Browsing by Author "Aref A.M."

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Antitumor potential of berberine and cinnamic acid against solid ehrlich carcinoma in mice
(Bentham Science Publishers B.V., 2019) Almeer R.S.; Aref A.M.; Hussein R.A.; Othman M.S.; Moneim A.E.A.; Department of Zoology; College of Science; King Saud University; Riyadh; Saudi Arabia; Faculty of Biotechnology; October University for Modern Science and Arts (MSA); Giza; Egypt; Department of Zoology and Entomology; Faculty of Science; Helwan University; Cairo; Egypt; Faculty of Preparatory year; University of Hail; Hail; Saudi Arabia
Background: Berberine and cinnamic acid are natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms. Objective: In the present study, we aimed to investigate the proapoptotic potential of cinnamic acid and berberine in cancer cells by examining their effect on the expression of proapoptotic and antiapoptotic genes. Moreover, the effects of berberine and cinnamic acid on the antitumor activity of cisplatin were investigated in Ehrlich solid tumor-bearing mice. Methods: For the study, 90 male mice were inoculated intramuscularly with Ehrlich ascites tumor cells (2.5 � 106/mouse), and then on day 4, mice were randomly divided into six experimental groups (group 1-untreated Ehrlich solid tumor (EST), group 2-EST treated CDDP, group 3-EST treated CA, group 4-EST treated BER, group 5-EST treated CA + CDDP, and group 6-EST treated BER + CDDP). Result: The results showed that berberine and cinnamic acid significantly decreased tumor growth and tumor volume (- 74.8 and -75.5%, respectively) both as single agents and in combination with cisplatin. Moreover, both berberine and cinnamic acid increased the ratio of tumor growth inhibition (-91.5 and -92.6%, respectively), mean survival time (61.5 and 26 days, respectively), and percentage increase in lifespan (559 and 263%, respectively) of the treated mice. Our results also showed that both berberine and cinnamic acid-induced apoptosis by increasing the Bax/Bcl-2 ratio (74.1 and 45.1, respectively) and caspase-3 expression (14.3- and 11.6-fold increase, respectively). Additionally, berberine and cinnamic acid decreased oxidative stress markers, as shown by the decrease in lipid peroxidation and nitric oxide levels and an increase in reduced glutathione level. Conclusion: These results suggest that berberine and cinnamic acid have potential as antitumor and antioxidant agents derived from natural sources, which could be used alone or in combination with regular chemotherapeutic agents, such as cisplatin. These effects could be attributed to the proapoptotic activity of berberine and cinnamic acid. � 2019 Bentham Science Publishers.
Azadirachta indica attenuates cisplatin-induced nephrotoxicity and oxidative stress
(Hindawi Publishing Corporation, 2014) Abdel Moneim A.E.; Othman M.S.; Aref A.M.; Department of Biochemistry and Molecular Biology; Asturias Institute of Biotechnology; University of Oviedo; Oviedo; 33006; Spain; Department of Zoology and Entomology; Faculty of Science; Helwan University; Cairo; 11795; Egypt; Department of Biochemistry and Molecular Biology; Faculty of Biotechnology; Modern Sciences and Arts University (MSA); Giza; 12111; Egypt; Department of Biological Science; Faculty of Dentistry; Modern Sciences and Arts University (MSA); Giza; 12111; Egypt
We investigated the effects of methanolic leaves extract of Azadirachta indica (MLEN, 500 mg/kg bwt) on cisplatin- (CP-) induced nephrotoxicity and oxidative stress in rats. CP (5 mg/kg bwt) was injected intraperitoneally and MLEN was given by gastric gavage for 5 days before or after CP injection. After 5 days of CP injection, CP-induced injury of the renal tissue was evidenced (i) as histopathological damage of the renal tissue, (ii) as increases in serum uric acid, urea, and creatinine, (iii) as increases in malondialdehyde (MDA) and nitric oxide (NO), (iv) as decreases in the level of glutathione and activities of superoxide dismutase, catalase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase, and (v) as increase in the expression of nuclear factor kappa B and apoptosis in kidney tissues. However, the oral administration of MLEN to CP-intoxicated rats for 5 days brought back MDA, NO production, and enzymatic and nonenzymatic antioxidants to near normalcy. Moreover, the histological observations evidenced that neem extract effectively rescues the kidney from CP-mediated oxidative damage. Furthermore, PCR results for caspase-3 and caspase-9 and Bax genes showed downregulation in MLEN treated groups. Therefore, Azadirachta indica can be considered a potential candidate for protection of nephrotoxicity induced by cisplatin. � 2014 Ahmed E. Abdel Moneim et al.
Can zinc levels predict response to pegylated-interferon and ribavirin therapy in hepatitis c genotype 4 infected Egyptian patients?
(Universa Press, 2014) Mohamed A.A.; Abbassi M.M.; Hamed W.A.; Ezzel-Arab M.A.; Aref A.M.; Biochemistry Department; National Hepatology and Tropical Medicine Research Institute; Cairo; Egypt; Clinical Pharmacy Department; Cairo University; Cairo; Egypt; Tropical Medicine Department; Ain Shams University; Cairo; Egypt; Internal Medicine Department; National Hepatology and Tropical Medicine Research Institute; Cairo; Egypt; Biotechnology Department; MSA University; Cairo; Egypt
Background and Aims: Zinc has been found to be low in chronic hepatitis patients. Its level was correlated with response to Interferon/ribavirin therapy in patients infected with hepatitis C genotype 1. In Egypt, inexpensive predictors to treatment response in Hepatitis C genotype 4 infected patients are desperately needed. We aim to explore if pretreatment zinc serum levels correlate with response to pegylated- interferon and ribavirin therapy in Egyptian patients. Methods: This is an observational prospective study where 57 treatment na�ve hepatitis C genotype 4 infected patients that were Hepatitis B and Human Immunodeficiency virus negative were recruited in a hospital setting. The study was performed from October 2010 till June 2012. Patients had Liver biopsy and basic biochemical profiles were performed pretreatment for all patients. Treatment consisted of 48 weeks of pegylated-interferon-alpha2a and ribavirin therapy. Blood samples were withdrawn from 21 healthy subjects to compare zinc levels and other biochemical markers. Patients were followed up to 72 weeks. Results: Pretreatment serum zinc levels were significantly lower in hepatitis C infected patients compared to healthy volunteers (p < 0.05). Moreover, zinc levels correlated to sustained virological response in treated patients (p = 0.00). Conclusion: Serum zinc levels can be used as an inexpensive predictor to effective Pegylated-interferon/ribavirin therapy in Egyptian patients infected with Hepatitic C genotype 4.
Evaluation of circulating ADH and MIC-1 as diagnostic markers in Egyptian patients with pancreatic cancer
(Elsevier, 2015) Mohamed A.A.; Soliman H.; Ismail M.; Ziada D.; Farid T.M.; Aref A.M.; Al Daly M.E.; Abd Elmageed Z.Y.; Departments of Biochemistry; National Hepatology and Tropical Medicine Research Institute; Egypt; Department of Tropical Medicine and Infectious Diseases; Faculty of Medicine; Tanta University; Egypt; Departments of Surgery; National Hepatology and Tropical Medicine Research Institute; Egypt; Department of Clinical Biochemistry; Faculty of Medicine; King Abdel Aziz University; Jeddah; Saudi Arabia; Department of Biological Sciences; Faculty of Dentistry; Modern Science and Arts University; Egypt; Clinical Oncology; Faculty of Medicine; Cairo University; Egypt; Tulane University Health Sciences Center; Tulane University School of Medicine; 1430 Tulane Ave; New Orleans; LA; United States
Background Despite the incidence rate of pancreatic cancer (PC) is uncommon in developing countries, it is considered as one of the most lethal disease. Improving patients' survival requires diagnosis of the disease at early stage. Therefore, it is imperative to identify more specific and sensitive marker(s) to be used for early detection of PC. Objectives Our aim is to evaluate the potential role of circulating ADH and MIC-1 to be used as diagnostic markers in Egyptian patients and assess their value either alone or combined with CA19-9 in early detection of PC. Methods Alcohol dehydrogenase (ADH), macrophage inhibitory cytokine (MIC-1) and CA19-9 were measured by ELISA in serum procured from PC patients (n = 50) versus normal subjects (n = 20). Results Our results demonstrate that the circulating levels of ADH, MIC-1 and CA19-9 in blood of PC were significantly higher than in healthy controls (HCs) (p < 0.001). The highest marker sensitivity observed at early stage was MIC-1 (90%) and specificity was ADH (83%). The level of all three markers was elevated significantly in early stage of PC in comparison to HCs. The addition of ADH and MIC-1 to CA19-9 significantly improved the efficacy of diagnosis (p = 0.023). Conclusion Our data demonstrate that not only the combination of ADH and MIC-1 to CA19-9 can be used in early detection of PC but also can improve the overall quality of diagnosis of this lethal disease. � 2014 IAP and EPC.
HCA519/TPX2: A potential T-cell tumor-associated antigen for human hepatocellular carcinoma
(Dove Medical Press Ltd., 2014) Aref A.M.; Hoa N.T.; Ge L.; Agrawal A.; Dacosta-Iyer M.; Lambrecht N.; Ouyang Y.; Cornforth A.N.; Jadus M.R.; Biological Science Department; Modern Sciences and Arts University; Cairo; Egypt; Southern California Institute for Research and Education; Veterans Affairs Medical Center; Long Beach; CA; United States; Research Health Care Group; Veterans Affairs Medical Center; Long Beach; CA; United States; Department of Medicine; Division of Basic and Clinical Immunology; University of California; Irvine; CA; United States; Pathology and Laboratory Medicine Department; Veterans Affairs Medical Center Long Beach; CA; United States; Department of Pathology and Laboratory Medicine; University of California; Irvine; CA; United States; California Stem Cells; Inc; CA; United States; Chao Comprehensive Cancer Center; University of California; Irvine; CA; United States
Background: Immunotherapy for human hepatocellular cancer (HCC) is slowly making progress towards treating these fatal cancers. The identification of new antigens can improve this approach. We describe a possible new antigen, hepatocellular carcinoma-associated antigen-519/targeting protein for Xklp-2 (HCA519/TPX2), for HCC that might be beneficial for T-cell specific HCC immunotherapy. Methods: HCC was studied for the expression for 15 tumor-associated antigens considered useful for immunotherapy within three HCC cell lines (HepG2, Hep3B, and PLC/PRF/5), lymphocytes, non-cancerous livers, and clinical HCC. The expression of tumor antigenic precursor proteins (TAPPs) messenger RNA was first screened by reverse transcriptase quantitative real-time polymerase chain reaction. Results: Four antigens (alpha fetoprotein, aspartyl/asparaginyl ?-hydroxylase, glypican-3 and HCA519/TPX2) proved to be the best expressed TAPPs within the HCC specimens by molecular analyses. HCA519/TPX2 was detected by intracellular cell flow cytometry within HCC cell lines by using a specific antibody towards this TAPP. This antibody also detected the protein within primary HCCs. We synthesized two HCA519/TPX2 peptides (HCA519464-472 and HCA519351-359) which can bind to human leukocyte antigen (HLA)-A*0201. Dendritic cells pulsed with these peptides stimulated cytolytic T lymphocytes (CTLs). These killer T-cells lysed HLA-Az.ast;0201+ T2 cells exogenously loaded with the correct specific peptide. The CTLs killed HepG2 (HLA-A2+ and HCA519+), but not the Hep3B and PLC/PRF/5 cell lines, which are HCA519+ but HLA-A2-negative. In silico analysis reveals that HCA519/TPX2 has the inherent ability to bind to a very wide variety of HLA antigens. Conclusion: HCA519/TPX2 is a viable immunotarget that should be further investigated within HCC patients. � 2014 Aref et al. This work is published by Dove Medical Press Limited.
Oxidative stress and apoptosis are markers in renal toxicity following Egyptian cobra (Naja haje) envenomation
(University of Punjab (new Campus), 2014) Dkhil M.A.; Al-Quraishy S.; Farrag A.R.H.; Aref A.M.; Othman M.S.; Moneim A.E.A.; Department of Zoology; College of Science; King Saud University; Riyadh; Saudi Arabia; Department of Zoology and Entomology; Faculty of Science; Helwan University; Cairo; Egypt; Pathology Department; Medical Research Division; National Research Centre; Cairo; Egypt; Biological Science Department; Faculty of Dentistry; Modern Sciences and Arts University; Giza; Egypt; Biochemistry and Molecular Biology Department; Faculty of Biotechnology; Modern Science and Arts; Giza; Egypt
Snakebite is a serious and important problem in tropical and subtropical countries including Egypt. The venom of Egyptian cobra (Naja haje; L.) is complex, and it has been considered as a good source of short neurotoxins and several cytotoxins. In this study, oxidative stress inductions as well as apoptotic effects of the Egyptian cobra crude venom at a dose of 0.025mg/kg (intraperitoneal injection; i.p.) has been investigated in kidney of rats after 4 h. Twelve rats divided into 2 groups, Group I served as control group, Group II received i.p. injection of 0.025mg/kg of crude venom. The venom enhanced lipid peroxidation and nitric oxide productions in the kidney with concomitant reduction in glutathione content and superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase activities were inhibited. Moreover, the venom induced a renal injury as indicated by histopathological changes in the kidney tissue with an elevation in serum creatinine and urea. In addition, the renal ultrastructural changes were in the form of blebbing of visceral epithelial cells, and foot process disorganization. Also, the glomerular capillaries lined by hypertrophied endothelial cells. These findings were associated with the pro-apoptotic action in the kidney. The results suggest that Egyptian cobra venom stimulates oxidative stress to induce apoptosis in renal tissue through inhibition of mitochondrial respiration in male rats. Copyright 2014 Zoological Society of Pakistan.
The potential protective effect of physalis peruviana L. against carbon tetrachloride-induced hepatotoxicity in rats is mediated by suppression of oxidative stress and downregulation of MMP-9 expression
(Elsevier Ltd., 2014) Al-Olayan E.M.; El-Khadragy M.F.; Aref A.M.; Othman M.S.; Kassab R.B.; Abdel Moneim A.E.; Zoology Department; Faculty of Science; King Saud University; Riyadh 11451; Saudi Arabia; Zoology and Entomology Department; Faculty of Science; Helwan University; Cairo 11795; Egypt; Biological Science Department; Faculty of Dentistry; Modern Sciences and Arts (MSA) University; Giza 12111; Egypt; Biochemistry and Molecular Biology Department; Faculty of Biotechnology; Modern Sciences and Arts (MSA) University; Giza 12111; Egypt; Experimental Biology Department; Faculty of Science; Masaryk University; 62500 Brno; Czech Republic; Biochemistry and Molecular Biology Department; Asturias Institute of Biotechnology; University of Oviedo; 33006 Oviedo; Spain
The active constituent profile in Cape gooseberry (Physalis peruviana L.) juice was determined by GC-MS. Quercetin and kaempferol were active components in the juice. In this study we have evaluated its potential protective effect on hepatic injury and fibrosis induced by carbon tetrachloride (CCl4). Twenty-eight rats divided into 4 groups: Group I served as control group, and Group II received weekly i.p. injection of 2 mL CCl4/kg bwt for 12 weeks. Group III were supplemented with Physalis juice via the drinking water. The animals of Group IV received Physalis juice as Group III and also were intraperitoneally injected weekly with 2 mL CCl4/kg bwt for 12 weeks. Hepatoprotective effect was evaluated by improvement in liver enzymes serum levels, reduction in collagen areas, downregulation in expression of the fibrotic marker MMP-9, reduction in the peroxidative marker malonaldehyde and the inflammatory marker nitric oxide, and restoration of the activity of antioxidant enzymatic and nonenzymatic systems, namely, glutathione content, superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities. The results show that the potential hepatoprotective effects of Physalis peruviana may be due to physalis acts by promotion of processes that restore hepatolobular architecture and through the inhibition of oxidative stress pathway. � 2014 Ebtisam M. Al-Olayan et al.
The potential protective role of Physalis peruviana L. fruit in cadmium-induced hepatotoxicity and nephrotoxicity
(Elsevier Ltd, 2014) Dkhil M.A.; Al-Quraishy S.; Diab M.M.S.; Othman M.S.; Aref A.M.; Moneim A.E.A.; Department of Zoology; College of Science; King Saud University; Riyadh; Saudi Arabia; Department of Zoology and Entomology; Faculty of Science; Helwan University; Cairo; Egypt; Department of Molecular Drug Evaluation; National Organization for Drug Control and Research (NODCAR); Giza; Egypt; Department of Biochemistry and Molecular Biology; Faculty of Biotechnology; Modern Sciences and Arts (MSA); Giza; Egypt; Department of Biological Science; Faculty of Dentistry; Modern Sciences and Arts University (MSA); Giza; Egypt; Department of Biochemistry and Molecular Biology; Asturias Institute of Biotechnology; University of Oviedo; Oviedo; Spain
This study aimed to investigate the potential protective role of Physalis peruviana L. (family Solanaceae) against cadmium-induced hepatorenal toxicity in Wistar rats. Herein, cadmium chloride (CdCl2) (6.5mg/kg bwt/day) was intraperitoneally injected for 5 days, and methanolic extract of physalis (MEPh) was pre-administered to a group of Cd-treated rats by an oral administration at a daily dose of 200mg/kg bwt for 5 days. The findings revealed that CdCl2 injection induced significant decreases in kidney weight and kidney index. Cadmium intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of uric acid, urea and creatinine were increased in the serum. The pre-administration of MEPh alleviated hepatorenal toxicity in Cd-treated rats. Physalis was noted to play a good hepatorenal protective role, reducing lipid peroxidation, nitric oxide, and enhancing enzymatic activities and non-enzymatic antioxidant molecule, glutathione, in hepatic and renal tissues of Cd-treated rats. Moreover, physalis treatment was able to reverse the histopathological changes in liver and kidney tissues and also increased the expression of Bcl-2 protein in liver and kidney of rats. Overall, the results showed that MEPh can induce antioxidant and anti-apoptotic effects and also exerts beneficial effects for the treatment of Cd-induced hepatorenal toxicity. � 2014 Elsevier Ltd.
The potential role of Azadirachta indica treatment on cisplatin-induced hepatotoxicity and oxidative stress in female rats
(2013) Dkhil M.A.; Al-Quraishy S.; Aref A.M.; Othman M.S.; El-Deib K.M.; Abdel Moneim A.E.; Department of Zoology; College of Science; King Saud University; Riyadh 11451; Saudi Arabia; Department of Zoology and Entomology; Faculty of Science; Helwan University; Cairo 11795; Egypt; Biological Science Department; Faculty of Dentistry; Modern Science and Arts University (MSA); Giza 12111; Egypt; Biochemistry and Molecular Biology Department; Faculty of Pharmacy; Modern Science and Arts (MSA); Giza 12111; Egypt; Molecular Drug Evaluation Department; National Organization for Drug Control and Research (NODCAR); Giza 12553; Egypt; Department of Biochemistry and Molecular Biology; Asturias Institute of Biotechnology; University of Oviedo; Oviedo 33006; Spain
Azadirachta indica A. Juss. (neem, family: Meliaceae) is perhaps the most commonly used traditional medicinal plant of India. In this study we investigated the protective effect of methanolic neem leaves extract (MNLE; 500 mg/Kg bwt) on rats treated with cisplatin (CDDP)-induced hepatotoxicity. Adult rats were randomly divided into four groups. CDDP was given to rats by intraperitoneal injection, while MNLE was given by oral gavage for 5 days after the CDDP injection. The injury and oxidative stress caused by CDDP on the liver and the effect of MNLE were evaluated by measuring (a) histological changes, (b) tissue biochemical oxidant and antioxidant parameters, and (c) investigating apoptosis markers immunohistochemically and by real time PCR. After treatment with MNLE, the histological damage and apoptosis induction caused by cisplatin were improved. Malondialdehyde and nitric oxide were significantly decreased; the antioxidant system, namely, glutathione content, glutathione-S-transferase, glutathione peroxidase, catalase, and superoxide dismutase activities were significantly elevated. In conclusion, MNLE may have a potential role when combined with cisplatin in chemotherapy to alleviate cisplatin-induced damage and oxidative stress in liver. 2013 Mohamed A. Dkhil et al.
The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4
(Makerere University, Medical School, 2019) Helal T.E.A.; Radwan N.A.; Mahmoud H.A.; Zaki A.M.E.; Ahmed N.S.; Wahib A.A.A.; Aref A.M.; Department of Pathology; Faculty of Medicine; Ain Shams University; Ramses Street- New Faculty Bldg. -5th floor; P.O. # 11566; Cairo; Egypt; Department of Internal Medicine; Faculty of Medicine; Al-Azhar University; Cairo; Egypt; Faculty of Biotechnology; October University for Modern Sciences and Arts (MSA); Giza; Egypt
Background: Interferon therapy is used as a line of treatment of chronic hepatitis C virus (HCV) in several areas of the world including Egypt. Objective: Our aim was to investigate the value of hepatic progenitor cells (HPCs) in predicting response of patients with chronic HCV, genotype 4 to pegylated interferon (PEGIFN) plus ribavirin (RBV) therapy. Methods: Pre-treatment liver biopsies obtained from 110 patients with chronic HCV, genotype 4 were examined immunohistochemically for HPCs using cytokeratin19. The mean number of HPCs as ductular reaction (DR) and as isolated progenitor cells (IPCs) was counted in each case. The patients were classified into: those with sustained virological response (SVR) and those who did not achieve SVR. The results were compared between the two groups. Also, the relationships between HPCs and other clinico-pathologic variables were estimated using multivariate analysis. Results: The mean number of HPCs was the only independent predictor of therapeutic response, being significantly higher in non-responders (P = 0 for DR and P = 0.03 for IPCs). On the other hand, fibrosis stage and steatosis were the only independent factors which showed a significant direct association with the mean number of HPCs in the form of DR and IPCs (P = 0 for each). Conclusion: The number of HPCs provides prognostic information in chronic HCV since it is significantly associated with stage of fibrosis. More importantly, it can be used as a marker to predict response of patients with chronic HCV to PEGIFN plus RBV therapy. � 2019 Helal et al. Licensee African Health Sciences.
Rutin and Selenium Co-administration Reverse 3-Nitropropionic Acid-Induced Neurochemical and Molecular Impairments in a Mouse Model of Huntingtons Disease
(Springer, 2020) Abdelfattah M.S.; Badr S.E.A.; Lotfy S.A.; Attia G.H.; Aref A.M.; Abdel Moneim A.E.; Kassab R.B.; Natural Products Research Unit (NPRU); Chemistry Department; Faculty of Science; Helwan University; Cairo; 11795; Egypt; Regional Center for Food and Feed (RCFF); Agriculture Research Center; Giza; Egypt; Department of Pharmacognosy; College of Pharmacy; Najran University; Najran; Saudi Arabia; Faculty of Biotechnology; Modern Sciences and Arts University (MSA); Giza; Egypt; Department of Zoology and Entomology; Faculty of Science; Helwan University; Cairo; 11795; Egypt
Systemic administration of 3-nitropropionic acid (3-NPA) is commonly used to induce Huntingtons disease (HD)-like symptoms in experimental animals. Here, the potential neuroprotective efficiency of rutin and selenium (RSe) co-administration on 3-NPA-induced HD-like symptoms model in mice was investigated. 3-NPA injection evoked severe alterations in redox status, as indicated via increased striatal malondialdehyde and nitric oxide levels, accompanied by a decrease in levels of antioxidant molecules including glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. Moreover, 3-NPA potentiated inflammatory status by enhancing the production of interleukin-1?, tumor necrosis factor-?, and myeloperoxidase activity. Pro-apoptotic cascade was also recorded in the striatum as evidenced through upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2. 3-NPA activated astrocytes as indicated by the upregulated glial fibrillary acidic protein and inhibited brain-derived neurotrophic factor. Furthermore, perturbations in cholinergic and monoaminergic systems were observed. RSe provided neuroprotective effects by preventing body weight loss, oxidative stress, neuroinflammation, and the apoptotic cascade. RSe inhibited the activation of astrocytes, increased brain-derived neurotrophic factor, and improved cholinergic and monoaminergic transmission following 3-NPA intoxication. Taken together, RSe co-administration may prevent or delay the progression of HD and its associated impairments through its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory effects. 2019, Springer Science+Business Media, LLC, part of Springer Nature.