Pharmacodynamics of Ginsenosides: Antioxidant Activities, Activation of Nrf2, and Potential Synergistic Effects of Combinations

Abstract

Ginseng has long been used in the Asian Countries for more than 2,000 years. Currently, in the “Western World or Western Medicines”, many reports have indicated that they have used herbal medicines, and Ginseng is one of the most popular herbs. Several recent reports have indicated that the antioxidant / anti-oxidative stress activities of ginseng play a role in the benefits of ginseng, however the precise mechanism is lacking. The antioxidant response element (ARE) is a critical regulatory element for the expression of many anti-oxidant enzymes and phase II/III drug metabolizing/transporter genes, mediated by the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The aim of this study was to examine the potential activation and synergism of Nrf2-ARE-mediated transcriptional activity between three common ginsenosides present in ginseng, ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1) and ginsenoside 20(S)-protopanaxytriol (20S). We tested whether these ginsenosides and their combinations, could induce Nrf2-ARE activities in HepG2-C8 cells with stably transfected ARE luciferase reporter gene. Cell proliferation, antioxidant and ARE activities, western blotting of Nrf2 protein and qPCR of mRNA of Nrf2 were conducted for Rb1, Rg1 and 20S as well as the combinations of 20S with Rb1 or Rg1. To determine the combination effects, the combination index (CI) was calculated. Rb1 and Rg1 are relatively non-toxic to the cells, while 20S at 50 μM or above significantly inhibited the cell proliferation. Rb1, Rg1 or 20S induced total antioxidant activity and ARE activity in a concentration-dependent manner. Furthermore, combinations of 20S with either Rb1 or Rg1 induced total antioxidant and ARE activity synergistically. Induction of Nrf2 protein and mRNA were also found to be synergistic with the combination treatments. In summary, in this study, we show that ginsenosides Rb1, Rg1 and 20S possess antioxidant activity, transcriptionally activating ARE as well as potential of synergistic activities. The Nrf2-ARE-mediated antioxidant pathway could play a role for the overall anti-oxidative stress activities, which could be important for ginseng's health beneficial effects such as cancer chemopreventive activities.

Effects of traditional Chinese medicine Xin-Ji-Er-Kang formula on 2K1C hypertensive rats: role of oxidative stress and endothelial dysfunction

“…Ginseng, Astragalus mongholicus, Radix Ophiopogo-nis and Polygonatum odoratum are the main components of XJEK formula. It has been reported that ginsenoside exists in ginseng, and total flavonoids of Astragalus (the active component of Astragalus mongholicus Bunge) and the decoction of Radix Ophiopogonis exhibit a potent antioxidant activity [28-30]. Our present study demonstrates that chronic treatment with XJEK prevents ED and OS in a doses-dependent mode.…”

Cardioprotective potential of Korean Red Ginseng extract on isoproterenol-induced cardiac injury in rats

“…It is well known that ginsenosides exert their antioxidant ability by increasing antioxidant enzymes and acting as a free-radical scavenger such as Rg1, Rg3, Re, Rd, Rh2, and Rg2 [35-39]. Among the many ginsenosides, it appears that Rb1 and Rg1 possess more potent antioxidant activity [40]. In present study, ginsenoside Rg1 and ginsenoside Rb1 are major compounds of KRG.…”

Spectroscopic and E-tongue evaluation of medicinal plants: A taste of how rasa can be studied

“…Although whole extracts and complex mixtures do not fit the conventional model of single active molecule, the growing interest in multitargeting and synergism in phytomedicines have opened new vistas in phytochemistry research [40], [41]. More importantly, the increasing attention on use of medicinal plants in Ayurveda has also necessitated identification of objective and reliable parameters for phytochemical evaluation of crude extracts.…”