Cellular stress response mechanisms as therapeutic targets of ginsenosides

Abstract

Ginseng, one of the most widely used traditional herbal medicines and dietary supplements, has historically been recognized as a tonic herb and adaptogen that can enhance the body's tolerance to various adversities. Ginsenosides are a diverse group of steroidal saponins that comprise the major secondary metabolites of ginseng and are responsible for its multiple pharmacological effects. Emerging evidence suggests that hormetic phytochemicals produced by environmentally stressed plants can activate the moderate cellular stress response mechanisms at a subtoxic level in humans, which may enhance tolerance against severe dysfunction or disease. In this review, we initially describe the role of ginsenosides in the chemical defense of plants from the genus Panax suffering from biotic and abiotic stress. Next, we summarize the diverse evolutionarily conserved cellular stress response pathways regulated by ginsenosides and the subsequent stress tolerance against various dysfunctions or diseases. Finally, the structure-activity relationship involved in the effect of ginsenosides is also analyzed. The evidence presented in this review implicates that ginseng as "the King of all herbs" could be regarded as a well-characterized example of the critical role of cellular stress response mechanisms in understanding the health benefits provided by herbal medicines from an evolutionary and ecological perspective.

Z‐Ligustilide Exerted Hormetic Effect on Growth and Detoxification Enzymes of Spodoptera litura Larvae

“…In an ecological environment, plants have evolved sophisticated defense systems to sense and resist a variety of biotic threats. Invertebrates, particularly insects, are the major biotic factor that interacts with plants in the microenvironment as insects have evolved to feed on plants at least 4 billion years ago, which leads to the formation of a close coevolutionary relationship [ 29 ]. The main approach employed by plants to avoid the attack from herbivorous insects is the chemical defense, which is partially mediated by the production of toxic and repellent compounds that accumulate after insect feeding [ 30 , 31 ].…”

Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress‐ and aging‐related diseases

“…Importantly, the term adaptogen is related to a physiological process—adaptation to environmental challenges, which is a multistep process including diverse mechanisms of extracellular and intracellular interactions. The renewed definition of adaptogens 16,17 is supported by the results of recent studies on the molecular mechanisms of action of adaptogens in a variety of regulatory systems from the cellular to entire organism levels 11,16–63 …”

Caffeine-Containing, Adaptogenic-Rich Drink Modulates the Effects of Caffeine on Mental Performance and Cognitive Parameters: A Double-Blinded, Placebo-Controlled, Randomized Trial

“…Most studied among these plants are Rhodiola rosea , Withania somnifera (ashwagandha) , Schisandra chinensis, and Eleutherococcus senticosus . As a class of compounds, adaptogens have been shown to modify cellular stress responses, exert anti-fatigue activity, and improve mental work capacity [ 26 , 27 ]. Although the precise mechanisms by which adaptogens may influence these cellular responses are poorly characterized their effects are most likely non-specific in nature via modification of a wide array of cellular signaling pathways [ 28 ].…”