Neurodegenerative diseases are normally distinguished as disorders with loss of neurons. Various compounds are being tested to treat neurodegenerative diseases (NDs) but they possess solitary symptomatic advantages with numerous side effects. Accumulative studies have been conducted to validate the benefit of phytochemicals to treat neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD). In this present review we explored the potential efficacy of phytochemicals such as epigallocatechin-3-galate, berberin, curcumin, resveratrol, quercetin and limonoids against the most common NDs, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The beneficial potentials of these phytochemicals have been demonstrated by evidence-based but more extensive investigation needs to be conducted for reducing the progression of AD and PD.
Doxorubicin (DOX), an anthracycline antineoplastic candidate is used to treat various malignancies. Around 41% of patients undergoing DOX treatment develop acute cardiotoxicity. Preventing DOX‐induced cardiac fibrosis and hypertrophy helps in evading cardiac remodeling leading to cardiomyopathy and heart failure. Neferine, an alkaloid from the lotus has numerous pharmacological activities. The present study was designed to evaluate the protective effect of neferine on DOX‐mediated fibrosis and hypertrophy. DOX‐induced fibrosis involves activation of transforming growth factor‐β1 (TGF‐β1), matrix metalloproteinase 2 (MMP‐2), and MMP‐9 with concomitant downregulation of tissue inhibitors of MMPs (TIMP)‐1 and TIMP‐2 expressions in H9c2 cardiomyoblasts. Furthermore, DOX treatment also resulted in hypertrophy with the increased cell volume and overexpression of hypertrophy markers calcineurin, brain natriuretic peptide, and atrial natriuretic peptide. Finally, DOX treatment resulted in apoptosis through activation of p53. Pretreatment with neferine markedly activated SIRT1 expression and modulated the expression levels of TGF‐β1 and p53, thereby significantly reducing DOX‐induced fibrosis, hypertrophy, and apoptosis in H9c2 cardiomyoblasts.
Ten chiral methyl 2‐(2‐oxo‐2H‐benzo[e][1,3]oxazin‐3(4H)‐yl)propanoate derivatives 6a‐6j have been synthesized from optically pure amino methyl phenol 5 and 4‐nitrophenyl chloroformate. These derivatives 6a‐6j are characterized by 1H NMR, 13C NMR, FT‐IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a‐6j were screened for their in vitro antioxidant activity. Among the compounds 6b‐d and 6h‐j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e‐g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC50 value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b, 6h, and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC50 value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT‐3 (PDB ID: 1BG1) and BCL‐2 (PDB ID: 4AQ3) proteins against the four active compounds 6b, 6h, 6i, and 6j. The binding energies of the tested compounds were in the range of −7.76 to −8.41 kcal/mol, which is very close to doxorubicin (−8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.
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