Toxicity Assessment of Cadinene Sesquiterpenes from Eupatorium adenophorum in Mice.

This study evaluated toxic efficacy of Eupatorium adenophorum extracts, against the Kunming mice. In acute study, we firstly tested median lethal dose (LD50) in mice of three cadinene sesquiterpenes 2-deoxo-2-(acetyloxy)-9-oxoageraphorone (DAOA), 9-oxo-agerophorone (OA) and 9-oxo-10,11-dehydro-agerophorone (ODA) from Eupatorium adenophorum (Ea). DAOA (215-4640 mg/kg BW, given orally) showed lowest LD50 at 926 mg/kg BW for male mice in contrast with OA (1470 mg/kg BW) and ODA (1470 mg/kg BW). In sub-acute study, repeated doses (75-300 mg/kg BW, for 7 days) of DAOA/OA increased blood parameters, liver and spleen index in dose dependent relationship, along with decrease in thymus index. The blood biochemical and histopathological examination showed that DAOA/OA dose 300 mg/kg BW significantly causes pathological changes of hepatic lobules and hepatocytes, which are consistent with cholestasis and hepatic injury. 75 mg/kg dose of DAOA/OA was found to be approximately/totally safe over the span of 7 days treatment showing no change in all above described parameters. Cadinene sesquiterpenes guarantee low risk to environment as a type of low toxic botanical components, which may find potential application in biopesticides development field.

[Analysis of BRAF mutation and extracellular regulated protein kinases activation in nasal mucosa melanomas].

OBJECTIVE: To determine the rate of BRAF gene mutation and the expression of activated extracellular regulated protein kinases (ERK) in nasal mucosa malignant melanomas and compare the results with those in cutaneous melanomas so as to explore the difference in the pathogenesis between nasal mucosa malignant melanomas and cutaneous melanomas. METHODS: Twenty nasal mucosa melanomas samples were collected. Genomic DNA was extracted and the BRAF mutation detected by PCR (polymerase chain reaction) and direct sequencing analysis. Total protein was obtained and the activated ERK detected by Western blot. RESULTS: BRAF mutation was detected in 5% (1/20) samples of all patients. The mutation rate was much lower than that in cutaneous melanomas. And phosphorylated ERK protein was detected in 60% (12/20). And the result was almost similar to that of cutaneous melanomas. CONCLUSIONS: The high expression of activated ERK is not caused mainly by BRAF gene mutation in nasal mucosa malignant melanomas. The pathogenic pathways are different between nasal mucosa malignant melanomas and cutaneous melanomas.