Oleuropein activates autophagy to circumvent anti-plasmodial defense

Praveen Sharma; Nikunj Tandel; Rajinder Kumar; Sushmita Negi; Prakriti Sharma; Sonia Devi; Kanika Saxena; Neil Roy Chaudhary; Sheetal Saini; Reetesh Kumar; Bharat Singh Chandel; Puran S Sijwali; Rajeev K Tyagi

doi:10.1016/j.isci.2024.109463

Oleuropein activates autophagy to circumvent anti-plasmodial defense

iScience. 2024 Mar 11;27(4):109463. doi: 10.1016/j.isci.2024.109463. eCollection 2024 Apr 19.

Authors

Praveen Sharma¹, Nikunj Tandel², Rajinder Kumar¹, Sushmita Negi^{1

3}, Prakriti Sharma¹, Sonia Devi^{1

3}, Kanika Saxena^{3

4}, Neil Roy Chaudhary¹, Sheetal Saini¹, Reetesh Kumar⁵, Bharat Singh Chandel⁶, Puran S Sijwali^{3

4}, Rajeev K Tyagi^{1

3}

Affiliations

¹ Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India.
² Institute of Science, Nirma University, SG highway, Ahmedabad 382481, India.
³ Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India.
⁴ CSIR-Centre for Cellular & Molecular Biology, Hyderabad, Telangana, India.
⁵ Faculty of Agricultural Sciences, Institute of Applied Sciences & Humanities, GLA University, Mathura 281406, India.
⁶ Department of Animal Biotechnology, College of Veterinary Science and AH, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar, Gujarat 385 506, India.

Abstract

Antimalarial drug resistance and unavailability of effective vaccine warrant for newer drugs and drug targets. Hence, anti-inflammatory activity of phyto-compound (oleuropein; OLP) was determined in antigen (LPS)-stimulated human THP-1 macrophages (macrophage model of inflammation; MMI). Reduction in the inflammation was controlled by the PI3K-Akt1 signaling to establish the "immune-homeostasis." Also, OLP treatment influenced the cell death/autophagy axis leading to the modulated inflammation for extended cell survival. The findings with MII prompted us to detect the antimalarial activity of OLP in the wild type (3D7), D10-expressing GFP-Atg18 parasite, and chloroquine-resistant (Dd2) parasite. OLP did not show the parasite inhibition in the routine in vitro culture of P. falciparum whereas OLP increased the antimalarial activity of artesunate. The molecular docking of autophagy-related proteins, investigations with MMI, and parasite inhibition assays indicated that the host activated the autophagy to survive OLP pressure. The challenge model of P. berghei infection showed to induce autophagy for circumventing anti-plasmodial defenses.

Keywords: Drug delivery system; Health sciences.