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Abstract In the current study, Streptomyces levis strain HFM-2 has been isolated from healthy human gut. Streptomyces sp. HFM-2 was identified based on the polyphasic approach that included cultural, morphological, chemotaxonomical, phylogenetic, physiological, and biochemical characteristics. 16S rRNA gene sequence of strain HFM-2 exhibited 100% similarity with Streptomyces levis strain 15423 (T). The EtOAc extract of Streptomyces levis strain HFM-2 showed potential antioxidant activity, along with 69.53 ± 0.19%, 64.76 ± 0.13%, and 84.82 ± 0.21% of scavenging activity for ABTS, DPPH, and superoxide radicals, respectively at 600 µg/mL. The IC50 values i.e. 50% scavenging activity for DPPH, ABTS, and superoxide radicals were achieved at 497.19, 388.13, and 268.79 (µg/mL), respectively. The extract's reducing power and total antioxidant capacity were determined to be 856.83 ± 0.76 and 860.06 ± 0.01 µg AAE/mg of dry extract, respectively. In addition, the EtOAc extract showed protection against DNA damage from oxidative stress caused by Fenton’s reagent, and cytotoxic activity against HeLa cervical cancer, Skin (431) cancer, Ehrlich-Lettre Ascites-E (EAC) carcinoma, and L929 normal cell lines. The IC50 values against HeLa, 431 skin, and EAC carcinoma cell lines were found to be 50.69, 84.07, and 164.91 µg/mL, respectively. The EtOAc extract showed no toxicity towards L929 normal cells. In addition, flow cytometric analysis exhibited reduced mitochondrial membrane potential (MMP), and enhanced levels of reactive oxygen species (ROS). The EtOAc extract was chemically analyzed using GCMS to determine the components executing its bioactivities.

Abstract Mitochondrial impairment, energetic crisis and elevated oxidative stress have been demonstrated to play a pivotal role in the pathological processes of Huntington’s disease (HD). 3-Nitropropionic acid (3-NPA) is a natural neurotoxin that mimics the neurological dysfunctions, mitochondrial impairments and oxidative imbalance of HD. The current investigation was undertaken to demonstrate the neuroprotective effect of 4-(methylthio)butyl isothiocyanate (4-MTBITC) against the 3-NPA induced neurotoxicity in human dopaminergic SH-SY5Y cells. The experimental evidence of oxidative DNA damage by 3-NPA was elucidated by pBR322 DNA nicking assay. In contrast, the 4-MTBITC considerably attenuated the DNA damage, suggesting its free radical scavenging action against 3-NPA and Fenton's reagent. The dose and time-dependent increase of 3-NPA revealed its neurotoxic dose as 0.5 mM after 24 h of treatment of SH-SY5Y cells in MTT assay. In order to determine the optimal dose at which 4-MTBITC protects cell death, the 3-NPA (IC50) induced cells were pretreated with different concentrations of 4-MTBITC for 1 h. The neuroprotective dose of 4-MTBITC against 3-NPA was found to be 0.25 μM. Additionally, the elevated GSH levels in cells treated with 4-MTBITC indicate its propensity to eliminate reactive species generated as a result of 3-NPA-induced mitochondrial dysfunction. Likewise, it was determined through microscopic and flow cytometric experiments that 3-NPA's induced overproduction of reactive species and a decline in mitochondrial membrane potential (MMP) could be efficiently prevented by pre-treating cells with 4-MTBITC. To elucidate the underlying molecular mechanism, the RT-qPCR analysis revealed that the pre-treatment of 4-MTBITC effectively protected neuronal cells against 3-NPA-induced cell death by preventing Caspase-3 activation, Brain-derived neurotrophic factor (BDNF) upregulation, activation of cAMP response element-binding protein (CREB) and Nrf2 induction. Together, our findings lend credence to the idea that pre-treatment with 4-MTBITC reduced 3-NPA-induced neurotoxicity by lowering redox impairment, apoptotic state, and mitochondrial dysfunction. The present work, in conclusion, presented the first proof that the phytoconstituent 4-MTBITC supports the antioxidant system, BDNF/TrkB/CREB signaling, and neuronal survival in dopaminergic SH-SY5Y cells against 3-NPA-induced oxidative deficits.

Abstract Medicinal plants possess range of phytochemicals accountable for their diverse biological activities. Presently, such compounds have been isolated from medicinal plants, characterized and evaluated for their pharmacological potential. In the present study, the efforts have been made to isolate the compound(s) from Grewia tiliaefolia Vahl., plant known for its ameliorative effect on brain related diseases such as anxiety, depression, cognitive disorders and Parkinson’s disease. Plant extract was subjected to isolation of compound(s) using column chromatography and isolated compound was characterized by NMR FTIR and LCMS. The isolated compound was novel with the IUPAC name of the compound is propyl 3-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylate, designated as A-1 and has not been reported before. A-1 was further evaluated for its antioxidant potential using in vitro antioxidant assays (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH assay and reducing power assay, RPA). Also, Acetylcholinesterase (AChE) inhibitory potential of A-1 and extract was analysed. Results showed that A-1 exhibited significantly higher antioxidant activity in both DPPH and RPA assay as compared to plant extract. In case of AChE inhibitory activity again, A-1 has shown significantly higher activity as compared to plant extract. In silico study was conducted to predict its action on proteins playing crucial role in neurological and neurodegenerative disorders such as gamma amino butyric acid (GABA) receptor and glutamate α amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu AMPA) receptor in epilepsy and AChE enzyme in Alzheimer’s diseases. The compound has shown interaction in following order: AChE > GABA receptor > Glu AMPA receptor. Further, molecular dynamic simulations and ADME studies of A-1 and AChE enzyme revealed that A-1 yielded good results in all parameters and hence can relieve Alzheimer’s like symptoms.

Ponds are self-sustaining and self-regulating ecosystems that are a vital part of the hydrological cycle and play a variety of roles in the biosphere. Ponds are diverse, extremely dynamic, and highly productive as they offer various services like harbor biodiversity, tool for combating water scarcity, have roles in pollution mitigation and carbon sequestration. Ponds also offer sustainable solutions to support climate change amelioration and aquatic resource management. However, ponds are the most neglected aquatic ecosystems, despite their huge ecological functions. Thus, ponds are debasing at an alarming rate as a result of increased anthropogenic activities and anthropogenically driven changes in natural processes, wreaking havoc on ecological health and water quality. In this context, the major threats to ponds include the dumping of solid waste, increased urbanization, pollution, encroachment and climate change which have resulted in the deterioration of ponds over the years. Sustainable management and restoration of ponds are crucial as this ecosystem offers a wide array of ecological functions. As a result, this research aims to assess the current state of ponds in India in terms of monitoring, ecological services provided, and the various threats to which they are subjected. Further, the discussions on management and perspective restoration strategies of this substantial ecosystem are also included. Thereby, this study suggests better conservation strategies for restoration, reclamation, and sustainable utilization of ponds.

Phthalates are endocrine disruptors, reported to cause deformities and reproductive damages in animals. Numerous studies reported the presence of phthalates in water samples of rivers, wetlands, and estuaries, while the scenario in case of ponds is different, however they are reported as an integral part of biosphere. In this study, the level of phthalates’ contamination in the water samples collected from the different ponds of Amritsar district for four consecutive seasons in two years was analysed. The maximal level of phthalate contamination was found in samples collected during the monsoon season (July 2015) of first year of sampling followed by post-monsoon (October 2015) and winter season (January 2016). S8 sampling site was found to be the most phthalate contaminated site followed by S1=S11>S2=S9=S4=S5=S7>S6=S3>S10. Benzyl butyl phthalate was most abundant (found in 32% water samples) followed by di-n-butyl and dimethyl phthalate, while diallyl phthalate and diethyl phthalate were not detected. The two main drivers for these seasonal variations were observed to be temperature and precipitation. Hence, this data will be useful to explain the temporal and spatial distributions of phthalates in aquatic ecosystem, as well as to devise cost-effective ways to reduce their ecological footprints.

Objectives: Non melanoma skin cancers are common neoplasms worldwide. In India, squamous cell carcinoma (SCC), is the most prevalent skin disorder and its incidence rises quickly with cumulative exposure to sun. Numerous techniques are available for SCC but reversion and metastasis are common concern that needs effective and safe strategies for its control. With this in view, the study was planned to investigate the activity of Bakuchiol (Bak), traditionally used in various countries for curing skin ailments but its mechanism of action is unexplored. In our study, we explored anti-proliferative, pro-apoptotic and anti-inflammatory potential of Bak toward human squamous carcinoma (A431) cell line. Methods: The pure compound Bak was isolated from the plant Psoralea corylifolia and characterized using NMR, HRMS and FTIR. To explore their bioefficacy, different in vitro assays were performed against A431 cell line. To have molecular insights, RT-qPCR investigation was done to analyzed the expression level of inflammatory markers (TLR 9, IFN β, IL 23, JAK 3 and STAT 3). Results: The results showed the growth inhibitory effect on A431 cells after Bak treatment in dose-dependent way. To understand mode of cell death, cells were initially analyzed under phase-contrast, fluorescence and scanning electron microscope that showed characteristics of apoptosis. Furthermore, cell cycle studies with a flow cytometer were carried out which showed increased level of ROS, reduced MMP and cells arrested at G0/G1 phase in Bak treated cells further strengthening the induction of apoptosis. Moreover, RT-qPCR analysis indicated the downregulation of inflammatory markers in Bak-treated A431 cells that further confirmed its therapeutic role. The molecular docking study also confirmed that Bak has perfect scaffold that can complete the pharmacophoric need for JAK3 kinase inhibition. Conclusion: A critical analysis of results points towards the role of Bak in ameliorating inflammatory markers along with apoptosis induction in A431 cells by regulating the expression level of variable markers.

Abstract Roylea cinerea (D.Don) Baillon an indigenous medicinal plant of Lamiaceae family used for the treatment of several diseases. In the present study, its aqueous (leaves) extract was tested for genoprotective action against atrazine-induced chromosomal aberrations in the root tip cells of Allium cepa. Atrazine is a herbicide of triazine class commonly used to inhibit the growth of broad leaf and grassy weeds. In order to find the concentration of atrazine that exhibits maximum toxicity, its different concentrations (1, 5 and 10 µg/mL) were tested. It was observed that 10 µg/mL concentration was more toxic as it reduced the mitotic index and also increased the chromosomal aberrations. Among all the tested concentrations of aqueous (leaves) extracts (0.25. 0.5, 1.0, 1.5 and 3.0 µg/mL), the3.0 µg/mL concentration in both modes of experiments i.e. pre and post showed a significant reduction in chromosomal aberrations induced by atrazine. To understand the mechanism of protection by plant extract on atrazine-induced chromosomal abnormalities the RT-qPCR studies were conducted to observe the expression of marker genes Cyclin-dependent kinases (CDKs) (CDKA:1, CDKB2:1 and CDKD1:1. For this, the RNA was extracted from root tips treated with extract along with atrazine by TRIzol®. It was observed that aqueous extract of Roylea cinerea (D.Don) Baillon leaves upregulated the CDKs gene expression in both the modes i.e. pre and post treatments. A critical analysis of results indicated that aqueous extract ameliorated the chromosomal aberrations caused by atrazine which may be be due to the increased expression level of CDKs genes.

Abstract Medicinal plants are in use of humankind since ancient and still they are playing an important role in effective and safer natural drug delivery systems. Acacia nilotica (native of Egypt) commonly known as babul belongs to family Fabaceae, widely spread in India, Sri Lanka and Sudan. Being a common and important plant, using in many ways from fodder (shoots and leaves to animals) to dyeing (leather coloration) to medicine (root, bark, leaves, flower, gum, pods). The present study is focused on investigating the natural chemistry and important biological activities of the plant. Employing bioassay guided fractionation coupled with TLC and column chromatography, a pure fraction named AN-10 was isolated from ethyl acetate fraction of crude methanol extract which identified as “Betulin (Lupan-3ß,28-diol)” by Liebermann-Burchard test and structure elucidation by UV–Vis, NMR and MS techniques. A battery of in vitro biological assays for antioxidant, anti-inflammatory and anticancer were performed and betulin showed excellent potential in all assays. It was found that the inhibitory potential in all assays were dose dependent manner and after a range of concentration, the activities get leveled off with no further increase in activity.

The study on Erucin (ER) has gained interest of nutraceutical and pharmaceutical industries because of its anti-cancer properties. Erucin is an isothiocyanate obtained from the seeds of Eruca sativa which possess certain drawbacks such as poor aqueous solubility and bioavailability. Therefore, the present study aimed at developing ER-cubosomes (CUB) by solvent evaporation technique followed by applying Central Composite Design to optimize ER loaded cubosomes. For this purpose, independent variables selected were Monoolein (MO) as lipid and Pluronic-84 (P-84) as a stabilizer whereas dependent variables were particle size, percentage of ER loading and percentage of its entrapment efficiency. The cubosomal nanocarriers exhibited particle size in the range of 26 nm, entrapment efficiency of 99.12 ± 0.04% and drug loading of 3.96 ± 0.0001%. Furthermore, to investigate the antioxidant potential, we checked the effect of ER and ER-CUB by DNA nicking assay, DDPH assay and Phosphomolybdate assay, and results showed significant improvement in antioxidant potential for ER-CUB than ER. Similarly, ER-CUB showed enhanced anticancer activity with a marked reduction in IC50 value than ER in MTT assay. These results suggested that ER-CUB produced notable escalation in antioxidant potential and enhanced anticancer activity than ER.

Porodaedalea pini (Brot.) Murrill. a member of the family Hymenochaetaceae and is a highly admirable traditional mushroom for the treatment of various diseases and disorders. The present study aimed to investigate the microscopic and macroscopic features, phytochemical analysis, and antioxidant potential of different extracts of Porodaedalea pini by using the 2, 2-diphenyl-1-picryhydrazyl, ferric reduction antioxidant potential assay, total antioxidant capacity, total phenolic content, and total flavonoid content. The DNA nicking assay and polyphenolic detection were carried out for the most potent fraction. After the complete study, it was concluded that the methanolic extract has shown higher antioxidant activity as compared to the hexane, ethyl acetate and chloroform extracts. In the plasmid DNA nicking assay, the methanolic extract has shown a concentration-dependent increase in protective activity. The UHPLC profiling of methanol extract for 12 different standard polyphenolic compounds has shown the presence of all compounds except rutin, ellagic acid, and kaempferol. The presence of these polyphenols might be responsible for its antioxidant activity.

Nanoformulation-based combinational drug delivery systems are well known to overcome drug resistance in cancer management. Among them, nanoemulsions are well-known and thermodynamically stable drug delivery systems suitable for carrying hydrophobic drugs and phytoconstituents to tackle drug-resistant cancers. In the present study, we have investigated the effect of paclitaxel in combination with erucin (natural isothiocyanate isolated from the seeds of Eruca sativa) loaded in the frankincense oil-based nanoemulsion formulation. The choice of frankincense oil for the current study was based on reported research investigations stating its magnificient therapeutic potential against breast cancer. Optimized nanoemulsion of paclitaxel (PTX) and erucin (ER) combination (EPNE) provided sustained release and exhibited enhanced cytotoxicity towards human epithelial breast cancer cells (T-47D) as compared to individual ER and PTX. EPNE was further assessed for its antitumor activity in the 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer mice model. EPNE significantly decreased the levels of hepatic and renal parameters along with oxidative stress in breast cancer mice. Furthermore, EPNE also showed decreased levels of inflammatory cytokines TNF-α, IL-6. Histopathological examinations revealed restoration of the tumorous breast to normal tissues in EPNE-treated breast cancer mice. Therefore, EPNE can act as a viable lead and therapeutic option for drug-resistant breast cancer.

Polyacrylamide-carboxymethylcellulose hydrogels lack mechanical strength, uncontrolled rate of degradation, and poor osteogenic properties which can be improved by the incorporation of bioceramics. Strontium and selenium doped bioceramics xSrO.(43-x)CaO.40SiO2.(12-y)P2O5.ySeO3.5MgO (where x = 6 mol%, y = 3 mol%) incorporated polyacrylamide-carboxymethylcellulose hydrogels were synthesized by free-radical polymerization. Above mentioned bioceramics were prepared by the sol-gel route. XRD analysis indicated an increase in crystallinity with the increment of bioceramics content. With the incorporation of bioceramics, the apatite phase formation was observed on 1st day of immersion in simulated body fluid at pH 7.4. Strontium and selenium doped bioceramics impregnated hydrogels exhibited an inhibitory effect on human osteosarcoma MG63 cell line. Moreover, bioceramics incorporated hydrogels provide a conducive environment for MC3T3-E1 osteoblast cell line proliferation, adhesion and also exhibited good alkaline phosphatase activity. Synthesized hydrogels indicated special osteogenic properties and can be potentially utilized in the hard tissue regeneration as well as for recovery of bone cancer patients.

Background: Phyllanthus fraternus is a pantropical weed of family phyllanthaceae, mainly found in northeast India. It has been used in the folklore medicine of Manipur tribe for treating type 2 diabetes. Objective: The present study was commenced to evaluate the anti-diabetic and renoprotective potential of P. fraternus (aerial parts) in alloxan-induced diabetes in rats. Materials and methods: Alloxan (130 mg/kg, ip) was used for the induction of diabetes in adult male wistar rats. Animals with blood glucose level greater than 280 mg/dL were treated once daily for 14 days with various test extracts. The biochemical parameters were measured from serum on the 15th day post-treatment. Necropsy samples harvested from pancreas and kidneys were examined for histopathological changes in these organs. Results: Alloxan-induced diabetes not only caused significant increases in blood glucose, triglycerides, total cholesterol, creatinine and urea levels, but also provoked high oxidative stress in pancreas and kidneys. Profound morphological injuries were observed in islets of Langerhans and kidneys of diabetic animals. Administration of methanol extract (200 and 400 mg/kg) and mother liquor (200 and 400 mg/kg) ameliorate the elevated levels of blood glucose, triglycerides, total cholesterol as well as other biochemical parameters, but highest reduction in blood glucose concentration was observed with the largest dose of ethyl acetate fraction (400 mg/kg) of P. fraternus. Histopathological examination of pancreas and kidneys also exhibited greater protection by treatment with acetate fraction (400 mg/kg). The HPLC analysis showed the presence of four polyphenols such as catechin, gallic acid, caffeic acid and ellagic acid in ethyl acetate fraction of P. fraternus during HPLC analysis. Conclusion: The results suggest that polyphenols present in P. fraternus may be responsible for the anti-diabetic and renoprotective activity in rats. Such protective effects of could be mediated through flavonol-induced anti-oxidant and anti-inflammatory activities in the pancreas and kidneys.

4-(methylthio)butyl isothiocyanate (4-MTBITC) is a hydrolytic product from the plant Eruca sativa Thell. In the present study, we explored the anti-cancer effect of 4-MTBITC against 7,12-dimethylbenz [a] anthracene (DMBA) induced breast cancer. Hypoxic conditions were developed using a single dose of 60 mg/kg DMBA. Hepatic and renal parameters were increased along with antioxidants in cancer-bearing rats which were lowered with the treatment of 4-MTBITC. Further, it inhibited the up-regulation of glycolytic enzymes caused by DMBA. The hypoxia pathway was evaluated using RT-PCR and it was found that the 40 mg/kg doses of 4-MTBITC statistically lowered the expression of HIF-1α. Akt/mTOR signaling pathway was one of the major pathways involved in 4-MTBITC-induced cell growth arrest by western blotting. Amino acid profiling serum-free plasma revealed the downregulation of specific amino acids required for vital components of fast-growing cancer cells. 4-MTBITC reduced the levels of serine, arginine, alanine, asparagines, and glutamic acid. Histological examination also showed neoplastic growth following DMBA doses. 4-MTBITC treated rats showed less infiltration and normal physiology. Our findings for the first time demonstrated the potential therapeutic significance of 4-MTBITC on modulation of glycolytic enzymes and hypoxia pathway in female rats.

Effect of the ethyl acetate seed extracts of two cultivars of broccoli, Brassica oleracea Italica, Palam Samridhi (PS) and Palam Vichitra (PV) on growth, development and nutritional physiology of an economically important insect pest, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) was evaluated by conducting bioassays and nutritional assays. The insect larvae were fed on diets amended with the seed extracts of two cultivars at different concentrations viz. 5, 25, 125, 625 and 3125 ppm and taking water as control. The response of the insect varied with plant varieties. The extracts disrupted the developmental cycle of the pest. Larval mortality and total adult emergence were negatively affected. Larval period and total development period were also negatively influenced. Nutritional indices of S. litura also showed considerable decrease in the RGR, RCR, ECI and ECD as compared to control. The AD values were also enhanced with both the cultivars. The findings of the study revealed a considerable anti-insect potential of the two extracts and needs to be further explored for identification and isolation of bioactive constituents from broccoli for efficient management of the pest population.

Abstract Background Different plant parts of Roylea cinerea (D. Don) Baill. (Lamiaceae), Clematis grata Wall. (Ranunculaceae), Cornus capitata Wall. (Cornaceae) are traditionally used in the management of diabetes and various other diseases. Method The air-dried plant parts from different plants were coarsely powdered and macerated in methanol to obtain their crude extracts. The crude extracts were evaluated for their α-glucosidase inhibitory activity. On the basis of results obtained, the methanolic crude extract of Cornus capitata Wall. was further sequentially fractionated in hexane, diethyl ether, ethyl acetate, n-butanol. Fractions obtained were also evaluated for their α-glucosidase inhibitory potential. The kinetic study was performed using Lineweaver Burk plot to evaluate the type of inhibition. Furthermore, in silico analysis was also carried with active sites of the enzyme (PDB ID: 3WY1) using Autodock4. Results Among all the plant extracts, Cornus capitata extract showed maximum inhibitory activity. Therefore its methanolic extract was further fractionated with the help of different solvents and the maximum activity was shown by the ethyl acetate fraction (IC50 50 μg/mL). Kinetic analysis indicated that Vmax and Km were increased indicating a competitive type of inhibition. In docking studies, among different constituents known in this plant, betulinic acid showed minimum binding energy (− 10.21 kcal/mol). The kinetic and docking studies have strengthened the observation made in the present study regarding the α-glucosidase inhibitory activity of Cornus capitata. Conclusion The study provided partial evidence for pharmacological basis regarding clinical applications of Cornus capitata in the treatment of diabetes suggesting it to be a suitable candidate for the treatment of postprandial hyperglycemia.

Abstract Background The present study was carried out to prepare multi-herbal combination via comparing antioxidant activity and polyphenolic composition of five medicinal plant extracts of Punica granatum L., Putranjiva roxburghii Wall., Swertia chirata Buch.-Ham., Tinospora cordifolia (Willd.) Miers and Trigonella corniculata L. Methods The herbs were individually evaluated using in vitro antioxidant assays and analyzed by HPLC-PDA. The resultant data was examined using principal component analysis (PCA). Further, herbal combination was prepared on the basis of PCA. Results The PCA divided the plants into three groups. The leading or primary group contained P. granatum and P. roxburghii with the highest antioxidant activity strongly correlated with high amount of kaempferol. S. chirata was acknowledged as nourisher herb in one and T. cordifolia and T. corniculata were identified as stimulator herbs in other group. The herbal combination exhibited high antioxidant activity as compared to the individual plants. The combination revealed good antiproliferative efficacy against hepatocellular carcinoma (HepG2) cells with IC50 of 75.864 μg/ml. Conclusions The activity observed in vitro with HepG2 cells suggests that the herbal combination can provide therapeutic activity in vivo in future. The study may provide information regarding precise preparation of multi-herbal formulations using PCA as a tool in pharmaceutical industries.

Diabetes mellitus (DM) is characterized by impaired insulin secretion or utilization, accompanied by hyperglycemia and glycosuria, as well as by a plethora of DM-induced complications, including nephropathy. The purpose of this investigation was 2-fold: to evaluate the antidiabetic potential of zingerone, and its protective effects against DM-induced nephropathy. It has been reported that oxidative stress is associated with DM and cellular nuclear factor (NF)-κB, tumour necrosis factor (TNF)-α and cyclooxygenase (COX)-2 proteins are overexpressed in DM-triggered nephropathy. The levels of these molecular biomarkers and renal functions were measured in zingerone treated diabetic animals. DM was produced in adult male Wistar rats with streptozotocin/nicotinamide. Zingerone (15, 30 and 60 mg/kg) was administered orally once daily to diabetic rats for 6 consecutive weeks. Significant increase in serum glucose, total cholesterol, low density lipoproteins (LDL), urea, uric acid, creatinine, glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) was observed in diabetic rats. All these biochemical parameters were significantly reduced in zingerone treated animals in a dose-dependent manner. There was a marked increase in renal levels of thio-barbituric acid reactive substance (TBARS), superoxide anion generation (SAG) and decrease in reduced glutathione (GSH) in diabetic rats. Whereas zingerone treatment showed statistically significant attenuation of all the oxidative stress parameters, in comparison with untreated counterparts. The overexpressed levels of NF-κB, TNF-α and COX-2 proteins in nephropathic rats were attenuated by zingerone. Histological examination of isolated kidneys confirmed the renoprotective effects of zingerone. Our results suggest that the antidiabetic and renoprotective effects of zingerone seem to be due to the combination of different actions: namely antioxidant and anti-inflammatory properties, inhibition of DM-induced oxidative stress by scavenging free radicals, and down-regulation of NF-κB, TNF-α and COX-2 proteins in the kidney tissue.

Roylea cinerea (D. Don) Baill. (Lamiaceae) is an indigenous plant of Western Himalayas, and has been used by the native population for the treatment of various diseases such as fever, malaria, diabetes, jaundice, and skin ailments. However, limited proportion of pharmacological and toxicological information is available on the bioactive properties of this plant. Therefore, the present study was designed to explore the anti-oxidant and anti-proliferative activities of Roylea cinerea. Methanolic extracts of leaves and stem of Roylea cinerea were prepared through maceration procedure and evaluated for the antioxidant activity using hydrogen/electron donating and hydroxyl radical scavenging assay. Significant antioxidant activity was observed for the methanolic extract of leaves in DPPH (EC50 239 µg/ml), molybdate ion reduction assay (29.73 µg ascorbic acid equivalent/mg dry weight of extract) as well as in plasmid nicking assay. Anti-proliferative and apoptotic activity in L6 rat skeletal muscle cell line was done using in vitro assays, i.e., MTT, Lactate dehydrogenase, mitochondrial membrane potential assay along with phase contrast, confocal, and scanning electron microscopy. The methanol extract of leaves and stem inhibited the growth of L6 cells with IC50 value of 69.41µg/ml and 124.93 µg/ml, respectively, and the lactate dehydrogenase activity was 20.29% and 0.3%, respectively. Cell cycle analysis by flow cytometry exhibited the arrest of cells in G1 and sub-G1 phase by methanolic leaves extract. Furthermore, the results of microscopic and docking analysis strengthened the observation made in the present study regarding the apoptotic mode of cell death in the L6 cell line. The in vitro findings of our studies revealed that the bioactive ingredients present in the methanolic extract of leaves and stem of Roylea cinerea have the anticancer potential. Further in vivo studies are needed to verify the in vitro results.

Abstract Background Oxidative stress in an intracellular environment created by the accumulation of reactive oxygen species results in oxidative damage to biomolecules which ultimately become a hallmark for severe diseases like cancer, aging, diabetes, and cardiovascular and neurodegenerative diseases. Methods Various in vitro assays were employed to assess the antioxidant potential of strain, DNA protective activity was demonstrated using DNA nicking assay and cytotoxicity of the extract was evaluated using MTT assay. Further identification of the compounds was done using UPLC analysis. Results The extract of Streptomyces cellulosae strain TES17 demonstrated significant antioxidant activity with percentage inhibition of 78.47 ± 0.23, 91.08 ± 0.98 and 82.08 ± 0.93 for DPPH, ABTS and superoxide radical assays at 5 mg/mL, respectively. Total antioxidant and reducing power were found to be 76.93 ± 0.76 and 231.96 ± 0.51 mg AAE/100 mg of dry extract, respectively. Moreover, the extract was shown to inhibit lipid peroxidation upto 67.18 ± 1.9% at 5 mg/mL. TPC and TFC measured in the extract was 55 mg GAE/100 mg and 11.17 ± 4.05 mg rutin/100 mg, respectively. The protective nature of the TES17 extract to oxidative stress induced damaged DNA was shown by percentage of supercoiled DNA i.e. Form I was increased from 26.38 to 38.20% at concentrations ranging from 2 μg to 10 μg. TES17 extract also showed the cytotoxic activity against lung cancer cell line with 74.7 ± 1.33% inhibition whereas, limited toxicity was observed against normal cell line with percentage viability of 87.71 ± 6.66 at same concentration (30 μg/mL) tested. The antioxidant capacity of extract was well correlated with its TPC and TFC and this in turn was in keeping with the UPLC analysis which also revealed the presence of phenolic compounds that were responsible for the antioxidant and cytotoxic potential of S. cellulosae strain TES17. Conclusions The present study describes that S. cellulosae strain TES17 isolated from the rhizosphere of Camellia sinensis (tea) plant; produces potent compounds with antioxidant activity, further might be developed into therapeutic drugs to combat oxidative stress.

India is one of the leading suppliers of agrochemicals and has the largest pesticide industry in Asia. Among various Indian states, Punjab is the primary user of pesticides. Presence of pesticide residue in water and food products of Punjab is well documented. The present study was designed to envisage the level of pesticide contamination in pond water of eleven villages of Amritsar district of Punjab, India. A rapid and concurrent method for the identification and quantification of pesticides in water samples was developed and validated. The method validation parameters exhibited high sensitivity of the developed method and the proficiency for the identification and quantification of pesticide residues in water samples. The RP-HPLC method described here • is a novel method which is applicable for simple, rapid and precise detection of pesticides. • 40.02% of water samples were found contaminated with multi-residue pesticides. • carbofuran was the most abundant pesticide which was present in 18.18% samples. Keywords: Quantitative analysis, Multi-residue pesticides, RP-HPLC, Pond water samples

Abstract Cancer, the main cause of human deaths in the modern world is a group of diseases. Anticancer drug discovery is a challenge for scientists because of involvement of multiple survival pathways of cancer cells. An extensive study on the regulation of each step of these pathways may help find a potential cancer target. Up-regulated HIF-1 expression and altered metabolic pathways are two classical characteristics of cancer. Oxygen-dependent (through pVHL, PHDs, calcium-mediated) and independent (through growth factor signaling pathway, mdm2 pathway, HSP90) regulation of HIF-1α leads to angiogenesis, metastasis, and cell survival. The two subunits of HIF-1 regulates in the same fashion through different mechanisms. HIF-1α translation upregulates via mammalian target of rapamycin and mitogen-activated protein kinase signaling pathways, whereas HIF-1β through calmodulin kinase. Further, the stabilized interactions of these two subunits are important for proper functioning. Also, metabolic pathways crucial for the formation of building blocks (pentose phosphate pathway) and energy generation (glycolysis, TCA cycle and catabolism of glutamine) are altered in cancer cells to protect them from oxidative stress and to meet the reduced oxygen and nutrient supply. Up-regulated anaerobic metabolism occurs through enhanced expression of hexokinase, phosphofructokinase, triosephosphate isomerase, glucose 6-phosphate dehydrogenase and down-regulation of aerobic metabolism via pyruvate dehydrogenase kinase and lactate dehydrogenase which compensate energy requirements along with high glucose intake. Controlled expression of these two pathways through their common intermediate may serve as potent cancer target in future.

Objective: Environmental pollutants are responsible for inducing a number of biochemical and physical changes in the various organs of an organism. The most potent pollutants is7,12-dimethylbenz(α)anthracene (DMBA) (a genotoxic carcinogen), a polyaromatic hydrocarbon. It is known to induce a number of genetic changes including the formation of DNA adducts. These genotypic changes in turn are responsible for inducing microstructural changes in the vital organs viz. kidneys, stomach and lungs of an organism. These changes in turn cause biochemical alterations in an animal and hence alter the normal functioning. Synthetic drugs provide a sigh of relief but a large number of side effects in addition to the growing resistance has made it necessary to find an efficient alternative. Plant secondary metabolites, especially glucosinolate hydrolytic products, are known for their high bioprotective activity. The current study was therefore designed to analyze the bioprotective role of erucin against DMBA-induced microstructural changes in kidneys, lungs and stomach of male Wistar rats using histological analysis. Material and Method: The bioprotective efficacy of erucin was evaluated in male Wistar rats against DMBA induced microstructural changes. The rats were divided into five groups where group I was untreated control, group II was DMBA treated and group III-V were treatment (DMBA + erucin) groups. Results: Erucin was able to protect the rats against DMBA-induced histopathological changes in the lungs and stomach. No changes were observed in the kidney following treatment with DMBA or erucin. Conclusion: Erucin has bioprotective activity against genotoxic carcinogen.

In the current investigation, we studied role of Rhododendron leaf extract in Vigna radiata grown under chromium metal stress. We observed that seed treatment with Rhododendron leaf extract resulted in the recuperation of seedling growth under chromium toxicity. Seed treatment with Rhododendron leaf extract significantly improved the contents of anthocyanin and xanthophyll pigments under stress. The antioxidative defense system triggered after Rhododendron extract treatment, resulting in the increased actions of antioxidant enzymes. Oxidative stress induced by the assembly of reactive oxygen species was reduced after Rhododendron extract treatment under chromium toxicity as indicated by the enhanced contents of non-enzymatic antioxidants, namely ascorbic acid, tocopherol, and glutathione. Furthermore, Rhododendron leaf extract treatment under chromium metal stress also encouraged the biosynthesis of organic acids, polyphenols, as well as amino acids in Vigna radiata. Statistical analysis of the data with multiple linear regression also supported that Rhododendron leaf extract can effectively ease chromium metal-induced phytotoxicity in Vigna radiata.

ABSTRACT Oxidative stress, being the main cause of most of the human diseases, has always been the highlight of research worldwide. This stress can be overcome by administration of natural polyphenols. The Acacia catechu Willd. has many refrences available in Ayurveda as important disease curative plant. Its leaves are investigated for ameliorating oxidative stress in present work. Leaves of A. catechu were extracted with 80% methanol to get methanol extract (AME). It was assessed for antioxidant activity using DPPH, ABTS, CUPRAC, ferric ion reducing, superoxide scavenging and peroxyl radical scavenging assays. DNA protective activity was also investigated using plasmid nicking assay. Further, antiproliferative activity was determined using MTT assay in various human cancer cell lines. The quantification of polyphenols was done by UHPLC analysis. Results confirmed that polyphenols of A. catechu were successful in normalizing oxidative stress. AME was found to be most effective in scavenging ABTS radicals while least effective in scavenging ferric ions. UHPLC analysis showed abundance of ellagic acid, rutin and quercetin in AME. Further, AME showed maximum antiproliferative activity against Hep G2 cancer cells. It is concluded that the polyphenols from A. catechu effectively remediates oxidative stress and hence can be used in curing numerous dreadful diseases.

3β, hydroxy-lup-20(29)-en-28-oic acid (Betulinic acid), a pentacyclic lupane-type triterpene has diverse pharmacological functions both in vitro and in vivo. The present study focuses its protective effect on polycyclic aromatic hydrocarbon (7,12- Dimethylbenz(a)anthracene or DMBA) induced alterations in membrane bound ATPases, detoxification enzymes and antioxidant enzymes in stomach and lungs of female Sprague Dawley rats. Healthy female Sprague Dawley rats were randomly assorted into six groups and the treatments were given orally for 7 weeks on alternate days. It was observed that betulinic acid facilitated the downregulation of elevated membrane bound ATPases (Na+/K+- ATPase, Ca2+-ATPase and Mg2+-ATPase) in DMBA administered rats. Likewise, the detoxification enzymes as well as antioxidant enzymes were modulated to normalcy in rats. Overall, betulinic acid was seen to be effective modulator of DMBA induced alterations in biochemical parameters.

Background: Several diseases are caused in the body due to oxidative stress of free radicals. The objectives of the present study were to investigate the antioxidant activity of Araucaria cunninghamii Aiton ex D. Don (Araucariaceae) leaf extract. The dried leaves of Araucaria cunninghamii Aiton ex D. Don (Araucariaceae) were extracted with 80% methanol. The antioxidant activity of the extract was predicted through in vitro model systems such as 1,1-diphenyl-2-picryl hydrazyl (DPPH), reducing power and nitric oxide scavenging assays. The total phenolic, flavonoid and tannin content of the extract were also estimated in order to draw the correlation with their bioactivities. The extract was also investigated for several polyphenolic compounds using High-performance liquid chromatography (HPLC). Results: The antioxidant activity of extract was found to be excellent in all the three assays. A positive correlation between the antioxidant activity and phenolic content was observed. HPLC analysis identified the presence of Gallic acid, Catechin, Chlorogenic acid, Epicatechin, Caffeic acid, Umbelliferone, Ellagic acid, Quercetin and Kaempferol in the methanol leaf extract of Araucaria cunninghamii Aiton ex D. Don. Conclusions: The results of the present study point towards the fact that Araucaria cunninghamii Aiton ex D. Don leaves possess good antioxidant potential. The strong antioxidant activity can be correlated with the polyphenolic compounds present in the leaves.

In this era of urbanization and environmental pollution, antioxidants and antimutagens derived from plants are promising safeguards for human health. In the current investigation, we analyzed the antioxidant and antimutagenic effects of the hexane, chloroform, and ethyl acetate fractions of Rhododendron arboreum Sm. leaves and determined their chemical composition. The different fractions inhibited lipid peroxidation, repressed the production of nitric oxide radicals, and prevented deoxyribose degradation. The antimutagenic activity of the leaf fractions was analyzed against 4-nitro-O-phenylenediamine, sodium azide and 2-aminofluorene mutagens in two test strains (TA-98 and TA-100) of Salmonella typhimurium. The experiment was conducted using pre- and co-incubation modes. The best results were obtained in the pre-incubation mode, and against indirect acting mutagen. The presence of a number of bioactive constituents was confirmed in the different fractions by GC-MS analysis. The study reveals the strong antioxidant and antimutagenic activity of R. arboreum leaves. We propose that those activities of R. arboreum might correspond to the combined effect of the phytochemicals identified by GC-MS analysis. To the best of our knowledge, this is the first report on the antimutagenic activity of R. arboreum leaves.

BACKGROUND: Liver is the primary metabolizing site of body and is prone to damage by exogenous as well as endogenous intoxicants. Polycyclic aromatic hydrocarbons such as 7, 12- dimethylbenz(α)anthracene (DMBA) is an exogenous hepatotoxin, which is well known for modulating phase I, II and anti-oxidative enzymes of liver. Plants contain plethora of polyphenolic compounds which can reverse the damaging effect of various xenobiotics. The present study investigated protective role of the ethyl acetate fraction of Acacia catechu Willd. (EAF) against DMBA induced alteration in hepatic metabolizing and anti-oxidative enzymes in rats. METHODOLOGY AND PRINCIPAL FINDINGS: The rats were subjected to hepatic damage by treating with DMBA for 7 weeks on alternative days and treatment schedule was terminated at the end of 14 weeks. The rats were euthanized at the end of protocol and livers were homogenized. The liver homogenates were used to analyse phase I (NADPH-cytochrome P450 reducatse, NADH-cytochrome b5 reductase, cytochrome P420, cytochrome b5), phase II (glutathione-S-transferase, DT diaphorase and γ-Glutamyl transpeptidase) and antioxidative enzymes (catalase, superoxide dismutase, ascorbate peroxidase, glutathione reductase, guiacol peroxidase and lactate dehydrogenase). Furthermore, other oxidative stress parameters (thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes and reduced glutathione) and liver marker enzymes (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and alkaline phosphatase) were also studied. The DMBA induced significant changes in activity of hepatic enzymes that was reversed by treatment with three dose levels of EAF. CONCLUSION: It is concluded that EAF affords hepato-protection against DMBA in rats through modulation of phase I, II and anti-oxidative enzymes.

Titanium complexes have been synthesized by the reaction between titanium tetrachloride (TiCl4), respective bidentate ligand [4,4′ -dimethoxy-2,2′ -bipyridine (bpome), 6,6′-dimethyl-2,2′-bipyridine (dpme), 1,2-diaminocyclohexane (dach), 1,10-phenanthroline (phen), and benzoylacetone (bzac)], and adamantylamine (ada) in 1 : 2 : 2 molar ratios, respectively. The structure of synthesized complexes was confirmed using elemental analysis, FTIR, UV-visible, 1H NMR, and mass spectrometry techniques. The nanocrystalline nature of complexes was confirmed by powder XRD study. The complexes were evaluated for cytotoxic potential in HeLa (cervical), C6 (glioma), and CHO (Chinese hamster ovarian) cell lines. The complex E was found to be more effective cytotoxic agent against HeLa cell line with an IC50 value of 4.06 µM. Furthermore, the effect of synthesized complexes was studied on different stages of the cell cycle in CHO cells. All complexes exhibited the dose dependent increase in cytotoxicity. The results have shown an increase in sub-G0 population with increase in concentration which is an indicative measure of apoptosis.

The toxicity induced by 7, 12-dimethylbenz(α)anthracene (DMBA) has been widely delineated by a number of researchers. This potent chemical damages many internal organs including liver, by inducing the production of reactive oxygen species, DNA-adduct formation and affecting the activities of phase I, II, antioxidant and serum enzymes. Glucosinolate hydrolytic products like isothiocyanates (ITCs) are well known for inhibiting the DNA-adduct formation and modulating phase I, II enzymes. Sulforaphane is ITC, currently under phase trials, is readily metabolized and inter-converted into erucin upon ingestion. We isolated erucin from Eruca sativa (Mill.) Thell. evaluated its hepatoprotective role in DMBA induced toxicity in male wistar rats. The rats were subjected to hepatic damage by five day regular intraperitoneal doses of DMBA. At the end of the protocol, the rats were euthanized, their blood was collected and livers were processed. The liver homogenate was analyzed for phase I (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, cytochrome P450, cytochrome P420 and cytochrome b5), phase II (DT diaphorase, glutathione-S-transferase and γ-glutamyl transpeptidase) and antioxidant enzymes (superoxide dismutase, catalase, guaiacol peroxidise, ascorbate peroxidise, glutathione reductase and lactate dehydrogenase). The level of thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes and reduced glutathione in the liver homogenate was also analyzed. The serum was also analyzed for markers indicating hepatic damage (alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, direct bilirubin and total bilirubin). Erucin provided significant protection against DMBA induced damage by modulating the phase I, II and antioxidant enzymes. The histological evaluation of liver tissue was also conducted, which showed the hepatoprotective role of erucin.