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
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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