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

Abstract

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, or 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 levels in blood is low—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 in 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 varied 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 10,000 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.

Network Pharmacology Approach for Medicinal Plants: Review and Assessment

“…The prediction of disease-related genes is a preliminary step to explore the molecular mechanism of medicinal herbs for treating multiple diseases and disorders [ 81 , 82 ]. Additionally, instead of relying on literature data, the target gene can also be obtained through real experiments; for example, researchers have now analyzed the transcriptome-wide gene expression microarray profiles of isolated cells in response to the exposure to plant extracts, their combinations, or purified compounds, followed by ingenuity pathway analyses in silico to elucidate their mechanisms of action and activated molecular networks behind predicted therapeutic effectiveness in various health conditions [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ].…”

Network Pharmacology of Ginseng (Part III): Antitumor Potential of a Fixed Combination of Red Ginseng and Red Sage as Determined by Transcriptomics

“…All the materials and methods used in this study have been recently described in detail in our recent publication [24], which was conducted by the same experimental protocol [24]. They include mRNA microarray hybridization conducted by the same experimental protocol, Ingenuity Pathway Analysis (IPA), and Statistical Analysis [24]. .…”

“…The antitumor, cardioprotective, and neuroprotective effects of both plants were demonstrated in numerous in vivo and in vitro experimental studies [14][15][16][17][18][19][20][21][22][23][24], suggesting their usefulness in the treatment of aging-related disorders and diseases, including dysfunctions of the central nervous system (CNS), particularly those associated with Alzheimer's disease, Huntington's disease, Parkinson's disease, traumatic brain injury, and ischemia. For example, ginsenosides modulate plentiful physiological and intracellular processes in the brain, including attenuation of oxidative stress, neuroinflammation, excitotoxicity, apoptosis, modulation of adaptive signaling pathways, maintenance of mitochondrial stability, and neurotransmitter homeostasis [21][22][23][24]. Regulations of these pathophysiological processes are associated with the beneficial effects of ginsenosides on cognitive function and stress-protective effects on the brain functions associated with neuroinflammation and neurodegenerative diseases [4,5,[21][22][23][24].…”

“…For example, ginsenosides modulate plentiful physiological and intracellular processes in the brain, including attenuation of oxidative stress, neuroinflammation, excitotoxicity, apoptosis, modulation of adaptive signaling pathways, maintenance of mitochondrial stability, and neurotransmitter homeostasis [21][22][23][24]. Regulations of these pathophysiological processes are associated with the beneficial effects of ginsenosides on cognitive function and stress-protective effects on the brain functions associated with neuroinflammation and neurodegenerative diseases [4,5,[21][22][23][24].…”

Some Common Medicinal Plants with Antidiabetic Activity, Known and Available in Europe (A Mini-Review)

“…Moreover, it improves blood circulation as well as protects against illnesses of the respiratory and nervous systems. It also improves liver activity, physical endurance, and bone metabolism and ensures the neutralization of changes in postmenopausal osteoporosis [178][179][180][181][182][183][184][185]. It is generally believed that ginseng improves metabolism and, thus, helps to improve and maintain good health, and, for this reason, it is an ingredient of dietary supplements [186].…”