Poblaciones linfocitarias, células dendríticas y perfil de citoquinas en ratones con melanoma tratados con Uncaria tomentosa

Abstract

RESUMENObjetivos. Evaluar el efecto inmunomodulador sobre poblaciones linfocitarias, células dendríticas (DC), citoquinas Th1/Th2/Th17 (T-helper) e inflamatorias en el ámbito sistémico y/o en el microambiente tumoral de ratones con o sin melanoma. Materiales y métodos. Se obtuvieron muestras de sangre periférica y/o de tumores primarios de ratones con melanoma B16 tratados o no con un extracto hidroalcohólico de Uncaria tomentosa (UT) con 5,03% de alcaloides oxindólicos pentacíclicos (UT-POA) obtenido de la corteza de la planta. Todos los ensayos de medición de células y citoquinas fueron realizados por citometría de flujo. Resultados. UT-POA a nivel sistémico incrementa la relación CD4/CD8a (Cluster of Differenciation), mientras que la activación celular es inversamente proporcional; incrementa la proporción de DCm (DC mieloides); induce un perfil Th1 proinflamatorio y reduce la respuesta Th17. TNF-a (tumor necrosis factor alpha) y IL-17A (interleuquina) correlacionan positiva y negativamente con la relación CD4/CD8a. Conclusiones. El incremento de Th1 (TNF-a) puede tener como consecuencia el incremento de linfocitos CD4 o la activación de macrófagos M1. Aunque UT-POA muestra un incremento de DCm, este no es dosis-dependiente. La disminución de Th17 (IL-17A) puede favorecer el funcionamiento de los linfocitos CD8a. UT-POA muestra mejores efectos inmunomoduladores en el ámbito sistémico que intratumoral. Palabras clave: Uncaria tomentosa; Activación de linfocitos; Células dendríticas; Melanoma (fuente: DeCS BIREME). LYMPHOCYTE SUBSETS, DENDRITIC CELLS AND CYTOKINE PROFILES IN MICE WITH MELANOMA TREATED WITH Uncaria tomentosa ABSTRACT Objectives.To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. Materials and methods: Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the plant. All cell assays and cytokine measurements were performed by flow cytometry. Results. UT-POA systemically increased CD4/CD8a relation while cell activation was inversely proportional; increased the proportion of DCm; induced a pro-inflammatory Th1 profile and reduced Th17 response. TNF-α and IL-17A positively and negatively correlated with CD4/CD8a relation. Conclusions. The increase of Th1 (TNF-α) may result in the increase of CD4 or M1 macrophage activation. Although UT-POA shows increased DCm, is not dose-dependent. Th17(IL-17A) decreased can support the function of CD8a lymphocytes. UT-POA shows better systemic immunomodulatory effects than intratumoral.

Anti-inflammatory and/or immunomodulatory activities of Uncaria tomentosa (cat’s claw) extracts: A systematic review and meta-analysis of in vivo studies

“…These findings explain, at least in part, the anti-inflammatory activity of this species. Most of the in vivo studies have demonstrated, directly or indirectly, that the inhibition of the activity of the transcription factor NF-κB by the extracts was accompanied by decreased levels of IL-1 or IL-6 (Aguilar et al, 2002;Sandoval et al, 2002;Sandoval et al, 2002;Lozada-Requena et al, 2015;Araujo et al, 2018;Azevedo et al, 2018;Elgawish et al, 2019;XU et al, 2021). Targeting IL-6 is an important strategy to treat inflammatory diseases.…”

“…Another important aspect to be considered is that U. tomentosa extracts preserve CD4 + and CD8 + T cells and possibly stimulate cytokines that favor the polarization of CD4 + Th2 cells. These cells play an important role in autoimmune diseases, such as rheumatoid arthritis, by modulating the excessive activity of Th1 cells (Domingues et al, 2011a;Domingues et al, 2011b;Lozada-Requena et al, 2015;Azevedo et al, 2018). In fact, an extract of U. tomentosa was superior to placebo in 50 patients with rheumatoid arthritis, decreasing the number of painful joints, morning stiffness, pain intensity, and joint edema (Mur et al, 2002).…”

“…Regarding the effectiveness of pentacyclic oxindole alkaloids in reducing inflammatory processes, the results are conflicting. Some authors claim that ethanolic extracts enriched with these alkaloids have better anti-inflammatory activity than aqueous extracts (Aguilar et al, 2002;Domingues et al, 2011a;Farias et al, 2011;Lozada-Requena et al, 2015;Xu et al, 2021). However, the antiinflammatory activity of aqueous extracts of U. tomentosa is well documented (Roque et al, 2009;Castilhos et al, 2015;Azevedo et al, 2018;Elgawish et al, 2019;Aldayel et al, 2021), and extracts without alkaloids have been shown to maintain their anti-inflammatory activity (Sandoval et al, 2002).…”

Análise Dos Índices De Transtornos Hipertensivos Na Gravidez

“…Nesse panorama, muitos estudos têm evidenciado que essa planta possui propriedades anti-inflamatórias, imunomoduladoras, pró-apoptótica e antioxidante, logo tornou-se alvo de estudos para tratar a endometriose e miomas uterinos. Portanto, faz-se necessário expandir as pesquisas acerca deste fitoterápico, afim de desenvolver novas modalidades terapêuticas e reduzir a onerosidade do tratamento de tais mazelas (LOZADA-REQUENA et al, 2015). Diante disso, o estudo objetivou buscar na literatura subsídios científicos capazes de elucidar a eficácia do uso de Uncaria tomentosa como terapêutica de doenças neoplásicas mamárias e disfunções da proliferação células uterinas.…”