Comparative Study of the Pharmacological Properties and Biological Effects of Polygonum aviculare L. herba Extract-Entrapped Liposomes versus Quercetin-Entrapped Liposomes on Doxorubicin-Induced Toxicity on HUVECs.

Mariana Mureşan,Ioana Baldea,Gabriela Adriana Filip,Felicia Gabriela Gligor,Annamaria Pallag,Simona Clichici,Diana Olteanu,Tunde Jurca,Bogdan Stancu,Laura Vicaș,Paula Svera,Eleonora Marian,Adina Frum

doi:10.3390/pharmaceutics13091418

Abstract

This study aimed to evaluate the comparative biological effects of Polygonum aviculare L. herba (PAH) extract and quercetin-entrapped liposomes on doxorubicin (Doxo)-induced toxicity in HUVECs. HUVECs were treated with two formulations of liposomes loaded with PAH extract (L5 and L6) and two formulations of liposomes loaded with quercetin (L3 prepared with phosphatidylcholine and L4 prepared with phosphatidylserine). The results obtained with atomic force microscopy, zeta potential and entrapment liposome efficiency confirmed the interactions of the liposomes with PAH or free quercetin and a controlled release of flavonoids entrapped in all the liposomes. Doxo decreased the cell viability and induced oxidative stress, inflammation, DNA lesions and apoptosis in parallel with the activation of Nrf2 and NF-kB. Free quercetin, L3 and L4 inhibited the oxidative stress and inflammation and reduced apoptosis, particularly L3. Additionally, these compounds diminished the Nrf2 and NF-kB expressions and DNA lesions, principally L4. PAH extract, L5 and L6 exerted antioxidant and anti-inflammatory activities, reduced γH2AX formation and inhibited extrinsic apoptosis and transcription factors activation but to a lesser extent. The loading of quercetin in liposomes increased the cell viability and exerted better endothelial protection compared to free quercetin, especially L3. The liposomes with PAH extract had moderate efficiency, mainly due to the antioxidant and anti-inflammatory effects and the inhibition of extrinsic apoptosis.

Highlights

The liposomes loaded with polyphenols from the Polygonum aviculare L. herb extract were prepared by the hydration method by using phosphatidylcholine, phosphatidylserine and cholesterol purchased from Sigma-Aldrich (Milan, Italy)
The identification and quantification of the bioactive phenolic compounds from the Polygonum aviculare L. herba (PAH) extract was performed by using a Shimadzu Nexera-i LC–2040C 3D plus liquid chromatograph system equipped with a photodiode array detector (PDA)
This study provided evidence of the mechanisms involved in the endothelial toxicity of Doxo and brought up arguments for the endothelial protection of liposomes loaded with quercetin and the PAH extract

Summary

Introduction

Liposomes have the ability to be selectively absorbed by tissues rich in the reticuloendothelial system, including the liver, spleen and small bones This property underpins the mechanism of vectorisation of the bioactive substance and its transport in the systemic circulation. The method proposed is an ultrasound-assisted thin-film hydration method Numerous compounds, such as polyphenols or anthocyanins, are secondary metabolites generated by plants as a defence mechanism against infections or rough pedoclimatic conditions. These phytochemicals are bioactive agents with proven antioxidant and anti-inflammatory properties and proapoptotic, antimicrobial and antifungal effects, which can reduce the toxicity of free radicals in the human body and preserve human health [1,2,3]

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