Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics

Version 1 : Received: 14 September 2021 / Approved: 15 September 2021 / Online: 15 September 2021 (12:36:42 CEST)

How to cite: Panossian, A.; Abdelfatah, S.; Efferth, T. Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics. Preprints 2021, 2021090258 (doi: 10.20944/preprints202109.0258.v1). Panossian, A.; Abdelfatah, S.; Efferth, T. Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics. Preprints 2021, 2021090258 (doi: 10.20944/preprints202109.0258.v1).

Abstract

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, loss of concentration, and during recovery. According to ancient records, Red Ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their level in blood is shallow - at concentrations from 10-6 to 10-18 M. In the present study, we compared the effects of Red Ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/ml with effects of White Ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression of isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up-or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially various effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10000 to 0.01 ng/ml. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.

Keywords

Red Ginseng; HRG80TM; Ginsenoside Rg5; Gene expression; IPA pathways; Network pharmacology,; Transcriptomics

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