Calixto Sanderson Dias, Simão Thatiana Lopes Biá Ventura, de Almeida Fabrício Moreira, Antunes Stella Schuenck, Romeiro Nelilma Correia, de Souza Borges Warley, das Chagas Fernanda Oliveira, Seldin Lucy, de Carvalho Eulógio Carlos Queiroz, Andrioli Willian Jonis, Guimarães Denise Oliveira, Lasunskaia Elena, Muzitano Michelle Frazão
Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro, Brazil.
Laboratório de Produtos Bioativos, Curso de Farmácia, Universidade Federal do Rio de Janeiro, Campus Macaé, Macaé, Rio de Janeiro, Brazil.
J Pharm Pharmacol. 2022 Mar 3;74(3):446-457. doi: 10.1093/jpp/rgab165.
This study aimed to evaluate endophytic fungi isolated from Tocoyena bullata and Humiria balsamifera plant species for their antimycobacterial and anti-inflammatory activities, focusing on severe pulmonary tuberculosis cases which are often associated with exacerbated inflammation.
Mycobacterium suspensions were incubated with the samples for 5 days. RAW 264.7 macrophages stimulated with LPS were also incubated with them for 24 h to assess the inhibition of inflammatory mediator production and cytotoxicity. C57BL/6 mice were infected with Mtb M299 and treated for 15 days with lasiodiplodin (Lasio).
Endophytic fungus Sordaria tamaensis, obtained from T. bullata, was the most promising. Its ethanolic extract impaired mycobacterial growth with MIC50 (µg/ml): 1.5 ± 0.6 (BCG), 66.8 ± 0.1 (H37Rv) and 80.0 ± 0.1 (M299). (R)-(+)-Lasio showed MIC50 92.2 ± 1.8 µg/ml (M299). In addition, Lasio was able to inhibit NO, IL-1β and TNF-α production and was not cytotoxic for macrophages. M. tuberculosis-infected C57BL/6 animals treated by Lasio reduced the number of acid-fast bacilli, lung pathology, leucocyte influx and proinflammatory cytokine production in the lungs. The class IIa fructose 1,6-bisphosphate aldolase was the predicted hypothetical target of Lasio.
(R)-(+)-Lasio stood out as a promising anti-TB compound, exhibiting anti-inflammatory and antimycobacterial effects, as well as low cytotoxicity.
本研究旨在评估从圆叶托科依纳（Tocoyena bullata）和香脂南美山榄（Humiria balsamifera）植物物种中分离出的内生真菌的抗分枝杆菌和抗炎活性，重点关注常伴有炎症加剧的严重肺结核病例。
将分枝杆菌悬液与样品孵育5天。用脂多糖刺激的RAW 264.7巨噬细胞也与它们孵育24小时，以评估炎症介质产生的抑制作用和细胞毒性。用结核分枝杆菌M299感染C57BL/6小鼠，并用拉西奥地菌素（Lasio）治疗15天。
从圆叶托科依纳获得的内生真菌塔玛斯索氏菌（Sordaria tamaensis）最具潜力。其乙醇提取物抑制分枝杆菌生长，MIC50（μg/ml）：1.5±0.6（卡介苗）、66.8±0.1（H37Rv）和80.0±0.1（M299）。（R）-（+）-拉西奥地菌素对M299的MIC50为92.2±1.8μg/ml。此外，拉西奥地菌素能够抑制一氧化氮、白细胞介素-1β和肿瘤坏死因子-α的产生，并且对巨噬细胞无细胞毒性。用拉西奥地菌素治疗的结核分枝杆菌感染的C57BL/6动物减少了肺中抗酸杆菌的数量、肺部病理、白细胞浸润和促炎细胞因子的产生。IIa类果糖1,6-二磷酸醛缩酶是拉西奥地菌素预测的假定靶点。
（R）-（+）-拉西奥地菌素作为一种有前景的抗结核化合物脱颖而出，具有抗炎和抗分枝杆菌作用以及低细胞毒性。
