Anti-mycobacterial and immunomodulatory activity of n-hexane fraction and spathulenol from Ocotea notata leaves

Isabela Francisca De Jesus Borges Costa,Tatiana Ungaretti Paleo Konno,Elena Lasunskaia,Rafaella Velloso Pereira,Luzineide Wanderley Tinoco,Michelle Frazão Muzitano,Thatiana Lopes Bia Ventura Simão,Shaft Corrêa Pinto,Ivana Correa Ramos Leal,Sanderson Dias Calixto

doi:10.1590/2175-7860202172041

Isabela Francisca De Jesus Borges Costa, Tatiana Ungaretti Paleo Konno + Show 8 more

Open Access

https://doi.org/10.1590/2175-7860202172041

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Abstract

Abstract Ocotea notata (Lauraceae) is popularly known as white-cinnamon. Ocotea species have several medicinal uses, especially for treating chest pain, rheumatism and wounds. The present study aimed to analyze the chemical composition of O. notata n-hexane fraction, in addition to its anti-mycobacterial and immunomodulatory activities. The n-hexane fraction was analyzed by GC-MS and was chromatographed to afford 15 subfractions (SF1-15), where SF5 was identified, by GC-MS and NMR, as the sesquiterpene spathulenol. The n-hexane fraction was the most potent in inhibiting nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) production on LPS-stimulated macrophages (IC50 8.3 ± 0.9 and 5.9 ±1.0 μg/mL, respectively). SF4, a major subfraction, that presents a spathulenol analogous as a constituent, also inhibited NO and TNF-α production. Spathulenol only modulated NO production (IC50 45.6 ± 1.4 μg/mL). The n-hexane fraction, SF4, and spathulenol revealed antimycobacterial activity against Mycobacterium bovis BCG, M. tuberculosis H37Rv, and M299 strains. Spathulenol inhibited the growth of Mtb H37Rv with MIC50 36.9 ± 1.5 μg/mL (167.5 ± 6.8 μM), and Mtb M299 with MIC5042.1 ± 0.5 μg/mL (191.0 ± 2.2 μM). This is the first report describing the isolation of spathulenol from O. notata leaves and its anti-mycobacterial activity.

Highlights

Tuberculosis (TB) is a major cause of death worldwide aggravated by the emergence of Mycobacterium tuberculosis (Mtb) multidrugresistant (MDR-TB) strains
The search for new molecules with dual anti-inflammatory and anti-mycobacterial activity has been encouraged for severe pulmonary TB therapy and 70% of the antibiotics in use are natural products or are derived from them (Singh & Macdonald 2010)
Plant material Leaves of Ocotea notata were collected in the early morning, on a sunny day, at Parque Nacional da Restinga de Jurubatiba, Quissamã, Rio de Janeiro, Brazil, under legal authorization (SISBIO 39673-2, SisGenAAA989F) at March 2011

Summary

Introduction

Tuberculosis (TB) is a major cause of death worldwide aggravated by the emergence of Mycobacterium tuberculosis (Mtb) multidrugresistant (MDR-TB) strains. The World Health Organization reported 10 million new TB cases in 2017, with a high mortality rate in developing countries (WHO 2018). The long treatment duration of at least 6 months and complex regimens which involve expensive and toxic drugs hinder improvement in therapy outcomes (Dartois 2014). Uncomplicated drug-sensitive pulmonary TB treatment is based on the use of multiple antibiotics. Severe destructive and disseminated forms of TB such as meningitis and tuberculosis pericarditis require anti-inflammatory adjunct therapy to prevent excessive inflammation (Zumla et al 2014). The search for new molecules with dual anti-inflammatory and anti-mycobacterial activity has been encouraged for severe pulmonary TB therapy and 70% of the antibiotics in use are natural products or are derived from them (Singh & Macdonald 2010)

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