Hepatoprotective effect of taxifolin on cyclophosphamide-induced oxidative stress, inflammation, and apoptosis in mice: Involvement of Nrf2/HO-1 signaling.

Taxifolin (TA) is a natural flavonoid found in many foods and medicinal plants with well-documented antioxidant and anti-inflammatory properties. Cyclophosphamide (CP) is an effective antineoplastic and immunosuppressive agent; however, it is associated with numerous adverse events, including hepatotoxicity. Herein, we aimed to investigate the potential protective effects of TA using a mouse model of CP-induced hepatotoxicity. Mice were co-treated with TA (25 and 50 mg/kg, orally) and CP (30 mg/kg, i.p.) for 10 consecutive days and sacrificed 24 hours later. CP induced increased transaminases (ALT and AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) paralleled with pronounced histopathological alterations in the liver. Moreover, hepatic tissues of CP-injected mice showed increased malondialdehyde (MDA), protein carbonyl, and nitric oxide (NO) levels, accompanied by decreased antioxidant defenses (glutathione [GSH], superoxide dismutase [SOD], and catalase [CAT]). Livers of CP-injected mice also showed increased inflammatory response (nuclear transcription factor kappa-B [NF-κB] p65 activation, increased levels of proinflammatory cytokines tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1ß], and IL-6) and apoptosis (decreased Bcl-2 and increased Bax and caspase-3 expression levels). Remarkably, TA ameliorated markers of liver injury and histological damage in CP-injected mice. TA treatment also attenuated numerous markers of oxidative stress, inflammation, and apoptosis in the liver of CP-injected mice. This was accompanied by increased nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) expression in the liver tissues of CP-injected mice. Taken together, this study indicates that TA may represent a promising new avenue to prevent/treat CP-induced hepatotoxicity and perhaps other liver diseases associated with oxidative stress and inflammation.

Investigation of in vitro Cytotoxicity of Chelidonium majus against Leishmania major.

One of the public health issues in the endemic areas, especially in the Middle East region would be the Leishmaniasis. The suggested cure for leishmaniasis is pentavalent antimonials. These medications have drastic side effects and the risk of relapse. On the other hand, nowadays use of herbal remedies as safe and cost-effective treatments have been increased. Therefore this study was designed to determine in vitro anti-leishmanial activity of methanol extracts of greater celandine (Chelidonium majus) against Leishmania major. Greater celandine extract was added to L. major promastigotes and intra-macrophagic amastigotes. After 24, 48 and 72 h in vitro culture the percentage of promastigotes viability was calculated by direct counting method and MTT assay. Cytotoxicity in intra-macrophagic amastigotes was evaluated by direct counting method. Viability in minimum dose and maximum dose-treated groups (1.5 and 90 µg/ml) after 24 h, was 55.52% and 36.34%, respectively. After 48 h, it was 40% and 25.26% and after 72 h, it was 62.18% and 38.45%, respectively. The half maximal inhibitory concentration (IC50) was 0.92 µg/ml, after 24 h. Cytotoxicity in intra-macrophagic amastigotes treated by 3 µg/ml dose after 24 and 48 h, was 33.23% and 50.34%, respectively. It could be concluded that greater celandine methanolic extract has in vitro cytotoxic effect on the L. major in time and dose-dependent pattern.

Neuropharmacological investigation, ultra-high performance liquid chromatography analysis, and in silico studies of Phyla nodiflora.

The increasing burden of neurological disorders is becoming a worldwide health challenge and researchers are continuously struggling to cure them by utilizing the miraculous medicinal properties of plants. The crude methanolic extract of whole herb of Phyla nodiflora (Pn.Cr) was subjected to phytochemical, antioxidant and neuropharmacological assessment. The Pn.Cr was initially exposed to the in vitro examination for phytocomposition through ultra-high performance liquid chromatography (UHPLC). The Sprague Dawley rats were chronically administered with various doses (100, 200 and 300 mg/kg) of Pn.Cr for one month with subsequent exposure to neurobehavioral and biochemical experimentation. The Pn.Cr exhibited a dose-dependent anxiolytic effect (P < 0.05 in comparison to control) as rats preferred central, illuminated and open arm zones in open field (OFT), light/dark (L/D) and elevated plus maze (EPM) tests. Likewise, scopolamine-induced amnesia was noticeably reversed with P < 0.05 by Pn.Cr as animals showed improved spontaneous alternation, discrimination index and shorter escape latencies in Y-maze, novel object recognition (NOR) and Morris water maze (MWM) tests. Subsequently, in vivo enzymatic assays depicted the reduced acetylcholinesterase and malondialdehyde levels. The levels of oxidative stress combating enzymes (glutathione peroxidase and superoxide dismutase) were increased in a dose-dependent style. The UHPLC detected 22 phytocompounds were further investigated in silico studied to predict the interaction of blood-brain barrier (BBB) crossing phytocompounds with human acetylcholinesterase. The four BBB crossing phytocompounds belonging to flavonoids, chalcones and alkaloids showed possible interaction with the target enzyme. We found that the phytocompounds owned by Pn.Cr might be playing multiple roles in modulation of different pathways to hinder the pathophysiology of neurological disorders including anxiety and Alzheimer's disease.

Spirulina platensis ameliorates the sub chronic toxicities of lead in rabbits via anti-oxidative, anti- inflammatory, and immune stimulatory properties.

Lead acetate (Pb) is an oldest and widespread environmental toxicant that led to cumulative injury in humans and all living organisms through induction of oxidative stress. Spirulina platensis (SP) is a cyanobacteria with strong antioxidant, anti-inflammatory, and immune stimulatory effects. In this study, the ameliorative effect of SP was evaluated against the dietary sub chronic lead toxicities in rabbits. A total number of 75 male New Zealand rabbits were allocated randomly into 5 groups; the first group feed on basal diet alone and served as control group, the second group feed on basal diet + 100 mg Pb /kg diet, the third, fourth, and the fifth groups feed on basal diet + 100 mg Pb /kg diet + SP (0.5, 1, or 1.5 g/kg diet; respectively), the experiment was extended for 8 weeks. Results revealed a significant improvement in some of growth parameters like final body weight and daily weight gain, blood parameters in rabbits treated with SP at level 1.5 g/kg diet followed by those receiving SP 1 g/kg diet. However, a significant decrease in blood parameters, liver function, renal parameters, lipid profiles, oxidative parameters (malondialdehyde and protein carbonyl), heart indices (creatine phosphokinase, creatine kinase-muscle/brain, lactate dehydrogenase), total Pb residues in muscles, and area percent of nuclear factor kappa b immune expression were reported in groups supplemented with different levels of SP. Pathologic analysis of liver, kidneys, and heart revealed moderate to severe degenerative and necrotic changes in Pb- exposed rabbits, which is ameliorated with supplementation of SP in different levels. Conclusively, dietary supplementation of SP at different levels attenuated the cumulative effect of lead in rabbits in dose-dependent manner; this attenuation may be attributed to its anti-oxidative, anti-inflammatory, as well as its immune stimulant effect.