Ginseng Extract For Diabetes & Cancer
What is ginseng?
Chronic inflammatory diseases like diabetes and cancer are the leading cause of death worldwide. Years of research have found that in the war against chronic diseases, a "prevention strategy" is much more effective than treatment. This made the scientific community interested in phytochemicals-rich ethnobotanical herbs from Asia, which have a strong antioxidant potential for preventing metabolic and degenerative disorders such as cancers, diabetes, and heart problems. Ginseng is one such traditional medicinal herb that has been used as a general health tonic to promote optimal health and longevity. (1, 2, 3)
Ginseng is a well-known herb in Korea and China. Its polyvalent actions show various therapeutic benefits, i.e., antioxidant, anti-inflammatory, anti-apoptotic, anti-mutagenic, anti-cancer, anti-diabetes, neurovascular, and immune-stimulatory effects, without any serious adverse effects. (3, 4) A 2009 review introduces the 'Yin and Yang' theory from traditional Chinese medicine (TCM) perspectives to understand how different varieties of ginseng (i.e., Panax ginseng, Panax quinquefolius, and Panax notoginseng, commonly referred to in English as Chinese ginseng) to balance the dynamic equilibrium of various human physiological processes to show anti-hyperglycemic and immunotherapeutic effects that may be beneficial for type II diabetics and cancer patients. (5)
Ginseng benefits for diabetes
Ginseng is found effective in hyperglycemia. (2) Panax notoginseng (Burk.) has wide-ranging pharmacological effects due to the presence of chemical compounds such as saponins, flavonoids, and cyclopeptides. (6) In a 2008 study, saponins from Panax notoginseng have shown anti-diabetes properties by effectively improving glucose tolerance; and reducing insulin resistance, fasting blood glucose, and triglyceride levels. (7) These results were confirmed by another 2014 study, where continuous administration of Panax notoginseng saponins (PNS) for 30 days is found effective in reducing insulin resistance and fasting blood glucose (FBG) and serum insulin levels. In this study, PNS also helped lower body weight growth, food consumption, adipose tissue, and leptin. This indicates that ginseng shows anti-hyperglycemic and anti-obesity activities by improving insulin and leptin sensitivities, which can help manage type 2 diabetes. (8)
A systematic review in 2013 reported that Panax ginseng shows promising results for improving glucose metabolism and can be explored as an effective treatment for type 2 diabetes. (9) These findings are further substantiated in a 2015 study, where supplementation with ginseng berry extract has significantly lowered serum insulin levels and insulin resistance scores through a molecular mechanism that improved insulin sensitivity. (10) A more recent study suggests that Rg3 ginsenoside, one of the active components of P. ginseng, improves insulin resistance in skeletal muscle by improving mitochondrial function and the expression of key genes involved in mitochondrial biogenesis. (11)
Another mechanism by which ginseng shows anti-diabetic influence was suggested by a 2007 study, where ginsenosides in ginseng extracts (GE) inhibited cytokine-induced apoptosis in beta-cells. (12) In 2012 another study confirmed this mechanism in beta-cell-deficient mice, where both red and green ginseng berry extract significantly reduced the blood glucose levels, increased glucose-stimulated insulin secretion, and improved overall glucose tolerance, possibly due to beneficial effects on beta-cell regeneration. (13) In a 2016 study, Korean red ginseng was found effective in normalizing hyper-insulinemia and hyper-glycemia in ovariectomized (OVX) mice, a mouse model of postmenopausal women, which proves ginseng as a promising drug for prevention, reversal, and treatment of obesity and related metabolic disorders in obese postmenopausal women. (14)
Ginseng benefits for cancer care
Natural agents, i.e., ginsenosides found in ginseng, can also help in cancer prevention by inducing apoptosis in cancer cells, suppressing cell proliferation, and cancer-promoting angiogenesis disrupting the tumor microenvironment. (1) A 2007 review found that ginsenosides in ginseng have a 'Yin and Yang' action on angiomodulation, where ginsenoside Rg1 stimulates angiogenesis and ginsenosides Rg3 and Rh2 show anti-tumor and anti-angiogenic effects. (15) Another study in the same year reported discovering a novel ginsenoside, i.e., dammarane triterpene sapogenin from the leaves of Panax notoginseng that inhibits growth and survival of cancer cells by inducing cell cycle arrest and apoptosis in human cancer cell lines. (16) As reactive oxygen species (ROS) have been implicated in a variety of inflammatory diseases, including cancer and diabetes, the unique antioxidant mechanisms are another way ginseng shows its pharmacological effect.
A 2012 study found that ginsenoside Rb1 significantly reduces two of the strongest ROS, i.e., hydroxyl radical (●OH) and hypochlorous acid (HOCl). (17) In the same year, another study reported that antagonistic action against hydrogen sulfide (H2S)-induced angiogenesis is the underlying mechanism by which Korean red ginseng extracts (KRGE) show their cancer-preventive effects. (18)
A 2014 review discusses another mechanism. Ginseng and ginsenosides activate a key sensor of cellular energy, which switches on catabolic pathways to generate adenosine triphosphate (ATP) and switches off biosynthetic pathways consuming ATP. This mechanism is useful in preventing or reversing metabolic disorders such as type 2 diabetes and cancer. (19) Furthermore, a 2016 study reports that combination treatment showed that ginsenoside enhances doxorubicin-treated anti-cancer activities in cancer cells. These findings suggest that ginseng has therapeutic potential for cancer treatment and can be used as a combination partner with more classic chemotherapeutic agents, such as doxorubicin. (20) A recent meta-analysis also indicates that ginseng consumption can significantly decrease cancer risk and this anti-cancer effect of ginseng is not organ-specific. (21)
1. Park JM1, Lee HJ2, Yoo JH3, Ko WJ4, Cho JY5, Hahm KB6. Overview of gastrointestinal cancer prevention in Asia. Best Pract Res Clin Gastroenterol. 2015 Dec;29(6):855-67. doi: 10.1016/j.bpg.2015.09.008. Epub 2015 Sep 11.
2. Tapsell LC1, Hemphill I, Cobiac L, Patch CS, Sullivan DR, Fenech M, Roodenrys S, Keogh JB, Clifton PM, Williams PG, Fazio VA, Inge KE. Health benefits of herbs & spices: the past, the present, the future. Med J Aust. 2006 Aug 21;185(4 Suppl):S4-24.
3. Ong YC1, Yong EL. Panax (ginseng)--panacea or placebo? Molecular & cellular basis of its pharmacological activity. Ann Acad Med Singapore. 2000 Jan;29(1):42-6.
4. Choi J1, Kim TH, Choi TY, Lee MS. Ginseng for health care: a systematic review of randomized controlled trials in Korean literature. PLoS One. 2013;8(4):e59978. doi: 10.1371/journal.pone.0059978. Epub 2013 Apr 1.
5. Jia L1, Zhao Y, Liang XJ. Current evaluation of the millennium phytomedicine- ginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Curr Med Chem. 2009;16(22):2924-42.
6. Wang T1, Guo R1, Zhou G1, Zhou X1, Kou Z1, Sui F1, Li C1, Tang L2, Wang Z3. Traditional uses, botany, phytochemistry, pharmacology & toxicology of Panax notoginseng (Burk.) F.H. Chen: A review. J Ethnopharmacol. 2016 Jul 21;188:234-58. doi: 10.1016/j.jep.2016.05.005. Epub 2016 May 3.
7. Chen ZH1, Li J, Liu J, Zhao Y, Zhang P, Zhang MX, Zhang L. Saponins isolated from the root of Panax notoginseng showed significant anti-diabetic effects in KK-Ay mice. Am J Chin Med. 2008;36(5):939-51.
8. Zhong ZD, Wang CM, Wang W, Shen L, Chen ZH. [Major hypoglycemic ingredients of Panax notoginseng saponins for treating diabetes]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2014 Mar;45(2):235-9. [Article in Chinese]
9. Shergis JL1, Zhang AL, Zhou W, Xue CC. Panax ginseng in randomized controlled trials: a systematic review. Phytother Res. 2013 Jul;27(7):949-65. doi: 10.1002/ptr.4832. Epub 2012 Sep 12.
10. Seo E1,2, Kim S3, Lee SJ4, Oh BC2,5, Jun HS6,7,8. Ginseng berry extract supplementation improves age-related decline of insulin signaling in mice. Nutrients. 2015 Apr 22;7(4):3038-53. doi: 10.3390/nu7043038.
11. Kim MJ1,2, Koo YD3, Kim M3, Lim S4, Park YJ1, Chung SS1,5, Jang HC4, Park KS6. Rg3 Improves Mitochondrial Function & the Expression of Key Genes Involved in Mitochondrial Biogenesis in C2C12 Myotubes. Diabetes Metab J. 2016 Aug 12. [Epub ahead of print]
12. Kim HY1, Kim K. Protective effect of ginseng on cytokine-induced apoptosis in pancreatic beta-cells. J Agric Food Chem. 2007 Apr 18;55(8):2816-23. Epub 2007 Mar 24.
13. Park EY1, Kim HJ, Kim YK, Park SU, Choi JE, Cha JY, Jun HS. Increase in Insulin Secretion Induced by Panax ginseng Berry Extracts Contributes to the Amelioration of Hyperglycemia in Streptozotocininduced Diabetic Mice. J Ginseng Res. 2012 Apr;36(2):153-60. doi: 10.5142/jgr.2012.36.2.153.
14. Lee H1, Choi J1, Shin SS2, Yoon M3. Effects of Korean red ginseng (Panax ginseng) on obesity and adipose inflammation in ovariectomized mice. J Ethnopharmacol. 2016 Feb 3;178:229-37. doi: 10.1016/j.jep.2015.12.017. Epub 2015 Dec 17.
15. Yue PY1, Mak NK, Cheng YK, Leung KW, Ng TB, Fan DT, Yeung HW, Wong RN. Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides. Chin Med. 2007 May 15;2:6.
16. Zhao Y1, Wang W, Han L, Rayburn ER, Hill DL, Wang H, Zhang R. Isolation, structural determination & evaluation of the biological activity of 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol [20(S)-25-OCH3-PPD], a novel natural product from Panax notoginseng. Med Chem. 2007 Jan;3(1):51-60.
17. Lü JM1, Weakley SM, Yang Z, Hu M, Yao Q, Chen C. Ginsenoside Rb1 directly scavenges hydroxyl radical and hypochlorous acid. Curr Pharm Des. 2012;18(38):6339-47.
18. Choi KS1, Song H, Kim EH, Choi JH, Hong H, Han YM, Hahm KB. Inhibition of Hydrogen Sulfide-induced Angiogenesis and Inflammation in Vascular Endothelial Cells: Potential Mechanisms of Gastric Cancer Prevention by Korean Red Ginseng. J Ginseng Res. 2012 Apr;36(2):135-45. doi: 10.5142/jgr.2012.36.2.135.
19. Jeong KJ1, Kim GW1, Chung SH1. AMP-activated protein kinase: An emerging target for ginseng. J Ginseng Res. 2014 Apr;38(2):83-8. doi: 10.1016/j.jgr.2013.11.014. Epub 2013 Dec 18.
20. Han S1, Jeong AJ2, Yang H3, Bin Kang K4, Lee H5, Yi EH6, Kim BH7, Cho CH8, Chung JW9, Sung SH10, Ye SK11. Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through targeting IL-6-induced JAK2/STAT3 pathway in human colorectal cancer cells. J Ethnopharmacol. 2016 Aug 23. pii: S0378-8741(16)30570-0. doi: 10.1016/j.jep.2016.08.039. [Epub ahead of print]
21. Jin X1, Che DB2, Zhang ZH3, Yan HM3, Jia ZY2, Jia XB3. Ginseng consumption & risk of cancer: A meta-analysis. J Ginseng Res. 2016 Jul;40(3):269-77. doi: 10.1016/j.jgr.2015.08.007. Epub 2015 Sep 2.