Deciphering and Predicting the Anti-Gastric Cancer Constituents of Actinidia eriantha Benth. Root via UPLC-Q-TOF-MS and In Vitro Mechanistic Validation
Tao Li, Bin Du, Shuang Liu, Jiale Mao, Yiping Ye, Houxing Lei, Shaochang Wu, Xiaoqin ZhangIntroduction:
The roots of Actinidia eriantha Benth. (AER) are a traditional herbal medicine of the She ethnic group in China, which has been clinically recognized for its significant anticancer effects, including those against liver cancer and gastric cancer. However, the mechanisms and components underlying the anti-gastric cancer effects of AER remain unclear.
Methods:
The components in the water extract of AER were analyzed using Liquid Chromatography- Mass Spectrometry (LC-MS) technology. A rat metabolic model was employed to further identify the absorbable components of AER that enter the body. Network pharmacology was then applied to predict the mechanisms of action of the components of AER that enter the body. Subsequently, the effects of AERcontaining serum on gastric cancer cell proliferation, migration, and invasion were evaluated using the SGC7901 gastric cancer cell system. The expression levels of genes related to cell proliferation, migration, and invasion were measured using quantitative real-time polymerase chain reaction(qPCR). Finally, Western Blot (WB) analysis was performed to determine the levels of Phosphatidylinositol 3-Kinase (PI3K), Protein Kinase B (AKT) total protein, and the levels of their phosphorylated proteins.
Results:
LC-MS analysis revealed that AER primarily contains phenolic compounds, flavonoids, and triterpenoids. Network pharmacology results indicated that the potential anti-gastric cancer components of AER mainly fall into two categories: pentacyclic triterpenoids (including Asiatic acid, Arjunolic acid, Tormentic acid, and Actinidic acid) and flavonoid compounds (such as Naringenin, Epicatechin, and Catechin). The anti-gastric cancer mechanisms of these components are closely associated with the PI3K-AKT signaling pathway. Subsequent experimental results demonstrated that AERcontaining serum significantly inhibited the proliferation, migration, and invasion of SGC7901 gastric cancer cells. Further mechanistic studies revealed that AER-containing serum significantly downregulated the expression of cancer-related genes, including PI3K, AKT, Vascular Endothelial Growth Factor (VEGF), Cyclin D1, and mechanistic Target of Rapamycin (mTOR). Western blot analysis confirmed that AER-containing serum notably reduced the levels of PI3K and AKT proteins, as well as their phosphorylated forms, thereby inhibiting the proliferation, migration, and invasion abilities of gastric cancer cells. These findings suggest that the anti-gastric cancer effects of AER are closely associated with suppression of the PI3K-AKT signaling pathway, and that this pathway may serve as a key target mediating its pharmacological actions.
Discussion:
These findings provide a scientific rationale for the traditional use of AER and offer data support for its further pharmaceutical development and clinical application.
Conclusion:
Our study has preliminarily identified pentacyclic triterpenoids and flavonoid compounds as potential anti-gastric cancer active components in AER. The combined experimental data suggest that AER-containing serum suppresses gastric cancer cell proliferation, migration, and invasion, and this effect is correlated with the downregulation of the PI3K-AKT signaling pathway. These findings provide a mechanistic basis for further in vivo validation and drug development.