By: Brianna Choyce

Ginseng

Ginseng, an herb from the genus Panax, has been used for centuries in traditional Chinese medicine. Biologically active compounds found in ginseng called ginsenosides have been extracted from the plant and are particularly concentrated in the root.[1]

Ginseng has been used historically to boost the immune system preventively and in times of illness, improve focus and cognition, and help with fatigue and appetite.[2][3] Recent studies have shown that ginsenosides have anticarcinogenic, cytotoxic, and growth inhibitory effects directly against tumor cells. The numerous pharmacological properties of ginseng are being studied in the field of oncology. Established evidence and emerging data demonstrates that ginseng’s mechanisms of action can be have positive effects in cancer chemotherapy and chemoprevention. Ginseng can also be utilized to relieve many common side effects of chemotherapy such as nausea, reduced cognition, appetite, fatigue, and neuropathic pain.[3]

 

Anti-Cancer Mechanisms:

Ginsenosides have shown evidence of tumor cell growth inhibition and ability to induce apoptosis. The mechanism involves suspension of the cell cycle in G1 and suppression of cyclin-dependent-kinase-2 activity. Upon gut metabolism, ginsenoside is converted to a modified form that inhibits proliferation of cancer cells and increases apoptosis proteins, leading to increased cancer cell death. The mechanisms of ginger’s anti-metastatic properties also involve inhibition of tumor cell adhesion and prevention of angiogenesis (growth of new blood vessels that can supply nutrients to tumors).[3]

Sister chromatid exchange (SCE) techniques are used to test the extent of DNA damage due to  exposure to suspected mutagens and carcinogens. Ginsenosides have been shown to suppress SCE in human and mice cells after long-term exposure to known carcinogens. The mechanism proposed for this protective effect is that ginseng enhances the ability of mammalian cell DNA proofreading through activation of polymerase and exonuclease activity.[3]

When eukaryotic stem cells become arrested at immature states or have less differentiation due to genetic damage of some sort, there is a greater risk for development of cancer cells. Biological stimulation of cell differentiation has been shown to reduce the risk of cancer development and inhibit metastasis. Cell differentiation with ginsenosides is thought to occur by activation of protein kinase C pathways, which regulate many cellular functions including cell growth and differentiation.[3]

Ginseng exhibits immunomodulatory and anticarcinogenic effects by enhancing humoral and cell-mediated immunity. It has been shown to increase immune cells including: macrophages, dendritic, natural killer (NK), and B and T cells.[4] This suggests that ginger may heighten the body’s natural cancer-fighting defenses. Additionally, maintenance of immune homeostasis during chemotherapy is vital to maintaining resistance to bacterial and viral pathogens.

 

Current Evidence:

Several studies in mice have explored the chemotherapeutic and chemopreventive attributes of ginseng and its compounds.

  • One study involved oral and subcutaneous administration of ginsenoside in mice who received transplanted human ovarian cancer cells. These mice experienced a significant increase in survival duration compared to those who received a traditional chemotherapeutic agent, cisplatin, and placebo alike. A decrease in the size of the tumor was also witnessed in the mice treated with ginsenoside compared to cisplatin and placebo. None of the mice experienced toxicity from any of the therapies utilized.[5]
  • Another study examined the inhibitory ability of ginseng on lung metastasis utilizing implanted tumor cells that exhibit a strong propensity for metastasis in mice. The cancer cells used were B16-BL6 melanoma and colon 26-M3.1 carcinoma. Both oral and intravenous administration of ginsenosides resulted in a decrease in lung metastasis of both tumor types.[6]

A study exploring the anti-mutagenic properties of ginsenoside utilized human peripheral blood lymphocytes and the SCE technique to evaluate the extent of DNA damage. Ginsenoside was paired with the chemotherapy drug mitomycin C and compared to mitomycin C therapy alone. The results were a statistically significant reduction in the SCE frequency in the ginsenoside group.[7] This was a significant finding because the reduction in SCE represents less DNA damage, suggesting that ginsenoside, used in conjunction with a traditional chemotherapeutic agent, can improve therapeutic outcomes.

In a case-control study, ginseng intake showed a dose-dependent relationship with reduction in risk of cancers including: cancer of the lips, mouth, pharynx, esophagus, stomach, colon and rectum, liver, pancreas, larynx, and ovaries among patients who smoke.[8] This supports the theory that ginseng’s anti-carcinogenic effects are non-organ-specific. This is especially noteworthy when considering the overwhelming evidence of smoking’s carcinogenicity.

Studies investigating the ability of ginsenosides to promote cell differentiation have been conducted. One such study was performed using the Wright-Giemsa stain method with nitroblue tetrazolium reduction. Ginsenosides were shown to induce differentiation of HL-60, human promyelocytic leukemia cells, into new generations with restored function.[9] The cells utilized in this experiment have very interesting properties that allow them to be easily identified as compared to differentiated cells. HL-60 cells have an over-expression of the c-myc proto-oncogene, which is characteristic of non-differentiated cells. These cells are also extremely proliferative and rapidly divide into copies with the same genetic material. Differentiation of HL-60 cells is easy to measure by reduction in the c-myc proto-oncogene expression.

 

Additional Health Benefits

Ginseng and its components have been heavily studied in cardiovascular disease and the central nervous system. There are multiple benefits of ginseng related to the physiological and pathological mechanisms of cardiovascular disease (CVD). Additionally, several benefits have been discovered pertaining to the function and protection of the nervous system.

Heart Benefits:

  • Improve Heart Function- Ginsenosides regulate intracellular ion channels, improving functionality of the heart and preventing hypertrophy (enlargement).[2]
  • Reduce High Blood Pressure- Ginseng has vasodilatory effects which can aid in normalization of blood pressure and allow for improved circulation.[2]
  • Protects Against Heart Damage- Ginseng protects the heart from myocardial damage resulting from various factors including: stress, ischemia, and oxidative injury.[2]
  • Improves Metabolic Syndrome Parameters- Ginsenosides improve lipid profile, reduce blood sugars, and helps maintain a healthy weight.[2]
  • Reduces Oxidative Damage- Ginseng has antioxidant activity that prevents the generation of systemic reactive oxygen species that affect the heart, lungs, and cellular mitochondria.[2]

Central Nervous System Benefits:

  • Modulates Neurotransmission- Ginseng regulates GABAergic neurotransmission and decreases the uptake of GABA, glutamate, dopamine, noradrenaline, and serotonin.[3]
  • Prevents Memory Loss- Ginsenosides prevent scopolamine-induced memory deficiencies.[3]
  • Promotes learning- Ginseng derivatives cause an increase in the uptake of the neurotransmitter acetylcholine and can promote nerve growth.[3]
  • Protects Neurons from Ischemic Damage- Ginsenosides can delay neuronal death resulting from lack of oxygen.[3]
  • Reduces pain perception- Through inhibition of calcium ion channels on sensory neurons, ginsenosides can exhibit antinociceptive properties to a similar degree as opioids.[3]

 

Ginseng is a traditional herbal medicine that has been used for centuries. Ginseng’s pharmacological benefits are due to its biologically active constituent ginsenosides and their several mechanisms of action. Used historically for its cardiovascular and cognitive benefits, ginger has countless promising health benefits that seem to be overlooked in today’s medicine. Research and studies dating back to the late 1980’s support the use of ginger in oncology. More current studies have even compared its use to traditional chemotherapeutic agents both alone and in conjunction. Evidence points to ginseng as having anticarcinogenic properties including inhibition of tumor cell growth, metastasis, promotion of apoptosis, and ability to target and kill cancer stem cells. Studies suggest that ginseng can stimulate cell differentiation and modulate the immune system to enhance cancer fighting abilities.

References

  1. Gafner S, et al: Evaluation of the efficiency of three different solvent systems to extract triterpene saponins from roots of Panex quinquefolius using high-performance liquid chromatography. J Agric Food Chem 52(6):1546–1550, 2004.
  2. Kim J-H. Cardiovascular Diseases and Panax ginseng: A Review on Molecular Mechanisms and Medical Applications. Journal of Ginseng Research. 2012;36(1):16-26. doi:10.5142/jgr.2012.36.1.16.
  3. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 1999 Dec 1;58(11):1685-93. Review. PubMed PMID: 10571242.
  4. Kang S, Min H. Ginseng, the “Immunity Boost”: The Effects of Panax ginseng on Immune System. Journal of Ginseng Research. 2012;36(4):354-368. doi:10.5142/jgr.2012.36.4.354.
  5. T. Tode, et al: Inhibitory effects by oral administration of ginsenoside Rh2 on the growth of human ovarian cancer cells in nude mice. J Cancer Res Clin Oncol, 120 (1993), pp. 24-26.
  6. Mochizuki M, et al. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng. Biol Pharm Bull. 1995 Sep;18(9):1197-202. PubMed PMID: 8845804.
  7. Zhu JH, Takeshita T, Kitagawa I, Morimoto K. Suppression of the formation of sister chromatid exchanges by low concentrations of ginsenoside Rh2 in human blood lymphocytes. Cancer Res. 1995 Mar 15;55(6):1221-3. PubMed PMID: 7882311.
  8. Yun TK, Choi SY. Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs. Cancer Epidemiol Biomarkers Prev. 1995 Jun;4(4):401-8. PubMed PMID: 7655337.
  9. Kim YS, Kim DS, Kim SI. Ginsenoside Rh2 and Rh3 induce differentiation of HL-60 cells into granulocytes: modulation of protein kinase C isoforms during differentiation by ginsenoside Rh2. Int J Biochem Cell Biol. 1998 Mar;30(3):327-38. PubMed PMID: 9611775.

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