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Article

Molecular Mechanisms of Panax japonicus var. major Against Gastric Cancer: Metabolite Analysis, Signaling Pathways, and Protein Targets

1
School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, China
2
Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
3
Department of Biology, Faculty of Science, Chiang Mai University, 239 Huay Kaew Road, Chiang Mai 50200, Thailand
4
Research Center of Deep Technology in Beekeeping and Bee Products for Sustainable Development Goals (SMART BEE SDGs), Chiang Mai University, 239 Huay Kaew Road, Chiang Mai 50200, Thailand
5
Southeast Asia Biodiversity Research Institute, Chinese Academy of Sciences, Yezin, Nay Pyi Taw 05282, Myanmar
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceuticals 2025, 18(6), 823; https://doi.org/10.3390/ph18060823
Submission received: 22 April 2025 / Revised: 24 May 2025 / Accepted: 27 May 2025 / Published: 30 May 2025
(This article belongs to the Section Natural Products)

Abstract

Background/Objectives: Ginseng (Panax japonicus var. major) is a traditional medicinal plant with anticancer properties. We aimed to assess the biological activity, potential targets, and molecular mechanisms of P. japonicus var. major in resisting gastric cancer. Methods: We developed a model that combines network pharmacology, molecular docking, untargeted metabolomics, and molecular dynamics simulations to predict which compounds from P. japonicus var. major might be active in the treatment of gastric cancer. We conducted in vitro experiments and immunoblot validation to test these predictions. Results: We identified 44 main active compounds from P. japonicus var. major and 29 core targets. These compounds showed anti-gastric cancer activity against the HGC-27 cell line by acting on TNF and T-cell receptor signaling pathways to diminish inflammatory factor production and promote apoptosis of gastric cancer cells. Clinical survival analysis identified four core proteins (CASP3, TNF, AKT1, and EGFR) whose abundance was associated with survival status in gastric cancer patients. Molecular docking, along with molecular dynamics simulations, revealed that these core proteins could be stably bound by the identified active compounds. The anti-gastric cancer effects of P. japonicus var. major compounds involved a lower Bcl-2/Bax ratio and upregulation of CASP3 and CASP9 levels, highlighting significant differences in anti-gastric cancer activity between extracts prepared from fresh versus dried P. japonicus var. major. Conclusions: Our results provide background for the indigenous medicinal use of P. japonicus var. major to treat gastric cancer and lay the foundation for further pharmacological experiments and clinical tests.
Keywords: Panax japonicus var. major; multiple pathways and targets; metabolite profiling; anti-gastric cancer activities; molecular mechanisms Panax japonicus var. major; multiple pathways and targets; metabolite profiling; anti-gastric cancer activities; molecular mechanisms

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MDPI and ACS Style

Huang, C.; Li, G.; Yan, X.; Disayathanoowat, T.; Inta, A.; Gao, L.; Yang, L. Molecular Mechanisms of Panax japonicus var. major Against Gastric Cancer: Metabolite Analysis, Signaling Pathways, and Protein Targets. Pharmaceuticals 2025, 18, 823. https://doi.org/10.3390/ph18060823

AMA Style

Huang C, Li G, Yan X, Disayathanoowat T, Inta A, Gao L, Yang L. Molecular Mechanisms of Panax japonicus var. major Against Gastric Cancer: Metabolite Analysis, Signaling Pathways, and Protein Targets. Pharmaceuticals. 2025; 18(6):823. https://doi.org/10.3390/ph18060823

Chicago/Turabian Style

Huang, Chao, Ge Li, Xiuxiang Yan, Terd Disayathanoowat, Angkhana Inta, Lu Gao, and Lixin Yang. 2025. "Molecular Mechanisms of Panax japonicus var. major Against Gastric Cancer: Metabolite Analysis, Signaling Pathways, and Protein Targets" Pharmaceuticals 18, no. 6: 823. https://doi.org/10.3390/ph18060823

APA Style

Huang, C., Li, G., Yan, X., Disayathanoowat, T., Inta, A., Gao, L., & Yang, L. (2025). Molecular Mechanisms of Panax japonicus var. major Against Gastric Cancer: Metabolite Analysis, Signaling Pathways, and Protein Targets. Pharmaceuticals, 18(6), 823. https://doi.org/10.3390/ph18060823

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