title: Oral subchronic toxicity evaluation of a novel antitumor agent 25-methoxydammarane-3, 12, 20-triol from Panax notoginseng in Sprague-Dawley rats.
abstract: Panax notoginseng and its main active ingredients ginsenosides have long been used as medicines and food additives in China. Comparing with the extensive uses and active researches of P. notoginseng and its products, the side effect and probable toxicity were rare. 25-Methoxydammarane-3,12,20-triol (25-OCH3-PPD), a novel dammarane-type triterpene sapogenin that was first isolated from the extract of P. notoginseng, was proven to have strong antitumor activities against prostate cancer, breast cancer and lung cancer. The aim of the present study was to investigate the potential subchronic toxicity of 25-OCH3-PPD after it was repeatedly orally administered to Sprague-Dawley rats (5/sex/group/each time-point) at dose levels of 0, 150, 300 or 600 mg/kg/day for 13 weeks and 4-week recovery. No mortality and treatment-related toxicity effects were observed as a result of the administration of 25-OCH3-PPD at any dose level (150, 300 and 600 mg/kg) for 92 consecutive days. Although there were some statistical changes, such as increased weights in female rats and decreased organ weights and coefficients of the liver, spleen, kidney, and adrenal gland compared with the control group at the corresponding time, the autopsy and histopathological examination of the target organs did not show any abnormal responses. As a result, 25-OCH3-PPD was well tolerated by SD rat at doses of up to 600 mg/kg and that it is a potential candidate for therapeutic use.
authors.affiliation: The College of Pharmacy, Jilin University, Jilin, 130021, China; Department of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Yaoxian
authors.initials: Y
authors.lastname: Xuan
authors.affiliation: The College of Pharmacy, Jilin University, Jilin, 130021, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Liu
authors.affiliation: The College of Pharmacy, Jilin University, Jilin, 130021, China. Electronic address: lipy@jlu.edu.cn.
authors.forename: Pingya
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: zyq4885@126.com.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009929:Organ Size / Q000187:drug effects; D005894:Panax / Q000737:chemistry / Q000633:toxicity*; D008517:Phytotherapy; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D013997:Time Factors; D059550:Toxicity Tests, Subchronic / Q000379:methods*; D014315:Triterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects; D000097669:Dammaranes
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; D014315:Triterpenes; C517965:25-methoxydammarane-3,12,20-triol; D000097669:Dammaranes
keywords: 25-methoxydammarane-3, 12, 20-triol; Panax notoginseng; Safety assessment