Majid Ahmad Ganaie

Synthesis, analgesic, anti-inflammatory and anti-ulcerogenic activities of certain novel Schiff's bases as fenamate isosteres

A series of certain novel Schiff bases as fenamate isosteres (VI:a-k) were synthesized to locate analgesic, anti-inflammatory agent with minimal ulcerogenic potential. The structures of the newly synthesized compounds were elucidated on the basis of their elemental analysis as well as IR, and NMR and mass spectroscopic data. All the compounds were evaluated for their anti-inflammatory activity by carrageenan induced paw oedema method. The compounds possessing good anti-inflammatory activity were further tested for analgesic, ulcerogenic, lipid peroxidation potentials and liver toxicity. Compounds (VI-c), (VI-f), (VI-h) and (VI-i) showed the best anti-inflammatory and significant analgesic activities at doses comparable to that of the standard drug Indomethacin. However, compounds (VI-c) and (VI-f) could be considered the most potent anti-inflammatory and analgesic molecules with maximum reduction in gastro-intestinal ulceration with no hepatocyte necrosis or liver degeneration.

Ameliorative effect of methanol extract of Rumex vesicarius on CCl4-induced liver damage in Wistar albino rats

Abstract Context: Rumex vesicarius L. (Polygonaceae), an edible plant, is reported to have many bioactive phytochemicals, especially flavonoids and anthraquinones with antioxidant and detoxifying properties. Objective: This study evaluated the methanolic extract of R. vasicarius (MERV) for hepatoprotective activity in rats against CCl4-induced liver damage. Materials and methods: The whole plant extract was prepared and investigated for its hepatoprotective activity. Rats were pretreated with MERV (100 and 200 mg/kg, p.o.) for 7 d prior to the induction of liver damage by CCl4. Animals were then sacrificed 24 h after CCl4 administration for the biochemical (AST, ALT, and ALP activity in serum; lipid peroxidation (LPO) and glutathione (GSH) levels in liver tissue) and histological analyses. Results: CCl4-induced hepatotoxicity was confirmed by an increase (p < 0.05) in serum AST (4.55-fold), ALT (3.51-fold), and ALP (1.82-fold) activities. CCl4-induced hepatotoxicity was also manifested by an increase (p < 0.05) in LPO (3.88-fold) and depletion of reduced glutathione (3.14-fold) activity in liver tissue. The multiple dose MERV administration at 200 mg/kg showed promising hepatoprotective activity as evident from significant decrease levels of serum AST (230.01 ± 13.21), serum ALT (82.15 ± 5.01), serum ALP (504.75 ± 19.72), hepatic LPO (3.38 ± 0.33), and increased levels of hepatic glutathione (0.34 ± 0.04) towards near normal. Further, biochemical results were confirmed by histopathological changes as compared with CCl4-intoxicated rats. Discussion and conclusion: The results obtained from this study indicate hepatoprotective activity of Rumex plant against CCl4-induced liver toxicity; hence, it can be used as a hepatoprotective agent.

Antioxidant potential of Rumex vesicarius L.: in vitro approach.

OBJECTIVE To assess in-vitro antioxidant activity of different fraction and perform high performance thin layer chromatography fingerprint analysis of most active fraction of Rumex vesicarius L. (R. vesicarius). METHODS In the present study, acetone, ethyl acetate, n-butanol, and methanol extracts of R. vesicarius were evaluated for radical scavenging activity by studying the inhibition of the level of lipid peroxidation induced by Fe(++)/ascorbate, DNA sugar damage, scavenging of hydrogen peroxide, diphenylphosphine DPPH radical scavenging activity, total phenolic content, total flavonoids content and total proanthocyanidin. High performance thin layer chromatography finger print profiling of R. vesicarius L. was also done. RESULTS Lipid peroxidation induced by the iron/ascorbate system, hydrogen peroxide, diphenylphosphine and DNA sugar damage were inhibited by the addition of different extract of R. vesicarius. Among them, methanolic extract showed maximum efficacy. The methanolic extract showed the highest total phenolic, total flavonoids and total proanthocyanidin contents. CONCLUSIONS The results suggest that the extracts can be a vital source of phytochemical antioxidants.

Hepatoprotective effect of Commiphora myrrha against d-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes

Abstract Context: Commiphora myrrha (Burseraceae), a shrub resembling a small tree, has been used for several centuries for the treatment of various diseases. Objective: This study investigates the hepatoprotective activity of C. myrrha ethanol extract against d-galactosamine/lipopolysaccharide (d-GalN/LPS)-induced acute hepatic injury in an animal model. Materials and methods: Rats were pretreated with ethanolic extract C. myrrha (250 and 500 mg/kg; p.o.) for 7 d prior to the induction of an acute phase response by d-GalN/LPS. Animals were sacrificed 24 h after d-GalN/LPS (800 mg/kg and 50 µg/kg i.p.) administration for the biochemical and histological analyses. Results: The administration of d-GalN/LPS increased plasma aminotransferases (174.47 ± 4.5761 and 260.96 ± 1.9839 µkat/l) and total bilirubin levels (1.012 ± 0.0288 mg/dl), which were attenuated by C. myrrha treatment. Hepatic lipid peroxidation activity and nitric oxide content also increased, while the antioxidant activity measured by GSH (0.76 nmol/g protein), SOD (81.91 U/mg protein), and CAT (15.78 U/mg protein) was reduced. Commiphora myrrha provided significant restoration of GSH (0.815 nmol/gm protein), SOD (140.57 U/mg protein), and CAT (27.02 U/mg protein) levels. Furthermore, the acute phase response elicited by d-GalN/LPS administration enhanced mRNA expressions of TNF-α, IL-6, IL-10, iNOS-2, and HO-1, which were ameliorated by C. myrrha treatment. Discussion and conclusion: These findings indicate that C. myrrha considerably reduces the oxidative stress of d-GalN/LPS-induced hepatic injury via multiple pathways including adown regulation of inflammatory mediators and cytokines. Such a property might be sufficient to combat cellular damage caused by various conditions that resemble fulminant hepatitis and could be of a potential clinical application.

Zingerone (4-(4-hydroxy-3-methylphenyl)butan-2-one) ameliorates renal function via controlling oxidative burst and inflammation in experimental diabetic nephropathy

Abstract Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals. The treatment with zingerone markedly abrogated ROS levels, inhibited the NF-кB activation and considerably reduced level of other downstream inflammatory molecules (TNF-α, IL-6, IL-1β), furthermore, zingerone treatment improved renal functioning by significantly decreasing the levels of kidney toxicity markers KIM-1, BUN, creatinine, and LDH and suppressed TGF-β. Collectively, these findings indicate that zingerone treatment improved renal function by anti-hyperglycaemic, anti-oxidant, and anti-inflammatory effects, suggesting the efficacy of zingerone in the treatment of DN.

Nepeta deflersiana attenuates isoproterenol-induced myocardial injuries in rats: Possible involvement of oxidative stress, apoptosis, inflammation through nuclear factor (NF)-κB downregulation

BACKGROUND Nepeta deflersiana (Lamiaceae) is a perennial herb used in the Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent. PURPOSE This study explores the phytochemistry of the plant and the cardioprotective effect of N. deflersiana ethanolic extract (NDEE) against isoproterenol (ISP)-induced myocardial injury in rats. DESIGN/METHODS Cardiac function, serum cardiac enzymes, myocardial antioxidants, inflammatory, and apoptotic biomarkers, and histopathological parameters were studied in ISP-injured Wistar rat heart tissues. RESULTS To the best of our knowledge, this is the first study to report the isolation of nine secondary metabolites from this plant: 1α-hydroxy-7α,14α,18-triacetoxy-isopimara-8,15-diene (1), β-sitosterol (2), lupeol (3), ursolic acid (4), 2,3-dihydroxy ursolic acid (5), caffeic acid (6), methyl rosmarinate (7), rosmarinic acid (8), and an irridoid glucoside 8-epi-7-deoxyloganic acid (9). To explain the mechanisms underlying the cardioprotective effect of NDEE, we evaluated the redox-sensitivity of NDEE in ISP-induced cardiac injury. The oral administration of NDEE (50 and 100 mg/kg b.w) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH, and NO) and myocyte injury marker enzymes and inhibited lipid peroxidation (MDA, MPO). Moreover, NDEE downregulated the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-10) and apoptotic markers (caspase-3 and Bax) and upregulated the anti-apoptotic protein Bcl2. Furthermore, NDEE pretreatment significantly downregulated cardiac NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity. Histological data showed that NDEE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the architecture of cardiomyocytes. CONCLUSION NDEE demonstrated strong antioxidant, cardioprotective, anti-inflammatory, and anti-apoptotic potential against myocardial damage. This further endorses the use of N. deflersiana in Yemeni folk medicine against cardiovascular diseases.

Target Based Designing of Anthracenone Derivatives as Tubulin Polymerization Inhibiting Agents: 3D QSAR and Docking Approach

Novel anthracenone derivatives were designed through in silico studies including 3D QSAR, pharmacophore mapping, and molecular docking approaches. Tubulin protein was explored for the residues imperative for activity by analyzing the binding pattern of colchicine and selected compounds of anthracenone derivatives in the active domain. The docking methodology applied in the study was first validated by comparative evaluation of the predicted and experimental inhibitory activity. Furthermore, the essential features responsible for the activity were established by carrying out pharmacophore mapping studies. 3D QSAR studies were carried out for a series of 1,5- and 1,8-disubstituted10-benzylidene-10H-anthracen-9-ones and 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-one derivatives for their antiproliferation activity. Based on the pattern recognition studies obtained from QSAR results, ten novel compounds were designed and docked in the active domain of tubulin protein. One of the novel designed compounds “N1” exhibited binding energy −9.69 kcal/mol and predicted Ki 78.32 nM which was found to be better than colchicine.

Antioxidant and Antimutagenic Activities of Different Fractions from the Leaves of Rhododendron arboreum Sm. and Their GC-MS Profiling

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.