Rosmarinic acid, the active component of Rubi Fructus, induces apoptosis of SGC-7901 and HepG2 cells through mitochondrial pathway and exerts anti-tumor effect

Sep 24, 2026

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Rosmarinic acid (RA), a phenolic acid found in many herbal species, was studied for its role in gastric and liver cancers where its mechanism remains unclear. RA was isolated from Rubi Fructus (RF) for the first time and evaluated on SGC-7901 and HepG2 cell models. Cells treated with 50–100 μg/mL RA for 48 h showed reduced viability, mobility, and Bcl-2, alongside increased apoptosis rate, Bax, cytochrome C, and cleaved caspase-3, with G0/G1 and G0/G1–S arrests. The findings indicate mitochondrial-pathway apoptosis, supporting RF anti-tumor use.

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Naunyn-Schmiedeberg's Archives of Pharmacology (2023) 396:3743–3755 [https://doi.org/10.1007/s00210-023-02552-z](https://doi.org/10.1007/s00210-023-02552-z) Rosmarinic acid, the active component of Rubi Fructus, induces apoptosis of SGC‑7901 and HepG2 cells through mitochondrial pathway and exerts anti‑tumor effect Changlun Chen1 · Yilin Liu1 · Yi Shen1 · Lili Zhu1 · Lumeng Yao1 · Xingxing Wang1 · Anna Zhang1 · Jiao Li1 · Jianjun Wu1 · Luping Qin1 Received: 22 March 2023 / Accepted: 23 May 2023 / Published online: 20 June 2023 © The Author(s) 2023 Abstract Rosmarinic acid (RA) is a well-known phenolic acid widely present in over 160 species of herbal plants and known to exhibit anti-tumor effects on breast, prostate, and colon cancers in vitro. However, its effect and mechanism in gastric cancer and liver cancer are unclear. Moreover, there is no RA report yet in the chemical constituents of Rubi Fructus (RF) . In this study, RA was isolated from RF for the first time, and the effect and mechanism of RA on gastric and liver cancers were evaluated using SGC-7901 and HepG2 cells models. The cells were treated with different concentrations ofRA (50, 75, and 100 μg/mL) for 48 h, and the effect of RA on cell proliferation was evaluated by the CCK-8 assay. The effect of RA on cell morphology and mobility was observed by inverted fluorescence microscopy, cell apoptosis and cell cycle were determined by flow cytometry, and the expression of apoptosis-related proteins cytochrome C, cleaved caspase-3, Bax, and Bcl-2 was detected by western blotting. The results revealed that, with an increase in the RA concentration, the cell viability, mobility, and Bcl-2 expression decreased, while the apoptosis rate, Bax, cytochrome C, and cleaved caspase-3 expression increased, and SGC-7901 and HepG2 cells could be induced to arrest their cell cycle in the G0/G1 and S phases, respectively. These results together indicate that RA can induce apoptosis of SGC-7901 and HepG2 cells through the mitochondrial pathway. Thus, this study supplements the material basis of the anti-tumor activity of RF and provides an insight into the potential mechanism of RA-inducing apoptosis of gastric cancer SGC-7901 cells and liver cancer HepG2 cells, thereby facilitating further developmental studies on and the utilization of the anti-tumor activity of RF. Keywords Rubi Fructus · Rosmarinic acid · Apoptosis · Mitochondria apoptosis pathway · Anti-tumor Introduction Rosmarinic acid (RA) is a water-soluble natural phenolic acid widely present across 160 species of herbal plants (Guan et al. 2022), originally isolated and named after rosemary (Rosmarinus officinalis, Lamiaceae) . Existing studies suggest that RA has anti-tumor effect in breast cancer (reducing methyltransferase activity and hypermethylation Changlun Chen and Yilin Liu contributed equally to this work. * Jianjun Wu [wjjpharmacy@163.com](wjjpharmacy@163.com) * Luping Qin [lpqin@zcmu.edu.cn](lpqin@zcmu.edu.cn) 1 College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China of DNA) (Paluszczak et al. 2010), prostate cancer (inducing apoptosis) (Yesil-Celiktas et al. 2010), and colon cancer (inhibiting the activity of COX2 protein promoter) (Scheckel et al. 2008) . For liver cancer and gastric cancer, RA led to decrease cell viability and morphological changes in HepG2 cells (Renzulli et al. 2004) as well as a decrease in the survival of SGC-7901 cells (Li et al. 2013) . However, these studies only demonstrated RA’s anti-tumor effect on gastric and liver cancers, with no establishment of the specific underlying mechanisms. Therefore, we aimed to explore the mechanism RA exerted anti-tumor effect on gastric and liver cancers. Rubus chingii Hu. , belonging to the family Rosaceae, whose fruits are known as Rubi Fructus (RF), is widely planted for its significant nutritional and medicinal values. The RF is both medicine and food and has been used as tradi

FAQs

What effect does rosmarinic acid have on SGC-7901 and HepG2 cells?

Rosmarinic acid induces apoptosis in SGC-7901 and HepG2 cells and shows an anti-tumor effect, as indicated by increased apoptosis markers and reduced cell viability and mobility.

How does rosmarinic acid trigger apoptosis according to the study?

The study indicates mitochondrial-pathway apoptosis, supported by increased cytochrome C and cleaved caspase-3, along with shifts in Bax and Bcl-2 expression.

What experimental assays and observations were used to evaluate the mechanism?

Cell proliferation was assessed by CCK-8, morphology and mobility by inverted fluorescence microscopy, apoptosis and cell cycle by flow cytometry, and apoptosis-related protein expression by western blotting.

Sep 24, 2026

Uploaded by Jasmine