RESUMO
Background: Azadirachta indica Juss. has been shown to suppress cancer progression through a variety of mechanisms. In order to treat cancer progression, cancer immunotherapy is used to stimulate the immune system where immunosuppression is present in tumor microenvironments. Many cancer cells produce a lot of interleukin-6 (IL-6) and signal transducer activator of transcription 3 (STAT3). STAT3 plays a key role in suppressing the expression of critical immune activation regulators. IL-6-mediated STAT3 activation is common in the tumor microenvironment. Inhibiting the IL-6/STAT3 signaling pathway has become a therapeutic option for cancer progression. As vimentin is also expressed in hepatic stellate cells boosting cancer survival. We focused on the precise effect of extract from leaves of Azadirachta indica Juss, on inhibiting the IL-6/STAT3 signaling cascade on hepatocellular carcinoma by in vitro and in vivo study. Methods: In the in vitro study, the effect of Azadirachta indica Juss. variant Indonesia and Philippines against the expression of IL-6 and STAT3 was examined in liver cancer cell line. In the in vivo study, 24 male rats ( Rattus norvegicus) strain Wistar were induced by diethylnitrosamine and carbon tetrachloride (CCl 4). Based on the therapy given, the groups were divided into negative control, positive control, Indonesia extract, and Philippine extract. Expression of IL-6, STAT3, and vimentin were tested using immunohistochemistry staining. The data were analyzed using analysis of variance, which was then followed by the Tukey test. Results: Statistically significant difference in IL-6 and STAT3 was observed between the treatment groups and positive control group by in vitro study and in vivo study. Generally, there is no significant difference between treatment using Indonesian and Philippine leaves. Conclusion: Both therapy doses of Azadirachta indica variant in Indonesia and Philippines were able to reduce IL-6, STAT3 and vimentin expression of hepatocellular carcinoma cell by in vitro and in vivo experiment.
RESUMO
ABSTRACT Background: Rheumatoid arthritis (RA) is a common immune-mediated inflammatory disease characterized by increased inflammation of synovial joint, and often associated with disability. Although several studies have demonstrated the medicinal properties of durian, little is known about the role of durian wood bark for medicinal purposes. Thus, this study investigated the anti-arthritic activity of durian wood bark extract in a rat model of rheumatoid arthritis. Methods: The rats were divided into five groups, including control, RA model, and RA model treated with durian wood bark extract (20, 30, and 40 mg/kg/day for 14 days). The effects of treatment were evaluated by clinical, as well as histological changes in the ankle joints, and the expression level of inducible nitric oxide synthase (iNOS). Results: A complete Freund's adjuvant (CFA)-induced RA model in rats was successfully, characterized by the swelling of hind limbs, histopathological changes in ankle joints, and the upregulation of iNOS expression. The administration of durian wood bark extract at a dose of 40 mg/kg attenuated all parameters analyzed in CFA-induced RA model in rats. Conclusion: Amelioration of hind limb swelling, histopathological changes, and iNOS expression in the RA model indicates that durian wood bark extract can be considered as a new treatment alternative that reduces joint symptoms, as well as a future area of research in humans.
RESUMEN Antecedentes: La artritis reumatoide (AR) es una enfermedad inflamatoria común mediada por el sistema inmunológico que se caracteriza por una mayor inflamación de la articulación sinovial, y a menudo se asocia con discapacidad. Aunque en varios estudios se han demostrado las propiedades medicinales del durián, se conoce poco sobre el papel de la corteza de madera de durián con fines médicos. Así pues, en este estudio se investigó la actividad antiartrítica del extracto de corteza de madera de durián en un modelo de AR en ratas. Métodos: Las ratas se dividieron en 5 grupos, incluyendo el control, el modelo de AR y el modelo de AR tratado con extracto de corteza de madera durián (20, 30 y 40mg/kg/día durante 14 días). Los efectos del tratamiento se evaluaron mediante cambios clínicos e histológicos en las articulaciones de los tobillos y el nivel de expresión de la sintasa de óxido nítrico inducible (iNOS). Resultados: Desarrollamos con éxito un modelo completo de AR inducida por adyuvantes de Freund (CFA) en ratas, caracterizado por la hinchazón de las extremidades posteriores, los cambios histopatológicos de las articulaciones del tobillo y el aumento de la expresión de la iNOS. La administración de extracto de corteza de madera de durián a una dosis de 40 mg/kg atenuó todos los parámetros analizados en el modelo de AR inducida por CFA en ratas. Conclusión: La mejora de la hinchazón de las extremidades traseras, los cambios histopatológicos y la expresión de iNOS en el modelo de AR indican que el extracto de corteza de madera dura puede considerarse una nueva alternativa de tratamiento para reducir los síntomas de las articulaciones, con un futuro campo de investigación en los seres humanos.
