International Journal of Nanomedicine (Dec 2023)
Fatty Oil of Descurainia Sophia Nanoparticles Improve Monocrotaline-Induced Pulmonary Hypertension in Rats Through PLC/IP3R/Ca2+ Signaling Pathway
Abstract
Yajuan Zheng,1,* Peipei Yuan,1,2,* Zhenkai Zhang,1 Yang Fu,1,2 Saifei Li,1 Yuan Ruan,1 Panying Li,1 Yi Chen,1 Weisheng Feng,1– 3 Xiaoke Zheng1– 3 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450008, People’s Republic of China; 2The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, 450046, People’s Republic of China; 3Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P. R. China, Zhengzhou, 450008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weisheng Feng; Xiaoke Zheng, Email [email protected]; [email protected]: Fatty oil of Descurainia Sophia (OIL) has poor stability and low solubility, which limits its pharmacological effects. We hypothesized that fatty oil nanoparticles (OIL-NPs) could overcome this limitation. The protective effect of OIL-NPs against monocrotaline-induced lung injury in rats was studied.Methods: We prepared OIL-NPs by wrapping fatty oil with polylactic-polyglycolide nanoparticles (PLGA-NPs) and conducted in vivo and in vitro experiments to explore its anti-pulmonary hypertension (PH) effect. In vitro, we induced malignant proliferation of pulmonary artery smooth muscle cells (RPASMC) using anoxic chambers, and studied the effects of OIL-NPs on the malignant proliferation of RPASMC cells and phospholipase C (PLC)/inositol triphosphate receptor (IP3R)/Ca2+ signal pathways. In vivo, we used small animal echocardiography, flow cytometry, immunohistochemistry, western blotting (WB), polymerase chain reaction (PCR) and metabolomics to explore the effects of OIL-NPs on the heart and lung pathological damage and PLC/IP3R/Ca2+ signal pathway of pulmonary hypertension rats.Results: We prepared fatty into OIL-NPs. In vitro, OIL-NPs could improve the mitochondrial function and inhibit the malignant proliferation of RPASMC cells by inhibiting the PLC/IP3R/Ca2+signal pathway. In vivo, OIL-NPs could reduce the pulmonary artery pressure of rats and alleviate the pathological injury and inflammatory reaction of heart and lung by inhibiting the PLC/IP3R/Ca2+ signal pathway.Conclusion: OIL-NPs have anti-pulmonary hypertension effect, and the mechanism may be related to the inhibition of PLC/IP3R/Ca2+signal pathway. Keywords: pulmonary hypertension, PLC/IP3R/Ca2+, nanoparticles, RPASMC, fatty oil