"Adverse Effects in Skeletal Muscle Following the Medicinal Use of Nicotiana glauca"

ANDREA VASCONSUELO; LORENA MILANESI; ANDREA VASCONSUELO; LORENA MILANESI; FLORENCIA MUSSO; LUCÍA PRONSATO; FLORENCIA MUSSO; LUCÍA PRONSATO; DARÍO LINCOR; M. BELÉN FARAONI; DARÍO LINCOR; M. BELÉN FARAONI

BIOL. PHARM. BULL.

PHARMACEUTICAL SOC JAPAN

Lugar: Tokyo; Año: 2019 vol. 42 p. 671 - 679

0918-6158

Nicotiana glauca is a cosmopolitan shrub, used in medicine to treat swellings, wounds, sores and cancer.However, its users lack of knowledge of the adverse effects. We seek to evaluate the effects of lipid extractsfrom N. glauca on myoblasts, identifying the compounds which cause undesirable effects. Myoblasts are importantin muscle homeostasis, thus a high death rate of them cause myopathies. We performed an ethanolicextraction from leaves of N. glauca and the extract was successively partitioned with hexane, chloroform andethyl acetate. The effects of extracts in C2C12 cells were analysed by terminal deoxynucleotidyl transferasemediateddeoxyuridine triphosphate nick-end labeling (TUNEL), Mitotracker and 4,6-diamidino-2-phenylindole(DAPI) staining, Western blotting, real-time PCR and immunofluorescence assays. Caspase activitywas studied. The fraction with the highest apoptotic effects was analysed by chromatography, NMR andGC-MS spectrometry were used to identify the apoptotic agent, after which its biological activity was evaluated.The extracts from N. glauca induced apoptosis in C2C12 cells involving caspase-3/7. We found that theextracts trigger a defence response in muscle through Akt and heat shock protein 27 (HSP27). We identifiedan apoptotic agent as palmitic acid. These data suggest that the use of N. glauca in hormone replacementtherapy, or in other therapies affects skeletal muscle homeostasis, worsening the negative effects of the menopause.Thus, the relevance of this work lies in the fact that it is the first time that a report about the molecularmechanism responsible for the side effects of medicinal use of N. glauca, has been shown. Moreover thecompound responsible for these effects has been identified.