Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions

Abstract

Ginseng has gained its popularity as an adaptogen since ancient days because of its triterpenoid saponins, known as ginsenosides. These triterpenoid saponins are unique and classified as protopanaxatriol and protopanaxadiol saponins based on their glycosylation patterns. They play many protective roles in humans and are under intense research as various groups continue to study their efficacy at the molecular level in various disorders. Ginsenosides Rb1 and Rg1 are the most abundant ginsenosides present in ginseng roots, and they confer the pharmacological properties of the plant, whereas ginsenoside Rg3 is abundantly present in Korean Red Ginseng preparation, which is highly known for its anticancer effects. These ginsenosides have a unique mode of action in modulating various signaling cascades and networks in different tissues. Their effect depends on the bioavailability and the physiological status of the cell. Mostly they amplify the response by stimulating phosphotidylinositol-4,5-bisphosphate 3-kinase/protein kinase B pathway, caspase-3/caspase-9-mediated apoptotic pathway, adenosine monophosphate-activated protein kinase, and nuclear factor kappa-light-chain-enhancer of activated B cells signaling. Furthermore, they trigger receptors such as estrogen receptor, glucocorticoid receptor, and N-methyl-d-aspartate receptor. This review critically evaluates the signaling pathways attenuated by ginsenosides Rb1, Rg1, and Rg3 in various tissues with emphasis on cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders.

20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

“…20(S)-Rg3 is a compound that has many biological effects of preventing ischemia-reperfusion injury, reducing oxygen free radicals, antioxidation, and inhibiting the activity of voltage-regulated pathways. Studies have reported that 20(S)-Rg3 as a nontraditional therapy has protective effects on diabetes itself, as well as diabetic cardiomyopathy, diabetic retinopathy, and atherosclerosis in DM [23,24]. Kang et al [20] reported 20(S)-Rg3 prevents the progression of renal damage and dysfunction in type 2 diabetic rats via inhibiting oxidative stress and advanced glycation end-product formation.…”

Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

“…Another molecule, ginseng, also known as red ginseng (Panax ginseng, Araliaceae), is a well-known medicinal plant and popular source of saponins. Several studies identified the biological active components of ginseng, the ginsenosides, that were shown to play many protective roles [416]. The most frequently used and studied ginsenosides, Rg1, Rg3, and Rb1, were investigated for their effect on α-syn aggregation in vitro [417,418].…”

An update on Chinese herbal medicines as adjuvant treatment of anticancer therapeutics

“…Much of the pharmacological research has shown that Panax ginseng has potent immune modulation, vasorelaxation, anti-oxidation, antiinflammation, and anticancer properties (14). Panax ginseng contains many active components such as ginsenosides, peptides, essential oil and polysaccharides, among which, ginsenosides (e.g., Rg3 and Rb1) are considered an excellent option for their anticancer property (15). Ginseng and its active components have been reported as an adjuvant treatment to synergistically enhance efficacy of conventional therapy (e.g., chemoand radio-therapeutics), reduce the risk of development and recurrence of some types of cancer (e.g., stomach, liver, pancreas, and colon cancer), and improve host intrinsic response to cancer and quality of patients' life (16).…”