Protective Effect of Borassus flabellifer Haustorium Extract against Alkoxyl Radical-Induced Cytotoxicity by Improving Glutathione Metabolism by Modulating Nrf2/Haeme Oxygenase-1 Expression.

AIM: The study was aimed to assess the ability of Borassus flabellifer haustorium methanolic extract (BHE) on de novo glutathione biosynthesis in normal and pro-oxidant exposed cells via Nuclear factor erythroid 2-related factor 2 (Nrf2) and haeme oxygenase-1 (HO1) signaling in 2,2'-Azobis(2-methylpropionamidine) di-hydrochloride (AAPH) induced cytotoxicity in normal intestinal epithelial cells (IEC-6 cells). METHODS: The in vitro antioxidant activity was determined in terms of radical scavenging and ex vivo hemolysis. The cytoprotective effect was studied using AAP H as the alkoxyl radical inducer in IEC-6 cell model. The mechanistic basis of protection is determined by Nrf2/HO1 expression using qPCR. RESULTS: In vitro screening observed DPPH, hydrogen peroxide and ABTS radical scavenging activity for the BHE; further, BHE also protected the oxidative hemolysis in the erythrocytes induced by AAPH. In IEC-6 cells, AAPH treatment significantly reduced the cell viability (p < 0.001) by inducing lipid peroxidation. Further, there observed a significant reduction in the activities of enzymes involved in the de novo glutathione biosynthesis (p < 0.01) and glutathione reductase in these cells. However, pretreatment with BHE (10, 25 and 50 µg/mL) dose-dependently protected from the cytotoxicity of AAPH-derived alkoxyl radicals (p < 0.05); besides, the de novo glutathione biosynthesis and regeneration of GSH from oxidized form was also increased in these cells. In corroboration with the biochemical parameters, the Nrf2/HO1 expression was upregulated by the BHE pretreatment concomitantly reducing the cellular lipid peroxidation products. The improvement glutathione biosynthesis was also observed in BHE alone treated cells. CONCLUSION: The study indicated the potential of methanolic extract of Borassus flabellifer haustorium in enhancing the de novo glutathione biosynthesis in normal and pro-oxidant exposed cells by Nrf2/HO1 dependent manner, concomitantly mitigating the toxicity of AAPH-derived alkoxyl radicals in intestinal epithelial cells.

Alteration in Cngb1 Expression upon Maternal Immune Activation in a Mouse Model and Its Possible Association with Schizophrenia Susceptibility.

OBJECTIVE: The cyclic nucleotide-gated channel (Cng) regulates synaptic efficacy in brain neurons by modulating Ca2＋ levels in response to changes in cyclic nucleotide concentrations. This study investigated whether the expression of Cng channel, cyclic nucleotide-gated channel subunit beta 1 (Cngb1) exhibited any relationship with the pathophysiology of schizophrenia in an animal model and whether genetic polymorphisms of the human gene were associated with the progression of schizophrenia in a Korean population. METHODS: We investigated whether Cngb1 expression was related to psychiatric disorders in a mouse model of schizophrenia induced by maternal immune activation. A case-control study was conducted of 275 schizophrenia patients and 410 controls with single-nucleotide polymorphisms (SNPs) in the 5'-near region of CNGB1. RESULTS: Cngb1 expression was decreased in the prefrontal cortex in the mouse model. Furthermore, the genotype frequency of a SNP (rs3756314) of CNGB1 was associated with the risk of schizophrenia. CONCLUSION: Our results suggest that CNGB1 might be associated with schizophrenia susceptibility and maternal immune activation. Consequently, it is hypothesized that CNGB1 may be involved in the pathophysiology of schizophrenia.

Effect of Ginseng Extracts on the Improvement of Osteopathic and Arthritis Symptoms in Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Ginsenosides are active compounds that are beneficial to bone metabolism and have anti-osteoporosis properties. However, very few clinical investigations have investigated the effect of ginseng extract (GE) on bone metabolism. This study aims to determine the effect of GE on improving bone metabolism and arthritis symptoms in postmenopausal women with osteopenia. A 12-week randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 90 subjects were randomly divided into a placebo group, GE 1 g group, and GE 3 g group for 12 weeks based on the random 1:1:1 assignment to these three groups. The primary outcome is represented by bone metabolism indices consisting of serum osteocalcin (OC), urine deoxypyridinoline (DPD), and DPD/OC measurements. Secondary outcomes were serum CTX, NTX, Ca, P, BsALP, P1NP, OC/CTX ratio, and WOMAC index. The GE 3 g group had a significantly increased serum OC concentration. Similarly, the GE 3 g group showed a significant decrease in the DPD/OC ratio, representing bone resorption and bone formation. Moreover, among all the groups, the GE 3 g group demonstrated appreciable improvements in the WOMAC index scores. In women with osteopenia, intake of 3 g of GE per day over 12 weeks notably improved the knee arthritis symptoms with improvements in the OC concentration and ratios of bone formation indices like DPD/OC.

Paecilomyces formosus MD12, a Biocontrol Agent to Treat Meloidogyne incognita on Brinjal in Green House.

The present study was carried out to analyze the potential of fungi isolated from the rhizosphere of soybean, brinjal, tomato, and potato plants. The density of fungi varied in the pot soil and rhizosphere after Paecilomyces formosus MD12 treatment. The P. formosus MD12 population was 6.3 ± 0.13 × 104 CFU g-1 in the pot planted with brinjal, and the population increased in the rhizosphere (6.72 ± 0.41 × 104 CFU g-1). P. formosus MD12 was cultured in the production medium, and the supernatant was used for egg inhibition studies on a root-knot nematode parasite, Meloidogyne incognita. It was revealed that maximum egg inhibition (94.7 ± 6.2%) was obtained at 100% concentration of extract. The culture supernatant from P. formosus MD12 affected the development of M. incognita juvenile, and the mortality rate was maximum after 96 h (95 ± 6%). Mortality was reduced when treated with 25%, 50%, and 75% supernatant. At 1 × 107 mL-1 of spore suspension, we found reductions of 71.6 ± 3.3% nematode populations in the soil, 60.7 ± 2.2% from the root, and 63.6 ± 2.4% egg mass compared with the control in the pot experiment. The culture supernatant applied at the 10% level showed a maximum mean reduction of the nematode population in roots (72.4 ± 2.2%), soil (77.9 ± 2.5%), and egg masses (73.2 ± 1.5%), respectively. The presence of P. formosus MD12 in a soil environment could antagonize nematode parasites and improve soil amendment. The P. formosus MD12 strain showed good biocontrol ability against the root-knot nematode, M. incognita, under in vitro and green house experimental condition.

Mango ginger (Curcuma amada Roxb.) rhizome essential oils as source of environmental friendly biocides: Comparison of the chemical composition, antibacterial, insecticidal and larvicidal properties of essential oils extracted by different methods.

The essential oil isolated from plants is widely utilized as eco-friendly biocides and antibacterial agents. Curcuma amada, commonly known as mango ginger, is well-known for its applications in the food and aromatics industry for its significant mango-like aroma. The present study compared the different C. amada essential oils prepared by hydrodistillation (CHD), steam distillation (CSD), microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE), for their chemical composition, antibacterial, larvicidal and insecticidal properties. GC/MS analysis indicated the presence of compounds including α-pinene, ß-myrcene, p-cymene, (Z)-ß-ocimene, Camphor, linalyl acetate, safrole, ar-curcumene, and ß-curcumene in the different C. amada essential oils. The antibacterial activity was observed against different strains of microbes, with a higher efficacy in the essential oils prepared by UAE and MAE methods. Apart from these, the MAE, UAE, CSD, and CHD were also shown to have significantly higher larvicidal activity against Aedes, Culex, and Armigeres species; however, no toxic effect was observed in non-targeted species like fishes and Allium cepa model of genotoxicity. Further, these essential oils were also found to have significant contact and fumigant toxicity as well as repellency against pests of stored grains (Sitophilus and Tribolium). Considering these results, the present study assumes that Curcuma amada essential oils may be a source of ecofriendly insecticides and antibacterial agents.

Profiling the phyto-constituents of Punica granatum fruits peel extract and accessing its in-vitro antioxidant, anti-diabetic, anti-obesity, and angiotensin-converting enzyme inhibitory properties.

This context was investigated to assess the in vitro antioxidant, anti-diabetic, anti-obesity, and angiotensin-converting enzyme (ACE) inhibition traits of Punica granatum fruits peel extract. Initially, among various extracts tested, aqueous and ethanolic peel extracts depicted the presence of diverse phytoconstituents. In vitro antioxidative properties of peel extracts were determined using standard methodologies. Results showed that aqueous and ethanolic extracts had IC50 values of 471.7 and 509.16 µg/mL, respectively in terms of 1,1,diphenyl 2,2,picrylhydrazyl scavenging. Likewise, IC50 values of aqueous and ethanol extract were obtained as 488.76 and 478.47 µg/mL towards the degradation of hydrogen peroxide. The ethanolic extract exhibited the highest inhibition of α-glucosidase by showing activity of 53.34 ± 2.0 to 15.18 ± 1.4 U/L in a dose dependent manner (100-1000 µg/mL). Ethanolic extract was reported as the most active inhibitor of lipase with an IC50 value of 603.50 µg/mL. Ethanolic extract showed increased inhibition of ACE in a concentration dependent manner (100-1000 µg/mL) with IC50 value of 519.45 µg/mL. Fourier transform-infrared spectrum revealed the availability of various functional groups in the ethanolic extract of peel. Gas chromatography-mass spectrometry chromatogram of peel extract illustrated 23 diversified chemical constituents including 1,2,3,4-butanetetrol, Dimethyl sulfone, 9-octadecenamide, and Pentadecanoic acid as predominant compounds. In summary, P. granatum fruits peel extract revealed promising antioxidant, anti-diabetic, anti-obesity, and anti-hypertensive properties.

Nephroprotective effect of pigmented violacein isolated from Chromobacterium violaceum in wistar rats.

The present study aimed to analyze the nephroprotective property of violacein obtained from the bacterium, Chromobacterium violaceum. The nephrotoxicity in the animal model was induced by gentamicin, potassium dichromate, mercuric chloride, and cadmium chloride-induced nephrotoxicity in the Wistar rats was analyzed by measuring the serum creatinine, uric acid, and urea level. The present investigation revealed the nephroprotective property on convoluted proximal tubule (S1 and S2 segments) and the straight proximal tubule (S3 segment). Also, violacein significantly improved the renal function by the renal protective property on S2 segment of proximal tubule from the nephrotoxicity stimulated by mercuric chloride, potassium dichromate, cadmium chloride and gentamicin in animal models. Animal model studies revealed that violacein at 20 and 40 mg/kg p.o improved the renal function and significantly reduced the increased amount of uric acid, creatinine, and blood urea compared to the control.

Fer1L5, a Dysferlin Homologue Present in Vesicles and Involved in C2C12 Myoblast Fusion and Membrane Repair.

Fer1L5 is a dysferlin and myoferlin related protein, which has been predicted to have a role in vesicle trafficking and muscle membrane fusion events. Mutations in dysferlin and otoferlin genes cause heredity diseases: muscular dystrophy and deafness in humans, respectively. Dysferlin is implicated in membrane repair. Myoferlin has a role in myogenesis. In this study, we investigated the role of the Fer1L5 protein during myoblast fusion and membrane repair. To study the functions of Fer1L5 we used confocal microscopy, biochemical fractionation, Western blot analysis and multiphoton laser wounding assay. By immunolabelling, Fer1L5 was detected in vesicular structures. By biochemical fractionation Fer1L5 was observed in low density vesicles. Our studies show that the membranes of Fer1L5 vesicles are non-resistant to non-ionic detergent. Partial co-staining of Fer1L5 with other two ferlin vesicles, respectively, was observed. Fer1L5 expression was highly detected at the fusion sites of two apposed C2C12 myoblast membranes and its expression level gradually increased at D2 and reached a maximum at day 4 before decreasing during further differentiation. Our studies showed that Fer1L5 has fusion defects during myoblast fusion and impaired membrane repair when the C2C12 cultures were incubated with inhibitory Fer1L5 antibodies. In C2C12 cells Fer1L5 vesicles are involved in two stages, the fusion of myoblasts and the formation of large myotubes. Fer1L5 also plays a role in membrane repair.

Effect of Helicanthes elasticus (Desv.) Danser extracts on immune profile of Wistar albino rats.

Helicanthes elasticus (Desv.) Danser is a common type of mistletoes of Indian origin. In Indian traditional and folklore medicines the plant is claimed to possess a range of medicinal values such as immunomodulator, anti-diabetic and anti-microbial properties. However, there is no experimental proof for its therapeutic claim. The aqueous and alcoholic extracts of H. elastica were evaluated for its immuno-modulatory effect on antibody formation against sheep red blood cells and on cell mediated immunity of immunological paw edema model. Ethanolic and aqueous extracts have shown dose dependent elevation in the antibody titer value in comparison to control group at 14th and 21st day of sensitization (**p < 0.01). There is a mild to moderate elevation were observed in the immunological paw edema at highest dose (400 mg/kg) during 21st day after sensitization. The histopathological observation shows that there is an increase in the white pulp of spleen and increased cellularity and formation of distinct germinal cells in lymph node. H. elasticus extracts possess marked antibody formation propensity without significant modification on cell mediated immunity.

Shrimp shells extracted chitin in silver nanoparticle synthesis: Expanding its prophecy towards anticancer activity in human hepatocellular carcinoma HepG2 cells.

In this study, a well-organized, simplistic, and biological route of AgNPs (AgNPs) was synthesized using shrimp shell extracted chitin as reducing, capping and stabilizing factor under the optimized conditions. Also, the anticancer potential of synthesized biogenic AgNPs was evaluated against human hepatocarcinoma (HepG2) cells. Ultraviolet visible spectroscopy (UV-Vis spec) study indicated that the development of AgNPs present in the colloidal solution was single peak at 446 nm. FTIR results showed a strong chemical interaction between the chitin and biogenic AgNPs; whereas, XRD studies confirmed AgNPs presence in the composites. The SEM TEM analytical studies confirmed the synthesized AgNPs had a spherical shape crystalline structure with size ranges from 17 to 49 nm; EDX study also confirmed the percentage of weight and atomic elements available in the colloidal mixture. Furthermore, the synthesized AgNPs showed significant cytotoxic effect on the HepG2 cells with an IC50 value shown at 57 ± 1.5 µg/ml. The apoptotic and necrotic cell death effects of AgNPs were also confirmed by flow cytometry. The upregulated apoptotic related proteins Bax, cytochrome-c, caspase-3, caspase-9, PARP and downregulated anti-apoptotic related proteins Bcl-2 and Bcl-xl in cancer cells, confirmed the anticancer potential of AgNPs. These findings suggest that the AgNPs possess significant anticancer activity against HepG2 cells which could play major role in the therapeutic drug development to treat cancer in future.

Probiotic and Antioxidant Potential of Lactobacillus reuteriLR12 and Lactobacillus lactisLL10 Isolated from Pineapple Puree and Quality Analysis of Pineapple-Flavored Goat Milk Yoghurt during Storage.

In recent years, studies have focused on the therapeutic properties of probiotics to eliminate pathogenic microorganisms associated with various diseases. Lactobacilli are important probiotics groups that have been found to possess many health-promoting activities. This study was carried out to isolate LactobacillusreuteriLR12 and L. lactisLL10 from pineapple puree. The invitro analysis to evaluate probiotic characteristics of the isolated bacteria included survival in bile and acid tolerance. The cell-free supernatant of L. reuteri LR12 was effective against various pathogenic bacteria and fungi compared with L. lactisLL10. These two bacterial strains have strong anti-biofilm activity (100%) against Enterococcus faecalis, Staphylococcus aureus, and Bacillus cereus. The bacterial strains exhibited adhesion properties to HT-29 cells (human colorectal adenocarcinoma). These bacteria showed DPPH- (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical scavenging activity, scavenging of hydroxyl radical activity, superoxide radical scavenging activity, and reducing power activity in the range of 72% ± 3%to 89.3% ± 1.7%, 64% ± 2.7%to 66.8% ± 1.5%, 59.8% ± 4.1% to 63.8% ± 2.1%, and 60.4% ± 1.8%to 66.1% ± 3.3%, respectively. Pineapple puree was used as the starter culture with milk for 2 days for yogurt preparation. Pineapple puree increased flavor and showed the physicochemical properties of yogurt. The finding of the sensory evaluation revealed no significant change compared with the control, except the appearance of yogurt. These findings show that Lactobacilli and pineapple puree have potential use in various probiotic preparations for the fermentation industry.

Synthesis and biocompatible role of hierarchical structured carbon nanoplates incorporated α-Fe2O3 nanocomposites for biomedical applications with respect to cancer treatment.

This study aimed to inspect the hierarchically structured spherical-like hematite (α-Fe2O3) nanoparticles synthesize by simple, low temperature solution combustion process. The uniformly distributed α-Fe2O3/carbon nanocomposite (α-Fe2O3/C nanocomposite) was prepared by incorporating carbon nanoplates into sphere-like α-Fe2O3 nanoparticles. The synthesized nanomaterials were characterized using various techniques such as XRD, FESEM, and EDS. The cytotoxicity of the material was evaluated by MTT assay and nuclear imaging based on the cell morphological changes on both human lung cancerous cell line A549 and chang liver as non cancerous cell line. The results demonstrated that the pure and composite material exhibited above 70% viability on non-cancerous cell line and around 60% inhibition on A549 lung cancer cell line indicates the α-Fe2O3/C nanocomposite is biocompatible and can be used for biological applications and anticancer therapy. Cell death induced by α-Fe2O3, carbon nanoplates and α-Fe2O3/C nanocomposites was further evidenced with DAPI.

Sub-lethal effect of synthetic pyrethroid pesticide on metabolic enzymes and protein profile of non-target Zebra fish, Danio rerio.

Extensive application of pesticide in agricultural field affects the enzymatic activity of non-target animals, including fishes. In this study, the impact of sublethal concentration of fenvalerate on marker enzymes of freshwater Zebra fish was evaluated. Pesticide-induced stress can specifically affect non target fishes, through elevated level of reactive oxygen species which is responsible for biochemical, cell metabolism and physiological activities. The oxidative stress mediated by fenvalerate at sub lethal concentrations after 28 days of exposure of Zebra fish. Following 28 days of exposure of pesticide, catalase, superoxide dismutase, aspartate amino transferases, alanine amino transferase, alkaline phosphatase and acid phosphatase were assessed. Results revealed reduction of superoxide dismutase activity after 28 days of exposure in sub lethal concentration of fenvalerate in liver and gills. In liver, catalase activity was found to be less in fenvalerate exposed fish than control fish. In liver, increase of 75.75% aspartate amino transferase and 38% increase in alanine amino transferase in gills. SGPT activity was relatively higher than SGOT suggests more contribution of phyruvalate than oxaloacetate formation. Fenvalerate induced changes in acid phosphatase and alkaline phosphatase activity in the liver and gills of Zebra fish after four weeks of exposure. Fenvalerate induced expression of various stress proteins in gill, liver, followed by muscle. Some proteins lost its intensity due to fenvalerate toxicity. Result revealed that enzyme assays and SDS-PAGE analysis for protein subunits determination is relevant tool to monitor stress in freshwater ecosystem. The findings suggest that in monitoring fenvalerate toxicity programme, enzyme activities can be potent diagnostic tool for fenvalerate induced toxicity.

Valeriana fauriei Exerts Antidepressant-Like Effects Through Anti-inflammatory and Antioxidant Activities by Inhibiting Brain-Derived Neurotrophic Factor Associated with Chronic Restraint Stress.

Although depression is the most common psychiatric disorder, its pharmacological properties are not well known yet. It has been reported that Valeriana fauriei (VF) extract is beneficial for several neurological diseases. However, little information is available regarding its antidepressant activity. Therefore, the objective of this study was to determine antidepressant activity of VF and the underlying mechanism involved in its effect on chronic restraint stress (CRS)-induced depression using a mouse model. Oral treatment of VF extract for 14 days significantly ameliorated depression-like behavior (immobility time) in forced swimming and tail suspension tests following CRS induction, in accordance with decreased levels of serum corticosterone. VF extract ameliorated c-Fos expression, microglial activation, phosphorylated p38 expression, and inflammatory response (protein expression levels of cyclooxygenase-2 and inducible nitric oxide) in the prefrontal cortex, hippocampus, and amygdala of mice after CRS induction. However, VF extract enhanced the stimulation of nuclear factor erythroid 2-related factor 2 pathways, in accordance with upregulation in protein expression of brain-derived neurotrophic factor (BDNF). Collectively, our findings demonstrate that VF extract has antidepressant-like activity against CRS-induced depression through its anti-inflammatory and antioxidant effects by inhibiting BDNF expression. Further studies are warranted to investigate VF extract's fraction and components to develop possible antidepressants.

Prophylactic efficacy of Boerhavia diffusa L. aqueous extract in toluene induced reproductive and developmental toxicity in Drosophila melanogaster.

BACKGROUND: Environmental exposure to toxicants poses high risk to develop reproductive and developmental chronic toxicity in man. Toluene is one of the commonest industrial agents whose exposure is attributed with potential to induce reproductive and developmental toxicity. Since they contaminate the immediate environment of air and water to which humans are exposed, its containment is of great public health importance. Conventional treatment modalities fail owing to the difficulty to detect these highly volatile agents in environment and human body. The peril of such hazardous exposures is evident only when irreversible structural and functional damages have incurred. In such instances, prevention gains an upper hand when compared to therapeutic interventions. Several natural compounds derived from medicinal herbs possess potential to curb toxicities induced by such xenobiotic agents. Among them Boerhavia diffusa Linn. is a widely distributed and common herb attributed with antitoxic potential and capability for antioxidant defence. A study was performed on the prophylactic efficacy of aqueous extract of B. diffusa in curbing toluene induced developmental toxicity in Drosophila melanogaster. METHODS: The study consisted of a preliminary phytochemical screening and HPTLC profiling of B. diffusa aqueous extract (BDAE). LC50 of toluene was assessed and a sublethal dose of 200ppm was fixed for the study. Four doses of BDAE; 25, 50, 100 and 200mg/ml designated as Low dose, medium dose 1, medium dose 2 and high dose was used for the study. The parameters used for the study included the determination of larval period, pupal period, percentage of egg hatching, morphometric analysis of egg, larvae, pupae and adults, fertility, fecundity, lifespan and levels of antioxidant enzymes such as catalase, glutathione-S-transferase and superoxide dismutase. RESULTS: The phytochemical and HPTLC characters were as per the pharmacopoeial standards. LC50 of toluene was found to be 430ppm in this study. BDAE at medium dose 2 and high dose significantly prevented the deterioration of reproductive and developmental toxicity parameters of larval period, pupal period, percentage of egg hatching, morphometric characters of larva, pupa and adult, fertility, fecundity and lifespan in drosophila. Also the drug significantly elevated the levels of antioxidant enzymes. CONCLUSION: Toluene exposure during lifetime is inevitable. B. diffusa, equipped with its rich active ingredients prevented toluene induced developmental and reproductive toxicity in Drosophila. This medicinal herb provides a ray of hope in preventing environmental toxin induced reproductive and developmental toxicity.

Coix lacryma-jobi var. ma-yuen Stapf sprout extract induces cell cycle arrest and apoptosis in human cervical carcinoma cells.

BACKGROUND: Cervical cancer is the second-leading cause of cancer-related mortality in females. Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf ex Hook. f. is the most widely recognized medicinal herb for its remedial effects against inflammation, endocrine system dysfunctions, warts, chapped skin, rheumatism, and neuralgia and is also a nourishing food. METHODS: To investigate the activity of Coix lacryma-jobi sprout extract (CLSE) on cell proliferation in human cervical cancer HeLa cells, we conducted a Cell Counting Kit-8 (CCK-8) assay. Flow-cytometric analysis and western blot analysis were performed to verify the effect of CLSE on the regulation of the cell cycle and apoptosis in HeLa cells. RESULTS: We observed that CLSE significantly inhibited cell proliferation. Furthermore, CLSE dose-dependently promoted cell cycle arrest at the sub-G1/ S phase in HeLa cells, as detected by bromodeoxyuridine (BrdU) staining. The cell-cycle-arrest effects of CLSE in HeLa cells were associated with downregulation of cyclin D1 and cyclin-dependent kinases (CDKs) 2, 4, and 6. Moreover, CLSE induced apoptosis, as determined by flow-cytometric analysis and nuclear DNA fragmentation with Annexin V/propidium iodide (PI) and 4'6'-diamidino-2-phenylindole (DAPI) staining. Induction of apoptosis by CLSE was involved in inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) and upregulation of the apoptotic proteins p53, cleaved poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, and cleaved caspase-8. Finally, we observed that CLSE inactivated the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) pathways. CONCLUSIONS: CLSE causes cell cycle arrest and apoptotic cell death through inactivation of the PI3K/AKT pathway in HeLa cells, suggesting it is a viable therapeutic agent for cervical cancer owing to its anticancer effects.

Neuroprotective and therapeutic effect of Cordyceps militaris on ischemia-induced neuronal death and cognitive impairments.

Cordyceps militaris is a type of fungus consumed by people all over the world and renowned for their nutritional benefits and herbal formulas to promote health and longevity. In the present study investigation was carried out to explore the therapeutic properties and neuroprotective effect of the C. militaris on ischemic brain neuronal injury, impairment of memory and learning in experimental rats induced by a global cerebral ischemia-reperfusion injury in WISTAR rats. Vascular Dementia with transient global brain injuries induced by a four-vessel occlusion (4-VO) in WISTAR rats. Further, donepezil (5 mg/kg) and C. militaris was (100 and 300 mg/kg, p.o.) were orally administered for 7 days in 4-VO WISTAR rats. C. militaris has the ability to improve memory impairments due to global cerebral ischemia and scopolamine-induced memory deterioration. Our present findings suggest that C. militaris may be a potential candidate for the neuroprotection of hippocampus and the recovery of various vascular dementia or neuroinflammatory disorders.

Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead.

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35-56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

Spirulina consumption effectively reduces anti-inflammatory and pain related infectious diseases.

BACKGROUND: Inflammation and pain triggers several pathological illnesses. Synthetic drugs used for the controlling of inflammatory conditions convey significant toxic effects. Global scientific community continually attempt to improve effective, economic and harmless naturally derived remedies against inflammation and pain. The present study aimed to quantify the phytochemical constituents of the freshly cultivated Spirulina and targeted to examining the anti-inflammatory and analgesic activity of Spirulina extract (SE) derived from Arthrospira platensis. METHODS: The anti-inflammatory effect of SE was evaluated in animal models including carrageenan-induced rat hind paw oedema, and cotton pellet-induced granuloma formation. Analgesic effects of SE were evaluated by acetic acid induced writhing response and hot plate test. RESULTS: Phytochemical quantification guided to identify seven carbohydrates, thirteen amino acids, eleven fatty acids and polyphenolic compounds respectively. The results indicated that SE significantly attenuated carrageenan-induced hind paw oedema, and cotton pellet-induced granuloma. Preliminary molecular mechanistic studies established that SE decreased the productions of TNF-α, IL-1ß, IL-6, PGE2 and NO, and suppressed the activities of COX-2 and iNOS. CONCLUSION: These results provide a strong scientific foundation for the anti-inflammatory and analgesic activities of SE against different studies in animal models.

Betulinic acid lowers lipid accumulation in adipocytes through enhanced NCoA1-PPARγ interaction.

BACKGROUND: Investigation for a naturally occurring anti-obesity drug has become the need of society all over the world. Betulinic acid (BA) is a lupane-type pentacyclic triterpene and is sourced from various organisms. This high potential biologically active molecule is reported to have anti-obesity effect. In this study, we report the molecular mechanism of action of BA that underlies anti-obesity activity and also an improved method of its isolation common teak tree. METHODS: Mouse pre-adipocyte cells were used to develop hyperlipidemic conditions in vitro. Change in expression of genes associated to adipogenesis was checked using quantitative real-time PCR (qPCR). Co-factor specificity of PPAR gamma was analyzed through immune precipitation and immunoblot. RESULTS: Betulinic acid was found to be effective in reducing the lipid content in 3T3L1 cells. Level of PPAR gamma and LXR alpha was reduced in connection to reduced adipogenesis. Change in steroid responsive co-activators (SRCs) during BA treatment proved that the compound can impart profound change in co-factor selectivity, which is crucial in determining the activity profile of PPAR gamma. BA treatment enhanced the SRC-1 interaction with PPAR gamma while reducing the levels of SRC-3. CONCLUSION: Present study has proved that betulinic acid, a promising candidate in anti-obesity drug development, has potential in regulating the activity of PPAR gamma through co-factor modulation.