Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl4-Induced Acute Liver Damage in C57BL/6 Mice.

Species of Cirsium (Asteraceae family) have been used in folk hepatoprotective medicine in Taiwan. We collected four Cirsium species—including the aerial part of Cirsium arisanense (CAH), the aerial part of Cirsium kawakamii (CKH), the flower part of Cirsium japonicum DC. var. australe (CJF), and Cirsii Herba (CH)—and then made extractions from them with 70% methanol. We compared the antioxidant contents and activities of these four Cirsium species extracts by a spectrophotometric method and high-performance liquid chromatography⁻photodiode array detector (HPLC-DAD). We further evaluated the hepatoprotective effects of these extracts on CCl4-induced acute liver damage in C57BL/6 mice. The present study found CAH possesses the highest antioxidant activity among the four Cirsium species, and these antioxidant activities are closely related to phenylpropanoid glycoside (PPG) contents. The extracts decreased serum ALT and AST levels elevated by injection with 0.2% CCl4. However, only CJF and CH decreased hepatic necrosis. Silibinin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic necrosis caused by CCl4. CJF and CH restored the activities of hepatic antioxidant enzymes and decreased hepatic malondialdehyde (MDA) levels. CJF further restored the expression of hepatic antioxidant enzymes including Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), and glutathione S-transferase (GST) proteins. HPLC chromatogram indicated that CKH, CJF, and CH contained silibinin diastereomers (α and β). Only CJF contained diosmetin. Hence, the hepatoprotective mechanism of CJF against CCl4-induced acute liver damage might be involved in restoring the activities and protein expression of the hepatic antioxidant defense system and inhibiting hepatic inflammation, and these hepatoprotective effects are related to the contents of silibinin diastereomers and diosmetin.

Herb-drug interaction of silymarin or silibinin on the pharmacokinetics of trazodone in rats.

Silymarin, one of the most popular herbal medicines, has been widely used for its hepatoprotective effects. This study investigates the effects of repeated dose of silymarin and its major ingredient, silibinin, on the pharmacokinetics of the antidepressant trazodone. Treatment groups included vehicle control group, concomitant silymarin at 1.0g/kg dose, and four 7-day repeated dose induction groups of 0.5 and 1.0g/kg silymarin and 0.175 and 0.35g/kg silibinin. Microdialysis coupled with high performance liquid chromatography (HPLC) was used to simultaneously monitor blood and bile concentrations of trazodone in the rats. Results indicate that pretreatment with an extremely high dose of 1.0g/kg silymarin significantly decreases trazodone's area under concentration curve (AUC), distribution half-life (t(1/2,alpha)), elimination half-life (t(1/2,beta)), and mean residence time (MRT). In conclusion, the present study finds no marked effects of silymarin and silibinin on the pharmacokinetics of trazodone under normal daily doses and the relative safety of taking the herb with trazodone.

Distribution of blood-muscle for clenbuterol in rat using microdialysis.

Clenbuterol is clinically used as a bronchodilator, but it is also illegally used to increase lean meat in animal husbandry. To investigate the muscle distribution of protein-unbound clenbuterol, a microdialysis technique coupled to liquid chromatography system was applied to simultaneously monitor clenbuterol in rat blood and muscle. Two microdialysis probes were implanted into the jugular vein/right atrium and hind leg muscle of rat for sampling after clenbuterol administration (10 mg/kg) through the femoral vein. Dialysate samples of clenbuterol were separated by a reversed-phase column (250 mm x 4 mm I.D., particle size 5 microm). The results indicate that the maximum concentration of clenbuterol in muscle was found at 30-45 min after clenbuterol administration (10 mg/kg) and the area under concentration curve (AUC) of clenbuterol in blood and in muscle were 942.75+/-101.92 and 174.81+/-13.03 min microg/mL, respectively. The AUC(muscle)/AUC(blood) was 0.20+/-0.03 representing about 20% of the clenbuterol distributing into the muscle. The elimination half-life of clenbuterol in the blood and muscle were about 2 and 6h, respectively. These results suggest that the protein-unbound concentration of clenbuterol sustained a high level and prolonged elimination in the muscle. The accumulation of clenbuterol might result in some clinical effects when clenbuterol-contaminated meat was consumed.