Salidroside Combats Aging and Cancers through Oxidative Stress Mitigation

Summary

This article systematically reviews the chemical properties of Salidroside (Sal), its pharmacological effects on cellular targets and signaling pathways. Sal exerts activities against aging and cancers, including the highly malignant pancreatic ductal adenocarcinoma, by ameliorating oxidative stress events.

Abstract

Salidroside (Sal) is the primary active constituent of the Rhodiola genus, which is usually processed into precious medicinal herbs and functional foods. Sal has emerged as a focal point in therapeutics against aging and cancer including the highly malignant pancreatic ductal adenocarcinoma, due to its multi-target biological activities. This review systematically summarizes the chemical properties of Sal, its pharmacological effects on cellular targets and signaling pathways, and the mechanisms underlying its anti-aging and anti-cancer effects. The molecular structure of Sal, characterized by glycosidic bonds and hydroxyl groups, provides it with antioxidant activity and the ability to interact with multiple proteins. By reducing the cellular levels of reactive oxygen species (ROS), Sal modulates several signaling axes related to human wellness, including Nrf2, SIRT1/2, PI3K/AKT, JAK2/STAT3, and other pathways. As a result, Sal exerts its anti-aging effects through alleviating oxidative stress, preventing cellular senescence, and improving cardiovascular function, while its anti-cancer activities are driven by inhibiting cell proliferation/survival, migration/metastasis, and modulating the tumor microenvironment/immunity. This review may contribute to a deeper understanding of Sal's biological activities and facilitate its transition from laboratory discoveries to clinical applications in aging and cancer management.

Introduction

Rhodiola genus (e.g., Rhodiola crenulata and Rhodiola rosea) is a class of relatively rare and valuable plants native to high-altitude regions of Asia, Europe, and North America. Rhodiola grows under the forest or on grassy slopes in cold areas at an altitude of 1800-2700 m, mostly distributed in the Northern Hemisphere¹. In China, the production areas of Rhodiola are concentrated in the Qinghai-Tibet Plateau and the high mountains in the southwest and northwest, including Tibet, Yunnan, Sichuan, Qinghai, Xinjiang, and Gansu². Traditionally, the root or extracts ....