ABSTRACT
Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.
ABSTRACT
Chemical constituents and biological activities of the aerial parts of Piper erecticaule C.DC. have been studied for the first time. Fractionation and purification of the extracts afforded aristolactam AII (1), aristolactam BII (2), piperolactam A (3), piperolactam C (4), piperolactam D (5), together with terpenoids of ß-sitosterol, ß-sitostenone, taraxerol, and lupeol. The structures of these compounds were obtained by analysis of their spectroscopic data, as well as the comparison with that of reported data. Acetylcholinesterase inhibitory activity revealed that compounds 1 and 3 showed strong AChE inhibitory effects with the percentage inhibition of 75.8% and 74.8%, respectively.
Se estudiaron por primera vez los constituyentes quiÌmicos y actividad bioloÌgica de las partes aeÌreas de Piper erecticaule C.DC. El fraccionamiento y la purificacioÌn de los extractos proporcionaron aristolactama AII (1), aristolactama BII (2), piperolactama A (3), piperolactama C (4), piperolactama D (5), junto con terpenoides de ß-sitosterol, ß-sitostenona, taraxerol, y el lupeol. Las estructuras de estos compuestos se obtuvieron mediante el anaÌlisis de sus datos espectroscoÌpicos, asiÌ como mediante la comparacioÌn con datos ya informados. La actividad inhibidora de la acetilcolinesterasa reveloÌ que los compuestos 1 y 3 mostraron un potente efecto inhibidor de la AChE con un porcentaje de inhibicioÌn del 75.8% y 74.8%, respectivamente.
Subject(s)
Aporphines/pharmacology , Acetylcholinesterase/drug effects , Plant Extracts/chemistry , Cholinesterase Inhibitors/pharmacology , Piper/chemistry , Alkaloids/pharmacology , Aporphines/chemistry , Terpenes/isolation & purification , Cholinesterase Inhibitors/chemistry , Indole Alkaloids/chemistry , Alkaloids/chemistry , Lactams/chemistryABSTRACT
Three phenolic aristolactams, aristolactam AII (3), velutinam (4) and piperolactam A (5), were identified from the leaves and stems of Aristolochia chilensis Bridges ex Lindl. The structures of these compounds were elucidated using a combination of HPLC-DAD, GC-MS and NMR experiments.
Tres aristolactamas fenólicas aristolactama AII(3), velutinam(4) y piperolactama A(5), se identificaron en hojas y tallos de Aristolochia chilensis Bridges ex Lindl. Las estructuras de estos compuestos se determinaron por combinación de CLAE-DAD, CG-EM y experimentos de RMN.