Polyphenolic-Rich Compounds From Dillenia pentagyna (Roxb.) Attenuates the Doxorubicin-Induced Cardiotoxicity: A High-Frequency Ultrasonography Assisted Approach

Abstract

Cardiovascular complications are the foremost concern in patients undergoing anticancer therapy. There is an unmet need to address the problems arising from the drug-induced toxicity for the long-term benefit of the patients undergoing chemotherapy. Alternative medicines are gaining their prosperity in addressing the various drug-induced organ toxicity. Dillenia pentagyna Roxb (DP) is an ethnomedicinal plant rich in flavonoids and phenolic contents. In India & Nepal, DP is a common ingredient of traditional medicines used to treat multiple ailments like inflammation, cancer, and diabetes. However, its protective role against doxorubicin (Dox) induced cardiotoxicity remains unexplored. Herein, we investigated the potential effects of various extracts/fractions obtained from the DP’s bark against Dox-induced cardiotoxicity, both in-vitro and in-vivo. The anti-oxidant content of the extracts/fractions was evaluated by using DPPH, ABTS and FRAP chemical assays. The results indicated that the hydroalcoholic (HA) extract of DP has intense anti-oxidant potential. Further fractionation of DP revealed that the phenolic-rich fraction (F1) has a high anti-oxidant potential. The protective effect of extract/fraction was also investigated in the H9c2 cell line following the Dox-induced cardiotoxicity model. We observed that the pre-treatment of extract/fraction in cardiomyocytes had exhibited increased cell viability. Fluorescence-based chemical assays indicated a decreased ROS levels in the treated groups in comparison to the Dox control group. The effect of DP was evaluated further in balb/c mice by the Dox-induced cardiotoxicity model. Non-invasive techniques like high-frequency ultrasonography and electrocardiogram revealed that the mice pre-treated with DP had improved cardiac functionality (left ventricular ejection fraction and stroke volume) and normalized the electrocardiograms compared to the Dox control group. Further, biochemical analysis with the cardiac tissues revealed that the cytoprotective proteins like HO-1, SOD-2, and Nrf-2 were elevated in the DP treated groups compared to the Dox control group. Overall, our results suggested that the bioactive extract/fractions of DP helped alleviate the Dox-induced cardiotoxicity. LC-QTOF-ESI-MS analysis of DP and F1 indicated that polyphenolic anti-oxidant compounds like gallic acid, syringic acid, and sinapic acid could be responsible for the potent -cardioprotective effect. Future understanding of the pharmacokinetics and pharmacodynamic parameters can help translate from the bench to the bedside.

Synthesis, characterization, method development, and validation of nor‐ethylmorphine hydrochloride reference material using established analytical techniques for dope control analysis

“…The synthesized nor-ethylmorphine HCl was characterized using 1 H-NMR and 13 C-NMR, HRMS, and FT-IR.…”

“…The organic solvent was removed under reduced pressure, and the crude product was further utilized for the synthesis of norethylmorphine by dissolving it in CHCl 3 (30 mL), adding Fe (0) powder (35.6 mg, 0.638 mmol), and stirring at room temperature for 4 h. After completion of the reaction, the product was isolated and purified by flash chromatography (mobile phase 15% methanol in DCM). 12 The purified nor-ethylmorphine HCl (100 mg) was characterized using 1 H-NMR, 13 C-NMR, ESI-HRMS, and Fourier transform infrared spectroscopy (FT-IR).…”

“…1 H-NMR and13 C-NMR spectra were recorded on Bruker 600-and 150-MHz spectrometers, respectively, in methanol-d 4 , tetramethyl silane as an internal reference standard. The data are presented as, chemical shift (δ), coupling constant J in Hertz (Hz).…”

“…The mixture was compressed using a hydraulic press and converted to KBr thin transparent pellet. This pellet was scanned for the IR region using an FT-IR spectrophotometer (Model-ALPHA II, make: Bruker) and functional groups of nor-ethylmorphine HCl was determined 13. HPLC METHOD DEVELOPMENT, OPTIMIZATION, PURITY, AND POTENCY ASSESSMENT The purity of the synthetic reference material is critical parameter, and HPLC with photodiode array detector (PDA/DAD) is well known and established technique for determining the purity of the reference compound.…”

Gallic Acid Ameliorates Atopic Dermatitis-Like Skin Inflammation Through Immune Regulation in a Mouse Model

“…Polyphenols are typified by antioxidant and protective effects in cardiovascular and neurological disorders. 7,8 One of the most important polyphenols is gallic acid (GA), which is present in grapes, mango, and green tea, 9 also known as 3,4,5-trihydroxybenzoic acid. GA was shown to have positive effects on hypertension, vascular calcification, cardiac remodeling, and fibrosis.…”