protopanaxadiol and panaxadiol

Based on the definite therapeutic benefits, such as neuroprotective, cardioprotective, anticancer, anti-diabetic and so on, the Panax genus which contains many valuable plants, including ginseng (Panax ginseng C.A. Meyer), notoginseng (Panax notoginseng) and American ginseng (Panax quinquefolius L.), attracts research focus. Actually, the biological and pharmacological effects of the Panax genus are mainly attributed to the abundant ginsenosides. However, the low membrane permeability and the gastrointestinal tract influence seriously limit the absorption and bioavailability of ginsenosides. The acid or base hydrolysates of ginsenosides, 20 (R,S)-panaxadiol and 20 (R,S)-protopanaxadiol showed improved bioavailability and diverse pharmacological activities. Moreover, relative stable skeletons and active hydroxyl group at C-3 position and other reactive sites are suitable for structural modification to improve biological activities. In this review, the pharmacological activities of panaxadiol, protopanaxadiol and their structurally modified derivatives are comprehensively summarized.

Topics: Antineoplastic Agents; Dammaranes; Drug Discovery; Ginsenosides; Humans; Neuroprotective Agents; Panax; Phytochemicals; Radiation-Protective Agents; Sapogenins; Triterpenes

The rare ginsenoside Rg3 is attracting more attention because of its good physiological activity and urgent need. There are many pathways to obtain ginsenoside Rg3, including chemical and biological methods. Among these, the conversion of the protopanaxadiol-type ginsenosides by microbial hydrolysis is a trend due to its high efficiency and mild conditions. For effectively extracting from the other panaxadiol saponins, the conversion process for ginsenoside Rg3 was investigated using β-glycosidase-producing endophytic fungus in Panax ginseng in this study. The metabolic pathways are as follows: ginsenoside Rb1 → Gyp-XVII and ginsenoside Rb1 → ginsenoside Rd → ginsenoside Rg3. Phylogenetic analysis of 16S rDNA gene sequence, showed that GE 32 strain belonged to Flavobacterium species. These results suggest that the process of rare ginsenoside Rg3 production by endophytic bacteria GE 32 is efficient for the industrial production and application. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on cultivable β-glycosidase-producing endophytic bacteria from Panax ginseng. Flavobacterium sp. GE32 could convert major ginsenoside Rb1 into Gyp-XVII and minor ginsenoside Rg3. Strain GE 32 has potential to be applied on the preparation for minor ginsenoside Rg3 in pharmaceutical industry.

Topics: Biotransformation; DNA, Ribosomal; Flavobacterium; Ginsenosides; Glycoside Hydrolases; Hydrolysis; Panax; Phylogeny; Sapogenins; Saponins

Panaxadiol is a novel antitumor agent extracted from the Chinese medical herb Panax ginseng. This agent is being developed for the treatment of tumor diseases. A rapid, selective, and simple method based on ultrafast liquid chromatography-tandem mass spectrometry was established and validated to determine panaxadiol in rat plasma following oral and sublingual intravenous administration of panaxadiol. The plasma samples were pretreated with acetic ether, and chromatographic separation was achieved on a Shim-pack XR-ODS III column using isocratic elution with the mobile phase of 0.1 % formic acid and acetonitrile. Analytes and protopanaxadiol (internal standard) were analyzed and identified using electrospray positive ionization mass spectrometry in the multiple reaction-monitoring mode. The MS/MS detection was carried out by monitoring the fragmentation of m/z 461.45 → m/z 127.1 for panaxadiol and m/z 425.4 → m/z 95.1 for protopanaxadiol (internal standard) on a triple-quadrupole mass spectrometer. The result showed good linearity over a wide concentration range (0.1-20 ng/mL) (R2 > 0.999) and its lower limit of detection and quantification were 0.03 and 0.1 ng/mL, respectively. The intra- and interday precision (RSD %) was within 15 % and the accuracy ranged from 94.9 % to 112.0 %. The absolute bioavailability was 12.5 %. The method was fully validated and successfully applied to the pharmacokinetic study of a single dose of panaxadiol.

Topics: Animals; Biological Availability; Chromatography, High Pressure Liquid; Drug Stability; Drugs, Chinese Herbal; Ginsenosides; Male; Panax; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sapogenins; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry