scholarly journals A Combination Extract of Gardeniae Fructus and Perillae Folium Exerts Anti-Inflammatory Effects on LPS-Activated RAW 264.7 Mouse Macrophages via an ER Stress-Induced CHOP Pathway

Processes ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1632
Author(s):  
Wansu Park

The aim of this study is to investigate the effects of a combination extract of Gardeniae Fructus and Perillae Folium (GP) on inflammatory reactions in lipopolysaccharide (LPS)-activated mouse macrophages RAW 264.7 cells. Multiplex cytokine assay, Fluo-4 calcium assay, Flow cytometry assay for phospho-P38 MAPK, and quantitative PCR were carried out. GP significantly reduced LPS-induced productions of macrophage inflammatory protein (MIP)-1α and monokine induced by gamma interferon (MIG) and release of intracellular calcium in LPS-activated RAW 264.7 cells. GP also significantly inhibited P38 MAPK phosphorylation and mRNA levels of Chop, Camk2a, Stat1, Stat3, Jak2, Fas, Nos2, and Ptgs2 in LPS-activated RAW 264.7 cells. Taken together, this study represents that GP exerts anti-inflammatory effects on LPS-activated RAW 264.7 cells via ER stress-induced CHOP pathway.

Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1050
Author(s):  
Hyun-Ju Kim ◽  
Inamullah Khan ◽  
Adnan Shahidullah ◽  
Syed Muhammad Ashhad Halimi ◽  
Abdur Rauf ◽  
...  

Diospyrin, plant-derived bisnaphthoquinonoid, is known to have anticancer activity. However, pharmacological activity of diospyrin on viral infection is not well known. We investigated effects of diospyrin on macrophages induced by polyinosinic-polycytidylic acid (poly I:C), a mimic of double-stranded viral RNA. Various cytokines, intracellular calcium, nitric oxide (NO), phosphorylated p38 MAPK, and phosphorylated ERK1/2 as well as mRNA expressions of transcription factors were evaluated. Diospyrin significantly reduced NO production, granulocyte-macrophage colony-stimulating factor production, and intracellular calcium release in poly I:C-induced RAW 264.7. The phosphorylation of p38 MAPK and ERK1/2 was also significantly suppressed. Additionally, diospyrin inhibited mRNA levels of nitric oxide synthase 2, C/EBP homologous protein (CHOP), calcium/calmodulin dependent protein kinase II alpha, signal transducers and activators of transcription 1 (STAT1), STAT3, STAT4, Janus kinase 2, first apoptosis signal receptor, c-Jun, and c-Fos in poly I:C-induced RAW 264.7. Taken together, this study represents that diospyrin might have the inhibitory activity against viral inflammation such as excessive production of inflammatory mediators in poly I:C-induced RAW 264.7 via ER stress-induced calcium-CHOP pathway.


2020 ◽  
Vol 34 ◽  
pp. 205873842095494
Author(s):  
Zhe Yang ◽  
Qin Yin ◽  
Opeyemi Joshua Olatunji ◽  
Yan Li ◽  
Shu Pan ◽  
...  

Introduction: Alpha-mangostin (MAN) possesses a wide variety of pharmacological effects. In this study, we investigated its effect on cholinergic anti-inflammatory pathway (CAP), and tested if CAP regulation was involved in the therapeutic action on acute lung injury (ALI). Methods: Male Sprague Dawley rats were pre-treated with MAN (40 mg/kg) for 3 days and ALI was induced with an intraperitoneal injection of lipopolysaccharide (LPS). Certain rats received monolateral vagotomy or sham surgery. The effects on inflammatory reactions and relevant pathways in ALI rats or LPS pre-treated RAW 264.7 cells were investigated by histological, immunohistochemical, immunoblotting, RT-qPCR, and immunofluorescence assays, while levels of proinflammatory cytokines, acetylcholine (Ach) and the enzymatic activity of acetylcholinesterase (AchE) were determined by corresponding quantitative kits. Results: Oral administration of MAN reduced the severity of ALI, while vagotomy surgery antagonized this effect. MAN restored the decline in α7 nicotinic acetylcholine receptor (α7nAchR) in the lungs of ALI rats, and promoted the expression of α7nAchR and choline acetyltransferase (CHAT) in RAW 264.7 cells. Although AchE expression was barely affected by MAN at 5 μg/ml, its catalytic activity was reduced by almost 95%. Extracellular rather than intracellular Ach was notably raised shortly after MAN treatment. Furthermore, MAN at 5 μg/ml effectively inhibited LPS-induced increase in phosphorylation and nucleus translocation of p65 subunit, and secretion of TNF-α and IL-1β, which was then offset by methyllycaconitine citrate hydrate. Conclusion: MAN activated CAP by increasing peripheral Ach and up-regulating α7nAchR expression, which eventually led to NF-κB inhibition and remission of acute inflammations.


Biomedicines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 11 ◽  
Author(s):  
Adnan Shahidullah ◽  
Ji-Young Lee ◽  
Young-Jin Kim ◽  
Syed Muhammad Ashhad Halimi ◽  
Abdur Rauf ◽  
...  

Diospyrin is a bisnaphthoquinonoid medicinal compound derived from Diospyros lotus, with known anti-cancer, anti-tubercular, and anti-leishmanial activities against Leishmania donovani. However, the effects of diospyrin on lipopolysaccharide (LPS)-induced macrophage activation and inflammation are not fully reported. In this study, the anti-inflammatory effects of diospyrin on LPS-induced macrophages were examined. Diospyrin showed no toxicity in RAW 264.7 at concentrations of up to 10 μM. Diospyrin moderated the production of nitric oxide (NO), monocyte chemotactic protein-1, macrophage inflammatory protein-1β, interleukin (IL)-6, IL-10, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, vascular endothelial growth factor, leukemia inhibitory factor, and RANTES/CCL5, as well as calcium release in LPS-induced RAW 264.7, at concentrations of up to 10 μM significantly (p < 0.05). Diospyrin also significantly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and mRNA expression of C/EBP homologous protein (CHOP), as well as tumor necrosis factor receptor superfamily member 6 (Fas), in LPS-induced RAW 264.7 cells at concentrations of up to 10 μM (p < 0.05). Diospyrin exhibits anti-inflammatory properties mediated via inhibition of NO, and cytokines in LPS-induced mouse macrophages via the ER-stressed calcium-p38 MAPK/CHOP/Fas pathway.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Kwang-Il Park ◽  
Sang-Rim Kang ◽  
Hyeon-Soo Park ◽  
Do Hoon Lee ◽  
Arulkumar Nagappan ◽  
...  

Lonicera japonica THUNB., which abundantly contains polyphenols, has been used as a traditional medicine for thousands of years in East Asian countries because of the anti-inflammation properties. This study aimed to investigate the anti-inflammatory mechanism of polyphenol components isolated from KoreaL. japonica T.by nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathway. Polyphenols significantly decreased lipopolysaccharide- (LPS-) induced mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as mRNA expression of tumor necrosis factor-alpha, interleukin- (IL-) 1β, and IL-6. Moreover, polyphenols inhibited nuclear translocation of NF-κB p65, phosphorylation/degradation of the inhibitor ofκB, and phosphorylation of p38 MAPK, whereas the extracellular signal-regulated kinase and Janus N-terminal kinase were not affected. These results indicate that polyphenol components isolated from KoreaL. japonica T.should have anti-inflammatory effect on LPS-stimulated RAW 264.7 cells through the decrease of proinflammatory mediators expression by suppressing NF-κB and p38 MAPK activity.


Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1859 ◽  
Author(s):  
Dawoon Jeong ◽  
Guang-zhi Dong ◽  
Hwa Jin Lee ◽  
Jae-Ha Ryu

In relation to anti-inflammatory agents from medicinal plants, we have isolated three compounds from Atractylodes macrocephala; 1, 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione; 2, 1-acetoxy-tetradeca-6E,12E-diene-8, 10-diyne-3-ol; 3, 1,3-diacetoxy-tetradeca-6E, 12E-diene-8, 10-diyne. Compounds 1–3 showed concentration-dependent inhibitory effects on production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Western blotting and RT-PCR analyses demonstrated that compounds 1–3 suppressed the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, compounds 1–3 inhibited transcriptional activity of nuclear factor-κB (NF-κB) and nuclear translocation of NF-κB in LPS-activated RAW 264.7 cells. The most active compound among them, compound 1, could reduce the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and suppress the phosphorylation of MAPK including p38, JNK, and ERK1/2. Taken together, these results suggest that compounds 1–3 from A. macrocephala can be therapeutic candidates to treat inflammatory diseases.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyun-Ju Kim ◽  
Young-Jin Kim ◽  
Wansu Park

AbstractBerberine is a well-known quaternary ammonium salt that is usually found in the roots of such plants as Phellodendron amurense and Coptis chinensis. However, the effects of berberine on double-stranded RNA (dsRNA)-induced macrophages have not been fully reported. In this study, we examined the anti-inflammatory effects of berberine on dsRNA [polyinosinic-polycytidylic acid; poly I:C]-induced macrophages. Levels of nitric oxide (NO), Prostaglandin E2 (PGE2), first apoptosis signal receptor (Fas; CD95), cytokines, intracellular calcium, phosphorylated I-kappa-B-alpha (IkB-α), phosphorylated p38 mitogen-activated protein kinase (MAPK), phosphorylated ERK1/2, phosphorylated signal transducer and activated transcription 3 (STAT3), and mRNA expression of inflammatory genes in poly I:C-induced RAW 264.7 mouse macrophages were evaluated. Berberine significantly inhibited the production of NO, PGE2, Fas, GM-CSF, LIF, LIX, RANTES, and MIP-2 as well as calcium release in poly I:C-induced RAW 264.7 cells at concentrations of up to 50 μM. Berberine also significantly inhibited the phosphorylation of p38 MAPK, ERK1/2, IkB-α, and STAT3 in poly I:C-induced RAW 264.7 cells. Additionally, berberine significantly decreased the mRNA expressions of Chop (GADD153), Stat1, Stat3, and Fas in poly I:C-induced RAW 264.7 cells. Taken together, berberine has anti-inflammatory properties related to its inhibition of NO, PGE2, Fas, GM-CSF, LIF, LIX, RANTES, and MIP-2 in dsRNA-induced macrophages via the endoplasmic reticulum stress-related calcium-CHOP/STAT pathway.


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