Anti-inflammatory effect of Apo-9′-fucoxanthinone via inhibition of MAPKs and NF-kB signaling pathway in LPS-stimulated RAW 264.7 macrophages and zebrafish model

Kim, Eun-A; Kim, Seo-Young; Ye, Bo-Ram; Kim, Junseong; Ko, Seok‐Chun; Lee, Won Woo; Kim, Kil-Nam; Choi, Il‐Whan; Jung, Won‐Kyo; Heo, Soo‐Jin

doi:10.1016/j.intimp.2018.03.034

Cited by 73 publications

(42 citation statements)

References 36 publications

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“…However, the levels of these pro-inflammatory cytokines were reduced to a range from 96.0% to 58.4% after oral administration of metformin, SR, CR, LSC or HSC ( Figure 3 ). MAPK pathway plays an important role in the inflammatory process [ 22 ], so the key targets in this pathway were investigated in this study. As the qPCR results show in Figure 4 A–G, mRNA expressions of P38, ERK, c-jun, c-fos, JNK, IKK and P65 were significantly increased in the model group.…”

Section: Resultsmentioning

confidence: 99%

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

Cui

Qian

Jiang

et al. 2018

IJMS

182

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Aim Scutellariae Radix (SR) and Coptidis Rhizoma (CR) have often been combined to cure type 2 diabetes mellitus (T2DM) in the clinical practice for over thousands of years, but their compatibility mechanism is not clear. Mitogen-activated protein kinase (MAPK) signaling pathway has been suggested to play a critical role during the process of inflammation, insulin resistance, and T2DM. This study was designed to investigate their compatibility effects on T2DM rats and explore the underlying mechanisms by analyzing the metabolic profiling and MAPK/PI3K/Akt signaling pathway. Methods The compatibility effects of SR and CR were evaluated with T2DM rats induced by a high-fat diet (HFD) along with a low dose of streptozocin (STZ). Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to discover potential biomarkers. The levels of pro-inflammatory cytokines; biochemical indexes in serum, and the activities of key enzymes related to glycometabolism in liver were assessed by ELISA kits. qPCR was applied to examine mRNA levels of key targets in MAPK and insulin signaling pathways. Protein expressions of p65; p-p65; phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K); phosphorylated-PI3K (p-PI3K); protein kinase B (Akt); phosphorylated Akt (p-Akt) and glucose transporter 2 (Glut2) in liver were investigated by Western blot analysis. Results Remarkably, hyperglycaemia, dyslipidemia, inflammation, and insulin resistance in T2DM were ameliorated after oral administration of SR and CR, particularly their combined extracts. The effects of SR, CR, low dose of combined extracts (LSC) and high dose of combined extracts (HSC) on pro-inflammatory cytokine transcription in T2DM rats showed that the MAPK pathway might account for the phenomenon with down-regulation of MAPK (P38 mitogen-activated protein kinases (P38), extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK)) mRNA, and protein reduction in p-P65. While mRNA levels of key targets such as insulin receptor substrate 1 (IRS1), PI3K, Akt2, and Glut2 in the insulin signaling pathway were notably up-modulated, phosphorylations of PI3K, Akt, and expression of Glut2 were markedly enhanced. Moreover, the increased activities of phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), glucose 6-phosphatase (G6Pase), and glycogen phosphorylase (GP) were highly reduced and the decreased activities of glucokinase (GK), phosphofructokinase (PFK), pyruvate kinase (PK), and glycogen synthase (GS) in liver were notably increased after treatment. Further investigation indicated that the metabolic profiles of plasma and urine were clearly improved in T2DM rats. Fourteen potential biomarkers (nine in plasma and five in urine) were identified. After intervention, these biomarkers returned to normal level to some extent. Conclusion The results showed that SR, CR, and combined extract groups were normalized. The effects of combined extracts were more remarkable than single herb treatm...

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Section: Resultsmentioning

confidence: 99%

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

Cui

Qian

Jiang

et al. 2018

IJMS

182

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“…When NF‐κB is activated by LPS stimulation, IκBα is phosphorylated and ubiquitinated. Consequently, the NF‐κB transcription factor is translocated to the nucleus, which then regulates the secretion of pro‐inflammatory cytokines and enzymes (Kim et al, 2018). As shown in Figure 7a,b, the expression levels of p‐NF‐κB‐p65 and p‐IκBα were significantly enhanced in LPS‐treated RAW 264.7 cells (negative control).…”

Section: Resultsmentioning

confidence: 99%

Antioxidant and anti‐inflammatory effects of Lilium lancifolium bulbs extract

et al. 2020

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Lilium lancifolium is native to Northeast Asia and its bulbs have been used for medicinal treatment. Moreover, Japan has been using L. lancifolium bulbs more actively as food ingredients than Korea. Therefore, this study was to investigate the characteristics of Korean L. lancifolium bulbs, with respect to food component and functionality. As a result of proximate composition analysis, L. lancifolium bulbs have an abundant carbohydrate content. HPLC analysis indicated p‐coumaric acid and ferulic acid contents of Korean L. lancifolium extract were 1.14 ± 0.01, 1.46 ± 0.00 mg/g, but only p‐coumaric acid was less detected in Japanese extract. Also, Korean L. lancifolium bulbs extract exhibited significant antioxidant effects, as evaluated with antioxidant activity and compound, than Japanese extract. Furthermore, Korean L. lancifolium bulbs extract significantly inhibited pro‐inflammatory protein expressions through MyD88 dependent pathway. Therefore, these results suggested Korean L. lancifolium bulbs have the potential to being functional food ingredients. Practical applications Lilium lancifolium is a perennial plant belonging to the Liliaceae family. The storage organ of L. lancifolium is surrounded by several fleshy nodes at the base of the stem, called the bulb, which has been used as food or medicine to treat pneumonia and bronchitis. L. lancifolium is widely found in countries of Northeast Asia, such as Korea, Japan, and China, and its bulbs have been studied for presence of bioactive compounds that have important functional activities. The bioactive compounds in the L. lancifolium bulbs may vary from region to region. In this study, the difference observed in the contents of different bioactive compounds and the efficacy of anti‐inflammatory effects of L. lancifolium bulbs from different regions were consistent in this regard. As a comparative study of food materials by region, these L. lancifolium bulbs have the potential to be used as a food material for preventing inflammatory diseases.

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“…Although the activity of apo-13-fucoxanthinone ( 2 ) has not been studied extensively, the activity of apo-9′-fucoxanthinone ( 3 ) has recently drawn attention. For example, anti-inflammatory effects [32,33,34] and hair growth effects [35] have been reported. Detailed examination of the fucoxanthin when decomposed will lead to the discovery of new activity of the degradation products.…”

Section: Resultsmentioning

confidence: 99%

Degradation of Fucoxanthin to Elucidate the Relationship between the Fucoxanthin Molecular Structure and Its Antiproliferative Effect on Caco-2 Cells

2018

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Fucoxanthin has an antiproliferative effect on cancer cells, but its detailed structure–activity correlation has not yet been elucidated. To elucidate this correlation, fucoxanthin was degraded by ozonolysis. The degraded compounds of fucoxanthin obtained by ozonolysis were purified by HPLC and analyzed by NMR. The polyene chain of fucoxanthin was cleaved by ozonolysis, and the fucoxanthin was divided into two types of cyclohexyl derivatives, one with a β,γ-epoxy ketone group and the other with an allenic bond. In order to elucidate the structure–activity correlation, Caco-2 cells (human colorectal carcinoma) were treated with fucoxanthin degradation compounds. It was found that the entire structure of fucoxanthin is not essential for its antiproliferative effect and that even a partial structure exerts this effect.

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Anti-inflammatory effect of Apo-9′-fucoxanthinone via inhibition of MAPKs and NF-kB signaling pathway in LPS-stimulated RAW 264.7 macrophages and zebrafish model

Cited by 73 publications

References 36 publications

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway

Antioxidant and anti‐inflammatory effects of Lilium lancifolium bulbs extract

Degradation of Fucoxanthin to Elucidate the Relationship between the Fucoxanthin Molecular Structure and Its Antiproliferative Effect on Caco-2 Cells

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