Neuroprotective potential of erucic acid via inhibition of N2a cell lines and rotenone induced Parkinson's disease rat model.

OBJECTIVE: The objective of this study was to investigate the potential for erucic acid (EA), an omega-9 monounsaturated fatty acid, to act as a neuroprotective agent. MATERIALS AND METHODS: In this study, EA was investigated against N2a cell lines and a rotenone (ROT)-induced model of Parkinson's disease for its neuroprotective potential. The N2a cell line was incubated with fetal bovine serum, penicillin, and streptomycin supplemented with Dulbecco's Modified Eagle's Medium, and the following assays were carried out: (i) MTT, (ii) biocompatibility, (iii) DCFDA, and (iv) diphenylamine. A cell morphology study was also performed. Further, ROT 1 mg/kg s.c. and EA 3 and 10 mg/kg p.o. were given to rats on a daily basis for 21 days, and the following parameters were assessed: (i) neurobehavioral studies, (ii) oxidative stress markers, (iii) neuroinflammatory markers, (iv) neurotransmitters, and (v) histopathological study. RESULTS: The cell viability assay revealed that EA showed protection against ROT-induced toxicity in N2a cells, which was confirmed by a cell morphology study. EA decreased oxidative stress and % DNA fragmentation significantly. EA also prevented ROT-induced motor impairment and altered levels of oxidative stress markers, neurotransmitters, and neuroinflammatory markers significantly. When compared to the ROT group, a histological investigation of the EA group showed partial neuronal loss with the existence of intact neurons in between the vacuolated gaps. CONCLUSION: This study revealed that EA possesses profound neuroprotective properties in in vitro and in vivo studies. Additional research can be carried out to study the mechanism of EA with respect to its neuroprotective potential.

Synthesis of Novel Aryl (4-Aryl-1H-Pyrrol-3-yl) (Thiophen-2-yl) Methanone Derivatives: Molecular Modelling, In Silico ADMET, Anti-Inflammatory and Anti-Ulcer Activities.

BACKGROUND: Due to the presence of both five-membered heterocyclics like pyrrole and thiophene in one molecule considerable attention was made for their enormous pharmacological activities out of which include anti-inflammatory and anti-ulcer activities. OBJECTIVE: Chalcones with toluenesulfonylmethyl isocyanide (TosMIC) undergo synthesis to form some new aryl (4-aryl-1H-pyrrol-3-yl) (thiophen-2-yl) methanone derivatives. Molecular docking of synthesized compounds with protein receptors of anti-inflammatory COX-1(3N8Y), COX-2 (1PXX) along with anti-ulcer H+/K+ATPase enzyme (2XZB) followed with drug-likeness, and in silico ADMET properties. MATERIALS AND METHODS: The multicomponent reaction was carried out by the intermediate formation of α, ß-unsaturated ketone from carbonyl compounds which on sequential addition undergoes [3+2] cycloaddition reaction in same medium affords aryl (4-aryl-1H-pyrrol-3-yl) (thiophen-2-yl) methanone derivatives by addition of TosMIC in basic medium had resulted in series of compounds PY1 to PY12. All the new synthesized compounds were screened for their in-vitro anti-inflammatory activity by bovine serum albumin method followe with COX assay, and in-vivo by using carrageenan-induced rat paw edema method of the selected compounds PY1, PY5 and PY12 which is also screened for anti-ulcer activity by pylorus ligation method, respectively. Molecular docking was performed using autodock tools, drug-likeness by OSIRIS property explorer and admetSAR properties. RESULTS AND DISCUSSION: From the synthesized compounds of aryl (4-aryl-1H-pyrrol-3-yl) (thiophen- 2-yl) methanone derivatives PY5 showed decent in-vitro and in-vivo anti-inflammatory along selectivity index of 6.2 for COX-1 with IC50(µM) value of 9.54 over diclofenac with 8.74 and PY1 showed decent in-vivo anti-ulcer activities along with drug-likeness and in silico ADMET predictions revealed that all the synthesized compounds have minimal toxic effects with good absorption as well as solubility characteristics. The selected compounds may serve as potential lead compounds for developing new anti-inflammatory and anti-ulcer drugs. CONCLUSION: From the newly synthesized molecules PY5 was found to be effective for anti-inflammatory and PY1 was found to be effective for anti-ulcer activities further derivitization and designed of modification to achieve more compounds with potent anti-inflammatory and anti-ulcer activities.