Computer aided and experimental study of cinnamic acid analog for oxidative stress treatment: The therapeutic validations

Objectives: The purpose of this study was to investigate the therapeutic activity of the cinnamic acid derivative KAD-3 (ethyl 3-(4-methoxyphenyl) acrylate) on Fe2+-induced oxidative hepatic damage via experimental and computer aided studies. Methods: Oxidative hepatic damage was induced via incubation of tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C ex vivo with different concentration of KAD-3. Molecular docking, ADMET profiling, and density functional theory were conducted on the candidate to filter the properties of the drug candidate for drug design. Key findings: GSH, CAT, and ENTPDase activities were reduced when hepatic damage was induced (p < 0.05). In contrast, a significant increase in MDA levels and an increase in ATPase activity were observed. When compared to control levels, KAD-3 treatment reduced these levels and activities (p < 0.05). KAD-3 demonstrated good bond formation (−5.8 kcal/mol, −5.6 kcal/mol), drug-likeness (no rule violation), and electronic properties (chemically reactive) as compared to the standard (quercetin). Molecular docking, ADMET profiling, and density functional theory predict the functional attributes of the drug candidate against ATPase and ENTPDase targets. Conclusion: The findings from our study indicated that KAD-3 can protect against Fe2+-induced hepatic damage by suppressing oxidative stress and purinergic activities

Profiling the antidiabetic potential of GC–MS compounds identified from the methanolic extract of <i>Spilanthes filicaulis</i>: experimental and computational insight

This study examines the nutritional composition, phytochemical profiling, and antioxidant, antidiabetic, and anti-inflammatory potential of a methanolic extract of Spilanthes filicaulis leaves (MESFL) via in vitro, ex vivo, and in silico studies. In vitro antioxidant, antidiabetic, and anti-inflammatory activities were examined. In the ex vivo study, liver tissues were subjected to FeSO4-induced oxidative damage and treated with varying concentrations of MESFL. MESFL contains a reasonable amount of nitrogen-free extract, moisture, ash content, crude protein, and fat, with a lesser amount of crude fiber. According to GC–MS analysis, MESFL contains ten compounds, the most abundant of which are 13-octadecenal and Ar-tumerone. In this study, MESFL demonstrated anti-inflammatory activities via membrane stabilizing properties, proteinase inhibition, and inhibition of protein denaturation (IC50 = 72.75 ± 11.06 µg/mL). MESFL also strongly inhibited both α-amylase (IC50 = 307.02 ± 4.25 µg/mL) and α-glucosidase (IC50 = 215.51 ± 0.47 µg/mL) activities. Our findings also showed that FeSO4-induced tissue damage decreased the levels of GSH, SOD, and CAT activities while increasing the levels of MDA. In contrast, treatment with MESFL helped to restore these parameters to near-normal levels, which signifies that MESFL has great potential to address complications from oxidative stress. Furthermore, the in silico interaction of the GCMS-identified phytochemicals with the active sites of α-amylase and α-glucosidase via molecular and ensembled-based docking displayed strong binding affinities of Ar-tumerone and 4-hydroxy-3-methylacetophenone to α-amylase and α-glucosidase, respectively. Taken together, the biological activities of MESFL might be a result of the effects of these secondary metabolites. Communicated by Ramaswamy H. Sarma</p

DataSheet1_GC-MS chemical profiling, antioxidant, anti-diabetic, and anti-inflammatory activities of ethyl acetate fraction of Spilanthes filicaulis (Schumach. and Thonn.) C.D. Adams leaves: experimental and computational studies.docx

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.</p