM reduces relative abundance of Bacteroidetes and increases Firmicutes in fecal samples at the end of the 2-week feeding. This phylum-level taxonomic shift is not observed in animals fed RS2. CONCLUSION: Through an approach to understand bacterial requirements related to starch utilization, a designed fiber type favors butyrogenic Firmicutes bacteria and provides higher mol% butyrate in the distal gut with potential benefit as an anti-inflammatory agent and to improve gut barrier function.

Effect of crude extracts and purified compounds of Alpinia galanga on nutritional physiology of a polyphagous lepidopteran pest, Spodoptera litura (Fabricius).

Secondary plant metabolites play an important role in providing protection to plants against herbivore insect pests. Keeping in view the increasing importance of biopesticides, the crude extracts from different plants are being investigated for insecticidal activities. Alpinia galanga, a medicinal plant belonging to family Zingiberaceae exhibits a wide range of biological activities. In the present study, crude extracts of A. galanga and its purified compounds i.e. 1'-acetoxychavicol acetate and galangin were evaluated for their effect on various nutritional parameters of Spodoptera litura (Fab.). All the extracts exhibited a significant influence on relative growth and consumption rates as well as efficiency of conversion of ingested and digested food. Ethyl acetate extract was found to be the most effective causing significant reduction in values of RGR, RCR, ECI and ECD of S. litura larvae in comparison to control larvae. The highest concentration of the ethyl acetate extract (2500 ppm) resulted in 44.95%, 10.99%, 38.08% and 37.04% decrease respectively in RGR, RCR, ECI and ECD in comparison to control. The purified compounds also showed inhibitory effects on various nutritional parameters. 1'-Acetoxychavicol acetate was found to be more effective in comparison to galangin.

Secondary metabolites from lichen as potent inhibitors of advanced glycation end products and vasodilative agents.

Secondary metabolites from lichens are known for exhibiting various biological effects such as anti-inflammatory, antioxidant and antibacterial activities. Despite this wide range of reported biological effects, their impact on the formation of advanced glycation end products (AGEs) remains vastly unexplored. The latter are known contributors to lifestyle and age-related diseases such as Alzheimer and Parkinson. Moreover, the development of atherosclerosis and arterial stiffness is causally linked to the formation of AGEs. With this in mind, the present work evaluated the inhibitory effects of secondary lichen metabolites on the formation of pentosidine-like AGEs' by using an in vitro, Maillard reaction based, fluorescence assay. Overall, thirty-seven natural and five synthetically modified compounds were tested, eighteen of which exhibiting IC50 values in the range of 0.05 to 0.70 mM. This corresponds to 2 to 32 fold of the inhibitory activity of aminoguanidine. Targeting one major inhibiting mechanism of AGEs formation, all compounds were additionally evaluated on their radical scavenging capacities in an DPPH assay. Furthermore, as both AGEs' formation and hypertension are major risk factors for atherosclerosis, compounds that were available in sufficient amounts were also tested for their vasodilative effects. Overall, and though some of the active compounds were previously reported cytotoxic, present results highlight the interesting potential of secondary lichen metabolites as anti-AGEs and vasodilative agents.

Organic cultivation of Ashwagandha with improved biomass and high content of active Withanolides: Use of Vermicompost.

Withania somnifera (Ashwagandha) has recently been studied extensively for its health-supplementing and therapeutic activities against a variety of ailments. Several independent studies have experimentally demonstrated pharmaceutical potential of its active Withanolides, Withaferin A (Wi-A), Withanone (Wi-N) and Withanolide A (Wil-A). However, to promote its use in herbal industry, an environmentally sustainable cultivation and high yield are warranted. In modern agriculture strategies, there has been indiscriminate use of chemical fertilizers to boost the crop-yield, however the practice largely ignored its adverse effect on the quality of soil and the environment. In view of these, we attempted to recruit Vermicompost (Vcom, 20-100%) as an organic fertilizer of choice during the sowing and growing phases of Ashwagandha plants. We report that (i) pre-soaking of seeds for 12 h in Vermicompost leachate (Vcom-L) and Vermicompost tea (Vcom-T) led to higher germination, (ii) binary combination of pre-soaking of seeds and cultivation in Vcom (up to 80%) resulted in further improvement both in germination and seedling growth, (iii) cultivated plants in the presence of Vcom+Vcom-L showed higher leaf and root mass, earlier onset of flowering and fruiting and (iv) leaves from the Vcom+Vcom-L cultivated plants showed higher level of active Withanolides, Withanone (Wi-N), Withanolide A (Wil-A) and Withaferin A (Wi-A) and showed anticancer activities in cell culture assays. Taken together, we report a simple and inexpensive method for improving the yield and pharmaceutical components of Ashwagandha leaves.

Synthesis, screening and docking of fused pyrano[3,2-d]pyrimidine derivatives as xanthine oxidase inhibitor.

In view of developing effective xanthine oxidase (XO) enzyme inhibitors, a series of 100 pyrano[3,2-d]pyrimidine derivatives was synthesized and evaluated for its in vitro XO enzyme inhibition. Structure activity relationship has also been established. Among all the synthesized compounds, 4d, 8d and 9d were found to be the most potent enzyme inhibitors with IC50 values of 8µM, 8.5µM and 7µM, respectively. Compound 9d was further investigated in enzyme kinetic studies and the Lineweaver-Burk plot revealed that the compound 9d was mixed type inhibitor. Molecular properties of the most potent compounds 4d, 8d and 9d, have also been calculated. Docking study was performed to investigate the recognition pattern between xanthine oxidase and the most potent XO inhibitor, 9d. The study suggests that 9d may block the activity of XO sufficiently enough to prevent the substrate from binding to its active site.

Elevated propionate and butyrate in fecal ferments of hydrolysates generated by oxalic acid treatment of corn bran arabinoxylan.

Previous work in our laboratory showed that alkali-solubilized corn arabinoxylan (CAX) has a slow initial, but later complete, in vitro human fecal fermentation. CAX and a moderately high molecular weight hydrolysate (CH) were propiogenic, and produced low levels of butyrate. Here, we show that oxalic acid-generated hydrolysates from CAX, which include a large xylooligosaccharide, and free arabinose fractions, increased short chain fatty acid (SCFA) production, which included relatively high levels of both propionate and butyrate, an unusual SCFA combination. Hydrolytic degradation of CAX by acid hydrolysis (0.05 M oxalic acid at 100 °C for 2 h) and subsequent graded ethanol precipitations were used to obtain mixtures with different molecular weight ranges. Ethanol-precipitated fractions (F 0-65%, F 65-75%, F 75-85%) were mostly lower than 100 kDa and F > 85% was composed of monosaccharides and oligosaccharides of DP 2-8. Oxalic acid treatment caused the removal of all single arabinose unit branch chains and some di/trisaccharide branch chains, producing lightly substituted xylan backbone fragments, most of which were in the oligosaccharide (DP < 10) size range. In vitro human fecal fermentation analyses showed all oxalic acid-hydrolysate fractions were slower fermenting than fructooligosaccharides (FOS), but produced similar or higher amounts of total SCFAs. Butyrate production in two hydrolyzate fractions was double that of CH, while propionate levels remained relatively high.

Kinetics studies with fruit bromelain (Ananas comosus) in the presence of cysteine and divalent ions.

The kinetics of cysteine and divalent ion modulation viz. Ca(2+), Cu(2+), Hg(2+) of fruit bromelain (EC 3.4.22.33) have been investigated in the present study. Kinetic studies revealed that at pH 4.5, cysteine induced V-type activation of bromelain catalyzed gelatin hydrolysis. At pH 3.5, Ca(2+) inhibited the enzyme noncompetitively, whereas, both K-and V-type activations of bromelain were observed in the presence of 0.5 mM Ca(2+) at pH 4.5 and 7.5. Bromelain was inhibited competitively at 0.6 mM Cu(2+) ions at pH 3.5, which changed to an uncompetitive inhibition at pH 4.5 and 7.5. An un-competitive inhibition of bromelain catalyzed gelatin hydrolysis was observed in the presence of 0.6 mM Hg(2+) at pH 3.5 and 4.5. These findings suggest that divalent ions modulation of fruit bromelain is pH dependent.

Antileishmanial compounds from Moringa oleifera Lam.

The antileishmanial activity of extracts and phytoconstituents of Moringa oleifera Lam. was investigated in vitro against promastigotes of Leishmania donavani. The 70% ethanolic extract of roots and the methanolic extract of leaves showed moderate inhibitory activity with IC50 values of 83.0 microg/ml and 47.5 microg/ml, respectively. Antileishmanial activity of the methanolic extract of leaves increased upon fractionation, as its ethyl acetate fraction was found to be more active with an IC50 value of 27.5 microg/ml. The most active antileishmanial compound niazinin, a thiocarbamate glycoside isolated from this fraction, showed an IC50 value of 5.25 microM. Results presented in this study indicate that extracts from M. oleifera may be developed as an adjuvant therapy for the treatment of leishmaniasis.