Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury

Abstract

Sakuranetin is the main isolate flavonoid from () leaves and exhibits anti-inflammatory and antioxidative activities. Acute respiratory distress syndrome is an acute failure of the respiratory system for which effective treatment is urgently necessary. This study investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Animals were treated with intranasal sakuranetin 30 min before or 6 h after instillation of LPS. Twenty-four hours after ALI was induced, lung function, inflammation, macrophages population markers, collagen fiber deposition, the extent of oxidative stress, and the expression of matrix metalloprotease-9 (MMP-9), tissue inhibitor of MMP-9 (TIMP-1) and NF-κB were evaluated. The animals began to show lung alterations 6 h after LPS instillation, and these changes persisted until 24 h after LPS administration. Preventive and therapeutic treatment with sakuranetin reduced the neutrophils in the peripheral blood and in the bronchial alveolar lavage. Sakuranetin treatment also reduced macrophage populations, particularly that of M1-like macrophages. In addition, sakurnaetin treatment reduced keratinocyte-derived chemokines (IL-8 homolog) and NF-κB levels, collagen fiber formation, MMM-9 and TIMP-1-positive cells, and oxidative stress in lung tissues compared with LPS animals treated with vehicle. Finally, sakuranetin treatment also reduced total protein, and the levels of TNF-α and IL-1β in the lung. This study shows that sakuranetin prevented and reduced pulmonary inflammation induced by LPS. Because sakuranetin modulates oxidative stress, the NF-κB pathway, and lung function, it may constitute a novel therapeutic candidate to prevent and treat ALI.

Protective Effects of Anti-IL17 on Acute Lung Injury Induced by LPS in Mice

“…There have been no previous studies analyzing the effects of anti-IL17 on oxidative stress in acute lung injury, but we speculate that the reduction in macrophages, TNF-α, IL-1β, and IL-17-positive cells seen in our study following IL-17 treatment could be responsible the reduction in oxidative stress, as demonstrated in other studies (Bittencourt-Mernak et al, 2017 ; Theodoro-Júnior et al, 2017 ; Camargo et al, 2018 ).…”

“…dose of 0.05 mL saline solution. After the procedure, the cervical incision was closed with a 5.0 silk suture, and the mice were returned to their cages (Bittencourt-Mernak et al, 2017 ).…”

“…Levels of TNF-α and IL-1β in the lung tissue were evaluated using ELISA in accordance with the manufacturer's instructions (Duo Set, R&D Systems, Minneapolis, MN, US) and previously used by (Bittencourt-Mernak et al, 2017 ).…”

“…The nuclear transcription factor kB (NFkB) is a transcription factor found in the cytoplasm. The increase activation of NFkB in alveolar macrophages of patients with established ALI/ARDS, resulting in pro-inflammatory cytokines increase, such as TNF-a, IL-1β, IL-6, IL-8, and oxidative stress activation (Bittencourt-Mernak et al, 2017 ). The continuous inflammation and activation of matrix metalloproteinase (MMP) 9 and 12 and tissue inhibitor of metalloproteinase 1 (TIMP-1) can be followed by alterations in the lung extracellular matrix, which can occur earlier in ARDS and contribute to decreased lung function (González-López and Albaiceta, 2012 ; Bittencourt-Mernak et al, 2017 ).…”

A Review on Sources and Pharmacological Aspects of Sakuranetin

“…Since sakuranetin modulates oxidative stress, the NF-κB pathway, and lung function, it may be a candidate for a novel therapeutic agent to prevent and treat acute lung injury (ALI). Bittencourt-Mernak et al investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced ALI in mice that were treated with this compound 30 min before or 6 h after instillation of LPS [72]. It was observed that the animals began to show lung alterations 6 h after LPS instillation and these changes persisted until 24 h after LPS administration.…”