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Ginsenosides or panaxosides are a class of steroid glycosides, and triterpene saponins, found exclusively in the plant genus Panax (ginseng).

Ginsenosides have been the target of research, as they are viewed as the active compounds behind the claims of ginseng's efficacy. Because ginsenosides appear to affect multiple pathways, their effects are complex and difficult to isolate.

Ginsenosides are separated by column chromatography. Ginsenoside content can vary widely depending on species, location of growth, and growing time before harvest.

The root, the organ most often used, contains saponin complexes. These are often split into two groups: the Rb1 group (characterized by the protopanaxadiol presence : Rb1, Rb2, Rc and Rd) and the Rg1 group (protopanaxatriol: Rg1, Re, Rf, and Rg2).[1]

Rb1 group[edit]


Ginsenoside Rb1 is the most abundant form in American ginseng (Panax quinquefolius).[citation needed]

Recent research shows that Rb1 affects rat embryo development[2] and has teratogenic effects, causing birth defects.[3] Another study[citation needed] shows that Rb1 may increase testosterone production in male rats indirectly through the stimulation of the luteinizing hormone. It appears to enhance the uptake of choline.[4]




Ginsenoside-Rc is a steroid molecule that can be found in the ginseng plant and produces more sedative related results than other ginsenosides, such as ginsenoside-Re or ginsenoside-Rg.[citation needed]

In one study on breast cancer and different ginsenosides, it was found that ginsenoside-Rc was capable of inhibiting the growth of these cancer cells. This suggests that there is a possibility that ginsenoside-Rc may have effects that prevent or limit the development of breast cancer.[5]

An experiment was performed on Caenorhabditis elegans and their survival in a cholesterol-absent medium with the presence of ginsenoside-Rc. While the lack of cholesterol for Caenorhabditis elegans had been expected to reduce the lifetime of the worm, results proved otherwise: The consumption of ginsenoside-Rc had elongated the normal life span of the worm.[6]

A further study was also able to demonstrate a possible effect of ginsenoside-Rc on the motility of sperm in vitro. Data from this experimentation showed a significant increase in motility when the sperm was in a ginsenoside-Rc solution.[7]


Ginsenoside Rd (Dammar-24(25)-ene-3,12,20(S)-triol-(20-O-β-D-gluco- pyranosyl)-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside) is one of the major ginsenosides in the ginseng root, and consequently has been accepted as one of the marker compounds of ginseng quality. In notoginseng, the content of Rd is even higher, accounting for 0.36%-1.47% of the fresh notoginseng weight, and 4.07% of total notoginseng saponins, making it inexpensive in pharmaceutical use. Rd is also an important metabolite in the transformation pathway of PPD-type ginsenosides in the human intestine.[8]

There is evidence that Rd exerts beneficial effects in a wide range of pathological conditions such as cardiovascular diseases,[9][10] cancer, immune deficiency, and aging.[11] Specifically, Rd has exhibited an encouraging neuroprotective efficacy in cerebral ischemia in both laboratory and clinical studies, see review from Ye et al.[12]

The efficacy of Rd against stroke was first investigated in in vitro models. Three types of injuries induced by hydrogen peroxide, glutamate, or oxygen-glucose deprivation were used to mimic the ischemic insults in the primary neuronal cultures. Rd observably attenuated the cell death and apoptosis following all three ischemia-like insults.[13][14][15] In OGD model, approximately 46% of total cell loss could be rescued if co-incubated with Rd, whereas in glutamate model, this number could be up to 79%, indicating a strong neuroprotection of Rd on the neurons per se.

In in vivo models, the neuprotective characteristics of Rd was further defined.[16][17][18][19] In the dose-escalation study, Ye et al assessed the efficacy of Rd with doses ranging from 0.1 to 200 mg/Kg. The neuroprotection of Rd was observed at 10 mg/Kg and greatest at 50 mg/Kg. On post-operative day 3, Rd could decrease the infarct size by 60%, while on day 14, the reduction of infarction still sustained up to 50%. In the therapeutic window study, Rd exhibited remarkable benefits even when administered at 4 hr after the recirculation of transient MCAO, or at 4 hr after the onset of permanent MCAO. Rd-induced morphological protection was associated with an improved neurological outcome for 6 weeks after the ischemia, and importantly, was significantly more effective than edaravone and slightly more effective than N-tert-butyl-alpha-phenylnitrone (PBN; the parent compound of NXY-059), at their optimal dosages. Furthermore, in female and aged male rodents, the salutary effects of Rd were also observed, indicating Rd-induced neuroprotection is independent of age and sex.

Phase II trial

The phase II dose-escalation clinical trial evaluating the efficacy of Rd in AIS was a randomized, double-blind, placebo-controlled, multicenter study and was conducted at 5 metropolitan general hospitals in China.[20] Eligible subjects included patients who had ischemic stroke with an onset of the first episode within the previous 72 hr, and had a score of 5-22 on the National Institutes of Health Stroke Scale (NIHSS). Patients were randomized in a 1:1:1 ratio to two doses of Rd (10 or 20 mg) and placebo for 14 days. Primary end point was NIHSS score at 15 days. 190 patients completed the trial, of whom 61 received Rd 10 mg, 65 received Rd 20 mg, and 64 received placebo. For the primary outcome, Rd-treated patients showed significant better NIHSS scores at 15 days than placebo group. However, the 20 mg dose did not have superior efficacy compared with 10 mg dose. For the secondary outcome measures, there was no significant difference in the change of Barthel Index (BI) and the modified Rankin scale (mRS) amongst three groups at day 15 and day 90. Rd did not affect the recurrence rate and mortality.

Phase III trial

In this context, a phase III randomized, double-blind, placebo-controlled, multicenter clinical trial was undertaken.[21] 390 patients from 10 sites across China were enrolled within their first 72 hr after the onset of symptoms. These patients were randomly assigned to Rd group and placebo group as a ratio of 3 to 1. Rd was administered 10 mg by intravenous infusion once daily, for 14 days. Median time from the onset of stroke to treatment was 48 h. The primary end point was the distribution of disability scores on the mRS at 90 days.

The efficacy analysis was based on 386 patients (Rd group: 290; placebo group: 96). Rd significantly improved the overall distribution of scores on the mRS, as compared with the placebo (OR, 1.74; 95% CI, 1.08-2.78). There were significant differences between the two groups when scores were categorized into 0-1 vs 2-5. 66.8% of subjects in the Rd group had a favorable outcome compared with 53.1% in the placebo group (absolute effect size = 13.7%; 95% CI, 1.1% to 26.3%). Subgroup analysis revealed that only the severe stroke patients gained benefits from Rd, while those with lacunar stroke could not. For the secondary outcome, Rd also improved NIHSS scores at day 15. However, there was no significant difference between groups in the change of BI at 90 days.

Rg1 group[edit]

Present in Panax ginseng; not present in American ginseng (Panax quinquefolius).[22]


Appears to be most abundant in Panax ginseng (Chinese/Korean Ginseng). Improves spatial learning and increase hippocampal synaptophysin level in mice, plus estrogen-like activity (which could account for the boosting of "yin" theory). A recent study demonstrated that Rg1, isolated from Panax ginseng is able to attenuate the oxidative stress in the liver of exhaustive exercised rats.[23]


Ginsenoside Rg2 appears also to be abundant in Panax ginseng and could protect memory impairment via anti-apoptosis in a rat model with vascular dementia.[24][25]

Rg2 is a α-L-Rha→β-D-Glc glycoside of panaxatriol.


















M1 (20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol) is a ppd-type monoglucoside ginsenoside metabolized by intestinal bacteria in humans.

See also[edit]


  1. ^
  2. ^ [][dead link]
  3. ^ Chan LY, Chiu PY, Lau TK (October 2003). "An in-vitro study of ginsenoside Rb1-induced teratogenicity using a whole rat embryo culture model". Human Reproduction 18 (10): 2166–8. doi:10.1093/humrep/deg401. PMID 14507839. 
  4. ^ Shergill, Amandeep (1998). "Ginseng and Memory". Nutrition Bytes 4 (2). Retrieved 2012-07-16. 
  5. ^ Murphy, Laura (August 2000). "American Ginseng in the Prevention and Treatment of Human Breast Cancer". Southern Illinois University Carbondale. [dead link]
  6. ^ Lee JH, Choi SH, Kwon OS, et al. (November 2007). "Effects of ginsenosides, active ingredients of Panax ginseng, on development, growth, and life span of Caenorhabditis elegans". Biological & Pharmaceutical Bulletin 30 (11): 2126–34. doi:10.1248/bpb.30.2126. PMID 17978487. 
  7. ^ Chen JC, Chen LD, Tsauer W, Tsai CC, Chen BC, Chen YJ (2001). "Effects of Ginsenoside Rb2 and Rc on inferior human sperm motility in vitro". The American Journal of Chinese Medicine 29 (1): 155–60. doi:10.1142/S0192415X01000174. PMID 11321473. 
  8. ^ Nah, SY; Kim DH; Rhim H (2007). "Ginsenosides: are any of them candidates for drugs acting on the central nervous system?". CNS Drug Rev 13 (4): 381–404. doi:10.1111/j.1527-3458.2007.00023.x. PMID 18078425. 
  9. ^ Li J, Xie ZZ, Tang YB, Zhou JG, Guan YY (2011). "Ginsenoside-Rd, a purified component from panax notoginseng saponins, prevents atherosclerosis in apoE knockout mice". Eur J Pharmacol 652 (1-3): 104–110. doi:10.1016/j.ejphar.2010.11.017. 
  10. ^ Cai BX, Li XY, Chen JH, et al (2009). "Ginsenoside-Rd, a new voltage-independent Ca2+ entry blocker, reverses basilar hypertrophic remodeling in stroke-prone renovascular hypertensive rats". Eur J Pharmacol 606 (1-3): 142–149. doi:10.1016/j.ejphar.2009.01.033. 
  11. ^ Yokozawa T, Satoh A, Cho EJ (2004). "Ginsenoside-Rd attenuates oxidative damage related to aging in senescence-accelerated mice". J Pharm Pharmacol 56 (1): 107–113. doi:10.1211/0022357022449. 
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  13. ^ Ye R, Han J, Kong X, Zhao L, Cao R, Rao Z, Zhao G (2008). "Protective effects of ginsenoside Rd on PC12 cells against hydrogen peroxide". Biol Pharm Bull 31 (10): 1923–1927. doi:10.1248/bpb.31.1923. PMID 18827356. 
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  15. ^ Zhang C, Du F, Shi M, Ye R, Cheng H, Han J, Ma L, Cao R, Rao Z, Zhao G (2012). "Ginsenoside Rd protects neurons against glutamate-induced excitotoxicity by inhibiting ca(2+) influx". Cell Mol Neurobiol 32 (1): 121–128. doi:10.1007/s10571-011-9742-x. PMID 21811848. 
  16. ^ Ye R, Kong X, Yang Q, Zhang Y, Han J, Li P, Xiong L, Zhao G (2011). "Ginsenoside rd in experimental stroke: superior neuroprotective efficacy with a wide therapeutic window". Neurotherapeutics 8 (3): 515–525. doi:10.1007/s13311-011-0051-3. PMC 3250281. PMID 21647765. 
  17. ^ Ye R, Yang Q, Kong X, Han J, Zhang X, Zhang Y, Li P, Liu J, Shi M, Xiong L, Zhao G (2011). "Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory response after transient focal ischemia in rats". Neurochem Int 58 (3): 391–398. doi:10.1016/j.neuint.2010.12.015. PMID 21185898. 
  18. ^ Ye R, Zhang X, Kong X, Han J, Yang Q, Zhang Y, Chen Y, Li P, Liu J, Shi M, Xiong L, Zhao G (2011). "Ginsenoside Rd attenuates mitochondrial dysfunction and sequential apoptosis after transient focal ischemia". Neuroscience 31 (178): 169–180. doi:10.1016/j.neuroscience.2011.01.007. PMID 21219973. 
  19. ^ Ye R, Kong X, Yang Q, Zhang Y, Han J, Zhao G (2011). "Ginsenoside Rd attenuates redox imbalance and improves stroke outcome after focal cerebral ischemia in aged mice". Neuropharmacology 61 (4): 815–824. doi:10.1016/j.neuropharm.2011.05.029. PMID 21664366. 
  20. ^ Liu X, Xia J, Wang L, Song Y, Yang J, Yan Y, Ren H, Zhao G (2009). "Efficacy and safety of ginsenoside-Rd for acute ischaemic stroke: a randomized, double-blind, placebo-controlled, phase II multicenter trial". Eur J Neurol 16 (5): 569–575. doi:10.1111/j.1468-1331.2009.02534.x. PMID 19236467. 
  21. ^ Liu X, Wang L, Wen A, Yang J, Yan Y, Song Y, Liu X, Ren H, Wu Y, Li Z, Chen W, Xu Y, Li L, Xia J, Zhao G (2012). "Ginsenoside-Rd improves outcome of acute ischaemic stroke - a randomized, double-blind, placebo-controlled, multicenter trial". Eur J Neurol 19 (6): 855–863. doi:10.1111/j.1468-1331.2011.03634.x. PMID 22233205. 
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  23. ^ Mallikarjuna, Korivi; Hou C.W.; Huang C.Y.; Lee S.D.; Hsu M.F.; Yu S.H.; Chen C.Y.; Liu Y.Y.; Kuo C.H. (2012). "Ginsenoside-Rg1 Protects the Liver against Exhaustive Exercise-Induced Oxidative Stress in Rats". Evid Based Complement Alternat Med 2012: 932165. doi:10.1155/2012/932165. PMC 3176525. PMID 21941591. 
  24. ^ Zhang G, Liu A, Zhou Y, San X, Jin T, Jin Y (February 2008). "Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia". Journal of Ethnopharmacology 115 (3): 441–8. doi:10.1016/j.jep.2007.10.026. PMID 18083315. 
  25. ^ Yoon SR, Nah JJ, Kim SK, et al. (July 1998). "Determination of ginsenoside Rf and Rg2 from Panax ginseng using enzyme immunoassay". Chemical & Pharmaceutical Bulletin 46 (7): 1144–7. doi:10.1248/cpb.46.1144. PMID 9692222.