Abstract
Saussurea involucrata (S. involucrata) had been reported to have anti-hepatoma function. However, the mechanism is complex and unclear. To evaluate the anti-hepatoma mechanism of S. involucrata comprehensively and make a theoretical basis for the mechanical verification of later research, we carried out this work. In this study, the total phenolic acids from S. involucrata determined by a cell suspension culture (ESPI) was mainly composed of 4,5-dicaffeoylquinic acid, according to the LC-MS analysis. BALB/c nude female mice were injected with HepG2 cells to establish an animal model of liver tumor before being divided into a control group, a low-dose group, a middle-dose group, a high-dose group, and a DDP group. Subsequently, EPSI was used as the intervention drug for mice. Biochemical indicators and differences in protein expression determined by TMT quantitative proteomics were used to resolve the mechanism after the low- (100 mg/kg), middle- (200 mg/kg), and high-dose (400 mg/kg) interventions for 24 days. The results showed that EPSI can not only limit the growth of HepG2 cells in vitro, but also can inhibit liver tumors significantly with no toxicity at high doses in vivo. Proteomics analysis revealed that the upregulated differentially expressed proteins (DE proteins) in the high-dose group were over three times that in the control group. ESPI affected the pathways significantly associated with the protein metabolic process, metabolic process, catalytic activity, hydrolase activity, proteolysis, endopeptidase activity, serine-type endopeptidase activity, etc. The treatment group showed significant differences in the pathways associated with the renin-angiotensin system, hematopoietic cell lineage, etc. In conclusion, ESPI has a significant anti-hepatoma effect and the potential mechanism was revealed.
Highlights
Saussurea involucrata (S. involucrata) is a rare and slow-growing herb growing in the Tianshan and Altay Mountains of Xinjiang Province, China, at altitudes over 2600 m
It has been shown that the methanol extracted from S. involucrata could inhibit the expression of cytokines stimulated by lipopolysaccharide (LPS), and the ethyl acetate extract could effectively inhibit phosphorylation and activation of the EGFR, Akt, and STAT3 pathway in PC-3 cells [9]
In order to explore the potential anti-hepatoma mechanism of EPSI more comprehensively and make a theoretical basis for later verification, this study depended on tumor-bearing BALB/c mice model combined with proteomics technology to verify the mechanism of action of S. involucrata on human hepatoma, while realizing the modern utilization of S. involucrata resources and the accurate analysis of its drug theory
Summary
Saussurea involucrata (S. involucrata) is a rare and slow-growing herb growing in the Tianshan and Altay Mountains of Xinjiang Province, China, at altitudes over 2600 m. S. involucrata has the effect of promoting blood circulation, relaxing tendons, dispersing cold, and removing dampness [1] It is mainly used for the treatment of coughs, rheumatoid arthritis, high-altitude response, and stomach pain [2]. S. involucrata has many bioactive compounds, including lignans [3], flavonoids [3], coumarins [4], sesquiterpene lactones [5], steroids, and phenylpropanoids [6]. These compounds show a wide range of biological activity, including anti-inflammatory [7], anti-aging [8], antioxidant, anti-fatigue [8], and anti-tumor effects [2]. In order to explore the potential anti-hepatoma mechanism of EPSI more comprehensively and make a theoretical basis for later verification, this study depended on tumor-bearing BALB/c mice model combined with proteomics technology to verify the mechanism of action of S. involucrata on human hepatoma, while realizing the modern utilization of S. involucrata resources and the accurate analysis of its drug theory
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