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Background: In medicinal chemistry, searching for new therapeutic entities to treat diabetes mellitus is of great concern. The piperidinyl-substituted chalcone scaffold has piqued our interest as a potential antidiabetic agent. Methods: A variety of piperidinyl-substituted chalcones 2-28 were synthesized and tested for α-amylase inhibitory and 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino- bis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activities. Results: Compared with the standard acarbose, all compounds inhibited α-amylase, with IC 50 values of 9.86-35.98 μM. Docking studies revealed an important binding interaction with the enzyme's catalytic site. The compounds also demonstrated promising radical-scavenging potential against  2,2-diphenyl-1-picrylhydrazyl and  2,2'-azino- bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals. Conclusion: This study has identified potential lead candidates for further advanced research searching for antidiabetic agents.

Ziziphus oxyphylla Edgew is in folk use in Pakistan as an analgesic, anti-inflammatory, and liver ailments. Therefore, we have investigated antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of the isolated compounds (ceanothic acid and zizybrenalic acid) from the chloroform fraction of Z. oxyphylla . Ceanothic acid and zizybrenalic acid showed significant DPPH and H 2 O 2 scavenging activity as compared to control. In the acute toxicity study, ceanothic acid and zizybrenalic acid showed no toxic effects upto 200 mg/kg. The antinociceptive activity shown by ceanothic acid and zizybrenalic acid at 50 mg/kg was 64.28% and 65.35% compared to diclofenac sodium (72.3%) at 50 mg/kg. The percent inhibition of xylene-induced ear edema exhibited by ceanothic acid and zizybrenalic acid at 50 mg/kg was 51.33% and 58.66%, respectively, as compared to diclofenac sodium (72.66%). Both the isolated compounds exhibited inhibition of carrageenan-induced paw edema as compared to control. Hepatoprotection exhibited by zizybrenalic acid was more pronounced than ceanothic acid as observed from the decrease in carbon tetrachloride (CCl 4 )-induced elevation of serum biomarkers, antioxidant enzymes and lipid peroxidation. Furthermore, zizybrenalic acid produced a marked decline in CCl 4 -induced prolongation of phenobarbital-induced sleeping duration. Zizybrenalic acid exhibited 55.4 ± 1.37% inhibition of hypotonic solution-induced hemolysis compared to sodium salicylate (75.6 ± 2.15%). The histopathological damage caused by CCl 4 was also countered by the administration of ceanothic acid and zizybrenalic acid. Ceanothic acid and zizybrenalic acid exhibited antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities. Zizybrenalic acid exhibited better antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activity than ceanothic acid.

The current study aimed to explore the crude oils obtained from the n-hexane fraction of Scutellaria edelbergii and further analyzed, for the first time, for their chemical composition, in vitro antibacterial, antifungal, antioxidant, antidiabetic, and in vivo anti-inflammatory, and analgesic activities. For the phytochemical composition, the oils proceeded to gas chromatography-mass spectrometry (GC-MS) analysis and from the resultant chromatogram, 42 bioactive constituents were identified. Among them, the major components were linoleic acid ethyl ester (19.67%) followed by ethyl oleate (18.45%), linolenic acid methyl ester (11.67%), and palmitic acid ethyl ester (11.01%). Tetrazolium 96-well plate MTT assay and agar-well diffusion methods were used to evaluate the isolated oil for its minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC), half-maximal inhibitory concentrations (IC 50 ), and zone of inhibitions that could determine the potential antimicrobial efficacy's. Substantial antibacterial activities were observed against the clinical isolates comprising of three Gram-negative bacteria, viz., Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa , and one Gram-positive bacterial strain, Enterococcus faecalis . The oils were also effective against Candida albicans and Fusarium oxysporum when evaluated for their antifungal potential. Moreover, significant antioxidant potential with IC 50 values of 136.4 and 161.5 µg/mL for extracted oil was evaluated through DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays compared with standard ascorbic acid where the IC50 values were 44.49 and 67.78 µg/mL, respectively, against the tested free radicals. The oils was also potent, inhibiting the α-glucosidase (IC50 5.45 ± 0.42 µg/mL) enzyme compared to the standard. Anti-glucosidase potential was visualized through molecular docking simulations where ten compounds of the oil were found to be the leading inhibitors of the selected enzyme based on interactions, binding energy, and binding affinity. The oil was found to be an effective anti-inflammatory (61%) agent compared with diclofenac sodium (70.92%) via the carrageenan-induced assay. An appreciable (48.28%) analgesic activity in correlation with the standard aspirin was observed through the acetic acid-induced writhing bioassay. The oil from the n-hexane fraction of S. edelbergii contained valuable bioactive constituents that can act as in vitro biological and in vivo pharmacological agents. However, further studies are needed to uncover individual responsible compounds of the observed biological potentials which would be helpful in devising novel drugs.

Soil salinity and drought stress (DS) are the massive problem for worldwide agriculture. Both stresses together become more toxic to the plant growth and development. Silicon (Si) being the second most abundant element in the earth's crust, exerts beneficial effects on plants under both stress and non-stress conditions. However, limited information is available to substantiate the beneficial role of Si in delaying the premature leaf senescence and imparting tolerance of mustard (Brassica juncea L.) plants to salinity and DS. Therefore, the present study aimed to explore the role of Si (source K 2 SiO 3 ) in chlorophyll (Chl) biosynthesis, nutrients uptake, relative water content (RWC), proline (Pro) metabolism, antioxidant system and delaying of premature leaf senescence in mustard plants under sodium chloride (NaCl) and DS conditions. Results of this study show that exogenous Si (1.7 mM) significantly delayed the salt plus DS-induced premature leaf senescence. This was further accompanied by the enhanced nutrients accumulation and activity of chlorophyll metabolizing enzymes [δ-aminolevulinic acid (δ-ALA) dehydratase and porphobilinogen deaminase] and levels of δ-ALA, and Chls a and b and also by decreased the Chl degradation and Chl degrading enzymes (Chlorophyllase, Chl-degrading peroxidase, pheophytinase) activity. Exogenous Si treatment induced redox homoeostasis in B. juncea L. plants, which is evident by a reduced generation of reactive oxygen species (ROS) resulting due to suppressed activity of their generating enzymes (glycolate oxidase and NADPH oxidase) and enhanced defence system. Furthermore, application of Si inhibited the activity of protease and triggered the activity of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) and plasma membrane H + -ATPase activity. In conclusion, all these results reveal that Si could help in the modulation of Chl metabolism, redox hemostasis, and the regulation of nutrients (nitrogen, phosphorus, Si and potassium) uptake in the mustard plants that lead to the postponement of premature leaf senescence under salinity plus DS., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The DPPH radical scavenging potentials of the fractions were determined in comparison to positive controls such as quercetin with EC 50 = 4.12±1.27, ascorbic acid with EC 50 = 6.20±1.67, gallic acid with EC 50 = 4.75±1.24 and α-tocopherol with EC 50 = 32.50±1.57 μg/mL. The experiment showed that aqueous fractions of the bark extracts of Abies pindrow (fraction: C 2 ) and Cedrus deodara (fraction: E2) showed significantly lower EC 50 values of 2.5±0.5 and 2.5±0.6 μg/mL, respectively. In reducing power assay, lower EC 50 values of 5.5 and 4.5μg/mL were recorded for the aqueous fraction (fraction: C 2 ) and final residue (fraction: C 5 ), of Abies pindrow, respectively. The ethyl acetate, acetone and final fractions of knot wood of Picea smithiana were found significantly active against all bacterial strains. Of the most sensitive fractions towards all the fungal strains was ethyl acetate fraction obtained from the bark of Cedrus deodara with a zone of inhibition ranging from 75 to 88 % that was more than the standard fluconazole.

Like other vegetables, Pisum sativum L. also faces storage and degradation problems. To enhance their resistance and make them enable to cope with the deterioration problems during storage, the current study was designed to develop two resistant lines of P. sativum in terms of phenolic contents and genotypes. The phenolic compounds generally have antioxidant properties and deterioration during storage which are usually due to oxidation caused by free radicals. Thus, if a variety has high phenolic contents these problems will be coped in a better way. The genotype of a plant is also important in this regard, and the best adopted species would survive in unfavorable conditions. First, the phenolic and flavonoid contents were determined in the crude extract using the Folin-Ciocalteu method. Then, the identification and quantification of phenolic compounds were carried out in the developed lines of selected plants PL-04 and PL-05, as well as in the parental varieties [Climax (female) and Falan (male)] via HPLC. DPPH assay was used to determine the free radical scavenging capabilities of the extracts of the developed verities. The genotypic differences were confirmed by DNA fingerprinting using advanced simple sequence repeat (SSR) markers. The HPLC analysis of PL-04 confirmed the presence of three phenolic compounds in an appreciable amount which exhibited a higher antioxidant activity against DPPH radicals, while in the parental varieties, two phenolic compounds were identified and exhibited lower antioxidant activities. PL-04 was found rich in phenolic compounds and affectively scavenge-free radicals which would therefore be resistant to oxidation and degradation caused by free radicals. Comparing the present findings with our previous one, P-04 was found to be resistant to powdery mildew; it was concluded that the most probable reason of the resistance was the high phenolic contents and thus long shelf life.

A new series of N-acylhydrazone derivatives of 2-mercaptobenzimidazole (2-MBI) has been synthesized through S-alkylation with 1-bromotetradecane and N-alkylation with ethyl-2-chloroacetate. The resulting ester was synthetically modified through hydrazine hydrate to acyl hydrazide which was condensed with aromatic aldehydes to afford the title N-acylhydrazones (4-17). Chemical structures of the newly synthesized compounds have been confirmed through mass, FT-IR and 1 HNMR techniques. In vitro free radical scavenging and α-glucosidase inhibition activities of the compounds were investigated with reference to the standard ascorbic acid and acarbose, respectively. Amongst the target compounds, 13 showed the highest inhibition in DPPH scavenging assay (IC 50  = 131.50 µM) and α-glucosidase inhibition potential (IC 50  = 352 µg/ml). We extended our investigations to explore the mechanism of enzyme inhibition and conducted docking analysis by using Molecular Operating Environment (MOE 2016.08). A homology model for α-glucosidase was constructed and validated using Ramachandran plot. Docking studies were also carried out on human intestinal α-glucosidases. In view of the importance of the nucleus involved, the synthesized compounds might find extensive medicinal applications as reported in the literature., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6β-Methoxy, 9β-dihydroxylheteratisine (1), 1α,11,13β-trihydroxylhetisine (2), 6,15β-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Viola canescens Wall. ex. Roxb. exhibits analgesic, antimalarial and antispasmodic activities. It is used folklorically for the treatment of liver diseases, hypertension, malaria and cancer. The current study investigates phytochemical constituents, antioxidant and hepatoprotective activity of solvent extracts of whole plant of Viola canescens., Methods: Phytochemicals, acute toxicity study and antioxidant activity of Viola canescens methanolic extract (VCME), ethyl acetate fraction (EAF), and partially purified EAF (90% EAF and combination of 80% EAF + 20% methanol fraction (EAF + Me) was carried out. Hepatoprotective activity of VCME, EAF (200 and 400 mg/kg body weight) and partially purified EAF (50 mg/kg body weight) was investigated in carbon tetrachloride (CCl 4 ) intoxicated BALB/c mice for 7 days. Membrane stabilization effect was determined by hypotonic solution induced hemolysis while DNA ladder assay was carried out by polyacrylamide gel electrophoresis., Results: Phytochemical screening of VCME showed the presence of alkaloids, phenols, flavonoids, saponins, carbohydrates, tannins and triterpenes. VCME, EAF (at 200 and 400 mg/kg body weight) and partially purified EAF (90% EAF and EAF + Me) at 50 mg/kg body weight significantly reduced the level of ALT, ALP, total bilirubin and restored the level of serum protein in comparison to CCl 4 treated group. A significant reduction in malondialdehyde (MDA) and elevation in catalase (CAT) and superoxide dismutase (SOD) level was observed in extract treated animals as compared to CCl 4 (p < 0.05). The IC 50 values in membrane stabilization potential for VCME, EAF and sodium salicylate were 3.7 ± 0.11, 3.4 ± 0.15 and 3.2 ± 0.09 mg/ml, respectively. Similarly, CCl 4 induced degradation of DNA was counteracted by VCME and EAF. The liver biopsy of mice treated with the solvent extracts showed remarkable restoration of normal histological archeitecture., Conclusions: Viola canescens showed significant hepatoprotective potential due to its antioxidant and membrane stabilization effect.

A lycoctonine-type norditerpenoid alkaloid, swatinine (1), along with four known norditerpenoid alkaloids, delphatine (3), lappaconitine (4), puberanine (5), and N-acetylsepaconitine (6), and were isolated from the aerial parts of Aconitum laeve Royle. Compound 2 has been isolated for the first time from a natural source. The structure of compound 1 was deduced on the basis of spectral data. The anti-inflammatory, antioxidant and tyrosinase inhibition studies on all six compounds have also been carried out.

Alzheimer's disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a wide spectrum of biological properties. In this regard, the antioxidant potentials of mono-carbonyl curcumin analogues (h1–h5) were investigated using in vitro antioxidant assays and hippocampal-based in vivo mouse models such as light–dark box, hole board, and Y-maze tests. In the in vitro assay, mono-carbonyl curcumin analogues h2 and h3 with methoxy and chloro-substituents, respectively, showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazo-line-6-sulfonate (ABTS) free radical scavenging activities. In the in vivo studies, scopolamine administration significantly (p < 0.001) induced oxidative stress and memory impairment in mice, in comparison to the normal control group. The pretreatment with mono-carbonyl curcumin analogues, specifically h2 and h3, significantly decreased (123.71 ± 15.23 s (p < 0.001), n = 8; 156.53 ± 14.13 s (p < 0.001), n = 8) the duration of time spent in the light chamber and significantly enhanced (253.95 ± 19.05 s (p < 0.001), n = 8, and 239.57 ± 9.98 s (p < 0.001), n = 8) the time spent in the dark compartment in the light–dark box arena. The numbers of hole pokings were significantly (p < 0.001, n = 8) enhanced in the hole board test and substantially increased the percent spontaneous alternation performance (SAP %) in the Y-maze mouse models in comparison to the stress control group. In the biomarker analysis, the significant reduction in the lipid peroxidation (MDA) level and enhanced catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) activities in the brain hippocampus reveal their antioxidant and memory enhancing potentials. However, further research is needed to find out the appropriate mechanism of reducing oxidative stress in pathological models. [ABSTRACT FROM AUTHOR]

Crataegus oxyacantha is an important herbal supplement and famous for its antioxidant potential. The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer's disease. The compounds isolated from C. oxyacantha were evaluated for cholinesterases inhibitory activity using Ellman's assay with Galantamine as standard drug. Total of nine (1-9) compounds were isolated. Compounds 1 and 2 were isolated for the first time from natural source. Important natural products like b-Sitosterol-3-O-b-D-Glucopyranoside (3), lupeol (4), b-sitosterol (5), betulin (6), betulinic acid (7), oleanolic acid (8), and chrysin (9) have also been isolated from C. oxyacantha. Overall, all the compounds exhibited an overwhelming acetylcholinesterase (AChE) inhibition potential in the range 5.22-44.47 μM. The compound 3 was prominent AChE inhibitor with IC50 value of 5.22 μM. Likewise, all the compounds were also potent in butyrylcholinesterase (BChE) inhibitions with IC50s of up to 0.55-15.36 mM. All the compounds, except 3, were selective toward BChE. Mechanism of the inhibition of both the enzymes were further studied by docking procedures using Genetic Optimization for Ligand Docking suit v5.4.1. Furthermore, computational blood brain barrier prediction of the isolated compounds suggest that these are BBBC. [ABSTRACT FROM AUTHOR]

Background: Viola canescens Wall. ex. Roxb. exhibits analgesic, antimalarial and antispasmodic activities. It is used folklorically for the treatment of liver diseases, hypertension, malaria and cancer. The current study investigates phytochemical constituents, antioxidant and hepatoprotective activity of solvent extracts of whole plant of Viola canescens. Methods: Phytochemicals, acute toxicity study and antioxidant activity of Viola canescens methanolic extract (VCME), ethyl acetate fraction (EAF), and partially purified EAF (90% EAF and combination of 80% EAF + 20% methanol fraction (EAF + Me) was carried out. Hepatoprotective activity of VCME, EAF (200 and 400 mg/kg body weight) and partially purified EAF (50 mg/kg body weight) was investigated in carbon tetrachloride (CCl4) intoxicated BALB/c mice for 7 days. Membrane stabilization effect was determined by hypotonic solution induced hemolysis while DNA ladder assay was carried out by polyacrylamide gel electrophoresis. Results: Phytochemical screening of VCME showed the presence of alkaloids, phenols, flavonoids, saponins, carbohydrates, tannins and triterpenes. VCME, EAF (at 200 and 400 mg/kg body weight) and partially purified EAF (90% EAF and EAF + Me) at 50 mg/kg body weight significantly reduced the level of ALT, ALP, total bilirubin and restored the level of serum protein in comparison to CCl4 treated group. A significant reduction in malondialdehyde (MDA) and elevation in catalase (CAT) and superoxide dismutase (SOD) level was observed in extract treated animals as compared to CCl4 (p < 0.05). The IC50 values in membrane stabilization potential for VCME, EAF and sodium salicylate were 3.7 ± 0. 11, 3.4 ± 0.15 and 3.2 ± 0.09 mg/ml, respectively. Similarly, CCl4 induced degradation of DNA was counteracted by VCME and EAF. The liver biopsy of mice treated with the solvent extracts showed remarkable restoration of normal histological archeitecture. Conclusions: Viola canescens showed significant hepatoprotective potential due to its antioxidant and membrane stabilization effect. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we investigated the effects of α-tocopherol (vitamin E, (α-T)) on residual free radicals in ultra-high molecular weight polyethylene (UHMWPE). More specifically, its effects on the carbon-centered polyenyl radical R1 [(–˙CH–[CH CH–]m–) with m > 3] and the oxygen-centered di-enyl or tri-enyl radical R2 in shelf-aged γ-irradiated UHMWPE stabilized (blended) with α-T were examined. For the UHMWPE/α-T blends, the α-T concentrations were 5000 ppm, 10,000 ppm, 100,000 ppm, and 150,000 ppm; the blends were γ-irradiated (∼30-kGy) at room temperature (23 °C) and shelf-aged under light for five years in air. Electron spin resonance (ESR) power saturation techniques had been employed at room temperature (23 °C), which revealed that α-T was more effective in reducing residual radicals when irradiation was performed in air as compared to a nitrogen environment. While the total quantities of residual radicals reduced for the α-T concentration of up to 10,000 ppm, unexpected increasing trends in radicals were observed for 100,000 ppm and 150,000 ppm of α-T concentrations. The average crystallite sizes were found to increase from approximately 40 nm to 65 nm at L (110) and from approximately 28 nm to 42 nm at L (200), as suggested by wide angle X-ray scattering (WAXS) data, which indicated that total amount of residual radicals had strong dependence on the average crystallite sizes, as opposite to % crystallinity of these UHMWPE/α-T blends. In addition, behavior of oxygen-centered di-enyle or tri-enyl radicals (R2) was investigated using Raman spectroscopic methods and it was reported experimentally for the first time, to our knowledge, that radical R2 resides at the interphase region of UHWMPE and has direct proportion with % interphase contents of UHMWPE. Our result may be relevant when considering the long-term resistance of UHMWPE/α-T blends to oxidation processes. [Copyright &y& Elsevier]