Untargeted metabolomics of fermented onion (Allium cepa L) using UHPLC Q-TOF MS/MS reveals anti-obesity metabolites and in vivo efficacy in Caenorhabditis elegans.

The bioconversion of onion extracts with P. acidilactici MNL5 enhances the metabolites and has a synergistic lipid-reduction impact that is beneficial for anti-obesity studies. The 48 h fermented onion extracts (FOE) demonstrated an enhanced inhibitory activity against pancreatic lipase (89.5 ± 1.25 %) as compared to the raw onion extract (ROE) (33.4 ± 0.86 %). The antioxidant properties of FOE significantly increased compared to the ROE inhibitory effect on DPPH (99.5 ± 2.40 mg vitamin C equiv./mg, DW FOE), and ABTS (104.5 ± 2.32 mg vitamin C equiv./mg, DW FOE). Based on FOE's higher antioxidant activity, UHPLC-Q-TOF-MS/MS demonstrated dramatic changes in the untargeted metabolite profile as compared to ROE. Moreover, C. elegans supplemented with FOE and quercetin exhibited an enhanced lifespan activity, lipid reduction, and decreased triglycerides. FOE can lower cholesterol and enhance quercetin to promote pancreatic lipase activity for synergistic anti-obesity effects.

Antibacterial, Antioxidant, Larvicidal and Anticancer Activities of Silver Nanoparticles Synthesized Using Extracts from Fruits of Lagerstroemia speciose and Flowers of Couroupita guianensis.

The present study aimed to analyze the in vitro antibacterial, antioxidant, larvicidal and cytotoxicity properties of green synthesized silver nanoparticles (Ag NPs) using aqueous extracts from fruits of Lagerstroemia speciosa and flowers of Couropita guinensis. Synthesized Ag NPs were characterized using UV-DRS, FTIR, XRD, DLS, and High-Resolution SEM and TEM analyses. Absorption wavelength was observed at 386 nm by UV-DRS analysis and energy band gap was calculated as 3.24 eV. FTIR analysis showed the existence of various functional groups in the aqueous extract and in the NPs. DLS analysis showed the stability and particle size of the synthesized Ag NPs. SEM analysis revealed that Ag NPs are in a face centered cubic symmetry and spherical shape with a size of 23.9 nm. TEM analysis showed particle size as 29.90 nm. Ag NPs showed antibacterial activity against both Gram-positive and Gram-negative bacteria. DPPH scavenging trait of Ag NPs was ranging from 20.0 ± 0.2% to 62.4 ± 0.3% and observed significant larvicidal activity (LC50 at 0.742 ppm and LC90 at 6.061 ppm) against Culex quinquefasciatus. In vitro cytotoxicity activity of Ag NPs was also tested against human breast cancer (MCF-7) and fibroblast cells (L-929) and found that cells viabilities are ranging (500 to 25 µg/mL) from 52.5 ± 0.4 to 94.0 ± 0.7% and 53.6 ± 0.5 to 90.1 ± 0.8%, respectively. The synthesized Ag NPs have the potential to be used in the various biomedical applications.

Anti-Obesity Efficacy of Pediococcus acidilactici MNL5 in Canorhabditis elegans Gut Model.

In the present study, thirty two lactic acid bacteria (LAB) were isolated from fermented Indian herbal medicine. In comparison to other strains, MNL5 had stronger bile salt hydrolase (BSH) and cholesterol-lowering properties. Furthermore, it can withstand the extreme conditions found in the GI tract, due to, e.g., pepsin, bile salts, pancreatin, and acids. Pediococcus acidilactici MNL5 was identified as a probiotic candidate after sequencing the 16S rRNA gene. The antibacterial activity of P. acidilactici MNL5 cell-free supernatants (CFS) against Escherichia coli, Staphylococcus aureus, Helicobacter pylori, Bacillus cereus, and Candida albicans was moderate. A Caenorhabditis elegans experiment was also performed to assess the effectiveness of P. acidilactici MNL5 supplementation to increase life span compared to E. coli supplementation (DAF-2 and LIU1 models) (p < 0.05). An immense reduction of the lipid droplets of C. elegans was identified through a fluorescent microscope. The drastic alteration of the expression of fat genes is related to obesity phenotypes. Hence, several paths are evolutionary for C. elegans; the results of our work highlight the nematode as an important model for obesity.

Biosynthesis of silver and gold nanoparticles using Musa acuminata colla flower and its pharmaceutical activity against bacteria and anticancer efficacy.

Synthesis of nanoparticles using plant sources as reducing agent has become important, as physical and chemical methods are costlier and affects environment. Hence it is important to develop environment friendly nanoparticle synthesis by avoiding the use of toxic chemicals. The present study aimed to synthesize silver nanoparticles (Ag Nps) and gold nanoparticles (AuNps) using Musa acuminata colla flower and its pharmaceutical activity against extended spectrum beta-lactamase (ESBL) gene producing bacteria and anticancer efficacy. The synthesized Ag and Au NPs were analysed by means of UV-Vis, FTIR, XRD,SEM and EDAX evidenced the bioreduction of Ag+ ions to Ag0 and Au3+ ions to Au0 respectively. Both nanoparticles and flower extracts were studied for antibacterial activity of ESBL gene producing bacteria by disc diffusion and microdilution (Resazurin) method. In vitro anticancer efficacy (MCF-7) and toxicity (VERO) of AgNPs, AuNPs, aqueous extract and ethanol extract of flowers were performed by MTT assay. IC50 value for DPPH analysis was at 390 µg and 460 µg for ethanol and aqueous extract respectively. Total antioxidant content was found be 740 µg/mg and 460 µg/mg for ethanol and aqueous extract. GCMS analysis authenticated the existence of the compounds namely, 9,12-octadecadienoic acid(z,z)- and n-hexadecanoic acid in the crude extract of the samples. Among the samples, AgNPs had best antibacterial activity. AgNPs and AuNPs were confirmed by colour change to reddish brown and ruby red. Further ƛmax were obtained at 474 and 540 nm by UV - visible spectrum. SEM analysis revealed the particle size ranges from 12.6 to 15.7 nm for silver and 10.1 to 15.6 nm for gold nanoparticles. The EDAX spectrum shows a strong signal for elemental Ag and Au at ~ 3 keV and 1.5 keV. The XRD patterns for silver and gold nanoparticles at 36.701, 42.900, 63.281 and 76.398 corresponding to the lattice planes 2.4467, 2.1064, 1.46839, 1.24564 nm and 27.32, 36.7228, 39.56, 42.888, 63.253, 63.253, 65.02 and 76.383 corresponding to the lattice planes 3.262, 2.44530, 2.276, 2.1070, 1.46897, 1.4332 and 1.24585 nm. The IC50 values for MCF-7 and VERO cells were 30.0 µg/ml and 55.0 µg/ml respectively.

Rapid biosynthesis and characterization of silver nanoparticles from the leaf extract of Tropaeolum majus L. and its enhanced in-vitro antibacterial, antifungal, antioxidant and anticancer properties.

Eco-friendly biosynthesis of nanoparticles from medicinal plants as reducing agent has gained importance due to its potential therapeutic uses. In the present study Silver nanoparticles (AgNPs) were eco-friendly synthesized using the leaf extracts of the medicinal plant Tropaeolum majus. The obtained AgNPs were characterized by UV - visible spectrum, FTIR, SEM and XRD which clearly showed the reduction of Ag+ ions to Ag0. In addition, the aqueous and ethanolic extracts were analyzed for phytochemicals and its antioxidant activities. GC-MS spectrum showed the presence of 25 compounds with benzeneacetic acid as the dominant contents. The synthesized AgNPs revealed maximum absorption spectrum at 463 nm and FTIR vibrational peaks at 3357.46, 21,966.52, 2118.42, 1637.27, 658.571 and 411.728 cm-1 respectively. SEM and XRD studies evidenced the nature of nanocrystalline with face centered cubic (fcc) crystal structure. Both AgNPs and plant extracts showed more inhibition activity against Pseudomonas aeroginosa compared to other bacteria with MIC value of 6.25 µg/ml. Antifungal activities was higher for Penicilium notatum with MIC value 31.2 µg/ml. The IC50 values for MCF7 for aqueous extract were found to be 4.68 µg/ml, ethanol extract 7.5 µg/ml, AgNPs 2.49 µg/ml, and doxorubicin 1.4 µg/ml. The IC50 values for VERO cell line for aqueous extract was 8.1 µg/ml, ethanol extract with 6.8 µg/ml, silver nanoparticles 5.3 µg/ml and doxorubicin 2.6 µg/ml respectively. Conclusively, the antibacterial, antifungal, antioxidant and anticancer properties of the synthesized AgNPs from Tropaeolum majus act as major therapeutic drug for microbial infectious disease and other health associated disorders.

Chemical analysis of Punica granatum fruit peel and its in vitro and in vivo biological properties.

BACKGROUND: The medical application of pomegranate fruits and its peel is attracted human beings. The aim of the present study was to evaluate the in vitro α-Glucosidase inhibition, antimicrobial, antioxidant property and in vivo anti-hyperglycemic activity of Punica granatum (pomegranate) fruit peel extract using Caenorhabditis elegans. METHODS: Various invitro antioxidant activity of fruit peel extracts was determined by standard protocol. Antibacterial and antifungal activities were determined using disc diffusion and microdilution method respectively. Anti-hyperglycemic activity of fruit peel was observed using fluorescence microscope for in vivo study. RESULTS: The ethyl acetate extract of P. granatum fruit peel (PGPEa) showed α-Glucosidase inhibition upto 50 % at the concentration of IC50 285.21 ± 1.9 µg/ml compared to hexane and methanol extracts. The total phenolic content was highest (218.152 ± 1.73 mg of catechol equivalents/g) in ethyl acetate extract. PGPEa showed more scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) with IC50 value 302.43 ± 1.9 µg/ml and total antioxidant activity with IC50 294.35 ± 1.68 µg/ml. PGPEa also showed a significant effecton lipid peroxidation IC50 208.62 ± 1.68 µg/ml, as well as high reducing power. Among the solvents extracts tested, ethyl acetate extract of fruit peel showed broad spectrum of antimicrobial activity. Ethyl acetate extract supplemented C.elegans worms showed inhibition of lipid accumulation similar to acarbose indicating good hypoglycemic activity. The normal worms compared to test (ethyl acetate extract supplemented) showed the highest hypoglycaemic activity by increasing the lifespan of the worms. GC-MS analysis of PGPEa showed maximum amount of 5-hydroxymethylfurfural and 4-fluorobenzyl alcohol (48.59 %). CONCLUSION: In the present investigation we observed various biological properties of pomegranate fruit peel. The results clearly indicated that pomegranate peel extract could be used in preventing the incidence of long term complication of diabetics.

Some biological activities of Epaltes divaricata L. - an in vitro study.

BACKGROUND: Novel chemical molecules recovered from endangered medicinal plants have wide applications and have the potential to cure different diseases caused by microorganisms. The aim of this study was to investigate In vitro antimicrobial, α-glucosidase inhibition and antioxidant activity of different solvent extracts of Epaltes divaricata L. METHODS: Antimicrobial activity of hexane, ethyl acetate and methanol extract of Epaltes divaricata was determined against bacteria and fungi using disc diffusion and microdilution method respectively. α-glucosidase inhibition, Total phenolic content (TPC), Reducing power activity, DPPH radical scavenging assay, hydroxyl radical scavenging activity, nitric oxide scavenging activity, superoxide scavenging activity and lipid peroxidation assay of plant extracts were performed according to standard protocol. Compound detection from the potential solvent extract was done through GC-MS analysis. RESULTS: Epaltes divaricata ethyl acetate extracts (EDEa) (1.25 mg/disc) showed significant inhibition for E. lentum (23 mm), E. aerogenes (18 mm), P. fluorescence (15 mm) and A. baumanii (15 mm). Minimum inhibitory concentration (MIC) of EDEa was found to be 31.25 µg/ml, 62.5 µg/ml and 62.5 µg/ml against A. flavus, A. niger and T. rubrum respectively. EDEa showed more α-glucosidase inhibition and antioxidant activity compared to hexane and methanol. EDEa showed 50% α-glucosidase inhibition at the concentration of 525.20 ± 2.37 µg/ml. The TPC of EDEa was 412.0 ± 2.21 mg of catechol equivalents/g extract. EDEa showed great scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) (IC50 560 ± 2.02 µg/ml), hydroxyl (IC50 314.75 ± 2.56 µg/ml), nitric oxide (IC50 648.20 ± 2.09 µg/ml) and superoxide (IC50 361.14 ± 1.45 µg/ml) radicals, as well as high reducing power. EDEa also showed a more suppressive effect on lipid peroxidation. Using Antioxidant ß-carotene linoleate method, the scavenging values of EDEa was significantly lower than BHT. GC-MS analysis of EDEa showed maximum amount of 2-butenamide, N-(4-fluorophenyl)-3-methyl trans-cinnamyl tiglate silane and trichlorocyclohexyl silane (36.86%). CONCLUSION: The results obtained in this study clearly indicate that EDEa can be used as a natural antimicrobial, α-glucosidase inhibition and antioxidant agent.

In-vitro antimicrobial, antibiofilm, cytotoxic, antifeedant and larvicidal properties of novel quinone isolated from Aegle marmelos (Linn.) Correa.

BACKGROUND: Plant metabolites have wide applications and have the potential to cure different diseases caused by microorganisms. The aim of the study was to evaluate the antimicrobial, antibiofilm, cytotoxic, antifeedant and larvicidal properties of novel quinine isolated from Aegle marmelos (Linn.) Correa. METHODS: A compound was obtained by eluting the crude extract, using varying concentrations of the solvents by the chromatographic purification. Broth micro dilution method was used to assess the antimicrobial activity and anticancer study was evaluated using MTT assay. Larvicidal activity was studied using leaf disc no-choice method. RESULTS: Based on the IR, 13C NMR and 1H NMR spectral data, the compounds were identified as quinone related antibiotic. It exhibited significant activity against Gram positive and Gram negative bacteria. The lowest Minimum Inhibitory Concentration (MIC) of the compound against Bacillus subtilis and Staphylococcus aureus was 100 and 75 µg mL(-1) respectively. Against Escherichia coli and Pseudomonas aeruginosa it exhibited MIC value of 25 µg mL(-1). The MIC of the compound against Aspergillus niger, A. clavatus, Penicillium roqueforti was 20 µg mL(-1) and that against Fusarium oxysporum (20 µg mL(-1)), A. oryzae (40 µg mL(-1)), and Candida albicans (60 µg mL(-1)), respectively. It showed effective antibiofilm activity against E. coli, S. typhii and P. aeroginosa at 8 µg mL(-1) and did not exhibit considerable cytotoxic activity against Vero and HEP2 cell lines. Additionally, the compound documented significant antifeedant and larvicidal activities against Helicoverpa armigera and Spodoptera litura at 125, 250, 500 and 1000 ppm concentrations. CONCLUSION: The results concluded that the compound can be evaluated further in industrial applications and also an agent to prepare botanical new pesticide formulations.

Gastroprotective effect of epoxy clerodane diterpene isolated from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in rats.

The present study evaluated the gastroprotective effect of epoxy clerodane diterpene (ECD), isolated from Tinospora cordifolia on indomethacin-induced gastric ulcer in rats. Administration of indomethacin exhibits extreme levels of ulcer index (UI) and myeloperoxidase (MPO) activity. Indomethacin down regulated PGE2, anti-inflammatory cytokines (IL-4, IL-10) and pro-angiogenic factors (VEGF and EGF). The ECD pretreatment considerably increased the levels of PGE2, anti-inflammatory cytokines and pro-angiogenic factors. The ulcer-healing activity of ECD was inhibited by pre-administration of the specific COX-1 inhibitor (SC560) and nonspecific NOS inhibitor (L-NAME), which indicates the involvement of PGE2 and NOS in ECD induced ulcer healing activity. These findings suggest that ECD exerts its antiulcer activity by reinforcement of defensive elements and diminishing the offensive elements.

Antidiabetic effect of plumbagin isolated from Plumbago zeylanica L. root and its effect on GLUT4 translocation in streptozotocin-induced diabetic rats.

Plumbago zeylanica L. root is widely used in Indian medicine to treat diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of plumbagin isolated from P. zeylanica L. root and its effect on GLUT4 translocation in STZ-induced diabetic rats. Plumbagin (15 and 30 mg/kg b wt) was orally administered to STZ-induced diabetic rats for 28 days. An oral glucose tolerance test was performed on 21st day. The effect of plumbagin on body weight, blood glucose, plasma insulin, total protein, urea, creatinine, liver glycogen, plasma enzymes (SGOT, SGPT and ALP) and carbohydrate metabolism enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase and hexokinase) were investigated. GLUT4 mRNA and protein expression in skeletal muscles were also studied. Plumbagin significantly reduced the blood glucose and significantly altered all other biochemical parameters to near normal. Further, plumbagin increased the activity of hexokinase and decreased the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase significantly in treated diabetic rats. Enhanced GLUT4 mRNA and protein expression were observed in diabetic rats after treatment with plumbagin. The results indicated that plumbagin enhanced GLUT4 translocation and contributed to glucose homeostasis. It could be further probed for use as a drug to treat diabetes.

In vitro antioxidant, antidiabetic and antilipidemic activities of Symplocos cochinchinensis (Lour.) S. Moore bark.

Symplocos cochinchinesis is used in Indian system of traditional medicine to treat diabetes mellitus. The present study investigates the in vitro antioxidant, antidiabetic and antilipidemic activities of S. cochinchinensis bark methanolic extract (SCBe) in streptozotocin (STZ) induced diabetic rats. In in vitro studies SCBe showed very good scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) (IC(50) 820.34 ± 1.74 µg/ml), hydroxyl (IC(50) 884.19 ± 0.45 µg/ml) and nitric oxide (IC(50) 860.21 ± 1.18 µg/ml) radicals, as well as high reducing power. SCBe (250 and 500 mg/kg) was administered to STZ (40 mg/kg) induced diabetic rats for 28 days. SCBe showed a significant decrease in blood glucose and significant increase in plasma insulin and liver glycogen levels in treated diabetic rats. Further, SCBe showed antilipidemic activity as evidenced by significant decrease in serum TC, TG, LDL-C levels and significant increase in HDL-C level in treated diabetic rats. SCBe also restored the altered plasma enzymes (SGOT, SGPT and ALP), total protein, urea and creatinine levels to near normal. The action of SCBe was comparable to the antidiabetic drug glibenclamide. Results of this experimental study indicated that SCBe possessed antioxidant, antidiabetic and antilipidemic activities.

Antidiabetic effect of Symplocos cochinchinensis (Lour.) S. Moore. in type 2 diabetic rats.

AIM: Symplocos cochinchinensis (Lour.) S. Moore. is used in Indian system of traditional medicine to treat diabetes mellitus. The present study aims to investigate the antidiabetic efficacy of the hexane extract of Symplocos cochinchinensis leaves in high fat diet-low streptozotocin (STZ) induced type 2 diabetic rats. MATERIALS AND METHODS: The doses for the study were fixed based on Irwin test. The hypoglycemic effect of the hexane extract of Symplocos cochinchinensis leaves were studied in normal rats. Oral glucose and insulin tolerance tests were carried out. The antihyperglycemic effect of the hexane extract at 250 and 500 mg/kg was studied in high fat diet-low STZ induced type 2 diabetic rats for 28 days. RESULTS: The extracts showed no adverse effects up to 5 g/kg concentration. In hypoglycemic study, after treatment with hexane extract at 250 and 500 mg/kg the blood glucose was mildly reduced. In oral glucose tolerance test, the treatment with the hexane extract at 250 and 500 mg/kg showed a highly significant reduction of 12.07% and 23.58% in plasma glucose levels, respectively 30 min after glucose load. The insulin tolerance test also showed improved insulin sensitivity after 60 min of insulin treatment. In high fat diet-low STZ induced type 2 diabetic rats, after 28 days treatment with the hexane extract at 250 and 500 mg/kg reduced the plasma glucose level by 17.04% and 42.10%, respectively. A significant reduction in plasma insulin, plasma and hepatic total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) and a significant increase in liver glycogen were observed in treated diabetic rats. CONCLUSION: This study demonstrated the potential antidiabetic property of hexane extract of Symplocos cochinchinensis leaves on type 2 diabetes mellitus, thus justifying its traditional usage.

Potential hepatoprotective activity of ononitol monohydrate isolated from Cassia tora L. on carbon tetrachloride induced hepatotoxicity in wistar rats.

Ononitol monohydrate, structurally similar to glycoside was isolated from Cassia tora L. leaves. Fifty Male rats were divided into five groups. Group I served as normal control. Group II, III and IV rats were induced hepatotoxicity by CCl(4) administering single dose of CCl(4) on 8th day only. Group III was treated with ononitol monohydrate (20mg/kg body weight) and group IV was treated with reference drug silymarin (20mg/kg body weight) both dissolved in corn oil and administering for 8 days. Ononitol monohydrate with corn oil alone was given for 8 days (group V). At the end of the experimental period all the animals were sacrificed and analyzed for biochemical parameters to assess the effect of ononitol monohydrate treatment in CCl(4) induced hepatotoxicity. In in vivo study, ononitol monohydrate decreased the levels of serum transaminase, lipid peroxidation and TNF-alpha but increased the levels of antioxidant and hepatic glutathione enzyme activities. Compared with reference drug silymarin ononitol monohydrate possessed high hepatoprotective activity. Histopathological results also suggested the hepatoprotective activity of ononitol monohydrate with no adverse effect. Hence we conclude that ononitol monohydrate is a potent hepatoprotective agent.

Chemopreventive potential of Epoxy clerodane diterpene from Tinospora cordifolia against diethylnitrosamine-induced hepatocellular carcinoma.

Medicinal plants are a promising source for identification of lead molecules for cancer therapy. In our continuous search to discover bioactive compounds from natural products, we isolated (5R, 10R)-4R, 8R-dihydroxy-2S, 3R:15, 16-diepoxycleroda-13(16), 17, 12S:18,1S-dilactone (ECD), a diterpenoid from Tinospora cordifolia and studied its chemopreventive potential in diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) rats. Fifty male Wistar rats were divided into five groups. Group I served as normal control. Group II-IV were given DEN (0.01% in drinking water) for twenty weeks. In addition, Group III (preventive treatment) received ECD (10 mg/kg body weight) throughout the study. Group IV (curative treatment) received ECD (10 mg/kg body weight) for the last 8 weeks. Group V received ECD alone (10 mg/kg body weight) throughout the experimental period. At the end of the experimental period all the animals were sacrificed and analyzed for biochemical end points to assess the effect of ECD treatment in DEN induced HCC. The animals treated with DEN showed a decrease in the activities of antioxidant (SOD, CAT) and detoxification enzymes (GSH, GPx) with increase in the activities of the hepatic markers (SGOT, SGPT, LDH). Treatment of ECD in both preventive and curative DEN induced animals increased the level of antioxidants and detoxification enzymes, and decreased serum transaminase level and hepatic marker enzymes to near normal. Histopathological and nodular incidence also confirmed that ECD remarkably reduced tumor incidence and reversed damaged hepatocytes to normal. Our findings confirm that ECD exhibits preventive effect against chemically induced HCC in rats. ECD can be a potent chemopreventive drug for HCC.