Targeting hyperlipidemia: A polarity-driven ternary extraction of Apium graveolens bioactives—A coupled in-vivo, in-vitro and in-silico investigation

Abstract

Introduction

An important factor in the onset and progression of atherosclerosis and coronary heart disease (CHD) is hyperlipidemia. Though numerous medication classes are available to regulate our body's fat content, the current fascination with natural products has accelerated the hunt for novel molecules from natural sources that decrease cholesterol. In our investigations, Apium graveolens (celery) has demonstrated a superior effect than the control medications.

Objective

Considering previous research (96 % Ethanol), we modified the solvent system (70 % methanol and 30 % aqueous acetone). In 96 % ethanol, mostly the hydrophobic compound can be dissolved. However, in our solvent system we enhance the polarity by adding 15 % water so more hydrophilic compounds could be present in the extract. Also, 15 % acetone would draw high molecular weight polyphenols. As a result, a wide array of compounds (hydrophilic, hydrophobic, and high molecular weight polyphenols will be present in our extract. However, in a previous study, the research used 96 % ethanol and we are using 70 % methanol, as a result, we will get a diminished concentration of hydrophobic compound. So, we aim to explore whether the hydrophilic anti-hyperlipidemic and high molecular weight polyphenol can compensate for the reduced concentration of hydrophobic anti-hyperlipidemic constituents.

Materials and methods

The Apium graveolens extract was prepared using a ternary extraction solvent. Under careful monitoring, the in-vivo study was conducted by distributing 95 healthy Wister albino male rats into 19 groups. Histopathological investigation was conducted using fluorescence microscope, followed by statistical assessment of the experimental data.

Results and discussion

According to the experimental data, rats with disrupted hyperlipidemic conditions showed a significant restoration in their HDL, LDL, triglycerides, and total cholesterol levels upon administration of Apium graveolens extract prepared with the ternary extraction solvent. Moreover, rats treated with the plant extract exhibited a significant reduction in their serum levels of the hepatic damage biomarkers and renal function biomarkers compared to the disease control group. The histopathological investigations showed that Apium graveolens at high doses can change the status of histopathological markers associated with liver damage. The findings of the in-silico studies revealed that the 3 top performing compounds (i.e. apiumoside, apiin and graveobioside B) showed high binding affinity to selected anti hyperlipidemic targets HMG CoA reductase and peroxisome proliferator-activated receptor-Alpha (PPAR-Alpha) with a very stable condition in the molecular dynamic simulation against the selected targets.

Conclusion

Based on our findings it can be inferred that Apium graveolens may contain some promising hydrophilic anti-hyperlipidemic constituents, antioxidants and some high molecular weight polyphenols.