Arora S

References (6)

Title : Neuroprotective activity of novel phenanthrene derivative from Grewia tiliaefolia by in vitro and in silico studies - Rajput_2023_Sci.Rep_13_2444
Author(s) : Rajput A , Sharma P , Kumar N , Kaur S , Arora S
Ref : Sci Rep , 13 :2444 , 2023
Abstract : Medicinal plants possess range of phytochemicals accountable for their diverse biological activities. Presently, such compounds have been isolated from medicinal plants, characterized and evaluated for their pharmacological potential. In the present study, the efforts have been made to isolate the compound(s) from Grewia tiliaefolia Vahl., plant known for its ameliorative effect on brain related diseases such as anxiety, depression, cognitive disorders and Parkinson's disease. Plant extract was subjected to isolation of compound(s) using column chromatography and isolated compound was characterized by NMR FTIR and LCMS. The isolated compound was novel with the IUPAC name of the compound is propyl 3-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylate, designated as A-1 and has not been reported before. A-1 was further evaluated for its antioxidant potential using in vitro antioxidant assays (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH assay and reducing power assay, RPA). Also, Acetylcholinesterase (AChE) inhibitory potential of A-1 and extract was analysed. Results showed that A-1 exhibited significantly higher antioxidant activity in both DPPH and RPA assay as compared to plant extract. In case of AChE inhibitory activity again, A-1 has shown significantly higher activity as compared to plant extract. In silico study was conducted to predict its action on proteins playing crucial role in neurological and neurodegenerative disorders such as gamma amino butyric acid (GABA) receptor and glutamate alpha amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu AMPA) receptor in epilepsy and AChE enzyme in Alzheimer's diseases. The compound has shown interaction in following order: AChE > GABA receptor > Glu AMPA receptor. Further, molecular dynamic simulations and ADME studies of A-1 and AChE enzyme revealed that A-1 yielded good results in all parameters and hence can relieve Alzheimer's like symptoms.
ESTHER : Rajput_2023_Sci.Rep_13_2444
PubMedSearch : Rajput_2023_Sci.Rep_13_2444
PubMedID: 36765125

Title : Mixture toxicity assessment of selected insecticides to silver perch fingerling, Bidyanus bidyanus - Arora_2021_Ecotoxicol.Environ.Saf_226_112790
Author(s) : Arora S , Kumar A
Ref : Ecotoxicology & Environmental Safety , 226 :112790 , 2021
Abstract : The organophosphorus (OP) and carbamate (CB) insecticides are responsible for inhibition of the Acetylcholinesterase (AChE) enzyme. The AChE activity, therefore, has been demonstrated to be a potent biomarker for these insecticides in terrestrial and aquatic environments. The objective of this study was to investigate the response of AChE in the brain of four-week old fingerlings of silver perch, Bidyanus bidyanus exposed to OP and CB insecticides. The fish fingeling were exposed to three OPs and one CB insecticide as individual and their binary mixtures for 48 h. The OP insecticides with oxon (PO) as well as thion (PS) group gets oxidized to oxon analogs in biological systems. The 50% AChE inhibition (48 h EC(50)) in fingerling exposed to chlorpyrifos (CPF) and triazophos (TRZ) was evident at 2.3 and 6.7 microg/L, respectively. The toxicological interaction of three OPs and one CB insecticide was evaluated using the toxic unit method. A strong synergism was observed for binary combination of CPF with profenofos (PRF), and CPF with TAZ. In contrast, the mixture of TAZ with PRF and carbofuran (CBF) with CPF and PRF showed antagonistic behavior. Although OP and CB insecticides can break down rapidly in the environment, this study suggests that non-target aquatic biota may be exposed to mixtures of ChE-inhibiting insecticides for a period of several months, in agricultural regions where insecticides are applied for extended periods of the year. And at environmentally relevant concentrations such mixtures may lead to deleterious effects in non-target organisms.
ESTHER : Arora_2021_Ecotoxicol.Environ.Saf_226_112790
PubMedSearch : Arora_2021_Ecotoxicol.Environ.Saf_226_112790
PubMedID: 34653840

Title : Phycocyanin alleviates ICV-STZ induced cognitive and molecular deficits via PI3-Kinase dependent pathway - Agrawal_2020_Food.Chem.Toxicol__111684
Author(s) : Agrawal M , Perumal Y , Bansal S , Arora S , Chopra K
Ref : Food & Chemical Toxicology , :111684 , 2020
Abstract : In this study, the effect of Phycocyanin (Pc) to ameliorate the cognitive dysfunction in experimental model of Alzheimer's disease (AD) was evaluated. Intracerebroventricular (ICV) induction of Streptozotocin (STZ) (3 mg/kg) was done bilaterally twice in rats on alternative days. Rats were injected with Pc (50, 100 mg/kg; i.p.) for 28 days daily for behavioural and cholinergic activity assessment. As the effect was only significant at 100 mg/kg, later molecular experiments were performed using the same only. STZ induction led to increased activity of hippocampal cholinesterases and BAX and decreased activity of BCL-2 and ChAT. It enhanced TNF-alpha, and NF-kappaB in rat's brain and reduced BDNF and IGF-1 levels. Dysfunctional insulin signaling and decreased gene expressions of PI3-K, AKT was also observed. However, Pc treatment significantly prevented STZ-induced increased activity of hippocampal cholinesterases and BAX as well as increased the levels of BCL-2 and ChAT. Neuroinflammation was significantly attenuated and BDNF and IGF-1 levels were upregulated. Further, Pc also alleviated dysfunctional insulin signaling as evidenced by increased gene expression of IRS-1, PI3-K, AKT. In conclusion, our study demonstrated the immense potential of Pc in attenuating STZ-induced cognitive decline and it may be further explored as a therapeutic agent in managing AD.
ESTHER : Agrawal_2020_Food.Chem.Toxicol__111684
PubMedSearch : Agrawal_2020_Food.Chem.Toxicol__111684
PubMedID: 32805344

Title : New coumarin-benzotriazole based hybrid molecules as inhibitors of acetylcholinesterase and amyloid aggregation - Singh_2020_Bioorg.Med.Chem.Lett_30_127477
Author(s) : Singh A , Sharma S , Arora S , Attri S , Kaur P , Kaur Gulati H , Bhagat K , Kumar N , Singh H , Vir Singh J , Mohinder Singh Bedi P
Ref : Bioorganic & Medicinal Chemistry Lett , 30 :127477 , 2020
Abstract : A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC(50) = 0.059 microM) with mixed type inhibition scenario. Structure-activity relationship revealed that three-carbon alkyl chain connecting coumarin and triazole is well tolerable for inhibitory potential. Hybrids obtained from 4-hydroxycoumarin and 1-benzotriazole were most potent AChE inhibitors. The inhibitory potential of all compounds against butyrylcholinesterase was also evaluated but all showed negligible activity suggesting that the hybrid molecules are selective AChE inhibitors. 13b (most potent AChE inhibitor) also showed copper-induced Abeta(1-42) aggregation inhibition (34.26% at 50 microM) and chelating properties for metal ions (Cu(2+), Fe(2+,) and Zn(2+)) involved in AD pathogenesis along with DNA protective potential against degenerative actions of OH radicals. Molecular modelling studies confirm the potential of 13b in blocking both PAS and CAS of AChE. In addition, interactions of 13b with Abeta(1-42) monomer are also streamlined. Therefore, hybrid 13b can act as an effective hit lead molecule for further development of selective AChE inhibitors as multifunctional anti-Alzheimer's agents.
ESTHER : Singh_2020_Bioorg.Med.Chem.Lett_30_127477
PubMedSearch : Singh_2020_Bioorg.Med.Chem.Lett_30_127477
PubMedID: 32781220

Title : Binary combinations of organophosphorus and synthetic pyrethroids are more potent acetylcholinesterase inhibitors than organophosphorus and carbamate mixtures: An in vitro assessment - Arora_2017_Toxicol.Lett_268_8
Author(s) : Arora S , Balotra S , Pandey G , Kumar A
Ref : Toxicol Lett , 268 :8 , 2017
Abstract : Anticholinesterase insecticides such as organophosphorous (OP) and carbamates pesticides (CB); and synthetic pyrethroids (SP) pesticides commonly co-occur in the environment. This raises the possibility of antagonistic, additive, or synergistic neurotoxicity in exposed organisms. Acetylcholinesterase (AChE) inhibition has been demonstrated to be useful as a biomarker for exposure to OP and CBs in many environments. This study investigated the response of housefly (Musca domestica) head AChE (HF-AChE) exposed to five OPs; chlorpyrifos (CPF), malathion (MLT), triazophos (TRZ), monocrotophos (MCP) and profenofos (PRF) and two CBs; carbaryl (CRB) and carbofuran (CBF) as individual compounds and as binary mixtures of OPs and CBs under in vitro conditions. In addition, the selected OPs and CBs were evaluated for their toxicity in binary combinations with two SPs; deltamethrin (DLT) and cypermethrin (CYP) at fixed concentrations of 0.1 and 10mug/L. The toxicological interaction of five OPs with two CBs pesticides was evaluated under oxidised and un-oxidised conditions using a toxic unit (TU) approach and a concentration addition (CA) model. Pyrethroid combinations were assessed only under oxidised conditions. Since OPs and CBs act by a similar mechanism of inhibition of AChE, a dose additive effect was expected, but not conclusively found. TRZ with either CBF or CRB exhibited synergism under oxidised and un-oxidised conditions but the degree of synergism was stronger under un-oxidised conditions. Additivity was exhibited by CBF+MCP, CRB+MCP, CRB+MLT and CBF+MCP under un-oxidised conditions and CRB+MCP and CRB+CPF under oxidised conditions. Pyrethorids in combination with OPs (TRZ, MLT and CPF) were highly synergistic. In the present study, we used pure housefly head AChE without any interference of monooxygenase and/or esterase enzyme activities. Therefore these other enzymes were not producing the observed deviations from concentration-addition in the binary combinations between OPs, CBs and SPs. The mechanisms of OP, CB and SP interactions in pesticide mixtures requires further investigation.
ESTHER : Arora_2017_Toxicol.Lett_268_8
PubMedSearch : Arora_2017_Toxicol.Lett_268_8
PubMedID: 27988393

Title : Binary combinations of organophosphorus pesticides exhibit differential toxicity under oxidised and un-oxidised conditions - Arora_2015_Ecotoxicol.Environ.Saf_115C_93
Author(s) : Arora S , Kumar A
Ref : Ecotoxicology & Environmental Safety , 115C :93 , 2015
Abstract : Acetylcholinesterase (AChE) inhibition has been demonstrated to be useful as a biomarker for exposure to organophosphorus (OP) insecticides in many environments. The objective of this study was to investigate the response of housefly (Musca domestica) head AChE (HF-AChE) exposed to five OPs as individual compounds and their binary mixtures under in vitro conditions. To examine the effects of oxidation on OP potency in the HF-AChE system, bromine water was used as an oxidisng agent. With oxidation, the sensitivity of HF-AChE to chlorpyrifos (CPF), malathion (MLT) and triazophos (TRZ) increased significantly. Monocrotophos (MCP) and profenofos (PRF) did not exhibit any significant differences in toxicity under oxidised and un-oxidised conditions. The toxicological interaction of five organophosphorus pesticides was evaluated using the concentration addition model, the combination index-isobologram equation and the toxic unit approach. All three models provided similar predictions for the 10 binary combinations of OPs under oxidised and un-oxidised conditions. In the present study, the antagonistic effects of the binary combination of OPs (CPF+PRF, CPF+MLT, MCP+MLT, PRF+MLT, MLT+TRZ and PRF+TRZ) were observed under oxidised conditions. This may be due to dispositional and/or receptor antagonism. Most of the binary combinations assayed under un-oxidised conditions exhibited synergistic responses. Triazophos showed very strong synergism in binary combinations with CPF, MCP and PRF un-oxidised conditions. In contrast, under oxidised conditions, only CPF+TRZ exhibited synergism. The results obtained indicate differential toxicity of binary combinations of OPs under oxidised and un-oxidised conditions. This information could be a valuable tool in understanding the mechanisms of OPs interactions and the interpretation of future in vivo studies with mixtures of OP insecticides.
ESTHER : Arora_2015_Ecotoxicol.Environ.Saf_115C_93
PubMedSearch : Arora_2015_Ecotoxicol.Environ.Saf_115C_93
PubMedID: 25682586