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

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

Pectinase-treated Panax ginseng ameliorates hydrogen peroxide-induced oxidative stress in GC-2 sperm cells and modulates testicular gene expression in aged rats

AbstractBackgroundTo investigate the effect of pectinase-treated Panax ginseng (GINST) in cellular and male subfertility animal models.MethodsHydrogen peroxide (H2O2)-induced mouse spermatocyte GC-2spd cells were used as an in vitro model. Cell viability was measured using MTT assay. For the in vivo study, GINST (200 mg/kg) mixed with a regular pellet diet was administered orally for 4 mo, and the changes in the mRNA and protein expression level of antioxidative and spermatogenic genes in young and aged control rats were compared using real-time reverse transcription polymerase chain reaction and western blotting.ResultsGINST treatment (50 μg/mL, 100 μg/mL, and 200 μg/mL) significantly (p < 0.05) inhibited the H2O2-induced (200 μM) cytotoxicity in GC-2spd cells. Furthermore, GINST (50 μg/mL and 100 μg/mL) significantly (p < 0.05) ameliorated the H2O2-induced decrease in the expression level of antioxidant enzymes (peroxiredoxin 3 and 4, glutathione S-transferase m5, and glutathione peroxidase 4), spermatogenesis-related protein such as inhibin-α, and specific sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor) in GC-2spd cells. Similarly, the altered expression level of the above mentioned genes and of spermatogenesis-related nectin-2 and cAMP response element-binding protein in aged rat testes was ameliorated with GINST (200 mg/kg) treatment. Taken together, GINST attenuated H2O2-induced oxidative stress in GC-2 cells and modulated the expression of antioxidant-related genes and of spermatogenic-related proteins and sex hormone receptors in aged rats.ConclusionGINST may be a potential natural agent for the protection against or treatment of oxidative stress-induced male subfertility and aging-induced male subfertility

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

Potential Nutrients from Natural and Synthetic Sources Targeting Inflammaging—A Review of Literature, Clinical Data and Patents

Inflammaging, the steady development of the inflammatory state over age is an attributable characteristic of aging that potentiates the initiation of pathogenesis in many age-related disorders (ARDs) including neurodegenerative diseases, arthritis, cancer, atherosclerosis, type 2 diabetes, and osteoporosis. Inflammaging is characterized by subclinical chronic, low grade, steady inflammatory states and is considered a crucial underlying cause behind the high mortality and morbidity rate associated with ARDs. Although a coherent set of studies detailed the underlying pathomechanisms of inflammaging, the potential benefits from non-toxic nutrients from natural and synthetic sources in modulating or delaying inflammaging processes was not discussed. In this review, the available literature and recent updates of natural and synthetic nutrients that help in controlling inflammaging process was explored. Also, we discussed the clinical trial reports and patent claims on potential nutrients demonstrating therapeutic benefits in controlling inflammaging and inflammation-associated ARDs

Apigenin Isolated from Carduus crispus Protects against H2O2-Induced Oxidative Damage and Spermatogenic Expression Changes in GC-2spd Sperm Cells

Testicular oxidative stress is one of the most common factors underlying male infertility. Welted thistle, Carduus crispus Linn., and its bioactive principles are attracting scientific interest in treating male reproductive dysfunctions. Here, the protective effects of apigenin isolated from C. crispus against oxidative damage induced by hydrogen peroxide (H2O2) and dysregulation in spermatogenesis associated parameters in testicular sperm cells was investigated. Cell viabilities, ROS scavenging effects, and spermatogenic associated molecular expressions were measured by MTT, DCF-DA, Western blotting and real-time RT-PCR, respectively. A single peak with 100% purity of apigenin was obtained in HPLC conditions. Apigenin treated alone (2.5, 5, 10 and 20 &micro;M) did not exhibit cytotoxicity, but inhibited the H2O2-induced cellular damage and elevated ROS levels significantly (p &lt; 0.05 at 5, 10 and 20 &micro;M) and dose-dependently. Further, H2O2-induced down-regulation of antioxidant (glutathione S-transferases m5, glutathione peroxidase 4, and peroxiredoxin 3) and spermatogenesis-associated (nectin-2 and phosphorylated-cAMP response element-binding protein) molecular expression in GC-2spd cells were attenuated by apigenin at both protein and mRNA levels (p &lt; 0.05). In conclusion, our study showed that apigenin isolated from C. crispus might be an effective agent that can protect ROS-induced testicular dysfunctions

Korean Red Ginseng (Panax ginseng Meyer) with enriched Rg3 ameliorates chronic intermittent heat stress–induced testicular damage in rats via multifunctional approach

Background: Panax ginseng Meyer, known as Korean Red Ginseng (KRG), is one of the important age-old traditional herbs used in boosting libido and improving male fertility. In this study, the effects of Rg3-enriched KRG extract (KGC04P) on heat stress–induced testicular damage in experimental rats was evaluated. Methods: Male rats (Sprague-Dawley) were divided into four groups (n = 10): normal control (NC), heat-stressed control (HC), heat-stressed plus KGC04P-100 mg/kg (HK100), and heat-stressed plus KGC04P-200 mg/kg (HK200) groups. Starting 1 week prior to heat stress, animals were administered orally with KGC04P (100 and 200 mg/kg) mixed with a regular pellet diet and continued for 25 weeks. Heat stress was induced to HC, HK100, and HK200 groups by intermittently exposing the animals to high temperatures (32 ± 1°C, 2 h/day). After 6 months, animals were euthanized under general anesthesia with carbon dioxide and evaluated for various parameters in serum and testicular tissue by using Western blotting, biochemical kits, and reverse transcription-polymerase chain reaction. Results: Significant (p < 0.05) alterations in several parameters, such as body/organ weight, sperm kinematics, and lipid metabolism marker levels, in the serum and testis of rats were observed. Further, the expression of testicular antioxidant enzymes, inflammatory cytokines, sex hormonal receptors, and spermatogenesis-related genes were also affected significantly (p < 0.05) in the heat-stressed group. However, KGC04P prevented the heat stress–induced changes in rats significantly (p < 0.05) at both concentrations. Conclusion: KGC04P attenuated heat stress–induced testicular damage by a multifunctional approach and can be developed as an excellent therapeutic agent for hyperthermia-mediated male infertility. Keywords: Antioxidants, Heat stress, Korean Red Ginseng, Sex hormones, Spermatogenesi

Cordycepin, an Active Constituent of Nutrient Powerhouse and Potential Medicinal Mushroom <i>Cordyceps militaris</i> Linn., Ameliorates Age-Related Testicular Dysfunction in Rats

Age-related male sexual dysfunction covers a wide variety of issues, together with spermatogenic and testicular impairment. In the present work, the effects of cordycepin (COR), an active constituent of a nutrient powerhouse Cordyceps militaris Linn, on senile testicular dysfunction in rats was investigated. The sperm kinematics, antioxidant enzymes, spermatogenic factors, sex hormone receptors, histone deacetylating sirtuin 1 (SIRT1), and autophagy-related mammalian target of rapamycin complex 1 (mTORC1) expression in aged rat testes were evaluated. Sprague Dawley rats were divided into young control (2-month-old; YC), aged control (12-month-old; AC), and aged plus COR-treated groups (5 (COR-5), 10 (COR-10), and 20 (COR-20) mg/kg). The AC group showed reduced sperm kinematics and altered testicular histomorphology compared with the YC group (p &lt; 0.05). However, compared with the AC group, the COR-treated group exhibited improved sperm motility, progressiveness, and average path/straight line velocity (p &lt; 0.05&#8211;0.01). Alterations in spermatogenesis-related protein and mRNA expression were significantly ameliorated (p &lt; 0.05) in the COR-20 group compared with the AC group. The altered histone deacetylating SIRT1 and autophagy-related mTORC1 molecular expression in aged rats were restored in the COR-20 group (p &lt; 0.05). In conclusion, the results suggest that COR holds immense nutritional potential and therapeutic value in ameliorating age-related male sexual dysfunctions

Pectinase-treated Panax ginseng protects against chronic intermittent heat stress-induced testicular damage by modulating hormonal and spermatogenesis-related molecular expression in rats

Background: Elevated testicular temperature disrupts spermatogenesis and causes infertility. In the present study, the protective effect of enzymatically biotransformed Panax ginseng Meyer by pectinase (GINST) against chronic intermittent heat stress-induced testicular damage in rats was investigated. Methods: Male Sprague–Dawley rats (4 wk old, 60–70 g) were divided into four groups: normal control (NC), heat-stress control (HC), heat-stress plus GINST-100 mg/kg (HG100), and heat-stress plus GINST-200 mg/kg (HG200) treatment groups. Each dose of GINST (100 mg/kg and 200 mg/kg) was mixed separately with a regular pellet diet and was administered orally for 24 wk. For inducing heat stress, rats in the NC group were maintained at 25°C, whereas rats in the HC, HG100, and HG200 groups were exposed to 32 ± 1°C for 2 h daily for 6 mo. At week 25, the testes and serum from each animal were analyzed for various parameters. Results: Significant (p < 0.01) changes in the sperm kinematic values and blood chemistry panels were observed in the HC group. Furthermore, spermatogenesis-related molecules, sex hormone receptors, and selected antioxidant enzyme expression levels were also altered in the HC group compared to those in the NC group. GINST (HS100 and HS200) administration significantly (p < 0.05) restored these changes when compared with the HC group. For most of the parameters tested, the HG200 group exhibited potent effects compared with those exhibited by the HG100 group. Conclusion: GINST may be categorized as an important medicinal herb and a potential therapeutic for the treatment of male subfertility or infertility caused by hyperthermia