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).
Recent research shows that Rb1 affects rat embryo development and has teratogenic effects, causing birth defects. Another study 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.
Ginsenoside-Rc is an 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.
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.
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.
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.
|This section relies on references to primary sources. (March 2014)|
||This section may be too technical for most readers to understand. (March 2014)|
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.
There is evidence that Rd exerts beneficial effects in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency, and aging. Specifically, Rd has exhibited an encouraging neuroprotective efficacy in cerebral ischemia in both laboratory and clinical studies, see review from Ye et al.
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. 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. 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. 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. 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.
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.
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.
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- Ginsenosides as Quality Indicators in Woods-grown American Ginseng
- Title: The Effect of Production Practices on the Quality of Ginseng Roots
- The King's University College Biology Department