HighlightsGinseng, a traditional folk medicine, is a medici- nal root containing steroid and saponin molecules known as ginsenosides[6].Considered largely safe[4], ginseng has a wide range of effects on multiple body systems[1, 2], thought to be through the regulation of cellular responses in different tissues[1].Ginseng has been recommended by some researchers as a complementary and alternative medicine[5] for a wide variety of conditions including Alzheimer’s disease and Parkinson’s disease[2, 3].BackgroundGinseng is the medicinal root of the Panax ginseng, P. quinquefolius, or P. japonicus – Asian, American, and Japanese, respectively – and has been widely used in folk medicine for the past 2000 years for the treatment of various conditions[6]. The major bioactive components of ginseng are the group of saponins known as ginseno- sides, of which over 50 have been found[6]. More modern research has also shown that polysaccharides also con- tribute a key role in the bioactivity of ginseng[7]. Addi- tionally, the type of ginseng and the way that it is ex- tracted has also been found to play a role in the efficacy of treatment[2].Ginseng is reported to have multiple effects, includ- ing adaptogenic properties, neuroprotection, relaxing of smooth heart muscles, anti-inflammatory, and immunos- timulant attributes[5].Ginseng’s efficacy regarding psychologic functioning is conflicted, while its efficacy on the immune system is considered effective[5].Ginseng is considered to be largely safe, as reported in dogs, rats, and humans[4], however, it is possible to experience unwanted side effects such as hypertension from excessive ginseng intake[4]. Another, more recent safety and efficacy review, concluded that while some studies indicated adverse effects such as constipation, hot flushes, or insomnia – that placebo-controlled clinical trials showed no statistical significance between ginseng and placebo groups regarding both the frequency and type of adverse symptoms[3]. More safety and efficacy studies need to be performed in order to draw definitive conclusions about ginseng’s safety and potential adverse effects.Mode of actionThe exact mode of action of ginseng’s bioactive com- pounds has not yet been fully elucidated across the variety of ginseng types and extracts. However, the mode of action of ginsenosides has been researched fairly extensively and some conclusions can be presented for cell lines, animal models, and limited human clinical trials. Ginsenosides are ampiphilic in nature, and have the ability to insert into the plasma membrane – eliciting a cellular response[1].Ginseng and ginsenosides affect the central nervous system (CNS) through a variety of mechanisms, namely by affecting the neurotransmission of acetyl choline and gamma-aminobutyric acid (GABA) by enzymatic ex- pression, altering brain plasticity and neurogenesis, and affecting a plethora of voltage-gated ion channels[2]. Ginseng exhibits both stimulatory and inhibitory effects on the CNS, with different ginsenosides playing different roles for different CNS cell types[1].In cell lines, anti-tumor activity has been found to be related to the effect of polysaccharides present in ginseng extracts in regulating the M2/G cycle phase of cell division[7]. In other cell lines, the polysaccha- rides were found to also increase the levels of TNF-α and interleukin-1[7]. Ginseng and ginsenosides have also shown to be neuroprotective agents in human cell lines through phosphorylation, induction of apoptosis, and preventionof free radical species[2].Ginseng’s immunomodulatory effect has found to be related to regulation of cyclooxygenase (COX)-1 expression, in addition to stimulating natural killer cells, T- cells, and macrophages[7].The mode of action in which ginseng works as an anti- inflammatory is not yet entirely clear.The regulation of the inflammatory response by ginseng and ginsenosides is regulated by cell type and the specific ginsenosidecomposition and is involved in a plethora of cellular signaling pathways[2]. One of the most widely documented modes of action for the antioxidant effects in vitro has the been the inhibition of hydroxyl radicals across a wide variety of as- says and cell lines[4]. In vivo, there have been many re- sults showing tissue antioxidant activity, mainly through modulation of tissue enzymatic activity andnitric-oxide receptor genes[4].Pharmacological effectsGinseng exhibits a diverse variety of pharmacological effects due to the large variety of ginsenosides and other plant bioactive constituents[1]. Ginsenosides are steroidal and saponin molecules, exhibiting similar form- function characteristics. Ginseng has been recommended by some researchers as a complementary and alternative medicine[5] for a wide variety of conditions.Animal models have shown that ginseng extracts were effective in combating depression-like and stress-related behaviors[2]. In mice, there is conflicting evidence for the anxiolytic effect of ginseng, with some studies showing an effect comparable to diazepam and other studies showing no effect at all[2].In early human clinical trials of ginseng extract for Alzheimer’s disease, it was shown that a 12-week treat- ment of encapsulated P. ginseng powder increased cog- nitive performance, and that taking away the extract resulted in a cognitive decline back to baseline[2].Other therapeutic roles of ginseng include protection against diabetic retinopathy, neural stem cell prolifera- tion, protection from oxidative stress and apoptosis, at- tenuation of pathogen virulence factor production, treat- ment of erectile dysfunction, and alleviation of fatigue in multiple sclerosis[5]. Additionally, some polysaccharides in gingseng exhibit activities which lower blood sugar[7],and can be useful as a part of certain diabetic treat- ments. In addition, ginseng has the ability to modulate insulin secretion by encouraging glucose-related insulin release in pancreatic β-cells[6].Potentil useAs described above, ginseng has a complex effect on multiple body systems, including the CNS[1, 2], im- mune system[7], and inflammatory and homeostatic systems[2, 4].Ginseng is recommended by many researchers as a complementary alternative medicine to many treatments and for a wide range of conditions including neurodegenerative and inflammatory diseases[1, 2, 5, 7] – however it is important to note that these uses are based on animal models and cell cultures[6]. Thus, more placebo double-blind human clinical studies are needed to truly determine the best use for ginseng and its components.References[1] A. Attele, J. Wu, and C. Yuan. Ginseng pharma- cology: Multiple constituents and multiple actions. Biochemical Pharmacology, 58(11):1685–1693, 1999.[2] H. Kim, P. Kim, and C. Shin. A comprehensive re- view of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous sys- tem. Journal of Ginseng Research, 37(1):8–29, 2013.[3] Y. Kim, J. Woo, C. Han, and I. Chang. Safety anal- ysis of panax ginseng in randomized clinical trials: A systematic review. Medicines, 2(2):106–126, 2015.[4] D. Kitts and C. Hu. Efficacy and safety of ginseng.Public Health Nutrition, 3(4a):473–485, 2000.[5] M. Shahrajabian, W. Sun, and Q. Cheng. A review of ginseng species in different regions as a multipurpose herb in traditional chinese medicine, modern herbol- ogy and pharmacological science. Journal of Medic- inal Plants Research, 13(10):213–226, 2019.[6] J. Wee, K. Mee, and A. Chung. Biological ac- tivities of ginseng and its application to human health. In I. Benzie and S. Wachtel-Galor, editors, Herbal Medicine: Biomolecular and Clinical Aspects, chapter 8. CRC Press/Taylor Francis, Boca Ra- ton (FL), 2nd edition edition, 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92776/.[7] B. Zhao, C. Lv, and J. Lu. Natural occurring polysac- charides from panax ginseng c. a. meyer: A review of isolation, structures, and bioactivities. International
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