Phytoformulation with hydroxycitric acid and capsaicin protects against high-fat-diet-induced obesity cardiomyopathy by reducing cardiac lipid deposition and ameliorating inflammation and apoptosis in the heart.

Background and aim: Phytoformulation therapy is a pioneering strategy for the treatment of metabolic disorders and related diseases. The aim of the present study was to investigate the protective effect of a phytoformulation consisting of hydroxycitric acid and capsaicin against obesity-related cardiomyopathy. Experimental procedure: Sprague-Dawley rats were fed HFD for 21 weeks, and phytoformulation (100 mg/kg body weight) was administered orally for 45 days starting at week 16. Results and conclusion: We found that HFD supplementation resulted in significant hyperglycemia and caused an increase in cardiac lipid deposition, inflammation and apoptosis in the heart. Phytoformulation therapy not only significantly decreased blood levels of glucose, cholesterol, triglycerides, free fatty acids, and inflammatory cytokines in obese rats, but also protected cardiac tissue, as shown by histological analysis. Conversely, phytoformulation therapy decreased mRNA levels for sterol regulatory element-binding factor 1, fatty acid synthase, acetyl-CoA carboxylase, and fatty acid binding protein 1 genes involved in fatty acid synthesis and absorption in obese rats. It increased the levels of lysosomal acid lipase, hormone-sensitive lipase, and lipoprotein lipase genes involved in fatty acid degradation in the heart. In addition, the phytoformulation improved cardiac inflammation and apoptosis by downregulating the genes nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumour necrosis factor α, interleukin-6, toll-like receptor-4 (TLR-4), BCL2-associated X and caspase-3. In conclusion, our results show that the phytoformulation improved insulin sensitivity and attenuated myocardial lipid accumulation, inflammation, and apoptosis in the heart of HFD-induced obese rats by regulating fatty acid metabolism genes and downregulating NF-kB/TLR-4/caspase-3.

Individualized Homeopathic Medicines for Low Back Pain in Lumbar Spondylosis: Double-Blind, Randomized, Placebo-Controlled Trial.

INTRODUCTION: Lumbar spondylosis (LS) is a degenerative disorder of the lumbar spine. Despite substantial research efforts, no gold-standard treatment for LS has been identified. The efficacy of individualized homeopathic medicines (IHMs) in LS has remained under-researched. In this study, the efficacy of IHMs was compared with identical-looking placebos in the treatment of low back pain associated with LS. METHODS: A double-blind, randomized (1:1), placebo-controlled trial was conducted at the National Institute of Homoeopathy, West Bengal, India. Patients were randomized to receive IHMs or placebos, along with standardized concomitant care for both the groups. The Oswestry low back pain and disability questionnaire (ODQ) was the primary outcome; the Roland-Morris questionnaire (RMQ) and the short form of the McGill pain questionnaire (SF-MPQ) were the secondary outcomes. Each was measured at baseline and every month for 3 months. The intention-to-treat (ITT) sample was analyzed to detect any inter-group differences using two-way repeated measures analysis of variance models overall and by unpaired t-tests at different time points. RESULTS: Enrolment was stopped prematurely because of time restrictions; 55 patients were randomized (verum: 28; control: 27); 49 were analyzed by ITT (verum: 26; control: 23). Inter-group differences in ODQ (F 1, 47 = 0.001, p = 0.977), RMQ (F 1, 47 = 0.190, p = 0.665) and SF-MPQ total score (F 1, 47 = 3.183, p = 0.081) at 3 months were not statistically significant. SF-MPQ total score after 2 months (p = 0.030) revealed inter-group statistical significance, favoring IHMs against placebos. Some of the SF-MPQ sub-scales at different time points were also statistically significant: e.g., the SF-MPQ average pain score after 2 months (p = 0.002) and 3 months (p = 0.007). Rhus toxicodendron, Sulphur and Pulsatilla nigricans were the most frequently indicated medicines. CONCLUSION: Owing to failure in detecting a statistically significant effect for the primary outcome and in recruiting a sufficient number of participants, our trial remained inconclusive. TRIAL REGISTRATION: CTRI/2019/11/021918.

In silico bioprospecting of antiviral compounds from marine fungi and mushroom for rapid development of nutraceuticals against SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) affects human respiratory function that causes COVID-19 disease. COVID-19 has spread rapidly all over the world and became a pandemic within no time. Therefore, it is the need of hour to screen potential lead candidates from natural resources like edible mushrooms and marine fungi. These natural resources are very less explored till now and known to be the source for many medicinal compounds with several health benefits. These medicinal compounds can be easily exploited for the faster development of nutraceuticals for controlling SARS-CoV-2 infections. Our Insilico research suggests, bioactive compounds originating from mushroom and marine fungi shows strong potential to interact with ACE2 receptor or main protease of SARS-CoV-2, showing the inhibition activity towards the enzymatic protease. We performed a series of Insilico studies for the validation of our results, which includes Molecular docking, drug likeness property investigation by Swiss ADME tools, MD simulation, and thermodynamically stable free binding energy calculation. Overall, these results suggest that Ganodermadiol and Heliantriol F bioactive compounds originating from edible mushroom has strong potential to be developed as low-cost nutraceutical against SARS-CoV-2 viral infection. The drug candidate isolated from marine fungi and edible mushroom are highly unexplored for the development of potential alternative drug against SARS-CoV-2 virus with minimum side effects. Though our in silico studies of these compounds are showing a promising results against SARS-CoV-2 main protease and ACE2 receptor binding domain, the effectiveness of these bioactive compounds should be further validated by proper clinical trials.Communicated by Ramaswamy H. Sarma.

Antioxidant properties, phenolics and flavonoids content of some economically important plants from North-west Indian Himalaya.

The present study investigated antioxidant properties, total phenolic and flavonoid contents in methanol extract of the leaf, stem bark, and fruit of Olea ferruginea Royle, Olea europaea L., and Tilia europaea L. grow naturally in the north-west Indian Himalaya. Phenolics and flavonoids content was found to be maximum in methanol extracts of stem bark and leaf (9.28 mg GAE/g fw and 14.73 mg QE/g fw, respectively) of O. ferruginea plants. Ferric reducing antioxidant power and DPPH radical scavenging activity were found to be maximum in leaf and stem bark (38.88 mM AAE/g fw and 20.31 mM AAE/g fw, respectively) of O. ferrugenia plants, whereas maximum ABTS radical scavenging activity (4.52 mM AAE/g fw) was recorded with stem bark of T. europaea plants. These tree species were found rich in natural compounds and also possess antioxidant activities. Therefore, their pharmaceutical and local uses for the health benefits are suggested.

Characterization, biological evaluation and molecular docking of mulberry fruit pectin.

Contemplating the exemplary benefits of pectin on human health, we precisely characterized and evaluated the antibacterial and anticancer activities from purified Mulberry Fruit Pectins (MFP). Here, we tested BR-2 and S-13 varieties of mulberry fruit pectins against six bacterial strains and two human cancer cell lines (HT-29 and Hep G-2), using MIC and an in vitro cell-based assay respectively. The BR-2 mulberry fruit pectin performs superior to S-13 by inhibiting strong bacterial growth (MIC = 500-1000 µg/mL) against tested bacterial strains and cytotoxic activities at the lowest concentration (10 µg/ml) against the Hep G-2 cell line. However, both tested drugs failed to exhibit cytotoxicity on the human colon cancer cell line (HT-29). Based on molecular interaction through docking, pectin binds effectively with the receptors (1e3g, 3t0c, 5czz, 6j7l, 6v40, 5ibs, 5zsy, and 6ggb) and proven to be a promising antimicrobial and anti-cancer agents. The pursuit of unexploited drugs from mulberry fruit pectin will potentially combat against bacterial and cancer diseases. Finally, future perspectives of MFP for the treatment of many chronic diseases will help immensely due to their therapeutic properties.

NMR Based Metabolomics: An Exquisite and Facile Method for Evaluating Therapeutic Efficacy and Screening Drug Toxicity.

Metabolomics is an analytical approach to metabolism and involves quantitative and comparative analysis of low-molecular-weight metabolites in body fluids or cellular/tissues extracts. Owing to its ability to reveal disease-specific metabolic patterns or metabolic changes produced in response to a therapeutic intervention; it is gaining widespread applications virtually in all aspects of biomedical and pharmaceutical research pertaining to human healthcare management. It has also started playing a strategic role in pharmacological and toxicological research for evaluating therapeutic efficacy/safety of promising drug candidates either alone or in conjunction with other omics tools such as genomics, transcriptomics and proteomics. The metabolic profiling capabilities of nuclear magnetic resonance (NMR) spectroscopy along with pattern recognition methods have successfully been applied for identifying a diagnostic panel of biomarkers, evaluating drug efficacy/safety, screening toxicity and disease mechanism. Particularly, the interest in applying NMR-based metabolomics for the assessment of therapeutic efficacy and safety is increasing among drug researchers and drug regulators owing to its nondestructive, non-selective and minimal sample preparation requirement. On top of this, it offers the potential for high-throughput (i.e. >100 samples a day is attainable) and provides highly reproducible results. In this review, we will discuss some of the recent developments related to NMR based metabolomics followed by some recent literature examples to highlight its potential in (a) the evaluation of therapeutic efficacy and safety of lead discovery compounds, (b) monitoring disease status and recovery after treatment and (c) identification and evaluation of biomarkers of systemic/organ-specific toxicity. Additionally, the review will also highlight its role to facilitate clinical trial testing and improve post-approval drug monitoring.

Effect of Aegle marmelos and Murraya koenigii in treatment of delayed pubertal buffaloes heifers.

AIM: This study aims to study the estrus induction, ovulation, and conception rate of delayed puberty in buffaloes heifers by feeding a herbal plants Aegle marmelos (bael/bili/bhel leaf) and Murraya koenigii (Curry leaf). MATERIALS AND METHODS: Totally, 24 buffalo heifers with delayed puberty were selected for the present study and divided randomly in four equal groups (n=6). Before experiment, all animals were dewormed with albendazole at 10 mg/kg body weight to prevent them from the stress of parasitism. In the present experiment, four group taken and Group I (n=6) treated with A. marmelos, Group II (n=6) treated with M. koenigii, Group III (n=6) treated with mixture of A. marmelos and M. koenigii and fed for 9 days. Group IV (n=6) considered as control and fed with concentrate only. The blood samples were collected from all the animals on day 0 (before treatment), 4, 9 (during treatment), on the day of estrus and day 8 after the onset of estrus. The 10 ml blood was collected from the jugular vein of all the experimental animals for estimation of serum calcium, inorganic phosphorus, and progesterone (P4). The estrus response, ovulation, conception rate along with serum calcium, inorganic phosphorus, and progesterone level were determined by the standard protocol. RESULTS: From Group III 4 heifers, from Group II 3 heifers, and from Group I and IV (Control) 2 heifers each, exhibited the estrus. The estrus response was recorded as 33.33%, 50.00%, 75.00%, and 33.33% in Group I, Group II, Group III, and Group IV, respectively. In treatment Group III, serum calcium found significantly more (p<0.05) on day 8 post-estrus as compared to other groups at a similar interval. Inorganic phosphorus and progesterone show no significant difference between groups. The ovulation and conception rates are comparatively better in Group III (75%) buffalo heifers than other groups. CONCLUSION: Herbal supplementation of A. marmelos and M. koenigii in combination, as well as M. koenigii alone, were found effective in fertility improvement in delayed pubertal buffalo heifers by increasing ovulation and conception rate.

Oligonucleotides--assembled Au nanorod-assisted cancer photothermal ablation and combination chemotherapy with targeted dual-drug delivery of Doxorubicin and Cisplatin prodrug.

External stimuli responsive dual drugs carrier was synthesized with Au nanorods (NRs) as the platform. On Au NRs, single stranded DNAs were assembled using 5' thiol end. Following this, complementary DNA (cDNA) strands were hybridized. This hybridized double stranded DNA facilitated doxorubicin (Dox) intercalation into the duplexes. The cDNA designed with the 5' amine functional group assisted to tether platinum [Pt(IV)] prodrugs by establishing amide bond with the acid group at the axial ligand. The other axial acid group in Pt(IV) prodrugs was conjugated with the folic acid (FA) to target folate receptors overexpressed in the cancer cells. This targeting vehicle provided remote-controlled delivery of this high toxic cargo cocktail at the tumor site, ensuring extra specificity that can avoid acute toxicity, where release of Dox and Pt(IV) was achieved upon NIR 808 nm diode laser irradiation. The dehybridization set the Dox free to bind the cell nucleus and cellular reductants reduced Pt(IV) to yield toxic Pt(II), becoming an active drug. The in vitro and in vivo studies revealed that this external stimulus responsive combination drug delivery was significantly effective.

Defluoridation from aqueous solutions by nano-alumina: characterization and sorption studies.

The present study was conducted to evaluate the feasibility of nano-alumina (Al(2)O(3)) for fluoride adsorption from aqueous solutions. The nature and morphology of pure and fluoride-sorbed nano-alumina were characterized by SEM with EDX, XRD, and FTIR analysis. Batch adsorption studies were performed as a function of contact time, initial fluoride concentration, temperature, pH and influence of competing anions. Fluoride sorption kinetics was well fitted by pseudo-second-order model. The maximum sorption capacity of nano-alumina for fluoride removal was found to be 14.0 mg g(-1) at 25°C. Maximum fluoride removal occurred at pH 6.15. The fluoride sorption has been well explained using Langmuir isotherm model. Fluoride sorption was mainly influenced by the presence of PO(4)(3-), SO(4)(2-) and CO(3)(2-) ions.

Composting of sugar-cane waste by-products through treatment with microorganisms and subsequent vermicomposting.

The waste by-products of the sugar-cane industry, bagasse (b), pressmud (p) and trash (t) have been subjected to bioinoculation followed by vermicomposting to shorten stabilization time and improve product quality. Press-mud alone and in combination with other by-products of sugar processing industries was pre-decomposed for 30 days by inoculation with combination of Pleurotus sajorcaju, Trichoderma viridae, Aspergillus niger and Pseudomonas striatum. This treatment was followed by vermicomposting for 40 days with the native earthworm, Drawida willsi. The combination of both treatments reduced the overall time required for composting to 20 days and accelerated the degradation process of waste by-products of sugar processing industry, thereby producing a nutrient-enriched compost product useful for sustaining high crop yield, minimizing soil depletion and value added disposal of waste materials.