Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents

Abstract

The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25–241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.

Safety and efficacy of a feed additive consisting of Macleaya cordata (Willd.) R. Br. extract and leaves (Sangrovit® extra) for all poultry species (excluding laying and breeding birds) (Phytobiotics Futterzusatzstoffe GmbH)

“…In addition, the negative results obtained in mice with different mutagenicity tests (sperm abnormality test, micronucleus test and chromosomal aberration test) confirmed the absence of genotoxic activity of an extract rich in protopine alkaloids (MPTA, containing 35% PRO and 15% ALL) obtained from the acidic waste stream used for the extraction of the benzophenanthridine alkaloids in M. cordata (Dong et al., 2022).…”

Halicin: A New Horizon in Antibacterial Therapy against Veterinary Pathogens

“…The Ames test, extensively applied to assess mutagenic and carcinogenic risks, has identified a total of 5000 chemical compounds with the risks [ 58 , 59 ]. The potential reproductive toxicity and mutagenicity of compounds can be evaluated through the mouse sperm abnormality test, chromosomal aberration test in bone marrow cells, and bone marrow micronucleus test [ 60 , 61 ]. In this study, the Ames test results for halicin ( Table 4 , Tables S5 and S6 ), conducted in the range from 0.0004176 μg/plate to 0.261 μg/plate with or without the metabolic activation system (S9), consistently showed no statistically significant differences ( p > 0.05) in average revertant colonies per plate compared to the negative control group for all Salmonella typhimurium strains.…”

Safety assessment of enzymatically converted chicken bile as a novel food material: Genotoxicity, teratogenicity, and acute and subchronic toxicity studies

“…While CB at 833 mg/kg showed no toxic effects in the subchronic toxicity test, it is necessary to perform teratogenicity tests on CB at this dose to observe whether maternal health and fetus growth and development are affected in pregnant rats (Dong et al., 2022; Sa et al., 2022). Throughout the teratogenicity test, all animals showed no abnormalities in skin, coat, eyes, mucous membranes, respiration, neurobehavior, limb movements, and so on.…”