Antidepressant activity of phytochemicals of Mangifera indica seeds assisted by integrated computational analysis.

Mangifera indica L., also known as mango, is a tropical fruit that belongs to the Anacardiaceae family and is prized for its juiciness, unique flavour, and worldwide popularity. The current study aimed to probe into antidepressant power (ADP) of MIS in animals and confirmation of ADP with in silico induced-fit molecular docking. The depression model was prepared by exposing mice to various stressors from 9:00 am to 2:00 pm during 42 days study period. MIS extract and fluoxetine were given daily for 30 min before exposing animals to stressors. ADP was evaluated by various behavioural tests and biochemical analysis. Results showed increased physical activity in mice under behavioural tests, plasma nitrite and malondialdehyde (MDA) levels and monoamine oxidase A (MAO-A) activity decreased dose-dependently in MIS treated mice and superoxide dismutases (SOD) levels increased in treated groups as compared to disease control. With the peculiar behaviour and significant interactions of the functional residues of target proteins with selected ligands along with the best absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, it is concluded that catechin could be the best MAO-A inhibitor at a binding energy of -8.85 kcal/mol, and two hydrogen bonds were generated with Cys406 (A) and Gly443 (A) residues of the active binding site of MAO-A enzyme. While catechin at -6.86 kcal/mol generated three hydrogen bonds with Ala263 (A) and Gly434 (A) residues of the active site of monoamine oxidase B (MAO-B) enzyme and stabilized the best conformation. Therefore, it is highly recommended to test the selected lead-like compound catechin in the laboratory with biological system analysis to confirm its activity as MAO-A and MAO-B inhibitors so it can be declared as one of the novel therapeutic options with anti-depressant activity. Our findings concluded that M. indica seeds could be a significant and alternative anti-depressant therapy.

Protection by vitamin D against high-glucose-induced damage in retinal pigment epithelial cells.

Diabetic retinopathy (DR) is a diabetes-associated complication characterized by irreversible deterioration of the microvessels within the retina, leading subsequently to severe retinal damage and vision loss. Vitamin D (VITD), a steroid hormone, plays multiple physiological functions in cellular homeostasis. Deficiency of VITD has been suggested to be associated with DR. To study the potential protective function of VITD in DR, high-glucose-treated ARPE-19 cells and STZ-induced diabetic mice were used as in vitro and in vivo models. The protective effects of VITD were assessed based on the changes of expression of antioxidant enzymes and cytokines in high-glucose-treated retinal pigment epithelial (RPE) cells and in the retina and RPE of diabetic and VITD-treated diabetic mice. The present study demonstrated that exposure to a high level of glucose caused upregulation of pro-inflammatory cytokines and a decrease in anti-oxidant enzyme expression in both in vitro and in vivo models. VITD treatment increased cell viability, reduced reactive oxygen species (ROS) production and caspase-3/7 activities in high-glucose-treated RPE cells. Our data suggest that VITD can protect the retina and RPE from high-glucose-induced oxidative damage and inflammation.

Anti-Tumor Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) Alone and in Combination with Cyclophosphamide and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice.

Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) decreased the tumor volume and inhibition rate, tumor markers (AFP and CEA), serum level of liver and kidney, LPO and NO, TNF-α level, as well as the expression level of Bcl-2 in comparison with the mice in the C2 group; while 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) improved the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. Conclusions: According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor; nevertheless, further investigations, particularly in clinical setting, are required to confirm these results.

Gypenosides attenuate retinal degeneration in a zebrafish retinitis pigmentosa model.

Retinitis pigmentosa (RP) is a collection of heterogenous genetic retinal disorders resulting in cumulative retinal deterioration involving progressive loss of photoreceptors and eventually in total blindness. Oxidative stress plays a central role in this photoreceptor loss. Gypenosides (Gyp) are the main functional component isolated from the climbing vine Gynostemma pentaphyllum and have been shown to defend cells against the effects of oxidative stress and inflammation, providing protection in experimentally-induced optic neuritis. The zebrafish model has been used to investigate a range of human diseases. Previously we reported early retinal degeneration in a mutant zebrafish line carrying a point-nonsense mutation in the retinitis pigmentosa GTPase regulator interacting protein 1 (rpgrip1) gene that is mutated in RP patients. The current study investigated the potential protective effects of Gyp against photoreceptor degeneration in the Rpgrip1 deleted zebrafish. Rpgrip1 mutant zebrafish were treated with 5 µg/ml of Gyp in E3 medium from 6 h post fertilization (hpf) till 1 month post fertilization (mpf). Rpgrip1 mutant zebrafish treated with 5 µg/ml of Gyp showed a significant decrease by 68.41% (p = 0.0002) in photoreceptor cell death compared to that of untreated mutant zebrafish. Expression of antioxidant genes catalase, sod1, sod2, gpx1, gclm, nqo-1 and nrf-2 was significantly decreased in rpgrip1 mutant zebrafish eyes by 61.51%, 77.40%, 60.11%, 81.17%, 72.07%, 78.95% and 85.42% (all p < 0.0001), respectively, when compared to that of wildtype zebrafish; superoxide dismutase and catalase activities, and glutathione levels in rpgrip1 mutant zebrafish eyes were significantly decreased by 87.21%, 21.55% and 96.51% (all p < 0.0001), respectively. There were marked increases in the production of reactive oxygen species (ROS) and malondialdehyde (MDA) by 2738.73% and 510.69% (all p < 0.0001), respectively, in rpgrip1 mutant zebrafish eyes; expression of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α was also significantly increased by 150.11%, 267.79% and 190.72% (all p < 0.0001), respectively, in rpgrip1 mutant zebrafish eyes, compared to that of wildtype zebrafish. Treatment with Gyp significantly counteracted these effects. This study indicates that Gyp has a potential role in the treatment of RP.

Carnosic acid attenuates acrylamide-induced retinal toxicity in zebrafish embryos.

Acrylamide (ACR) is a water-soluble chemical used widely in industry, which can be formed in tobacco smoke and in starchy foods cooked at high temperatures. ACR is considered to be a neurotoxin, genotoxin and carcinotoxin. Previous studies reported that ACR-exposed workers and experimental animals exhibited visual function defects, although the underlying mechanisms have not been elucidated. In this study, we found that zebrafish embryos exposed to 1 mM and 2 mM ACR showed significantly increased reactive oxygen species (ROS), decreased expression of the antioxidant genes Sod1, Sod2, Catalase, Gpx1 and Nrf2, reduced activity of superoxide dismutase (SOD) and catalase, and elevated malondialdehyde (MDA), compared with control embryos. ACR exposure caused loss of both rod and cone photoreceptor cells through Caspase-3-dependent apoptotis. When embryos were simultaneously exposed to ACR and the natural antioxidative substance carnosic acid (CA), the presence of the latter (10 µM) markedly counteracted the above ACR-induced toxic effects. Our data suggest that CA can protect photoreceptor cells against ACR-induced oxidative damage and has a potential for neuroprotection of visual function in humans exposed to ACR.

Community pharmacists' skills and practice regarding dispensing fiscalized substances: a cross-sectional survey.

Background: The use of drugs containing fiscalized substances is essential in different medical areas, including pain management, obstetric emergencies, and the treatment of mental disorders. However, due to their potential for abuse and negative health effects, the dispensing of these substances demands pharmacists with the requisite skills and practice. Objective: This study assesses the skills and practices of pharmacy personnel in the United Arab Emirates (UAE) regarding the dispensing of tramadol, a medication containing fiscalized substances, in community pharmacies. Methodology: A cross-sectional study was conducted. Community Pharmacies were chosen via random sampling, and seven well-trained final year pharmacy students visited them and conducted face-to-face interviews. The survey tool covered items highlighting the demographic data of the subjects, and items on the practice and skills regarding dispensing the fiscalized substances. The content validity ratio values of all tool questions were more than 0.78, suggesting acceptable validity and the Cronbach's α of 0.75 showed as acceptable internal reliability. The primary outcome measures of interest were the skills and practice regarding dispensing Fiscalized substances. Results: A total of 612 pharmacists were recruited in the study. The average practice score was 80%. There was a statistically significant association (p < 0.05) between practices about dispensing fiscalized substances and gender, age group, pharmacy type, work experience, university of graduation, and receiving training on epilepsy and antiepileptic drugs. Conclusion: The results implied that competency and experience are vital factors for the dispensing of tramadol. Contextually, the majority of the pharmacists evidently have the requisite competencies to provide high-quality and proper medical care, with regards to dispensing tramadol, which will minimize drug abuse and medication errors, and assist outpatients to manage their drugs containing fiscalized substances.

Community pharmacists' perspectives on cardiovascular disease pharmaceutical care in the United Arab Emirates: a questionnaire survey-based analysis.

Background: Community pharmacists play an intermediary role between prescribing physicians and patients in the United Arab Emirates (UAE) and thus are responsible for ensuring that patients receive optimal cardiovascular disease (CVD) pharmaceutical care. Methods: we used a cross-sectional design to assess the perceptions and practices of community pharmacists concerning pharmaceutical care for patients with CVD. A trained researcher visited randomly selected community pharmacies and used a structured questionnaire to conduct in-person interviews with pharmacists. The questionnaire collected demographic data and information on perceptions and practices regarding CVD pharmaceutical care. Results: Five hundred and fifty-one participants were recruited. The average participant age (mean ± SD) was 35 ± 2.7 years. The average perception score regarding CVD prevention and management was 75.6% (95% confidence interval [CI] 77.1%-74.2%), and the average practice score for CVD prevention and management was 87.1% (95% CI 76.5%-79.6%). Bivariate analysis revealed that gender (p = 0.001), education level (p < 0.001), pharmacy position (p = 0.004), work experience (p < 0.001), number of patients served per day (p < 0.001) and being trained on CVD prevention and management (p < 0.001) were significantly associated with perceptions about the prevention and management of CVD. Better practice scores were seen among older participants (OR 1.01; 95% CI 1-1.019), postgraduates (OR 1.77; 95% CI 1.66-1.89), workers at chain pharmacies (OR 1.24; 95% CI 1.11-1.39), pharmacists in charge (OR 1.22; 95% CI 1.01-1.47), pharmacists with >10 years of experience (OR 11.3; 95% CI 6.01-15.62), pharmacists with 6-10 years of experience (OR 4.42; 95% CI 3.90-5) and pharmacists trained on CVD prevention and management (OR 1.29; 95% CI 1.15-1.46). Conclusion: Pharmacy practitioners working in community pharmacies in the UAE actively engage in delivering pharmaceutical care to patients, playing a role in CVD management and prevention. However, they showed low levels of involvement in other healthcare services, specifically in screening and measuring patients' weight, glucose levels, and blood pressure, monitoring treatment responses, maintaining medical records, and reviewing medication refill histories. Activities such as educating patients, providing medication counseling, offering support for treatment adherence, and fostering collaborative relationships with other healthcare providers should be encouraged among UAE community pharmacists to ensure the provision of high-quality patient care.

Factors influencing community pharmacists' knowledge about women's issues in epilepsy.

Background: Previous studies have highlighted instances where pharmacists lacked knowledge regarding women's health issues related to epilepsy. Objectives: To assess UAE community pharmacists' knowledge, toward women's issues in epilepsy. Methods: a cross-sectional research method was employed. A team of seven pharmacy students in their final year visited a randomly selected sample of community pharmacies in the UAE and face-to-face interviews were conducted with the pharmacists using a structured questionnaire. The questionnaire includes two parts; Eight questions designed to elicit data about the demographics of the study participants and 12 questions eliciting insights into the participants' knowledge of women's issues in epilepsy. Results: A total of 412 community pharmacist were recruited in the study. The overall level of knowledge about women's issues in epilepsy was good and the average knowledge score was 81% with a 95% confidence interval (CI) [79.1, 82.7%]. The results of multivariate analysis showed higher knowledge scores in chain pharmacies (OR 1.37; 95% CI 1.12-1.67), Chief pharmacists (OR 1.44; 95% CI 1.01-2.06), Pharmacists in charge (OR 3.46; 95% CI 2.7-4.45), pharmacists with 1-5 Years of experience (OR 2.87; 95% CI 1.71-4.82), pharmacists with 6-10 Years (OR 2.63; 95% CI 1.58-4.38), pharmacists with >10 years (OR 3.13; 95% CI 2.03-4.83), graduation form regional universities (OR 1.37; 95% CI 1.12-1.67), graduation form international universities (OR 1.73; 95% CI 1.36-2.20) and receiving a training on epilepsy (OR 1.36; 95% CI 1.12-1.67). Conclusion: While the findings reveal an overall promising level of knowledge among community pharmacists regarding the issues faced by women with epilepsy, pinpointing which clinical and demographic factors have the most significant impact on this knowledge would permit the implementation of tailored educational interventions. Workshops and modules targeting the issues faced by women with epilepsy would further raise the knowledge and competence among community pharmacists in this area, ensuring better pharmaceutical care for this population.

Antitumor Activity of Royal Jelly and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice.

Objective: The present study was aimed at evaluating the antitumor effects of royal jelly (RJ) obtained from Apis mellifera compared with cyclophosphamide against the Ehrlich solid tumors (EST) in mice. Methods: Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO), nitric oxide (NO), antioxidant enzymes (glutathione peroxidase (GPx), catalase enzyme (CAT), and superoxide dismutase enzyme activity (SOD)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in EST mice treated with RJ (200 and 400 mg/kg orally once a day for 2 weeks). Results: The results showed that treatment of EST-suffering mice with RJ at the doses of 200 and 400 mg/kg causes significant reduction in tumor volume and inhibition rate, body weight, tumor markers (AFP and CEA), serum level of liver and kidney, LPO and NO, TNF-α level, as well as the expression level of Bcl-2 in comparison with the EST mice receiving the normal saline; whereas RJ at the doses of 200 and 400 mg/kg/day significantly increased (p < 0.05) the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. Conclusion: The findings revealed that oral administration of royal jelly especially at the doses of 200 and 400 mg/kg exhibited promising antitumor effects against EST in mice through induction of apoptosis as well as its antioxidant and anti-inflammatory effects, which suggest it as a novel anticancer agent against tumor; however, additional surveys especially in clinical setting are necessary to approve these findings.

Anti-kindling effect of Ginkgo biloba leaf extract and L-carnitine in the pentylenetetrazol model of epilepsy.

Epilepsy is one of the most common serious brain disorders, affecting about 1% of the population all over the world. Ginkgo biloba extract (GbE) and L-carnitine (LC) reportedly possess the antioxidative activity and neuroprotective potential. In this report, we investigated the possible protective and therapeutic effects of GbE and LC against pentylenetetrazol (PTZ)-induced epileptic seizures in rat hippocampus and hypothalamus. Adult male albino rats were equally divided into eight groups: control, GbE (100 mg/kg), LC (300 mg/kg), PTZ (40 mg/kg), protective groups (GbE + PTZ and LC + PTZ), and therapeutic groups (PTZ + GbE and PTZ + LC). The oxidative stress, antioxidant, and neurochemical parameters, viz., malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), acetylcholine esterase (AchE), dopamine (DA), norepinephrine (NE), and serotonin (5-HT), in the hippocampal and hypothalamic regions have been evaluated. PTZ injection leads to an increase in the seizure score, the levels of MDA and NO, and to a decrease in the activity of GSH, SOD, CAT, and GPx. Besides, monoamine neurotransmitters, DA, NE, and 5-HT, were depleted in PTZ-kindled rats. Furthermore, PTZ administration caused a significant elevation in the activity of AchE. Hippocampal and hypothalamic sections from PTZ-treated animals were characterized by severe histopathological alterations and, intensely, increased the ezrin immunolabeled astrocytes. Pre- and post-treatment of PTZ rats with GbE and LC suppressed the kindling acquisition process and remarkably alleviated all the aforementioned PTZ-induced effects. GbE and LC have potent protective and therapeutic effects against PTZ-induced kindling seizures via the amelioration of oxidative/antioxidative imbalance, neuromodulatory, and antiepileptic actions.

Sarcococca saligna Hydroalcoholic Extract Ameliorates Arthritis in Complete Freund's Adjuvant-Induced Arthritic Rats via Modulation of Inflammatory Biomarkers and Suppression of Oxidative Stress Markers.

Traditionally, Sarcococca saligna has been used for the treatment of arthritis and many other inflammatory disorders. The current study was planned to give scientific evidence to this traditional use of S. saligna. Phytochemical profiling of SSME was carried out by using electrospray ionization mass spectrometry (ESI-MS/MS). Complete Freund's adjuvant (CFA), 150 µL was injected in the subplantar region of the left hind paw to induce arthritis in rats. Aqueous methanolic extract of S. saligna (SSME) was administered orally at 250, 500, or 1000 mg/kg dose from the 7th day to the 28th day of the study to explore its anti-arthritic potential. Histopathological and radiographic assessment of joints and enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) analyses were performed. Determination of oxidative stress biomarkers in the serum was also carried out. ESI-MS/MS identified ten such phytoconstituents which have reported strong anti-inflammatory and anti-arthritic activity. The SSME extract considerably reduced paw inflammation and arthritic index, subdued cachexia, and significantly improved biochemical and hematological changes. Oxidative stress decreased in SSME administered rats dose-dependently. Histopathological and radiographic evaluations also showed the anti-arthritic activity of SSME, which was associated with the downregulation of tumor necrosis factor (TNF)-α, nuclear factor (NF)-kB, COX-2, interleukin (IL)-6, and IL-1ß and upregulation of I-kB, IL-4, and IL-10, in contrast to disease group rats. The outcomes of the study proposed that S. saligna have anti-arthritic potential, supporting its traditional use for rheumatoid arthritis treatment.

Cross-Talk between Obesity and Diabetes: Introducing Polyphenols as an Effective Phytomedicine to Combat the Dual Sword Diabesity.

Obesity-associated diabetes mellitus, a chronic metabolic affliction accounting for 90% of all diabetic patients, has been affecting humanity extremely badly and escalating the risk of developing other serious disorders. It is observed that 0.4 billion people globally have diabetes, whose major cause is obesity. Currently, innumerable synthetic drugs like alogliptin and rosiglitazone are being used to get through diabetes, but they have certain complications, restrictions with severe side effects, and toxicity issues. Recently, the frequency of plant-derived phytochemicals as advantageous substitutes against diabesity is increasing progressively due to their unparalleled benefit of producing less side effects and toxicity. Of these phytochemicals, dietary polyphenols have been accepted as potent agents against the dual sword "diabesity". These polyphenols target certain genes and molecular pathways through dual mechanisms such as adiponectin upregulation, cannabinoid receptor antagonism, free fatty acid oxidation, ghrelin antagonism, glucocorticoid inhibition, sodium-glucose cotransporter inhibition, oxidative stress and inflammation inhibition etc. which sequentially help to combat both diabetes and obesity. In this review, we have summarized the most beneficial natural polyphenols along with their complex molecular pathways during diabesity.

Assessment of the Antigenotoxic Effects of Alginate and ZnO/Alginate-Nanocomposites Extracted from Brown Alga Fucus vesiculosus in Mice.

Mitomycin C (MMC) is an alkylating chemotherapy drug that could induce DNA damage and genetic alteration. It has been used as a model mutagen for in vivo and in vitro studies. The current study aimed to evaluate the protective role of Zinc oxide alginate-nanocomposites (ZnO-Alg/NCMs) against MMC-induced genotoxicity in mice. Animals were treated as follows: the control group, the groups treated with Algin (400 mg/kg b.w), the groups treated with ZnO-Alg/NCMs (400 mg/kg b.w), the group treated with MMC, and the groups treated with MMC plus Algin or ZnO-Alg/NCMs. Pre-treatment with Algin and ZnO-Alg/NCMs was repeated for one or seven days. Zinc oxide alginate-nanocomposites (ZnO-Alg/NCMs) were synthesized with the aim of incorporating the intrinsic properties of their constituents as an antigenotoxic substance. In this study, alginate was extracted from the brown marine alga Fucus vesiculosus, Zinc oxide nanoparticles were synthesized by using water extract of the same alga, and loaded in alginate to synthesize ZnO-Alg/NCMs. ZnO-NPs and ZnO-Alg/NCMs were characterized by TEM, SEM, EDX, and Zeta potential. The obtained results confirmed that by TEM and SEM, ZnO-NPs are rod shaped which modified, when loaded in alginate matrix, into spherical shape. The physical stability of ZnO-Alg/NCMs was reported to be higher than ZnO-NPs due to the presence of more negative charges on ZnO-Alg/NCMs. The EDX analysis indicated that the amount of zinc was higher in ZnO-NPs than ZnO-Alg/NCMs. The in vivo results showed that treatment with MMC induced genotoxic disturbances. The combined treatment with Algin and ZnO-Alg/NCMs succeeded in inducing significant protection against MMC. It could be concluded that ZnO-Algin/NCMs is a promising candidate to protect against MMC-induced genotoxicity.

Oxysterols and retinal degeneration.

Retinal degeneration, characterised by the progressive death of retinal neurons, is the most common cause of visual impairment. Oxysterols are the cholesterol derivatives produced via enzymatic and/or free radical oxidation that regulate cholesterol homeostasis in the retina. Preclinical and clinical studies have suggested a connection between oxysterols and retinal degeneration. Here, we summarise early and recent work related to retina oxysterol-producing enzymes and the distribution of oxysterols in the retina. We examine the impact of loss of oxysterol-producing enzymes on retinal pathology and explore the molecular mechanisms associated with the toxic or protective roles of individual oxysterols in different types of retinal degeneration. We conclude that increased efforts to better understand the oxysterol-associated pathophysiology will help in the development of effective retinal degeneration therapies. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.

Overexpression of STARD3 attenuates oxidized LDL-induced oxidative stress and inflammation in retinal pigment epithelial cells.

Age-related macular degeneration (AMD) is the most common cause of visual disorder in aged people and may lead to complete blindness with ageing. The major clinical feature of AMD is the presence of cholesterol enriched deposits underneath the retinal pigment epithelium (RPE) cells. The deposits can induce oxidative stress and inflammation. It has been suggested that abnormal cholesterol homeostasis contributes to the pathogenesis of AMD. However, the functional role of defective cholesterol homeostasis in AMD remains elusive. STARD proteins are a family of proteins that contain a steroidogenic acute regulatory protein-related lipid transfer domain. There are fifteen STARD proteins in mammals and some, such as STARD3, are responsible for cholesterol trafficking. Previously there was no study of STARD proteins in retinal cholesterol metabolism and trafficking. Here we examined expression of the Stard3 gene in mouse retinal and RPE cells at ages of 2 and 20 months. We found that expression of Stard 3 gene transcripts in both mouse RPE and retina was significantly decreased at age of 20 months when compared to that of age 2 months old. We created a stable ARPE-19 cell line overexpressing STARD3 and found this resulted in increased cholesterol efflux, reduced accumulation of intracellular oxidized LDL, increased antioxidant capacity and lower levels of inflammatory cytokines. The data suggested that STARD3 is a potential target for AMD through promoting the removal of intracellular cholesterol and slowing the disease progression.

Gypenosides Alleviate Cone Cell Death in a Zebrafish Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a group of visual disorders caused by mutations in over 70 genes. RP is characterized by initial degeneration of rod cells and late cone cell death, regardless of genetic abnormality. Rod cells are the main consumers of oxygen in the retina, and after the death of rod cells, the cone cells have to endure high levels of oxygen, which in turn leads to oxidative damage and cone degeneration. Gypenosides (Gyp) are major dammarane-type saponins of Gynostemma pentaphyllum that are known to reduce oxidative stress and inflammation. In this project we assessed the protective effect of Gyp against cone cell death in the rpgrip1 mutant zebrafish, which recapitulate the classical pathological features found in RP patients. Rpgrip1 mutant zebrafish were treated with Gyp (50 µg/g body weight) from two-months post fertilization (mpf) until 6 mpf. Gyp treatment resulted in a significant decrease in cone cell death compared to that of untreated mutant zebrafish. A markedly low level of reactive oxygen species and increased expression of antioxidant genes were detected in Gyp-incubated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Similarly, the activities of catalase and superoxide dismutase and the level of glutathione were significantly increased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Gyp treatment also decreased endoplasmic reticulum stress in rpgrip1 mutant eyes. Expression of proinflammatory cytokines was also significantly decreased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Network pharmacology analysis demonstrated that the promotion of cone cell survival by Gyp is possibly mediated by multiple hub genes and associated signalling pathways. These data suggest treatment with Gyp will benefit RP patients.

Anti-Parkinson's evaluation of Brassica juncea leaf extract and underlying mechanism of its phytochemicals.

Background: Parkinson's disease (PD) is associated with progressive neuronal damage and dysfunction. Oxidative stress helps to regulate neurodegenerative and neuronal dysfunction. Natural compounds could attenuate oxidative stress in a variety of neurological disorders. B. juncea is a rich source of antioxidants. The present study aimed to evaluate the therapeutic potential of B. juncea leaves for the treatment of PD by applying behavioral, in vivo and in silico studies. For in vivo studies rats were divided into six groups (n = 6). Group-I served as normal control (vehicle control). Group-II was disease control (haloperidol 1 mg/kg). Group-III was kept as a standard group (L-Dopa 100 mg/kg + carbidopa 25 mg/kg). Groups (IV-VI) were the treatment groups, receiving extract at 200-, 400- and 600 mg/kg doses respectively, for 21 days orally. Results: In vivo study results showed that the extract was found to improve muscles strength, motor coordination, and balance in PD. These behavioral outcomes were consistent with the recovery of endogenous antioxidant defence in biochemical analysis which was further corroborated with histopathological ameliorations. Dopamine levels increased and monoamine oxidase B (MAO-B) levels decreased dose-dependently in the brain during the study. Herein, we performed molecular docking analysis of the proposed extracted phytochemicals has explained that four putative phytochemicals (sinapic acid, rutin, ferulic acid, and caffeic acid) have presented very good results in terms of protein-ligand binding interactions as well as absorption, distribution, metabolism, excretion & toxicity (ADMET) profile estimations. Conclusion: The undertaken study concluded the anti-Parkinson activity of B. juncea and further suggests developments on its isolated compounds in PD therapeutics.

Tauroursodeoxycholic Acid Protects Retinal Pigment Epithelial Cells from Oxidative Injury and Endoplasmic Reticulum Stress In Vitro.

Retinal degeneration is characterized by the dysfunction of retinal cells. Oxidative and endoplasmic reticulum (ER) stress play an important role in the pathogenesis and progression of retinal degeneration. Tauroursodeoxycholic acid (TUDCA) has been demonstrated to have protective effects in in vitro and in vivo retinal degeneration models. To fully understand the molecular mechanisms of TUDCA's protection, we first treated human retinal pigment epithelial (RPE) cells, ARPE-19, with H2O2 or H2O2 plus TUDCA for 24 h. RPE cells co-exposed to TUDCA had higher cell viability and lower cell death rate compared to cells exposed to H2O2 alone. TUDCA significantly increased antioxidant capacity in H2O2-treated RPE cells by decreasing the generation of reactive oxygen species (ROS) and Malondialdehyde (MDA), upregulating the expression of antioxidant genes, and increasing the generation of glutathione (GSH). TUDCA also inhibited inflammation in H2O2-challenged RPE cells by decreasing the expression of proinflammatory cytokines. Furthermore, TUDCA suppressed thapsigargin-induced ER stress in RPE cells, as demonstrated by decreased the expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and apoptosis. Our present study suggests that TUDCA can protect RPE cells against oxidative damage, inflammation, and ER stress and may benefit patients with retinal degeneration.

Vitamin D Attenuates Oxidative Damage and Inflammation in Retinal Pigment Epithelial Cells.

Age-related macular degeneration (AMD), the most common visual disorder in elderly people, is characterized by the formation of deposits beneath the retinal pigment epithelium (RPE) and by dysfunction of RPE and photoreceptor cells. The biologically active form of vitamin D, 1,25-(OH)2D3 (VITD), is categorized as a multifunctional steroid hormone that modulates many transcriptional processes of different genes and is involved in a broad range of cellular functions. Epidemiological and genetic association studies demonstrate that VITD may have a protective role in AMD, while single nucleotide polymorphisms in the vitamin D metabolism gene (CYP24A1) increase the risk of AMD. However, the functional mechanisms of VITD in AMD are not fully understood. In the current study, we investigated the impact of VITD on H2O2-induced oxidative stress and inflammation in human RPE cells. We demonstrate that exposure to H2O2 caused significantly reduced cell viability, increased production of reactive oxygen species (ROS), lowered expression of antioxidant enzymes and enhanced inflammation. VITD exposure notably counteracted the above H2O2-induced effects. Our data suggest that VITD protects the RPE from oxidative damage and elucidate molecular mechanisms of VITD deficiency in the development of AMD.

Gypenosides protect retinal pigment epithelium cells from oxidative stress.

Oxidative stress plays a critical role in the pathogenesis of retinal degeneration. Gypenosides are the major functional components isolated from Gynostemma pentaphyllum. They have been shown to protect against oxidative stress and inflammation and have also demonstrated a protective effect on experimental optic neuritis. In order to determine the protective properties of gypenosides against oxidative stress in human retinal pigment epithelium (RPE) cells, ARPE-19 cells were treated with H2O2 or H2O2 plus gypenosides for 24 h. ARPE-19 cells co-treated with gypenosides had significantly increased cell viability and decreased cell death rate when compared to cells treated with H2O2 alone. The level of GSH, the activities of SOD and catalase, and the expression of NRF2 and antioxidant genes were notably decreased, while there were marked increases in ROS, MDA and pro-inflammatory cytokines in ARPE-19 cells exposed to H2O2; co-treatment with gypenosides significantly counteract these changes. Our study suggests that gypenosides protect RPE cells from oxidative damage and offer therapeutic potential for the treatment of retinal degeneration.