Mammalian maltase-glucoamylase and sucrase-isomaltase inhibitory effects of Artocarpus heterophyllus: An in vitro and in silico approach.

Alpha-glucosidase (maltase, sucrase, isomaltase and glucoamylase) activities which are involved in carbohydrate metabolism are present in human intestinal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI). Hence, these proteins are important targets to identify drugs against postprandial hyperglycemia thereby for diabetes. To find natural-based drugs against MGAM and SI, Artocarpus heterophyllus leaf was explored for MGAM and SI inhibition in in vitro and in silico. A. heterophyllus leaf aqueous active fraction (AHL-AAF) was prepared using Soxhlet extraction followed by silica column chromatography. The phytoconstituents of AHL-AAF were determined using LC-ESI-MS/MS. AHL-AAF showed dose-dependent and mixed inhibition against maltase (IC50 = 460 µg/ml; Ki = 300 µg/ml), glucoamylase (IC50 = 780 µg/ml; Ki = 480 µg/ml), sucrase (IC50 = 900 µg/ml, Ki = 504 µg/ml) and isomaltase (IC50 = 860 µg/ml, Ki = 400 µg/ml). AHL-AAF phytoconstituents interaction with N-terminal (Nt) and C-terminal (Ct) subunits of human MGAM and SI was analyzed using induced-fit docking, molecular dynamics (MD), and binding free energy calculation. In docking studies, rhamnosyl hexosyl methyl quercetin (RHMQ), P-coumaryl-O-16-hydroxy palmitic acid (PCHP), and spirostanol interacted with active site amino acids of human MGAM and SI. Among these RHMQ stably interacted with all the subunits (Nt-MGAM, Ct-MGAM, Nt-SI and Ct-SI) whereas PCHP with Ct-MGAM and Nt-SI during MD analysis. In molecular docking, the docking score of RHMQ with NtMGAM, CtMGAM, NtSI and CtSI was -8.48, -12.88, -11.98 and -11.37 kcal/mol. The docking score of PCHP for CtMGAM and NtSI was -8.59 and -8.4 kcal/mol, respectively. After MD simulation, the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values further confirmed the stable protein-ligand interaction. The RMSD value of all the complexes were around 2.5 Šand the corresponding RMSF values were also quite low. In MM/GBSA analysis, the involvement of Van der Waals and lipophilic energy in the protein/ligand interactions are understood. Further binding free energy for Nt-MGAM-PCHP, Nt-MGAM-RHMQ, Nt-SI-PCHP, Nt-SI-RHMQ, Ct-MGAM-PCHP, Ct-MGAM-RHMQ and Ct-SI-RHMQ complexes was found to be -24.94, -46.60, -46.56, -44.48, -40.3, -41.86 and -19.39 kcal/mol, respectively. Altogether, AHL-AAF showed inhibition of α-glucosidase activities of MGAM and SI. AHL-AAF could be further studied for its effect on diabetes in in vivo.

Exploring the interaction of phytochemicals from Hibiscus rosa-sinensis flowers with glucosidase and acetylcholinesterase: An integrated in vitro and in silico approach.

Targeting multiple factors such as oxidative stress, alpha glucosidase and acetylcholinesterase (AChE) are considered advantageous for the treatment of diabetes and diabetes associated-cognitive dysfunction. In the present study, Hibiscus rosa-sinensis flowers anthocyanin-rich extract (HRA) was prepared. Phytochemical analysis of HRA using LC-ESI/MS/MS revealed the presence of various phenolic acids, flavonoids and anthocyanins. HRA showed in vitro antioxidant activity at low concentrations. HRA inhibited all the activities of mammalian glucosidases and AChE activity. The IC50 value of HRA for the inhibition of maltase, sucrase, isomaltase, glucoamylase and AChE was found to be 308.02 ± 34.25 µg/ml, 287.8 ± 19.49 µg/ml, 424.58 ± 34.75 µg/ml, 408.94 ± 64.82 µg/ml and 264.13 ± 30.84 µg/ml, respectively. Kinetic analysis revealed mixed-type inhibition against all the activities except for glucoamylase (competitive) activity. In silico analysis confirmed the interaction of two active constituents cyanidin 3-sophoroside (CS) and quercetin 3-O-sophoroside (QS) with four subunits, n-terminal and c-terminal subunits of human maltase-glucoamylase and sucrase-isomaltase as well as with AChE. Molecular dynamics simulation, binding free energy calculation, DCCM, PCA, PCA-based free energy surface analysis ascertained the stable binding of CS and QS with target proteins studied. HRA could be used as complementary therapy for diabetes and cognitive improvement.

Synthesis and Characterization of Plumbagin S-Allyl Cysteine Ester: Determination of Anticancer Activity In Silico and In Vitro.

In recent years, derivatives of natural compounds are synthesized to increase the bioavailability, pharmacology, and pharmacokinetics properties. The naphthoquinone, plumbagin (PLU), is well known for its anticancer activity. However, the clinical use of PLU is hindered due to its toxicity. Previous reports have shown that modification of PLU at 5'-hydroxyl group has reduced its toxicity towards normal cell line. In accordance, in the present study, 5'-hydroxyl group of PLU was esterified with S-allyl cysteine (SAC) to obtain PLU-SAC ester. The drug-likeness of PLU-SAC was understood by in silico ADME analysis. PLU-SAC was characterized by UV-visible spectroscopy, mass spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. Molecular docking and dynamics simulation analysis revealed the interaction of PLU-SAC with proteins of interest in cancer therapy such as human estrogen receptor α, tumor protein p53 negative regulator mouse double minute 2, and cyclin-dependent kinase 2. MMGBSA calculation showed the favorable binding energy which in turn demonstrated the stable binding of PLU-SAC with these proteins. PLU-SAC showed apoptosis in breast cancer cell line (MCF-7) by inducing oxidative stress, disturbing mitochondrial function, arresting cells at G1 phase of cell cycle, and initiating DNA fragmentation. However, PLU-SAC did not show toxicity towards normal Vero cell line. PLU-SAC was synthesized and structurally characterized, and its anticancer activity was determined by in silico and in vitro analysis.

Protection of pancreatic beta cells against high glucose-induced toxicity by astaxanthin-s-allyl cysteine diester: alteration of oxidative stress and apoptotic-related protein expression.

Purpose: High glucose (HG)-induced oxidative stress is associated with apoptosis in pancreatic ß-cells. The protective effect of astaxanthin-s-allyl cysteine diester (AST-SAC) against HG-induced oxidative stress in pancreatic ß-cells (ßTC-tet cell line) in in vitro was studied.Materials and Methods: ßTC-tet cell line was exposed to HG in the presence and absence of AST-SAC. Various parameters such as cell viability, reactive oxygen species generation, mitochondrial membrane potential, DNA fragmentation and expression of proteins involved in apoptosis [p53, B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), cytochrome c and caspase 3] were studied.Results: Pre-treatment of ßTC-tet cells with AST-SAC (4, 8 and 12 µg/ml) in the presence of HG (25 mM) protected the viability of the cells in a dose-dependent manner. AST-SAC treatment mitigated the oxidative stress thereby preventing the mitochondrial dysfunction, DNA damage and apoptosis in ßTC-tet cells against HG toxicity. Treatment with AST-SAC prevented the increased expression of p53 under HG conditions. Further, AST-SAC treatment maintained the level of pro-apoptotic (Bax, cleaved caspase-3 and cytochrome c) and anti-apoptotic (Bcl-2) proteins to that of the control level under HG exposed conditions in ßTC-tet cells.Conclusion: Altogether, AST-SAC alleviated HG-induced oxidative damage and apoptosis in pancreatic ß-cells by enhancing the antioxidant status and altering apoptotic-related protein expression.

In silico and in vitro investigation of anticancer effect of newly synthesized nonivamide-s-allyl cysteine ester.

Nonivamide (NOV), less pungent analogue of capsaicin present in various Capsicum species is known for various biological properties. S-allyl cysteine (SAC) abundantly present in aged garlic extract is gaining importance for anticancer property. NOV was esterified with SAC to increase the biological activity. In silico ADME analysis revealed the drug-likeness of NOV-SAC. Molecular docking and dynamics simulation analysis were done to understand the interaction of NOV-SAC with therapeutic target proteins (human estrogen receptor α, tumo protein negative regulator mouse double minute 2, B-cell lymphoma 2 and cyclin-dependent kinase 2) to treat cancer. NOV-SAC interacted with these proteins stably with favorable binding energy which was calculated through MMGBSA method. In line with in silico results, NOV-SAC showed antiproliferative activity against breast cancer cell line (MCF-7). NOV-SAC treatment increased ROS generation, decreased the antioxidant level, arrested cells at G1/S phase, disrupted mitochondrial membrane potential and initiated DNA fragmentation. The expression of p53 is increased by NOV-SAC treatment, in concordance the ratio of Bcl-2/Bax was decreased. Altogether, NOV-SAC was synthesized for the first time and it induced apoptosis in MCF-7 cells through triggering ROS generation and increasing the expression of p53. The in silico results has been mirrored in in vitro analysis of NOV-SAC against cancer cell line.Communicated by Ramaswamy H. Sarma.

Astaxanthin-s-allyl cysteine diester against high glucose-induced neuronal toxicity in vitro and diabetes-associated cognitive decline in vivo: Effect on p53, oxidative stress and mitochondrial function.

Neuroprotective effect of astaxanthin-s-allyl cysteine diester (AST-SAC) against high glucose (HG)-induced oxidative stress in in vitro and cognitive decline under diabetes conditions in in vivo has been explored. Pretreatment of AST-SAC (5, 10 and 15 µM) dose-dependently preserved the neuronal cells (SH-SY5Y) viability against HG toxicity through i) decreasing oxidative stress (decreasing reactive oxygen species generation and increasing endogenous antioxidants level); ii) protecting mitochondrial function [oxidative phosphorylation (OXPHOS) complexes activity and mitochondrial membrane potential (MMP)]; and iii) decreasing p53 level thereby subsequently decreasing the level of apoptotic marker proteins. Male Spraque-Dawley rats were orally administered AST-SAC (1 mg/kg/day) for 45 days in streptozotocin-induced diabetes mellitus (DM) rats. AST-SAC administration prevented the loss of spatial memory in DM rats as determined using the novel object location test. AST-SAC administration alleviated the DM-induced injury in brain such as increased cholinesterases activity, elevated oxidative stress and mitochondrial dysfunction. Altogether, the results from the present study demonstrated that AST-SAC averted the neuronal apoptosis and preserved the cognitive function against HG toxicity under DM conditions.

In silico, theoretical biointerface analysis and in vitro kinetic analysis of amine compounds interaction with acetylcholinesterase and butyrylcholinesterase.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are considered important target for drug design against Alzheimer's disease. In the present study in silico analysis; theoretical analysis of biointerface between ligand and interacting amino acid residues of proteins; and in vitro analysis of enzyme inhibition kinetics were carried out to delineate the inhibitory property of amine compounds against AChE/BChE. High throughput virtual screening of amine compounds identified three compounds (2-aminoquinoline, 2-aminobenzimidazole and 2-amino-1-methylbenzimidazole) that best interacted with AChE/BChE. Molecular docking analysis revealed the interaction of these compounds in the active site gorge of AChE/BChE, in particular with amino acid residues present in the peripheral anionic site. Molecular dynamics simulation confirmed the stable binding of these compounds with AChE/BChE. Binding energy calculated through MMGBSA method identified the non-covalent interactions (electrostatic and Van der Waals interactions) have contributed to the stable binding of the amine compounds with the AChE/BChE. Biointerface between amine compounds and AChE/BChE were visualized through Hirshfeld surface analysis. The inter-fragment interaction energies for the possible contacts between amine compounds and amino acid residues were carried out for the first time. All the amine compounds showed mixed-type of inhibition with moderate Ki value in in vitro analysis.

Inhibition of glutathione and s-allyl glutathione on pancreatic lipase: Analysis through in vitro kinetics, fluorescence spectroscopy and in silico docking.

Inhibition of pancreatic lipase (PL) is considered one of the important therapeutic interventions against obesity. In the present study, the inhibition of porcine (mammalian) PL (PPL) by two tripeptides glutathione (GSH) and s-allyl glutathione (SAG) was studied. In vitro kinetic analysis was done to determine the inhibition of GSH and SAG against PPL. The binding of GSH and SAG with PPL was elucidated by fluorescence spectroscopy analysis. Docking and molecular dynamics (MD) simulation analysis was carried out to understand the intermolecular interaction between both GSH and SAG with PPL as well as human PL (HPL). Both GSH and SAG inhibited PPL in mixed non-competitive manner. The IC50 value for GSH and SAG against PPL was found to be 2.97 and 6.4 mM, respectively. Both GSH and SAG quenched the intrinsic fluorescence of PPL through static quenching that is through forming complex with the PPL. SAG and GSH interacted with amino acids involved in catalysis of both PPL and HPL. MD simulation showed interactions of SAG and GSH with both PPL and HPL were stable. These results would lead to the further studies and application of GSH and SAG against obesity through inhibition of PL.

Purification of fucoxanthin from Sargassum wightii Greville and understanding the inhibition of angiotensin 1-converting enzyme: An in vitro and in silico studies.

The isolation and purification of active components from the brown algae Sargassum.wightii is highly limited. In the present study, fucoxanthin was purified from S. wightii using simple methods. Ethyl acetate fraction obtained by Soxhlet extraction contained high concentration of fucoxanthin. Fucoxanthin-rich fraction was further subjected to open silica column chromatography and thin layer chromatography to obtain purified fucoxanthin. Purified fucoxanthin showed in vitro antioxidant activity. Fucoxanthin showed inhibition of angiotensin I-converting enzyme (ACE) with half maximal inhibitory value of 822.64 ± 17.69 µM. Kinetic analysis revealed mixed non-competitive inhibition with inhibitory constant of 600 µM for fucoxanthin against ACE. Molecular docking analysis showed the interaction of fucoxanthin with amino acids and zinc ion present in the active site of the human ACE. Molecular dynamics analysis demonstrated the stability of the fucoxanthin and ACE complex in in silico. These results show that S. wightii may be used as food ingredient to overcome hypertension.

In vitro and in silico analysis of novel astaxanthin-s-allyl cysteine as an inhibitor of butyrylcholinesterase and various globular forms of acetylcholinesterases.

In Alzheimer's disease (AD) and diabetes-associated cognitive decline, the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity is increased. AChE exists as different globular molecular forms: tetramer (G4), dimer (G2) and monomer (G1). In adult brain, G4 form is abundant however in AD, the ratio of lower molecular forms (G1) to G4 form increased. Hence, the present study delineated the inhibition of novel astaxanthin-s-allyl cysteine (AST-SAC) against BChE and various molecular forms of AChE. Cobra venom, human erythrocyte and Electrophorus electricus was used as source of G1, G2 and G4 form of AChE. AST-SAC showed inhibition against G1 (IC50 = 0.72 µM, competitive, Ki = 0.66 µM), G2 (IC50 = 0.65 µM, mixed, Ki = 0.50 µM) and G4 (IC50 = 0.67 µM, competitive, Ki = 0.67 µM) form of AChE. AST-SAC inhibited human brain AChE (IC50 = 0.84 µM, competitive, Ki = 0.53 µM) and human serum BChE (IC50 = 0.80 µM, competitive, Ki = 0.58 µM). In silico analysis revealed the interaction of AST-SAC with the amino acids present in peripheral anionic and catalytic site of human AChE and BChE. Molecular dynamics simulation confirmed the stable interaction of AST-SAC in the active site gorge of AChE and BChE.

Green synthesized selenium nanoparticles using Spermacoce hispida as carrier of s-allyl glutathione: to accomplish hepatoprotective and nephroprotective activity against acetaminophen toxicity.

s-allyl glutathione (SAG) an analogue of glutathione is explored for its antioxidative and liver protection property in recent years. Selenium nanoparticles (Sh-SeNPs) were synthesized using medicinal plant Spermacoce hispida and conjugated with SAG (SAG-Sh-SeNPs). SAG-Sh-SeNPs and Sh-SeNPs were characterized using by Fourier transform infrared spectroscopy, Transmission electron microscopy, Energy dispersive X-ray analysis, X-ray diffraction analysis and zeta potential analysis. SAG-Sh-SeNPs and Sh-SeNPs were evaluated against acetaminophen (APAP)-induced liver and kidney injury in rat. Pretreatment of NPs attenuated the APAP toxicity-induced elevation of kidney and liver injury markers in the blood circulation. Histological observation showed that NPs pretreatment protected the morphology of liver and kidney tissue. SAG-Sh-SeNPs showed enhanced protection against APAP toxicity in comparison to Sh-SeNPs due to synergistic effect of SAG and Sh-SeNPs. SAG-Sh-SeNPs protected the liver and kidney against APAP toxicity through reducing oxidative stress, enhancing endogenous antioxidants and protecting mitochondrial functions.

S-allyl cysteine as potent anti-gout drug: Insight into the xanthine oxidase inhibition and anti-inflammatory activity.

S-allyl cysteine (SAC) is known for its various beneficial effects such as neuroprotection and immunomodulation. The beneficial effect of SAC against gout has not been explored. The present study aims to describe the two roles of SAC: (1) inhibitory effect against xanthine oxidase (XO) enzyme activity; and (2) anti-inflammatory property against MSU crystal-induced gouty inflammation in rat. The inhibitory effect of SAC against bovine XO enzyme activity was determined in vitro. In silico analysis was carried out to determine the intermolecular interaction between SAC and bovine XO. MSU crystal was injected in the right paw of the rat to induce gouty inflammation. SAC (40 mg/kg body weight) and colchicine (positive control; 1 mg/kg body weight) was given for 3 days. At the end of the treatment, the oxidative stress, antioxidant parameters and mitochondrial function were determined in the ankle joint tissue. The concentration of inflammatory cytokines such as TNF-α and IL-1ß was measured in the serum using ELISA. SAC inhibited (IC50 value, 33 µg/ml) XO enzyme activity in a competitive mode with corresponding Ki value of 4 µg/ml. In silico analysis predicted the interaction of SAC with the amino acids such as Arg880, Phe798, Phe914 and Phe1009 of XO enzyme. The root mean square deviation, root mean square fluctuation and free energy calculation values confirmed the stable SAC-XO interaction. The inhibition of SAC on XO enzyme activity in in vivo was further confirmed by silkworm model. SAC through reducing oxidative stress, enhancing antioxidants, protecting mitochondrial function has shown anti-inflammatory effect against MSU crystal-induced gout which was observed as reduced level of inflammatory markers in the serum. The medicinal potential of SAC as a preventive agent through its XO inhibitory property as well as curative agent through its anti-inflammatory property against gout has been understood from the present study.

Biological interaction of newly synthesized astaxanthin-s-allyl cysteine biconjugate with Saccharomyces cerevisiae and mammalian α-glucosidase: In vitro kinetics and in silico docking analysis.

In humans, alpha-glucosidase activity is present in sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM). α-glucosidase is involved in the hydrolyses of disaccharide into monosaccharides and results in hyperglycemia. Subsequently chronic hyperglycemia induces oxidative stress and ultimately leads to the secondary complications of diabetes. Hence, identifying compounds with dual beneficial activity such as efficient antioxidant and α-glucosidase inhibition property has attracted the attention in recent years. Keeping these views, in the present study astaxanthin (AST; a natural antioxidant present in marine microalgae) was biconjugated with allyl sulfur amino acid such as s-allyl cysteine (SAC). The synthesized AST-SAC (with molecular weight of 883.28) was characterized using UV-visible spectrophotometer, ESI-MS, and NMR analysis. AST-SAC showed potent antioxidant property in vitro. AST-SAC inhibited Saccharomyces cerevisiae α-glucosidase (IC50 = 3.98 µM; Ki = 1 µM) and mammalian α-glucosidase [rat intestinal maltase (IC50 = 6.4 µM; Ki = 1.3 µM) and sucrase (IC50 = 1.6 µM; Ki = 0.18 µM)] enzyme activity in a dose-dependent manner. Kinetic analysis revealed that AST-SAC inhibited all the α-glucosidases in a competitive mode. In silico analysis determined the interaction of AST-SAC with the amino acids present in the active site of S. cerevisiae and human (MGAM and SI) α-glucosidases.

Plant extract as environmental-friendly green catalyst for the reduction of hexavalent chromium in tannery effluent.

The aqueous extract of various plants like Coriandrum sativum (AECS), Alternanthera tenella colla (AEAT), Spermacoce hispida (AESH) and Mollugo verticillata (AEMV) was studied for its hexavalent chromium (CrVI) reduction property. Even though antioxidant activity was present, AEAT, AESH and AEMV did not reduce CrVI. AECS showed rapid and dose-dependent CrVI reduction. The efficient reduction of 50 mg/L of CrVI using AECS was attained in the presence of 250 µg/mL of starting plant material, incubating the reaction mixture at pH 2, 30°C and agitation at 190 rpm. Under such conditions, about 40 mg/L of CrVI was reduced at 3 h of incubation. FT-IR analysis revealed the involvement of phenols, alcohols, alpha-hydroxy acid and flavonoids present in the AECS for the CrVI reduction. These results indicate that not all the plant extracts with rich antioxidants are capable of reducing CrVI. Using the conditions standardized in the present study, AECS reduced about 80% of CrVI present in the tannery effluent. These results signify the application of AECS as an eco-friendly method in the wastewater treatment.

Rapid biosynthesis of Bauhinia variegata flower extract-mediated silver nanoparticles: an effective antioxidant scavenger and α-amylase inhibitor.

Silver nanoparticles (AgNPs) were biosynthesized using Bauhinia variegata flower extract (BVFE). The BVF-AgNPs was found to be spherical shaped with the size of 5-15 nm. The phytoconstituents analysis and FTIR spectrum indicated that bioactive compounds like, phenols, flavonoids, benzophenones, nitro compounds, aromatics and aliphatic amines from BVFE might absorb on the surface of BVF-AgNPs. The synthesized BVF-AgNPs showed potent antioxidant property and α-amylase enzyme activity inhibition. The IC50 value of BVF-AgNPs was found to be 4.64 and 16.6 µg/ml for DPPH and ferric reducing power assay, respectively. The IC50 value of BVF-AgNPs for α-amylase inhibition was found to be 38 µg/ml. The Ki value of BVF-AgNPs for α-amylase inhibitory effect was found to be 21 µg/ml with the non-competitive mode of inhibition. These results suggest that BVF-AgNPs might be an effective nano-drug to treat diabetic conditions.

S-allyl-glutathione, a synthetic analogue of glutathione protected liver against carbon tetrachloride toxicity: Focus towards anti-oxidative efficiency.

A simple analogue of well known natural antioxidant glutathione (GSH) called S-allyl-glutathione (SAG) was evaluated against carbon tetrachloride (CCl4)-induced oxidative stress liver injury in rat. Pretreatment of SAG attenuated the CCl4-toxicity induced elevation of liver injury markers such as enzymes (AST, ALT, GGT, ALP and LDH) and bilirubin in the blood circulation. Such protective effect of SAG resulted in preservation of liver function observed as normal level of total protein and albumin in plasma as well as inhibition of dyslipidemia in liver. In addition, in silico analysis has proved that SAG has strong affinity with the amino acids present in active site of the human cytochrome P450 2E1 and 3A4. Three important mechanisms provided by SAG such as scavenging of reactive oxidants, replenishing of endogenous antioxidants (SOD, catalase, GPx, GSH and vitamin C) and protection of mitochondrial function (oxidative phosphorylation complex activities) are involved in the optimal function of liver against CCl4-toxicity.

Asiatic acid prevents the quinolinic acid-induced oxidative stress and cognitive impairment.

Increased accumulation of endogenous neurotoxin quinolinic acid has been found in various neurodegenerative diseases. Oxidative stress caused by quinolinic acid is considered as imperative factor for its toxicity. Asiatic acid, a natural triterpene is widely studied for its various medicinal values. In the present study the effects of asiatic acid in preventing the cognitive impairment and oxidative stress caused by quinolinic acid was investigated. Male Spraque-Dawley rats were orally administered asiatic acid (30 mg/kg/day) for 28 days, while quinolinic acid toxicity-induced animals received quinolinic acid (1.5 mmol/kg/day) from day 15 to day 28 for 14 days. Asiatic acid administration prevented the loss of spatial memory caused due to quinolinic acid-induced toxicity as determined using the novel object location test. In addition, asiatic acid administration alleviated the deleterious effect of quinolinic acid in brain such as increased oxidative stress, decreased antioxidant status and mitochondrial oxidative phosphorylation dysfunction. These data demonstrate that asiatic acid through its potent antioxidant and cognition enhancement property prevented the neuronal impairments caused by quinolinic acid.