Indigofera tinctoria Linn (Fabaceae) attenuates cognitive and behavioral deficits in scopolamine-induced amnesic mice

Purpose: To investigate the cognition-enhancing effects of aqueous extract of Indigofera tinctoria Linn (ITE, Fabaceae) in experimental amnesic mice.Methods: Scopolamine (2 mg/kg, i.p.) was used to induce amnesia in mice. The cognitive-enhancing activity of the ITE (5, 10 and 20 μg/mL) was studied by passive avoidance response, elevated plus maze and Y-maze behavioral paradigm in normal and scopolamine-induced amnesic mice. Antioxidant activities were also determined based on the ability of ITE to inhibit lipid peroxide, superoxide and hydroxyl radicals.Results: Scopolamine-induced cognitive deficits were significantly reversed by ITE (p < 0.001 at 20 mg/kg) in a dose-dependent fashion in all the behavioral paradigms tested. Furthermore, ITE dosedependently scavenged lipid peroxide, superoxide and hydroxyl free radicals with 50 % inhibition concentration (IC50) of 7.28 ± 0.37, 5.25 ± 0.28 and 7.62 ± 0.43 μg/mL, respectively.Conclusion: ITE possesses cognitive-enhancing properties in amnesic mice due to its potent antioxidant action.Keywords: Indigofera tinctoria, Scopolamine, Lipid peroxidation, Amnesia, Antioxidant, Cognitio

Cuminum cyminum Linn (Apiaceae) extract attenuates MPTP-induced oxidative stress and behavioral impairments in mouse model of Parkinson’s disease

Purpose: To evaluate the protective effects of Cuminum cyminum Linn (Apiaceae, CCY) against 1- methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced oxidative stress and behavioral impairments in mouse model of Parkinson’s disease (PD).Methods: MPTP-intoxicated mice model of PD was used for evaluating the effect of CCY extract on behavioral deficits through rota rod, passive avoidance and open field tasks. The effect of CCY extract on oxidative stress levels were assessed by estimating enzyme status, including superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation(LPO) in brain tissues of MPTP-induced mice.Results: MPTP (25 mg/kg, i.p.)-treated mice resulted in a significant (p < 0.001) behavioral deficit in locomotor behavior (from 56.24 ± 1.21 to 27.64 ± 0.94) and cognitive functions (from 298 ± 3.68 s to 207.28 ± 4.12 s) compared with their respective control groups. Administration of CCY extract (100, 200 and 300 mg/kg, p.o.) for three weeks significantly and dose-dependently improved (p < 0.001 at 300 mg/kg) locomotor and cognitive deficits in MPTP-treated mice. CCY treatment also significantly (p < 0.001 at 300 mg/kg) inhibited MPTP-induced decrease in antioxidant enzyme levels (superoxide dismutase and catalase) and lipid peroxides in mice brain tissues.Conclusion: CCY extract exhibits strong protection against MPTP-induced behavioral deficit through enhancement of antioxidant defense mechanisms. Therefore, CCY may be developed as a therapeutic strategy in the treatment of neurodegeneration seen in PD.Keywords: Cuminum cyminum, Neurodegeneration, Catalase, Superoxide dismutase, Oxidative stress, Parkinson’s diseas

Reactive Oxygen Species and Inhibitors of Inflammatory Enzymes, NADPH Oxidase, and iNOS in Experimental Models of Parkinson's Disease

Reactive oxygen species (ROSs) are emerging as important players in the etiology of neurodegenerative disorders including Parkinson's disease (PD). Out of several ROS-generating systems, the inflammatory enzymes nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and inducible nitric oxide synthase (iNOS) were believed to play major roles. Mounting evidence suggests that activation of NADPH oxidase and the expression of iNOS are directly linked to the generation of highly reactive ROS which affects various cellular components and preferentially damage midbrain dopaminergic neurons in PD. Therefore, appropriate management or inhibition of ROS generated by these enzymes may represent a therapeutic target to reduce neuronal degeneration seen in PD. Here, we have summarized recently developed agents and patents claimed as inhibitors of NADPH oxidase and iNOS enzymes in experimental models of PD

Phosphoinositide 3-kinase inhibitor AS605240 ameliorates streptozotocin-induced Alzheimer’s disease like sporadic dementia in experimental rats

The quest for chemical entities able to curb the action of the phosphoinositide 3-kinase, (PI3K)/protein kinase B (AKT) signaling pathways is evolving as a potential therapeutic strategy for the treatment and/or prevention of neurodegenerative disorders including Alzheimer’s disease (AD). In this study, the effects of a PI3K inhibitor, AS605240 on cognitive dysfunction and antioxidative defense parameters against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced rat model of sporadic AD was evaluated. ICV administration of a single dose of STZ (3 mg/kg) was performed to induce behavioral and biochemical changes in rats using the stereotaxic technique. Animals were administered with varying doses of AS605240 (5, 10 and 15 mg/kg) orally, 1 h before ICV-STZ on day 1 and continued once daily for four weeks. The behavioral parameters (passive avoidance and Morris water maze), antioxidative defense parameters, amyloid-beta (Aβ) protein expression by Western blotting and immunostaining technique were estimated in brain tissue. AS605240 dose-dependently and significantly (p < 0.05 and p < 0.01 and p < 0.001) improved ICV-STZ-induced cognitive impairment and attenuated the altered antioxidative related parameters including superoxide dismutase, lipid peroxidation, glutathione and nitrite levels. Further, the increased Aβ protein expression levels in brain tissue were markedly restored with AS605240 treatment. In conclusion, our study demonstrated that AS605240 exhibited immense potential in attenuating STZ-induced sporadic AD features in rats and may be developed as a therapeutic agent in the treatment and management of sporadic AD

Role of C-Reactive Protein in the Development of Atherosclerosis in Diet-induced Lipidemia in Albino Rats

Purpose: Anethum graveolens Linn. (Umbelliferae, A. graveolens) is a widely used spice with a long history of traditional medicinal use for the treatment of various ailments. The present study examines the anti-stress and cognition-improving effects of A. graveolens extract in a rat model. Methods: Urinary vanillylmandelic acid (VMA) and ascorbic acid were estimated as biomarkers for evaluating antistress activity in rats. Conditioned avoidance response using Cook’s pole climbing apparatus in normal and scopolamine-induced amnestic rats was used to assess cognitive-improving activities. Thiobarbituric acid reactive substances (TBARS) assay was used to evaluate antioxidant activity. Results: Daily administration of A. graveolens at doses of 100, 200 and 300 mg/kg body weight 1 h prior to induction of stress inhibited stress-induced urinary biochemical changes in a dose-dependent manner without altering the levels in normal control groups. Changes in cognition (as determined by the acquisition), retention and recovery in rats were dose-dependent. The extract also produced significant lipid peroxidation inhibition in both rat liver and brain, compared to a reference standard antioxidant, ascorbic acid. Conclusion: The aqueous extract of A. graveolens exhibited significant anti-stress, antioxidant and memory enhancing activities. The study provides a scientific basis for the traditional use of the plant as a culinary spice in food

Anti-Stress and Anti-Amnesic Effects of Coriandrum sativum Linn (Umbelliferae) Extract – an Experimental Study in Rats

Purpose: Coriandrum sativum Linn. (Umbelliferae, C. sativum) is cultivated throughout the world for its use as spice and as a folk medicine. This study deals with the anti-stress and anti-amnestic properties of C. sativum extract in rats. Methods: Urinary levels of vanillylmandelic acid (VMA) and ascorbic acid were used to evaluate antistress activity in rats, while conditioned avoidance response test in normal and scopolamine-induced amnesic rats was used to evaluate anti-amnesic effects. C. sativum extract was also evaluated for its antioxidant activities by inhibition of lipid peroxidation in brain and liver homogenates of the rats. Results: Daily administration of C. sativum extract (100, 200 and 300 mg/kg body weight) 1 h prior to induction of stress significantly decreased the stress-induced urinary levels of VMA from 382.79 ± 10.70 to 350.66 ± 15.15, 291.21 ± 16.53 and 248.86 ± 13.56 μg/kg/24 h and increased the ascorbic acid excretion levels from 66.73 ± 9.25 to 69.99 ± 7.37, 105.28 ± 13.74 and 135.32 ± 12.54 μg/kg/24 h at 100, 200 and 300 mg/kg, respectively, in a dose-dependent fashion without affecting the normal levels in control groups. The amnesic deficits (acquisition, retention and recovery) induced by scopolamine (1mg/kg, i.p.) in rats was reversed by C. sativum dose dependently. The extract also inhibited lipid peroxidation in both rat liver and brain to a greater extent than the standard antioxidant, ascorbic acid. Conclusion: C. sativum may be useful remedy in the management of stress and stress related disorders on account of its multiple actions such as anti-stress, anti-amnestic and antioxidant effects

Inhibitors of Microglial Neurotoxicity: Focus on Natural Products

Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. Recently, much attention has been paid to therapeutic strategies aimed at inhibiting neurotoxic microglial activation. Pharmacological inhibitors of microglial activation are emerging as a result of such endeavors. In this review, natural products-based inhibitors of microglial activation will be reviewed. Potential neuroprotective activity of these compounds will also be discussed. Future works should focus on the discovery of novel drug targets that specifically mediate microglial neurotoxicity rather than neuroprotection. Development of new drugs based on these targets may require a better understanding of microglial biology and neuroinflammation at the molecular, cellular, and systems levels

Salicornia bigelovii Torr Attenuates Neuro-Inflammatory Responses in Lipopolysaccharide-Induced BV-2 Microglia by Regulation of NF-kappa B Signaling

Purpose: To investigate the anti-oxidant and anti-neuroinflammatory effects of Salicornia bigelovii extract (SBE) in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Methods: Anti-oxidant activity was measured using 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay. Cell viability was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyl-tetrazolium bromide (MTT) assay. BV- microglial cells were stimulated with LPS to study the protein expression and production of inflammatory mediators, determined by Western blot analysis. Results: SBE significantly inhibited the DPPH-generated free radicals showing maximum inhibition at 40 µg/mL (p < 0.001). SBE alone did not exhibit any signs of cytotoxicity to BV-2 cells up to 200 µg/mL concentration. The LPS-induced increase in the production of nitric oxide was concentration-dependently suppressed by SBE (p < 0.05 for 10 µg/mL, p < 0.01 at 20 µg/mL and p < 0.001 at 40 µg/mL, respectively). SBE also inhibited the LPS-induced increase in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. Further, the production of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 by LPS-stimulation in BV-2 cells was inhibited by SBE pretreatment. Mechanistic study revealed that SBE acts by regulation of nuclear factor kappa-B signaling pathway in LPS-stimulated BV-2 microglial cells. Conclusion: This study revealed for the first time that SBE possesses anti-oxidant and anti-neuroinflammatory effects and can be developed as a potential therapeutic target in ameliorating microglia-mediated neuroinflammation

Potential Natural Biomolecules Targeting JAK/STAT/SOCS Signaling in the Management of Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by the dysregulation of cytokines and other immune mediators. JAK/STAT is a classical signal transduction pathway involved in various biological processes, and its dysregulation contributes to the key aspects of AD pathogenesis. Suppressor of cytokine signaling (SOCS) proteins negatively regulate the immune-related inflammatory responses mediated by the JAK/STAT pathway. JAK/STAT-mediated production of cytokines including IL-4, IL-13, IL-31, and TSLP inhibits the expression of important skin barrier proteins and triggers pruritus in AD. The expression of SOCS proteins regulates the JAK-mediated cytokines and facilitates maintaining the skin barrier disruptions seen in AD. STATs are crucial in dendritic-cell-activated Th2 cell differentiation in the skin, releasing inflammatory cytokines, indicating that AD is a Th2-mediated skin disorder. SOCS proteins aid in balancing Th1/Th2 cells and, moreover, regulate the onset and maintenance of Th2-mediated allergic responses by reducing the Th2 cell activation and differentiation. SOCS proteins play a pivotal role in inflammatory cytokine-signaling events that act via the JAK/STAT pathway. Therapies relying on natural products and derived biomolecules have proven beneficial in AD when compared with the synthetic regimen. In this review, we focused on the available literature on the potential natural-product-derived biomolecules targeting JAK/STAT/SOCS signaling, mainly emphasizing the SOCS family of proteins (SOCS1, SOCS3, and SOCS5) acting as negative regulators in modulating JAK/STAT-mediated responses in AD pathogenesis and other inflammatory disorders