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Analgesic, anti-inflammatory, and GC-MS studies on Castanospermum australe A. Cunn. & C. Fraser ex Hook.

ABSTRACT: The present study was aimed to evaluate the analgesic and anti-inflammatory properties of Castanospermum australe and to profile phytochemicals by GC-MS. The ethanolic extracts were prepared by successive solvent extraction using Soxhlet apparatus. The analgesic activity was analyzed by hot plate method and acetic acid-induced writhing test whereas anti-inflammatory study was done by carrageenan induced paw oedema model. The acute toxicity study revealed that ethanol extracts of leaf and bark of C. australe were safe even at a higher dose of 2000 mg/kg whereas ethanol extract of seed was toxic at the same dose. In both hot plate method (5.85 s) and acetic acid-induced writhing test (57%), the leaf ethanol extract exhibited significant analgesic activity (P < 0.001) at a dose of 400 mg/kg. The anti-inflammatory activity of leaf extract was exhibited by the reduction in paw linear diameter by 64.76% at 400 mg/kg in carrageenan induced paw oedema. The GC-MS analysis of the ethanol extract of leaf revealed sixteen major compounds of which 1,7-dimethyl-4,10-dioxa-1,7-diazacyclododecane, (+)-N-methylephedrine, and permethylspermine were found to be pharmaceutically and the most important. These findings justify that C. australe can be a valuable natural analgesic and anti-inflammatory source which seemed to provide potential phytotherapeutics against various ailments.

SUBMITTER: Sajeesh T

PROVIDER: S-EPMC3929379 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Project description:Osteoporosis affects millions of people worldwide. As such, this study assessed the macrophage-dependent in vitro anti-osteoporosis, phytochemical profile and hepatotoxicity effects in zebrafish larvae of the stem bark extracts of P. africana. Mouse bone marrow macrophages (BMM) cells were plated in 96-well plates and treated with P. africana methanolic bark extracts at concentrations of 0, 6.25, 12.5, 25, and 50 µg/ml for 24 h. The osteoclast tartrate-resistant acid phosphatase (TRAP) activity and cell viability were measured. Lipopolysaccharides (LPS) induced Nitrite (NO) and interleukin-6 (IL-6) production inhibitory effects of P. africana bark extracts (Methanolic, 150 µg/ml) and β-sitosterol (100 µM) were conducted using RAW 264.7 cells. Additionally, inhibition of IL-1β secretion and TRAP activity were determined for chlorogenic acid, catechin, naringenin and β-sitosterol. For toxicity study, zebrafish larvae were exposed to different concentrations of 25, 50, 100, and 200 µg/ml P. africana methanolic, ethanolic and water bark extracts. Dimethyl sulfoxide (0.05%) was used as a negative control and tamoxifen (5 µM) and dexamethasone (40 µM or 80 µM) were positive controls. The methanolic P. africana extracts significantly inhibited (p < 0.001) TRAP activity at all concentrations and at 12.5 and 25 µg/ml, the extract exhibited significant (p < 0.05) BMM cell viability. NO production was significantly inhibited (all p < 0.0001) by the sample. IL-6 secretion was significantly inhibited by P. africana methanolic extract (p < 0.0001) and β-sitosterol (p < 0.0001) and further, chlorogenic acid and naringenin remarkably inhibited IL-1β production. The P. africana methanolic extract significantly inhibited RANKL-induced TRAP activity. The phytochemical study of P. africana stem bark revealed a number of chemical compounds with anti-osteoporosis activity. There was no observed hepatocyte apoptosis in the liver of zebrafish larvae. In conclusion, the stem bark of P. africana is non-toxic to the liver and its inhibition of TRAP activity makes it an important source for future anti-osteoporosis drug development.

Project description:Highlights • Malondialdehyde (MDA) is an important biomarker of oxidative stress (lipid peroxidation)• MDA and [1,3-dideutero]MDA (d2-MDA) for use as internal standard react with pentafluorobenzyl bromide (PFB-Br) in aqueous acetone to form di-PFB derivatives.• GC–MS/MS allows for highly accurate measurement of MDA in human plasma, serum and urine.• Many pre-analytical factors including hemolysis may compromise measurement of biological MDA.• Sample storage and study design of long-term clinical studies are important factors to be considered. Malondialdehyde (MDA; 1,3-propanedial, OHC-CH2-CHO) is one of the most frequently measured biomarkers of oxidative stress in plasma and serum. L-Arginine (Arg) is the substrate of nitric oxide synthases (NOS), which convert L-arginine to nitric oxide (NO) and L-citrulline. The Arg/NO pathway comprises several members, including the endogenous NOS-activity inhibitor asymmetric dimethylarginine (ADMA) and its major metabolite dimethyl amine (DMA), and nitrite and nitrate, the major NO metabolites. Reliable measurement of MDA and members of the Arg/NO pathway in plasma, serum, urine and in other biological samples, such as saliva and cerebrospinal fluid, is highly challenging both for analytical and pre-analytical reasons. In our group, we use validated gas chromatography-mass spectrometry (GC–MS) and gas chromatography-tandem mass spectrometry (GC–MS/MS) methods for the quantitative determination in clinical studies of MDA as a biomarker of oxidative stress, and various Arg/NO metabolites that describe the status of this pathway. Here, the importance of pre-analytical issues, which has emerged from the use of GC–MS and GC–MS/MS in clinico-pharmacological studies, is discussed. Paradigmatically, two studies on the long-term oral administration of L-arginine dihydrochloride to patients suffering from peripheral arterial occlusive disease (PAOD) or coronary artery disease (CAD) were considered. Pre-analytical issues that were addressed include blood sampling, plasma or serum storage, study design (notably in long-term studies), and the alternative of measuring MDA in human urine.

Project description:BackgroundAnacyclus pyrethrum L. (Akarkara root), a valuable Ayurvedic remedy, is reported to exhibit various pharmacological activities. Akarkara root was subjected to bioassay-guided fractionation, to isolate its active constituents and discover their potential bioactivities, followed by computational analysis.MethodsThe methanol extract and its fractions, methylene chloride, and butanol, were assessed for their antioxidant, anti-inflammatory, and anticholinergic potentials. The antioxidant activity was determined using DPPH, ABTS, FRAP, and ORAC assays. The in vitro anticholinergic effect was evaluated via acetyl- and butyryl-cholinesterase inhibition, while anti-inflammatory effect weas determined using COX-2 and 5-LOX inhibitory assays. The methylene chloride fraction was subjected to GC/MS analysis and chromatographic fractionation to isolate its major compounds. The inhibitory effect on iNOS and various inflammatory mediators in LPS-activated RAW 264.7 macrophages was investigated. In silico computational analyses (molecular docking, ADME, BBB permeability prediction, and molecular dynamics) were performed.ResultsForty-one compounds were identified and quantified and the major compounds, namely, oleamide (A1), stigmasterol (A2), 2E,4E-deca-2,4-dienoic acid 2-phenylethyl amide (A3), and pellitorine (A4) were isolated from the methylene chloride fraction, the most active in all assays. All compounds showed significant in vitro antioxidant, anticholinergic and anti-inflammatory effects. They inhibited the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in activated RAW macrophages. The isolated compounds showed good fitting in the active sites of acetylcholinesterase and COX-2 with high docking scores. The ADME study revealed proper pharmacokinetics and drug likeness properties for the isolated compounds. The isolated compounds demonstrated high ability to cross the BBB and penetrate the CNS with values ranging from 1.596 to -1.651 in comparison with Donepezil (-1.464). Molecular dynamics simulation revealed stable conformations and binding patterns of the isolated compounds with the active sites of COX-2 and acetyl cholinesterase.ConclusionsUltimately, our results specify Akarkara compounds as promising candidates for the treatment of inflammatory and neurodegenerative diseases.

Project description:Introduction: This study aimed to investigate the chemical profile of GC-MS, antioxidant, anti-diabetic, and anti-inflammatory activities of the ethyl acetate fraction of Spilanthes filicaulis leaves (EFSFL) via experimental and computational studies. Methods: After inducing oxidative damage with FeSO4, we treated the tissues with different concentrations of EFSFL. An in-vitro analysis of EFSFL was carried out to determine its potential for antioxidant, anti-diabetic, and anti-inflammatory activities. We also measured the levels of CAT, SOD, GSH, and MDA. Results and discussion: EFSFL exhibited anti-inflammatory properties through membrane stabilizing properties (IC50 = 572.79 μg/ml), proteinase inhibition (IC50 = 319.90 μg/ml), and inhibition of protein denaturation (IC50 = 409.88 μg/ml). Furthermore, EFSFL inhibited α-amylase (IC50 = 169.77 μg/ml), α-glucosidase (IC50 = 293.12 μg/ml) and DPP-IV (IC50 = 380.94 μg/ml) activities, respectively. Our results indicated that induction of tissue damage reduced the levels of GSH, SOD, and CAT activities, and increased MDA levels. However, EFSFL treatment restores these levels to near normal. GC-MS profiling shows that EFSFL contains 13 compounds, with piperine being the most abundant. In silico interaction of the phytoconstituents using molecular and ensembled-based docking revealed strong binding tendencies of two hit compounds to DPP IV (alpha-caryophyllene and piperine with a binding affinity of -7.8 and -7.8 Kcal/mol), α-glucosidase (alpha-caryophyllene and piperine with a binding affinity of -9.6 and -8.9 Kcal/mol), and to α-amylase (piperine and Benzocycloheptano[2,3,4-I,j]isoquinoline, 4,5,6,6a-tetrahydro-1,9-dihydroxy-2,10-dimethoxy-5-methyl with a binding affinity of -7.8 and -7.9 Kcal/mol), respectively. These compounds also presented druggable properties with favorable ADMET. Conclusively, the antioxidant, antidiabetic, and anti-inflammatory activities of EFSFL could be due to the presence of secondary metabolites.

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Analgesic, anti-inflammatory, and GC-MS studies on Castanospermum australe A. Cunn. & C. Fraser ex Hook.

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