Search

At present, the colorectal cancer (CRC) is a malignant tumor of the colon and rectum that is often found at the junction of the two, and it will invade many visceral organs and organizations, causing very serious damage to the body of the patient. Patrinia villosa Juss. (P.V), is a well-known traditional chinese medicine (TCM), and is recorded in the Compendium of Materia Medica as a necessary article for the treatment of intestinal carbuncle. It has been incorporated into traditional cancer treatment prescriptions in modern medicine. While the mechanism of action of P.V in the treatment of CRC remains unclear. Aim of the study: To investigate P.V in treating CRC and clarify the underlying mechanism. This study was based on Azoxymethane (AOM) combined with the Dextran Sulfate Sodium Salt (DSS)-induced CRC mouse model to clarify the pharmacological effects of P.V. The mechanism of action was found by metabolites and metabolomics. The rationality of metabolomics results was verified through the clinical target database of network pharmacology, and find the upstream and downstream target information of relevant action pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using quantitative PCR (q-PCR) and Western blot. The number and the diameter of tumors were decreased when mice were treated with P.V. P.V group section results showed newly generated cells which improved the degree of colon cell injury. Pathological indicators presented a trend of recovery to normal cells. Compared to the model group, P.V groups had significantly lower levels of the CRC biomarkers CEA, CA19-9, and CA72-4. Through the evaluation of metabolites and metabolomics, it was found that a total of 50 endogenous metabolites had significant changes. Most of these are modulated and recovered after P.V treatment. It alters glycerol phospholipid metabolites, which are closely related to PI3K target, suggesting that P.V can treat CRC though the PI3K target and PI3K/Akt signaling pathway. q-PCR and Western blot results also verified that the expression of VEGF, PI3K, Akt, P38, JNK, ERK1/2, TP53, IL-6, TNF- α and Caspase-3 were significantly decreased, whereas that of Caspase-9 was increased after treatment. P.V is dependent on PI3K target and PI3K/Akt signaling pathway for CRC treatment. [Display omitted] • Patrinia villosa has a certain therapeutic effect on the CRC. • Patrinia villosa could up-regulate in 41 kinds, including sn-glycero-3-Phosphocholine, 1-Acyl-sn-glycero-3-phosphocholine, Diacylglycerol, etc. And down-regulate in 9 kinds, including Phytosphingosine, etc. These changes are mainly related to glycerophospholipid metabolism, sphingolipid metabolism, cysteine and methionine metabolism, glycine, serine and threonine metabolism. • Patrinia villosa treat CRC though the PI3K target and PI3K/Akt signaling pathway. • Patrinia villosa reduced the protein expression of PI3K, Akt, VEGFA, P38, JNK, ERK1/2, TP53, IL-6, TNF- α , Caspase-3, and VEGFA and increased the protein expression of Caspase-9. [ABSTRACT FROM AUTHOR]