Evaluation of chronic toxicological profile of herbo-mineral formulations: Shwaskas Chintamani Rasa and its marketed formulation namely Kas Shwas Hari Rasa.

BACKGROUND: Shwaskas Chintamani Rasa (SKC) and Kas Shwas Hari Rasa (KSH) are the Ayurvedic herbo-mineral formulations. These Ayurvedic formulations contain heavy metals which is the reason of concern and might bring up the safety issue. OBJECTIVE: This research article is aimed to study chronic toxicity of SKC and KSH for safety aspect in Wistar rats. MATERIAL AND METHOD: A study group of 220 healthy rats were divided into six groups. These rats were administered with SKC and KSH formulations where both the formulations were administered for 180 consecutive days. SKC was administered at doses of 58 mg/kg (equivalent to therapeutic dose i.e. TD), 145 mg/kg (2.5 TD), 290 mg/kg (5 TD) and KSH was administered at dose of 58 mg/kg (TD). According to OECD guideline 452, the effect of these formulations was examined on hematology, serum biochemistry and histopathology of various organs. RESULTS: Both the formulations did not produce any signs or symptoms of treatment related toxicity in both male and female Wistar rats at therapeutic dose (TD), 2.5 times TD and 5 times TD. CONCLUSION: Based on these findings, the NOAEL (No observed adverse effect level) for test formulations SKC and KSH tablets in male and female wistar rats concluded to be preclinically safe.

Body mass-normalized moderate dose of dietary nitrate intake improves endothelial function and walking capacity in patients with peripheral artery disease.

Peripheral artery disease (PAD) is characterized by the accumulation of atherosclerotic plaques in the lower extremity conduit arteries, which impairs blood flow and walking capacity. Dietary nitrate has been used to reduce blood pressure (BP) and improve walking capacity in PAD. However, a standardized dose for PAD has not been determined. Therefore, we sought to determine the effects of a body mass-normalized moderate dose of nitrate (0.11 mmol nitrate/kg) as beetroot juice on serum nitrate/nitrite, vascular function, walking capacity, and tissue oxygen utilization capacity in patients with PAD. A total of 11 patients with PAD received either nitrate supplement or placebo in a randomized crossover design. Total serum nitrate/nitrite, resting BP, brachial and popliteal artery endothelial function (flow-mediated dilation, FMD), arterial stiffness (pulse-wave velocity, PWV), augmentation index (AIx), maximal walking distance and time, claudication onset time, and skeletal muscle oxygen utilization were measured pre- and postnitrate and placebo intake. There were significant group × time interactions (P < 0.05) for serum nitrate/nitrite, FMD, BP, walking distance and time, and skeletal muscle oxygen utilization. The nitrate group showed significantly increased serum nitrate/nitrite (Δ1.32 µM), increased brachial and popliteal FMD (Δ1.3% and Δ1.7%, respectively), reduced peripheral and central systolic BP (Δ-4.7 mmHg and Δ-8.2 mmHg, respectively), increased maximal walking distance (Δ92.7 m) and time (Δ56.3 s), and reduced deoxygenated hemoglobin during walking. There were no changes in PWV, AIx, or claudication (P > 0.05). These results indicate that a body-mass normalized moderate dose of nitrate may be effective and safe for reducing BP, improving endothelial function, and improving walking capacity in patients with PAD.

Therapeutic Effects of Curcumol in Several Diseases; An Overview.

Curcumae Rhizoma, also known as Ezhu is a traditional Chinese medicine that has been used for many centuries against several diseases. The rhizome of the plant is composed of curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin), and essential volatile oils including curcumol, curdione, and germacrone. While curcuminoids have been extensively studied for their antimicrobial, antioxidant, anti-inflammatory and anticancer properties, the therapeutic efficacy of curcumol is still emerging. Recent studies have shown anticancer properties of curcumol against multiple solid tumors such as breast, colorectal, head and neck, and lung adenocarcinomas. The underlying anti-tumor mechanisms revealed inhibition of several signaling pathways (NF-κB, MAPK, PI-3K/AKT, and GSK-3ß) associated with cell proliferation, survival, anti-apoptosis, invasion and metastasis. Besides curcumol, extracts from the Curcumae Rhizoma roots possess many other terpenoids such as ß-elemene, δ-elemene, germacrone, furanodiene and furanodienone with known anticancer properties. In this review, we comprehensively focused on the composition of Curcumae Rhizoma essential oils, their structure, isolation and therapeutic uses of curcumol to aid in the improvement and development of novel drugs with minimal cytotoxicity, enhanced efficacy, and less cost.

Combined anthocyanins and bromelain supplement improves endothelial function and skeletal muscle oxygenation status in adults: a double-blind placebo-controlled randomised crossover clinical trial.

Anthocyanins and bromelain have gained significant attention due to their antioxidative and anti-inflammatory properties. Both have been shown to improve endothelial function, blood pressure (BP) and oxygen utility capacity in humans; however, the combination of these two and the impacts on endothelial function, BP, total antioxidant capacity (TAC) and oxygen utility capacity have not been previously investigated. The purpose of this study was to investigate the impacts of a combined anthocyanins and bromelain supplement (BE) on endothelial function, BP, TAC, oxygen utility capacity and fatigability in healthy adults. Healthy adults (n 18, age 24 (sd 4) years) received BE or placebo in a randomised crossover design. Brachial artery flow-mediated dilation (FMD), BP, TAC, resting heart rate, oxygen utility capacity and fatigability were measured pre- and post-BE and placebo intake. The BE group showed significantly increased FMD, reduced systolic BP and improved oxygen utility capacity compared with the placebo group (P < 0·05). Tissue saturation and oxygenated Hb significantly increased following BE intake, while deoxygenated Hb significantly decreased (P < 0·05) during exercise. Additionally, TAC was significantly increased following BE intake (P < 0·05). There were no significant differences for resting heart rate, diastolic BP or fatigability index. These results suggest that BE intake is an effective nutritional therapy for improving endothelial function, BP, TAC and oxygen utility capacity, which may be beneficial to support vascular health in humans.

Core/shell nanoassembly of amphiphilic naproxen-polyethylene glycol: synthesis, characterisation and evaluation as drug delivery system.

Small molecule-based amphiphiles self-assemble into nanostructures (micelles) in aqueous medium which are currently being explored as novel drug delivery systems. Here, naproxen-polyethylene glycol (N-PEG), a small molecule-derived amphiphile, has been synthesised, characterised and evaluated as hydrophobic drug carrier. 1H, 13C Nuclear magnetic resonance (NMR), mass spectrometry (MS) and Fourier-transform infrared spectroscopy (FTIR) confirmed the formation of N-PEG and dynamic light scattering (DLS) revealed the formation of nano-sized structures of ∼228 nm. Transmission electron microscope (TEM) analysis showed aggregation behaviour of the structures with average size of ∼230 nm. Biodegradability aspect of the micellar-structured N-PEG was demonstrated by lipase-mediated degradation studies using DLS and TEM. High encapsulation efficiency followed by release in a sustained manner of a well-known anticancer drug, doxorubicin, demonstrated the feasibility of the new drug delivery system. These results advocate the promising potential of N-PEG micelles as efficient drug delivery system for specific delivery to cancerous cells in vitro and in vivo.

Consumption patterns of wild edibles by the Vasavas: a case study from Gujarat, India.

BACKGROUND: Wild edibles continue to be a significant contributor to the global food basket in much of the developing world. A consensus has now been formed that information on wild edibles is an important part of ethnobotanical knowledge and hence elucidating region-specific patterns of habitat management and consumption assists policy making with regard to natural conservation, human nutrition, and human health. Using an original data set from Gujarat, India, the present research aims to document the collective knowledge of wild edibles possessed by the local Vasava tribe, as well as the habitat usage and consumption trends of these species. METHODS: Data were collected using three approaches: key informant interviews to record the local knowledge of wild edibles and methods of collection, village group discussions to quantify past and present consumption trends, and expert interviews to elucidate the reasons for changing consumption patterns. RESULTS: Through key informant interviews, 90 species of wild edibles from 46 botanical families were identified along with their Vasavi names, plant parts utilized, habitats, and cooking methods. Of these, 60 species were also used medicinally and 15 carried economic value. Different habitats were preferred for collection at different times of the year. Village group discussions unanimously concluded that the consumption of wild edibles has significantly reduced over time. Expert interviews identified the decreased availability of these species in their natural habitats as the most important reason for their reduced consumption. CONCLUSION: The present study has demonstrated that the Vasavas' collective knowledge of wild edibles is vast and that these species contribute to their dietary diversity throughout the year. The finding of the present study, namely that anthropogenically managed habitats were often preferred over natural environments for the collection of wild edibles, suggests that conservation efforts should be extended beyond wild and human-uninhabited landscapes.

Cyclocondensation of arylhydrazines with 1,3-bis(het)arylmonothio-1,3-diketones and 1,3-bis(het)aryl-3-(methylthio)-2-propenones: synthesis of 1-aryl-3,5-bis(het)arylpyrazoles with complementary regioselectivity.

Two efficient highly regioselective routes for the synthesis of unsymmetrically substituted 1-aryl-3,5-bis(het)arylpyrazoles with complementary regioselectivity starting from active methylene ketones have been reported. In the first protocol, the newly synthesized 1,3-bis(het)aryl-monothio-1,3-diketone precursors (prepared by condensation of active methylene ketones with het(aryl) dithioesters in the presence of sodium hydride) were reacted with arylhydrazines in refluxing ethanol under neutral conditions, furnishing 1-aryl-3,5-bis(het)arylpyrazoles 7, in which the het(aryl) moiety attached to the thiocarbonyl group of monothio-1,3-diketones is installed at the 3-position. In the second method, the corresponding 3-(methylthio)-1,3-bis(het)aryl-2-propenones (prepared in situ by base-induced alkylation of 1,3-monothiodiketones) were condensed with arylhydrazines in the presence of potassium tert-butoxide in refluxing tert-butyl alcohol, yielding 1-aryl-3,5-bis(het)arylpyrazoles 9 with complementary regioselectivity (method A). The efficiency of this protocol was further improved by developing a one-pot, three-component procedure for the synthesis of pyrazoles 9, directly from active methylene ketones, by reacting in situ generated 3-(methylthio)-1,3-bis(het)aryl-2-propenones with arylhydrazines in the presence of sodium hydride (instead of potassium tert-butoxide as base). The structures and regiochemistry of newly synthesized pyrazoles were confirmed from their spectral and analytical data along with X-ray crystallographic data of three pairs of regioisomers.

Simultaneous production of alkaline lipase and protease by antibiotic and heavy metal tolerant Pseudomonas aeruginosa.

An efficient bacterial strain capable of simultaneous production of lipase and protease in a single production medium was isolated. Thirty six bacterial strains, isolated from diverse habitats, were screened for their lipolytic and proteolytic activity. Of these, only one bacterial strain was found to be lipase and protease producer. The 16S rDNA sequencing and phylogenetic analyses revealed that strain (NSD-09) was in close identity to Pseudomonas aeruginosa. The maximum lipase (221.4 U/ml) and protease (187.9 U/ml) activities were obtained after 28 and 24 h of incubation, respectively at pH 9.0 and 37 °C. Castor oil and wheat bran were found to be the best substrate for lipase and protease production, respectively. The strain also exhibited high tolerance to lead (1450 µg/ml) and chromium (1000 µg/ml) in agar plates. It also showed tolerance to other heavy metals, such as Co(+2) , Zn(+2) , Hg(+2) , Ni(+2) and Cd(+2) . Therefore, this strain has scope for tailing bioremediation. Presumably, this is the first attempt on P. aeruginosa to explore its potential for both industrial and environmental applications.

A novel thermotolerant Pediococcus acidilactici B-25 strain for color, COD, and BOD reduction of distillery effluent for end use applications.

The present study was aimed to characterize physico-chemical and microbial population of distillery effluent and isolate a novel thermotolerant bacterium for color, COD, and BOD reduction of spentwash. The level of alkalinity, TSS, DO, COD, BOD, TN, ammonical nitrogen, nitrate nitrogen, phosphorous, potassium, chloride, and calcium of spentwash (SW), bioreactor effluent (BE), and secondary treated effluent (STE) were well above the permissible limits. The level of color, TS, and TDS were under the permissible limits for STE but not for SW and BE. The microbial population was higher in BE. The results revealed that effluent was highly polluted and require suitable treatment before discharge. A novel thermotolerant bacterium, identified as Pediococcus acidilactici, was isolated which exhibited maximum 79 % decolorization, 85 % COD, and 94 % BOD reduction at 45 °C using 0.1 %, glucose; 0.1 %, peptone; 0.05 %, MgSO4; 0.05 %, K2HPO4; pH 6.0 within 24 h under static condition. The ability of this strain to decolorize melanoidin at minimum carbon and nitrogen supplementation warrants its possible application for effluent treatment at industrial level. In addition, it is first instance when melanoidin decolorization was reported by P. acidilactici. This study could be an approach towards control of environmental pollution and health hazards of people in and around the effluent distillery unit.

Developmental strategies for sustainable ecosystem on mine spoil dumps: a case of study.

An important goal of ecological rehabilitation is to accelerate natural successional processes to increase biological productivity, soil fertility and biotic control over biogeochemical fluxes within the recovering ecosystems. A new approach called Microbe Assisted Green Technology (MAGT) is an integrated biotechnological approach developed at National Environmental Engineering Research Institute (NEERI) through exhaustive laboratory as well as field studies and serve as a model for land reclamation and development of lush green vegetation on mine overburdens. One year old seedlings of native tree species were planted on 6.3 ha area of manganese mine overburden at Gumgaon under Manganese Ore India Ltd., Maharashtra, India. Continuous efforts resulted in nutrient rich soil with high N, P, K and organic carbon; well developed biodiversity, including bacteria, fungi, higher plants (more than 350 species) and different classes of animals. Planted trees accumulated 698 t ha( - 1) above ground biomass and 143 t ha( - 1) below ground mass. This was achieved in 18 years by MAGT, which otherwise takes hundreds of years.

Diallylsulfide attenuates asbestos-induced genotoxicity.

It is well known that asbestos fibers induced genotoxicity is mediated by reactive oxygen species (ROS) and insufficient endogenous antioxidant protection. Asbestos exposure can result in ROS generation in two different ways: (a) by catalyzation of Fe(2+), which is present in asbestos fibers, and (b) via oxidative bursts during phagocytosis of the fibers. On the other hand, it has been discussed that the physical presence of the fibres may mechanically influence the normal segregation of chromosomes during mitosis resulting in the induction of micronuclei in late ana/telophase, and aneuploidy. Glutathione and the glutathione redox system protect cells from the oxidative damage after exposure to xenobiotics. Glutathione depletion occurs during oxidative stress conditions and it is observed that supplementation of a precursor of glutathione and other sulphur containing compounds results in reduced toxicity. In the present study, diallyl sulfide (DAS), a lipid soluble allyl sulphur compound present in fresh extracts of garlic was evaluated for its protective effects. The micronucleus (MN) assay was performed in human mesothelial cells (HMC) exposed to 1 microg/cm(2) of crocidolite and chrysotile. Simultaneously, the cells were treated with 5 and 10 microM DAS, incubated for 48 and 66 h. Asbestos fibers induced significant genetic damage in HMC. The assay revealed a significant reduction in MN induction after treatment of cells with 5 microM but not with 10 microM DAS in mesothelial cells. The study revealed that at appropriate concentrations DAS protects mesothlelial cells against asbestos induced genotoxicity.