Multiple targeted self-emulsifying compound RGO reveals obvious anti-tumor potential in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a highly vascularized, inflammatory, and abnormally proliferating tumor. Monotherapy is often unable to effectively and comprehensively inhibit the progress of HCC. In present study, we selected ginsenoside Rg3, ganoderma lucidum polysaccharide (GLP), and oridonin as the combined therapy. These three plant monomers play important roles in anti-angiogenesis, immunological activation, and apoptosis promotion, respectively. However, the low solubility and poor bioavailability seriously hinder their clinical application. To resolve these problems, we constructed a new drug, Rg3, GLP, and oridonin self-microemulsifying drug delivery system (RGO-SMEDDS). We found that this drug effectively inhibits the progression of HCC by simultaneously targeting multiple signaling pathways. RGO-SMEDDS restored immune function by suppressing the production of immunosuppressive cytokine and M2-polarized macrophages, reduced angiogenesis by downregulation of vascular endothelial growth factor and its receptor, and retarded proliferation by inhibiting the epidermal growth factor receptor EGFR/AKT/epidermal growth factor receptor/protein kinase B/glycogen synthase kinase-3 (GSK3) signaling pathway. In addition, RGO-SMEDDS showed considerable safety in acute toxicity tests. Results from this study show that RGO-SMEDDS is a promising therapy for the treatment of HCC.

Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy – A comprehensive review

“…Total lipid content, especially triglycerides, was estimated after the addition of ORI to the free fatty acid cell model for 24 h. Furthermore, studies revealed that ORI can enhance autophagy and decrease the liver cells steatosis (Cheng et al., 2021 ). Similarly, ORI, combined with ginsenoside and the fungus Ganoderma lucidum , is reported to enhance immunological processes and ultimately the apoptosis in hepatocellular carcinoma (HCC) cells (He et al., 2021 ).…”

The pharmacological role of Ginsenoside Rg3 in liver diseases: A review on molecular mechanisms

“…The drug was found to be effective in inhibiting the progression of HCC by targeting multiple pathways. Moreover, the drug was found to be safe during the acute toxicity tests [ 96 ].…”

Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology

“…The ginsenoside Rg3, oridonin, and Ganoderma lucidum polysaccharide (GLP) were introduced into a self-microemulsifying drug delivery system (RGO-SMEDDS) as an anti-angiogenic agent, immune regulator, and apoptosis inducer, respectively. The system evinced a combined strategy against HCC via triggering angiogenesis inhibition, anti-proliferation, and decreasing immunosuppressive cytokines and M2-polarized macrophages, for the suppression of the p-EGFR/AKT/GSK3 axis ( He et al, 2021 ).…”