Pharmacokinetic Characterizations of Ginsenoside Ocotillol, RT₅ and F₁₁, the Promising Agents for Alzheimer’s Disease from American Ginseng, in Rats and Beagle Dogs

Abstract

Background: Ocotillol, RT₅ and F₁₁, the main active components of ocotillol type ginsenosides, have attracted a lot of attention due to their beneficial effects on neurodegenerative disease models of Alzheimer’s disease. Pharmacokinetic (PK) is a bridge linking the herbal medicines and their pharmacological responses. However, few data are available regarding PK behaviors of ocotillol type ginsenosides. Methods: The liquid chromatography-tandem mass spectrometry methods were developed and validated to calculate the concentrations of 3 ginsenosides in different biological matrices. Rat and beagle dog plasma samples were deproteinized with methanol and separated on Shim-pack GIST C₁₈ column. All of the analytes were detected in positive ion mode using multiple reaction monitoring. Results: The methods showed good linearity (r > 0.996) in the established concentration range. All validated data, such as specificity, intra- and inter-day precision, accuracy, extraction recovery, matrix effect, and stability were within required limits. The values of C_max and AUC_(0–t) indicated ocotillol type ginsenosides had low systemic exposure and poor absorption into blood. T_1/2 and MRT_(0–t) demonstrated the elimination process of ocotillol type ginsenosides might be slow. Double peaks were observed in the mean plasma concentration versus time profiles of ocotillol, RT₅, and F₁₁ after oral intake. Conclusions: This was the first PK investigation of the ocotillol type ginsenosides in rats and beagle dogs. The results we found here were helpful to our understanding of the absorption mechanism of ocotillol type ginsenosides and provided the scientific basis for further pre-clinical research.

Identification of Multi-Target Anti-AD Chemical Constituents From Traditional Chinese Medicine Formulae by Integrating Virtual Screening and In Vitro Validation

“…TCM has been widely used in the prevention and treatment of disease for more than 2000 years and there are many Traditional Chinese medicine formulae used to improve cognitive function (Cai et al, 2016). Some chemical components contained in Radix salviae (Zhang et al, 2016), Panacis quinquefolii Radix (Li et al, 2019), Zingiberis rhizoma (Adalier and Parker, 2016), Radix bupleuri (Zeng et al, 2019) and Zingiber officinale Roscoe (Mohd Sahardi and Makpol, 2019) have been used in the study of AD, which is consistent with the predicted results in this paper. From the prediction results of this paper, most of the chemical components in the anti-AD TCM compounds database could act on the targets in the multi-target anti-AD prediction platform.…”

Protective Effect of Ocotillol, the Derivate of Ocotillol-Type Saponins in Panax Genus, against Acetic Acid-Induced Gastric Ulcer in Rats Based on Untargeted Metabolomics

“…However, ocotillol showed the highest inhibitory effect among these three ginsenosides [15]. Another example, pseudoginsenosides F11, was metabolized to ocotillol via pseudoginsenoside RT5 [32]. Furthermore, ocotillol could enhance neuronal activity [33], which was similar to the effect of pseudoginsenoside F11 [34].…”

Advances and challenges in ginseng research from 2011 to 2020: the phytochemistry, quality control, metabolism, and biosynthesis

“…The concentrations of three OT-type saponins (octillol, RT5, and F11) in the plasma of rats and beagle dogs were determined by LC-MS, revealing the low systematic exposure and poor absorption into the blood, together with the slow elimination process of OT-type ginsenosides. 357 The pharmacokinetics, tissue distribution and excretion of Rd in rodents were determined by HPLC and a radioactive tracer method. The concentration of Rd labelled at 3 h peaked rapidly in plasma and was distributed to various tissues, with the highest concentration in the lung.…”

“…Ginsenosides can be converted into hydrophobic compounds by the intestinal microbial enzymes, and are then transported to the liver, which metabolizes these hydrophobic metabolites into hydrophilic compounds through phase I–III enzymes. Information from the literature concerning the PK studies of ginseng is given in Table S8 † 336,342,346–370 . These studies involve a systematic description of the absorption, distribution, metabolism, excretion, and blood concentration of ginsenosides over time after administering pure compounds (involving Rh4/Rk3, 346 25-OCH 3 -PPD/25-OH-PPD, 347 neopanaxadiol, 348 26-OH-PPD, 349 PPD, 350 24-OH-PPD, 351 Rb3, 352 Rc, 353 noto-Fc, 355 CK, 336 Rb1, 356 octillol/RT5/F11, 357 and Rd 358 ) or ginseng extracts (white ginseng, 342 fermented and nonfermented P. ginseng , 359 red ginseng, 362 P. quinquefolius , 365 and P. notoginseng 366) to healthy humans or animals.…”