Red Panax Ginseng Studies

1. Efficacy of Panax ginseng Meyer Herbal Preparation HRG80 in Preventing and Mitigating Stress-Induced Failure of Cognitive Functions in Healthy Subjects: A Pilot, Randomized, Double-Blind, Placebo-Controlled Crossover Trials

March 2020

Abstract
Background: The aim of this pilot study was to compare the efficacy of hydroponically cultivated red Panax ginseng Meyer root preparation (HRG80) and traditionally harvested six-year-old white P. ginseng standard preparation (PGS) with placebo in preventing symptoms of stress.

Methods: The effects of HRG80, PGS, and placebo capsules were studied in 50 tired healthy subjects in a three-arm, randomized, double-blinded, placebo-controlled crossover trial. Efficacy-outcome measures included the accuracy of processing the d2 test for cognitive functions, obtained accuracy score in a computerized memory test, and the perceived-stress (PS) score.

Results: A statistically significant interaction effect between time and treatment (p < 0.0001) was observed in the attention d2 and memory tests, indicating that HRG80 treatment was more beneficial than that with a placebo. The effects of PGS were better than those of the placebo, but the difference was not statistically significant. There was significant difference between the effects of HRG80 and PGS (p < 0.0001) that were observed after single (Day 1) and repeated administrations on Days 5 and 12 of treatment.

Conclusion: Overall, HRG80 treatment was significantly superior compared to that with the PGS and placebo regarding attention, memory, and PS scores after single and repeated administrations for 5 and 12 days.

Keywords: Panax ginseng; cognitive performance; fatigue; hydroponic cultivation; stress.

Conflict of interest statement
P.A.M. declares a conflict of interest since he is co-CEO at Botalys SA (Ath, Belgium); A.P. has an independent-contractor agreement with Europharma USA, and is head of research and development company Phytomed AB. A.H. declares no competing interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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2. Effects of red and white ginseng preparations on electrical activity of the brain in elderly subjects: a randomized, double-blind, placebo-controlled, three-armed cross-over study.

Abstract: Background: Recently, the superior efficacy of hydroponically cultivated red ginseng preparation HRG80® compared to wild growing white ginseng (WG) in preventing stress‐induced symptoms related to the daily work situation of healthy subjects was reported. The aim of this study was to compare the effects of HRG80®, WG, and placebo on the electrical activity in the brain of elderly human subjects during relaxation and mental challenges. Methods: Changes in the electroencephalogram (EEG) frequency ranges of 17 different brain regions were measured after single and repeated administration of HRG80®, WG, and placebo across a four‐week randomized, doubleblind, placebo‐controlled three‐armed cross‐over trial. Results: Both red and white ginseng preparations had a strong impact on brain activity, with different effects on various brain regions depending on the mental load during relaxation and cognitive tasks associated with memory, attention, and mental performance. Both ginseng preparations exhibited significant effects on spectral powers compared to placebo, reflecting an activating action. The spectral changes in the quantitative EEG induced by HRG80® indicated an improvement in mood as well as calming effects, evidenced by the modulation of β2 waves, representing changes in GABA‐ergic neurotransmission. HRG80® attenuated δ/θ powers during relaxation, suggesting the potential improvement of pathologically enhanced spectral power in aging. Conclusion: The results of this study suggest that both hydroponically cultivated red and wild growing white ginseng have similar beneficial effects on the cognitive functions of elderly subjects, as reflected by electric brain activity, but their modes of action on the brain are different. [Dimpfel W, Mariage PA, Panossian AG. Effects of red and white ginseng preparations on electrical activity of the brain in elderly subjects: a randomized, double-blind, placebo-controlled, three-armed cross-over study. Pharmaceuticals. 2021;14:182.


3. Efficacy of Panax ginseng Meyer herbal preparation HRG80 in preventing and mitigating stress-induced failure of cognitive functions in healthy subjects: a pilot, randomized, double-blind, placebo-controlled crossover trial. 

Background: The aim of this pilot study was to compare the efficacy of hydroponically cultivated red Panax ginseng Meyer root preparation (HRG80) and traditionally harvested six-year old white P. ginseng standard preparation (PGS) with placebo in preventing symptoms of stress.

Methods: The effects of HRG80, PGS, and placebo capsules were studied in 50 tired healthy subjects in a three-arm, randomized, double-blinded, placebo-controlled crossover trial. Efficacy-outcome measures included the accuracy of processing the d2 test for cognitive functions, obtained accuracy score in a computerized memory test, and the perceived-stress (PS) score.

Results: A statistically significant interaction effect between time and treatment (p < 0.0001) was observed in the attention d2 and memory tests, indicating that HRG80 treatment was more beneficial than that with a placebo. The effects of PGS were better than those of the placebo, but the difference was not statistically significant. There was significant difference between the effects of HRG80 and PGS (p < 0.0001) that were observed after single (Day 1) and repeated administrations on Days 5 and 12 of treatment.

Conclusion: Overall, HRG80 treatment was significantly superior compared to that with the PGS and placebo regarding attention, memory, and PS scores after single and repeated administrations for 5 and 12 days. [Mariage PA, Hovhannisyan A, Panossian AG. Efficacy of Panax ginseng Meyer herbal preparation HRG80 in preventing and mitigating stress-induced failure of cognitive functions in healthy subjects: a pilot, randomized, double-blind, placebo-controlled crossover trial. Pharmaceuticals. 2020;13:57.] 



4. Panax ginseng Meyer herbal preparation HRG80 for preventing and mitigating stress-induced failure of cognitive functions in healthy subjects. 

A large body of evidence suggests that ginsenoside metabolites contribute substantially to the pharmacological effects of ginseng. These metabolites (rare ginsenosides) are present in minor amounts in white Ginseng and in larger amounts in steam processed red Ginseng. A recent study aimed to obtain evidence that rare ginsenosides significantly contribute in the overall efficacy of Ginseng. The efficacy of two Ginseng preparations containing approximately the same amounts of major ginsenosides but substantially different (7.8-fold) amounts of rare ginsenosides was compared in a three-arm, randomized, double-blinded, placebo-controlled, crossover trial. A hydroponically cultivated red Panax ginseng Meyer root preparation (HRG80®) was compared with traditionally harvested 6-year old white P. ginseng (WG) and placebo for their ability to prevent symptoms of stress such as fatigue, impaired memory, reduced concentration, and attention deficit related to daily work in healthy subjects. The effects of HRG80® (daily dose: 418 mg of red ginseng powder, 63.5.mg of ginsenosides, and 52 mg of rare ginsenosides), PGS Arkopharma (daily dose: 764 mg of white ginseng powder, 19.8 mg of ginsenosides, and 6.1 mg of rare ginsenosides), and placebo capsules, taken orally once a day for 14 days in 50 tired but otherwise healthy subjects, were studied. The efficacy outcomes included the accuracy of processing in the d2 test for cognitive functions, an accuracy score obtained using a computerized memory test, and the perceived stress score. A statistically significant interaction effect between time and treatment was observed in the d2 attention and memory tests, indicating that HRG80 was more beneficial than placebo. The effects of WG were better than those of placebo, but the difference was not statistically significant. There was a significant difference between the effects of HRG80 and WG, which was observed after both single (day 1) and repeated administration (days 5 and 12). Importantly, the effective therapeutic daily dose of HRG80 (418 mg) was at least 10-fold lower than the commonly used effective dose red ginseng (4500–9000 mg per day). 

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5. Panax ginseng preparations enhance long term potentiation in rat 1 hippocampal slices by glutamatergic NMDA and kainate receptor 2 mediated transmission.

Background: Root of the Korean red ginseng (Panax ginseng C.A. Meyer) is used in traditional medicinal systems to enhance cognitive function. In this study we compared the effects of HRG80 with a standard Ginseng preparation (SGP) on the excitability of pyramidal cells in the hippocampus of rats by using hippocampal long-term potentiation. The aim of the study: The aim of this study was to compare the effects of HRG80 with SGP on the excitability of pyramidal cells in the hippocampus of rats, and to elucidate a possible mechanism of their action by using hippocampal long-term potentiation, a memory model based on modulation of glutamatergic neurotransmission.

Methods: Red Ginseng preparations were orally administered at daily doses of 10 mg/kg, 25 mg/kg, and 50 mg/kg to rats for 1 week before ex vivo analysis of the excitability of hippocampus slices was performed the following day. Hippocampal slices were stimulated in vitro with single stimuli (SS) or theta burst stimuli (TBS) in order to activate the Schaffer Collaterals targeting pyramidal cells in the presence or absence of six various glutamatergic receptor antagonists.

Results: Both P. ginseng preparations induced a dose dependent increase in the population spike in the presence of SS as well as in the presence of TBS leading to long-term potentiation (LTP) compared to the placebo (glucose 1% 1 ml/kg). Comparison of the efficacy of both P. ginseng preparations revealed a superior action of HRG80 Ginseng, reached considerably and statistically significantly higher population spike peak amplitudes than SGP in the presence of both stimulation modi. Only glutamatergic NMDA and Kainate receptor antagonists selectively reversed the actions of HRG80 and SGP.

Conclusions: Ginseng HRG80 preparation from hydroponically cultivated roots is more active than SGP. Ginseng induced higher excitability of pyramidal cells by modulation of ionotropic glutamate NMDA and Kainate receptor mediated transmission. [Dimpfel W, Schombert L, Panossian AG. Panax ginseng preparations enhance long term potentiation in rat 1 hippocampal slices by glutamatergic NMDA and kainate receptor 2 mediated transmission. J Altern Complement Integr Med. 2020;6:106.] 

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