An Integrated Proteomics and Bioinformatics Approach Reveals the Anti-inflammatory Mechanism of Carnosic Acid

Abstract

Drastic macrophages activation triggered by exogenous infection or endogenous stresses is thought to be implicated in the pathogenesis of various inflammatory diseases. Carnosic acid (CA), a natural phenolic diterpene extracted from Salvia officinalis plant, has been reported to possess anti-inflammatory activity. However, its role in macrophages activation as well as potential molecular mechanism is largely unexplored. In the current study, we sought to elucidate the anti-inflammatory property of CA using an integrated approach based on unbiased proteomics and bioinformatics analysis. CA significantly inhibited the robust increase of nitric oxide and TNF-α, downregulated COX2 protein expression, and lowered the transcriptional level of inflammatory genes including Nos2, Tnfα, Cox2, and Mcp1 in LPS-stimulated RAW264.7 cells, a murine model of peritoneal macrophage cell line. The LC-MS/MS-based shotgun proteomics analysis showed CA negatively regulated 217 LPS-elicited proteins which were involved in multiple inflammatory processes including MAPK, nuclear factor (NF)-κB, and FoxO signaling pathways. A further molecular biology analysis revealed that CA effectually inactivated IKKβ/IκB-α/NF-κB, ERK/JNK/p38 MAPKs, and FoxO1/3 signaling pathways. Collectively, our findings demonstrated the role of CA in regulating inflammation response and provide some insights into the proteomics-guided pharmacological mechanism study of natural products.

Rosmarinus officinalis L. (rosemary) as therapeutic and prophylactic agent

“…Antitumor[176]d. Anti-inflammatory[177]e. Inhibitory effect of digestive enzymes (lipase, α-amylase, and α-glucosidase)[178]f.…”

Based on Proteomics Reveals the Anti-inflammatory Mechanism of Phillygenin by Inhibition NF-κB Pathway

“…Nowadays, the proteomics technology has become an important support for the rapid development of modern biotechnology. Proteomics essentially refers to studying the characteristics of proteins on a large scale and understanding key pathways through information network analysis [31]. In this work, a comprehensive approach combining proteomics and pharmacological experimental studies is used to research the anti-in ammatory effects of PHI and mechanism of action.…”

Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway

“…In the current study, we reported that isosibiricin exerts a significant anti-neuroinflammatory effect on LPS-treated BV-2 cells. LPS is a common inflammation inducer that is used to investigate different types of inflammatory pathology, such as tissue inflammation [ 23 ], vascular inflammation [ 34 ] and myocarditis [ 35 ]. Dopaminergic neurons play an important role in the pathological process of Parkinson’s disease [ 36 ], and LPS is widely used to induce neuroinflammation to establish models of Parkinson’s disease.…”

“…A single cycle was carried out at 95 °C for 30 s, 58 °C for 30 s and 63 °C for 30 s, and this cycle was repeated 40 times. The relative transcriptional levels of DRD1 and DRD2 normalized to those of GAPDH was calculated by the comparative 2 −ΔΔCT method [ 23 ].…”