Amomum tsao-ko Suppresses Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Macrophages via Nrf2-Dependent Heme Oxygenase-1 Expression

Abstract

Amomum tsao-ko Crevost et Lemaire, used as a spice in Asia, is an important source of Chinese cuisine and traditional Chinese medicines. A. tsao-ko is reported to exert a variety of biological and pharmacological activities, including anti-proliferative, anti-oxidative and neuroprotective effects. In this study, NNMBS227, consisting of the ethanol extract of A. tsao-ko, exhibited potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS227 in the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-1β) in LPS stimulated macrophages. NNMBS227 also inhibited the phosphorylation and degradation of IκB-α, as well as the nuclear translocation of nuclear factor kappa B (NF-κB) p65 caused by stimulation with LPS. In addition, NNMBS227 induced heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. Using tin protoporphyrin (SnPP), an HO activity inhibitor, we confirmed an association between the anti-inflammatory effects of NNMBS227 and the up-regulation of HO-1. These findings suggest that Nrf2-dependent increases in the expression of HO-1 induced by NNMBS227 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

Anti-inflammatory activity of Sanghuangporus sanghuang by suppressing the TLR4-mediated PI3K/AKT/mTOR/IKKβ signaling pathway

“…Furthermore, large amounts of neutrophils, as well as signicantly increased MPO activity can be found in microvessels in lung biopsy tissue sections. 26 This study reported similar ndings, indicating that neutrophils play an important role in the process of inammation caused by endotoxins. This is mainly because activated neutrophils can release large amounts of free radicals and proteases that promote pulmonary edema and microvascular permeability.…”

“…[21][22][23] However, an excessive or continuous inammatory response is closely related to the development of numerous diseases, such as acute lung injury (ALI), asthma, inammatory bowel disease, sepsis, or cancer. [24][25][26] In the process of development of these diseases, the inammatory response plays a critical role. Previous studies have found that at the site of inammation, macrophages release large amounts of proinammatory factors.…”

“…However, when cells are subjected to a variety of stimuli, the Nrf2 protein binds to the antioxidant response agent (ARE), and participates in the regulation of expression of related antioxidant enzymes, such as HO-1 and Trx-1, to remove oxidative stress. 22,26,47,50 Based on the results of this study, SS contains many polyphenolic compounds, which bear OH groups in their structure and exhibit free radical scavenging ability. Thus, it plays a synergistic role with antioxidant enzymes in eliminating LPS-induced ROS in tissues and therefore, alleviating lung tissue injury.…”

“…This shows that since the cytoskeleton may contract when epithelial cells are damaged, changes occur in the space within epithelial cells, leading to an increase in vascular permeability, and this subsequent increase in vascular permeability allows moisture in the blood to enter the interstitial space in the lungs more easily, resulting in formation of pulmonary edema. [26][27][28][29] In cases of more severe damage to epithelial cells, the accompanying changes in vascular permeability allow large protein molecules to enter the interstitial space in the lungs, causing an increase in the concentration of proteins in bronchial washings.…”

Anti-inflammatory Activity of <em>Sanghuangporus sanghuang</em> Mycelium

“…Tissue and cells have a series of defensive mechanisms in response to oxidative stress and injury to alleviate cell injury [38]. Nrf2 is currently considered a key transcription factor that regulates the defense of cells against oxidative injury [39][40][41][42]. Upon exposure to ROS or the indirect effect of phosphorylation, Nrf2 is released from Keap1 and translocated into the nucleus to bind to the ARE sequence, triggering the transcription of downstream phase II antioxidant genes, such as catalase (CAT), NADPH: quinone oxidoreductase (NQO1), superoxide dismutase (SOD), thioredoxin 1 (Trx-1), and heme oxygenase-1 (HO-1), and enhancing the antioxidant capacity of cells [12,13,43,44].…”