Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH3-PPD in beagle dogs

Abstract

BackgroundGinsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol (25-OCH3-PPD), a new derivative of ginsenoside, in beagle dogs.MethodsTwenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with 25-OCH3-PPD capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of 25-OCH3-PPD.ResultsThere was no 25-OCH3-PPD–induced systemic toxicity in beagle dogs at any doses. The level of 25-OCH3-PPD at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of 25-OCH3-PPD administrated groups compared to the vehicle control group. There were also no significant differences between 25-OCH3-PPD administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay.ConclusionThe highest dose level of 25-OCH3-PPD at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. 25-OCH3-PPD is an extremely safe candidate compound for antitumor treatment.

A narrative review of the pharmacology of ginsenoside compound K

“…In a beagle toxicity study, animals in the 36 mg/kg group showed reversible hepatotoxicity and significant weight loss during the study period. Animals in the 4 and 12 mg/kg groups did not show any significant toxicity (61).…”

Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases

“…During a beagle toxicity investigation, dogs in the 36 mg/kg group experienced considerable weight loss and reversible hepatotoxicity. There was no discernible toxicity in the animals in the 4 and 12 mg/kg groups [ 39 ]. Table 2 elucidated the cytotoxicity of CK on different cell lines.…”

Microorganisms for Ginsenosides Biosynthesis: Recent Progress, Challenges, and Perspectives

“…CK has been shown to have antidiabetic, antitumor, anti-inflammatory, and hepatoprotective activities [ 23 ]. A new derivative of ginsenoside from P. notoginseng , 25-OCH 3 -PPD, not only inhibited various types of cancer cell lines, such as pancreatic, breast, and lung cancer, but also exhibited nongenotoxic properties for antitumor treatment [ 24 ]. Noticeably, differences in the position of sugar linkers and hydroxyl groups give direction to biological activities.…”

“…Furthermore, CK shows the ability to inhibit and migrate human glioblastoma U87MG and U373MG cells via an arrested cell cycle progression at the G0/G1 phase [ 23 ]. Moreover, 25-OCH 3 -PPD has significant effects on decreasing the survival and inhibiting the proliferation of human prostate and breast cancer cell lines [ 24 ]. Thus, ginsenosides likely have therapeutic potential for the treatment of various cancer diseases.…”