Rats safety evaluation of acteoside

doi:10.19803/j.1672-8629.20220344

Abstract

Abstract: Objective To preliminarily evaluate the safety of acteoside through toxicity tests of single and repeated dose, thus laying the foundation for in-depth and comprehensive safety evaluation. Methods Single dose toxicity test: SD rats were randomly divided into a solvent control group and a medication group(5 000 mg·kg^-1), and were administered orally in single dose. The general clinical symptoms,mortality,and weight of rats within 14 days were observed and recorded,and the main organs were visually observed.Repeated dose toxicity test: SD rats were randomly divided into a solvent control group, and acteoside low (100 mg·kg^-1), medium (500 mg·kg^-1), and high dose group(2 000 mg·kg^-1), 30 in each group, and were continuously administered for 28 days and recoverded for 28 days. Their general clinical symptoms, body weight, food intake, urine routine, and other related indicators were observed and tested. Results The single dose toxicity test results showed that compared with the solvent control group, there were no deaths or abnormalities in rats; there was no statistically significant difference in body weight (P>0.05), and there were no visible lesions in organ tissues. The repeated toxicity test results showed that compared with the solvent control group, there was no statistically significant difference in body weight, food intake, coagulation indicators, organ wet weight and organ coefficient of rats(P>0.05). There was no toxicological effect on hematology, liver function and kidney function, and there was no obvious histopathology change related to drug administration in the high dose group; the positive detection rate of white blood cells and ketone bodies in the urine routine of female animals in the high-dose group was relatively high (P<0.05 or P<0.01), indicating reversibility. Conclusion In the single dose toxicity test, the maximum tolerated dose (MTD) of single dose for acteoside was greater than 5000 mg·kg^-1, and in the repeated dose toxicity test, the no observed adverse effect level (NOAEL) of acteoside was 500 mg·kg^-1.

Key words: acteoside, SD rats, toxicity test, reversible changes, maximum tolerated(MTD), toxicity

CLC Number:

R994.1

NIE Yunan, ZHANG Li, SHAO Mingxiang, GAO Li, YAN Ming. Rats safety evaluation of acteoside[J]. Chinese Journal of Pharmacovigilance, 2023, 20(7): 758-762.

References

[1] WANG WG, YANG ZQ, WANG P, et al.Pharmacological effects of verbascoside:advances[J]. International Journal of Pharmaceutical Research,2020, 47(12): 1078-1087.
[2] LEE HD, KIM JH, PANG Q, et al.Antioxidant activity and acteoside analysis of abeliophyllu- -m distichum[J]. Antioxidants, 2020, 9(11): 1148.
[3] WANG H, XU Y, YAN J, et al.Acteoside protects human neuroblastoma SH-SY5Y cells aga inst β-amyloid-induced cell injury[J]. Brain research, 2009, 1283: 139-147.
[4] LUO JN, MA DD, HUANG Y, et al.The protective effect and mechanism of action of paeoni florin on myocardial ischemia reperfusion injury in rats[J]. Pharmacology and Clinics of Chinese Materia Medica, 2016, 32(6): 56-60.
[5] TAN X, GAO L, YAN M, et al.To improve the effect of acteoside on learning and memory impairment in mice induced by scopolamine[J]. China Journal of New Drugs, 2018, 27(23): 2812-2818.
[6] WANG DQ, GAO L, YAN M, et al.Acteoside regulates AKT/NFκB pathway to improve cognitive impairment in APP/PS1 double-transgenic mice[J]. Chinese Pharmacological Bulletin,2021,37(2): 258-263.
[7] AHMAD M, RIZWANI GH, AFTAB K, et al.Acteoside: a new antihypertensive drug[J]. Phytotherapy research, 1995, 9(7): 525-527.
[8] SONG X, HE J, XU H, et al.The antiviral effects of acteoside and the underlying IFN-γ-inducing action[J]. Food & function, 2016, 7(7): 3017-3030.
[9] KHAN R A, HOSSAIN R, ROY P, et al.Anticancer effects of acteoside: Mechanistic insights and therapeutic status[J]. European Journal of Pharmacology, 2022, 916: 174699.
[10] WU M, YU S, CHEN Y, et al.Acteoside promotes B cell-derived IL-10 production and ameliorates autoimmunity[J]. Journal of Leukocyte Biology, 2022, 112(4): 875-885.
[11] ZHOU ZX, ZHANG T, LIANG GD, et al.Study on acute and long-term toxicity of Ganlanqianggu Tablets[J]. Journal of Pharmaceutical research, 2022, 41(2): 83-87, 121
[12] State Food and Drug Administration. Technical guidelines for the study of single dose toxicity of drugs[EB/OL]. (2014-05-13)[2022-06-06].https://www.nmpa.gov.cn/yaopin/ypggtg/ypqtgg/20140513120001448.html.
[13] State Food and Drug Administration. Technical guidelines for drug repeated administration toxicity test[EB/OL]. (2014-05-13) [2022-06-06].https://www.nmpa.gov.cn/yaopin/ypggtg/ypqtgg/20140513120001448.html.
[14] ICH. S4 Guideline: Duration of chronic Toxicity Testing in Animals(Rodent and non Rodent Toxicity Testing)[EB/OL].(1998-09-02)[2022-06-06].https://www.ich.org/page/safty-guideli nes.
[15] ICH.M3(R2) Guideline: Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals[EB/OL].(2009-06-11)[2022-06-06].https://www.ich.org/page/safty-guidelines.
[16] State Food and Drug Administration. Good Laboratory Practice[EB/OL].(2017-07-27)[2022-06-06].https://www.samr.gov.cn/zw/zfxxgk/fdzdgknr/bgt/art/2023/art_2959b53d3b6a429e866c514a76a790db.html.
[17] CHEN JY, GAO L, YAN M, et al.Effects of acteoside on behavioral and hormonal changes in APP/PS1 double-transgenic mice[J]. China Medical herald, 2020, 17(8): 9-12.
[18] HU WM, ZHANG L, WANG Y, et al.Effect of estrogen and its receptor in fat metabolism[J]. China Journal of New Drugs, 2016, 25(11): 1253-1257.
[19] MICHAELSON GS, WISNIACKI N, BURKLY LC, et al.Role of TWEAK in Lupus Nephr itis: a bench-to-bedside review[J].Autoimmun, 2012, 39: 130-142.
[20] LU J, SZETO CC, TAM LS, et al.Relationship of intrarenal gene expression and the histolo gical class of lupus nephritis-a study on repeat renal biopsy[J]. Rheumatol, 2012, 39: 1942-1947.
[21] ZHI-CJUN L, QIAO-LING Z, ZHI-QIN L, et al.Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) mediates p38 mitogen-activated protein kinase activation and signal transduction in peripheral blood mononuclear cells from patients with lupus nephritis[J]. Inflammation, 2012, 35: 935-943.
[22] HUANG J.Estrogen-induced expression of TWEAK accelerates the progression of lupus ne phritis Abstract[D]. Suzhou: Soochow University, 2016.
[23] WEI Z, LUO HB, SHANG N.Study on cerebral estrogen synthesis and its effects on cognitive function and pathogenesis in Alzheimer’s disease[J]. Journal of Hubei University for Nationa- -lities(Medical Sciences), 2017, 34(1): 56-59.
[24] HUANG Y, WEI HX, QIAN LJ.Observation on value of abnormal liver enzyme abnormalities in health status assessment[J]. Clinical Research of Traditional Chinese Medicine, 2016, 8(5): 111-113.
[25] Symposium on Experimental Design and Data Analysis for Non-clinical Safety Evaluation of Drugs-The second session SD Advanced Training Course Courseware. Significance and influencing factors of blood biochemical indexes[EB/OL].(2016-09-06)[2022-06-06].https://www.nifdc.org.cn//nifdc/xxgk/ggtzh/gonggao/20160906162501334.html.
[26] Symposium on Experimental Design and Data Analysis for Non-clinical Safety Evaluation of Drugs-The second session SD Advanced Training Course Courseware. Data statistics and results analysis of general toxicity test[EB/OL].(2016-09-06)[2022-06-06].https://www.nifdc.org.cn//nifdc/xxgk/ggtzh/gonggao/20160906162501334.html.
[27] WANG Y, LIU Y, YUAN JL.et al.Research progress on drug-induced liver injury[J]. China Journal of Pharmaceutical Economics, 2013(5): 52-54.
[28] XIAO WL.The study of general toxicology for new anticoccidial triazine drug ethanam izuril[D]. Beijing: Chinese Academy of Agricultural Sciences,2014.