Specific Interaction With Human Serum Albumin Reduces Ginsenoside Cytotoxicity in Human Umbilical Vein Endothelial Cells

Abstract

Human serum albumin (HSA) is an important component of plasma, which has the functions of maintaining colloid osmotic pressure and capillary membrane stability, promoting blood circulation, and anti-oxidation. Three-dimensional structure of HSA determines its ability to bind and transport hormones and other substances. In this study we examined the interactions between HSA and ginsenoside Rg3, Rg5, Rk1, Rh2, and Rh4, which are the main cytotoxic ginsenosides extracted from red ginseng. Heat transfer generated by the specific interaction between HSA and each ginsenoside was measured using isothermal titration calorimetry (ITC) assay, which demonstrated that all these 5 ginsenosides bound to HSA with binding constants of 3.25, 1.89, 6.04, 2.07, and 5.17 × 10 5 M −1 , respectively. Molecular docking also displayed that these ginsenosides interact with HSA at different sites of the HSA surface. Importantly, cell viability assay showed that the cytotoxicity of these ginsenosides reduced significantly at the presence of HSA in human vascular endothelial cells (HUVEC). Taken together, this study reveals the mechanism by which these ginsenosides are transported in vivo by not causing damage in vascular endothelium, and also suggests HSA might be an ideal carrier help to transport and execute these ginsenoside functions in human body.

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

“…It has been reported that human serum albumin (HSA) can interact with (20S)G-Rh2, (20S)G-Rg3, G-Rk1, G-Rg5, G-Rh4, and CK because of the sequence homology between HSA and BSA. Additionally, the binding sites are located in different domains of HSA [ 39 , 40 ]. Taken together, we can summarize some characteristics of ginsenosides.…”

“…Herein, we showed that G-Rk1 and G-Rg5 both have cytotoxic effects on MHCC-97H cells by inducing apoptosis. In our previous study, we determined the cell viability of human umbilical vein endothelial cells (HUVEC) in treatment with G-Rk1 and G-Rg5 by MTT, with an IC 50 of 12.272 μg/mL and 10.182 μg/mL, respectively [ 39 ]. Combined with the results of this study, it demonstrated that the cytotoxic effect of G-Rk1 and G-Rg5 on normal tissue cells is less than that on MHCC-97H cells.…”

Prognostic value of pretreatment serum albumin−globulin ratio in urothelial carcinoma: A systematic review and meta-analysis

“…Albumin and globulins are the two most abundant proteins in human blood plasma and can be easily and cost-effectively measured. As the major serum protein, albumin plays an vital role in carrying out antioxidant activities, maintaining colloidal osmotic pressure, binding and transporting hormones, cations and fatty acids, as well as in maintaining capillary membrane stability ( 41 , 42 ). Similarly, the albumin level either reflects the body nutritional status or represents the systemic inflammation ( 43 ).…”

Ginsenoside Rg3 overcomes tamoxifen resistance through inhibiting glycolysis in breast cancer cells

“…Ginsenoside Rg3 is the original ginsenoside compound and is one of the active components of ginseng stems, leaves, and roots (Lee et al, 2020; Nakhjavani et al, 2020). Rg3 can produce a variety of pharmacological effects, such as anti‐oxidation, anticancer, anti‐inflammation, and antiaging (Li et al, 2020; Min et al, 2006; Shi et al, 2020; Zhang et al, 2018, 2020). In addition, Rg3 can induce memory impairment, neurotoxicity, depression‐like behavior defects, and other potential effects (Aalinkeel et al, 2018; Kang et al, 2017; Li et al, 2020).…”