The water extract of Veratrilla baillonii could attenuate the subacute toxicity induced by Aconitum brachypodum.
BACKGROUND
Aconitum brachypodum Diels (Family Ranunculaceae) is a Chinese ethnodrug and is well known for both its therapeutic application and high toxicity. However, no detoxication strategy is available for the complete elimination of the toxicity of Aconitum plants. Veratrilla baillonii Franch is believed to possess antitoxic effects on the toxicity induced by Aconitum plants and has been clinically used for hundreds of time by Naxi and Lisu nationalities in Yunnan Province of China. To further address the mechanism of the detoxication of Veratrilla baillonii, the effect of water decoction of Veratrilla baillonii (WVBF) on subacute toxicology of SD rats induced by Aconitum brachypodum (CFA), a genus Aconitum, was determined and studied in the present work.


METHODS
The clinical behavior and number of survivors for different dosage of WVBF (25, 50, 100mg/kg) on CFA (4mg/kg) induced rats were observed until day 28. Histological changes and haematological parameters were evaluated. Moreover, Na+-K+-ATPase pathway in heart as well as key enzymes in liver were determined to further discuss the mechanism.


RESULTS
The results showed that the exposure of CFA led to some subacute toxicity to rats, especially male ones, accompanied with abnormality of serum biochemical index in rats' serum. The toxicological target organs of CFA may be the heart, liver, kidney and brain. It is demonstrated that WVBF could attenuate the toxicity induced by Aconitum brachypodum via promoting the metabolic enzymes CYP3A1 and CYP3A2 in liver, downregulating the expression of Sodium/Calcium exchanger 1 (NCX1) and SCN5A sodium channal mRNA, and inducing Na+/K+-ATPase activity in heart. This study provides insights into detoxifying measures of Aconitum plants.


CONCLUSIONS
Aconitum brachypodum may lead to subacute toxicity of rats after long term of administration, and the toxicity could be attenuated by Veratrilla baillonii via promoting the metabolic enzymes in liver, downregulating the expression of NCX1 and SCN5A mRNA, and inducing Na+/K+-ATPase activity in heart.
College of Pharmacy, South-Central University for Nationalities, Wuhan, 430074, PR China.
You
Y
Yu
College of Pharmacy, South-Central University for Nationalities, Wuhan, 430074, PR China.
Xue-Jia
XJ
Yi
College of Pharmacy, South-Central University for Nationalities, Wuhan, 430074, PR China.
Zhi-Yi
ZY
Mei
College of Pharmacy, South-Central University for Nationalities, Wuhan, 430074, PR China. Electronic address: lijun-pharm@hotmail.com.
Jun
J
Li
College of Pharmacy, South-Central University for Nationalities, Wuhan, 430074, PR China. Electronic address: xianju@mail.scuec.edu.cn.
Xian-Ju
XJ
Huang
College of Pharmacy, South-Central University for Nationalities, Wuhan, 430074, PR China.
Guang-Zhong
GZ
Yang
College of life sciences, South-Central University for Nationalities, Wuhan, 430074, PR China.
Li-Qun
LQ
Ma
Beijing Institute of Radiation Medicine, Department of Pharmacology & Toxicology, Beijing, 100850, PR China.
Yue
Y
Gao
D031841:Aconitum / Q000633:toxicity*; D000818:Animals; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D029965:Gentianaceae / Q000737:chemistry*; D006321:Heart / Q000187:drug effects; D008658:Inactivation, Metabolic / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008516:Medicine, Chinese Traditional; D010936:Plant Extracts / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D010936:Plant Extracts; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; C465260:Cyp3a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A; D000254:Sodium-Potassium-Exchanging ATPase
Aconitum brachypodum (Ranunculaceae family); Cytochrome P450; Na(+)/K(+)-ATPase; Sodium channal; Subacute toxicology; Veratrilla baillonii (family Gentianaceae)