scholarly journals Immunomodulatory Properties of a γ-Aminobutyric Acid-Enriched Strawberry Juice Produced by Levilactobacillus brevis CRL 2013

2020 ◽  
Vol 11 ◽  
Author(s):  
Pablo G. Cataldo ◽  
Julio Villena ◽  
Mariano Elean ◽  
Graciela Savoy de Giori ◽  
Lucila Saavedra ◽  
...  
Keyword(s):  
Current Trend ◽  
Starter Culture ◽  
Aminobutyric Acid ◽  
Inflammatory Factors ◽  
Food Ingredient ◽  
Protein Amino Acid ◽  
Anti Inflammatory ◽  
Strawberry Juice

Gamma-aminobutyric acid (GABA) plays a key role in mammals as the major inhibitory neurotransmitter of the central nervous system. Although GABA may not be able to cross the human blood-brain barrier, it was approved as a food ingredient because of its benefits to the host after oral administration including anti-hypertensive, anti-depressant and anti-inflammatory activities. Considering the current trend toward the development of new functional and natural products and that microbial fermentation is one of the most promising methods to produce this non-protein amino acid, the in situ production of GABA through fermentation of strawberry and blueberry juices by the efficient GABA producer strain, Levilactobacillus brevis (formerly known as Lactobacillus brevis) CRL 2013, was evaluated. A high GABA production (262 mM GABA) was obtained after fermenting strawberry juice supplemented with yeast extract for 168 h, being GABA yield significantly higher in strawberry juices than in the blueberry ones. Thus, GABA-enriched fermented strawberry juice (FSJ) was selected to carry out in vivo and in vitro studies. The in vitro functional analysis of the GABA-enriched FSJ demonstrated its ability to significantly decrease the expression of cox-2 gene in LPS stimulated RAW 264.7 macrophages. In addition, in vivo studies in mice demonstrated that both, L. brevis CRL 2013 and the GABA-enriched FSJ were capable of reducing the levels of peritoneal, intestinal and serum TNF-α, IL-6, and CXCL1, and increasing IL-10 and IFN-γ in mice exposed to an intraperitoneal challenge of LPS. Of note, the GABA-enriched FSJ was more efficient than the CRL 2013 strain to reduce the pro-inflammatory factors and enhance IL-10 production. These results indicated that the CRL 2013 strain exerts anti-inflammatory effects in the context of LPS stimulation and that this effect is potentiated by fermentation. Our results support the potential use of L. brevis CRL 2013 as an immunomodulatory starter culture and strawberry juice as a remarkable vegetable matrix for the manufacture of GABA-enriched fermented functional foods capable of differentially modulating the inflammatory response triggered by TLR4 activation.

Advances in Anti-inflammatory Activity, Mechanism and Therapeutic Application of Ursolic Acid

2021 ◽  
Vol 21 ◽  
Author(s):  
Mingzhu Luan ◽  
Huiyun Wang ◽  
Jiazhen Wang ◽  
Xiaofan Zhang ◽  
Fenglan Zhao ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Inflammatory Activity ◽  
Inflammatory Factors ◽  
Inflammatory Stimuli ◽  
Bowel Diseases ◽  
Anti Inflammatory

: In vivo and in vitro studies reveal that ursolic acid (UA) is able to counteract endogenous and exogenous inflammatory stimuli, and has favorable anti-inflammatory effects. The anti-inflammatory mechanisms mainly include decreasing the release of histamine in mast cells, suppressing the activities of lipoxygenase, cyclooxygenase and phospholipase, and reducing the production of nitric oxide and reactive oxygen species, blocking the activation of signal pathway, down-regulating the expression of inflammatory factors, and inhibiting the activities of elastase and complement. These mechanisms can open up new avenues for the scientific community to develop or improve novel therapeutic approaches to tackle inflammatory diseases such as arthritis, atherosclerosis, neuroinflammation, liver diseases, kidney diseases, diabetes, dermatitis, bowel diseases, cancer. The anti-inflammatory activity, the anti-inflammatory mechanism of ursolic acid and its therapeutic applications are reviewed in this paper.

scholarly journals Dangguijakyak-San Protects against 1-Methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-Induced Neuronal Damage via Anti-Inflammatory Action

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Deok-Sang Hwang ◽  
Hyo Geun Kim ◽  
Jun-Bock Jang ◽  
Myung Sook Oh
Keyword(s):  
Neuronal Damage ◽  
Cell Damage ◽  
Substantia Nigra Pars Compacta ◽  
Inflammatory Factors ◽  
Dopaminergic Cell ◽  
Therapeutic Implications ◽  
Anti Inflammatory ◽  
Inflammatory Action

Dangguijakyak-san (DJS), a famous traditional Korean multiherbal medicine, has been used to treat gynecological and neuro-associated disease. Recent studies demonstrated that DJS has multiple bioactivities including neuroprotection. In the present study, we were to investigate the effect of DJS and its mechanism in anin vitroandin vivomodel of Parkinson’s disease (PD). In primary mesencephalic culture system, DJS attenuated the dopaminergic cell damage induced by 1-methyl-4-phenylpyridine toxicity, and it inhibited production of inflammatory factors such as tumor necrosis factorα(TNF-α), nitric oxide (NO), and activation of microglial cells. Then, we confirmed the effect of DJS in a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the pole test, DJS at 50 mg/kg/day for 5 days showed increase of motor activity showing shortened time to turn and locomotor activity compared with the MPTP only treated mice. In addition, DJS significantly protected nigrostriatal dopaminergic neuron from MPTP stress. Moreover, DJS showed inhibition of gliosis in the substantia nigra pars compacta. These results have therapeutic implications for DJS in the treatment of PD via anti-inflammatory effects.

Ulinastatin Activated The ERK5/Mer Signaling Pathway To Promote Macrophage Efferocytosis And Ameliorate Lung Inflammation

2021 ◽  
Author(s):  
Jinju Li ◽  
Rongge Shao ◽  
Qiuwen Xie ◽  
XueKe Du
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Lung Inflammation ◽  
Raw264.7 Cells ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
Dependent Manner ◽  
Anti Inflammatory

Abstract Purpose:Ulinastatin (UTI) is an endogenous protease inhibitor with potent anti-inflammatory, antioxidant and organ protective effects. The inhibitor has been reported to ameliorate inflammatory lung injury but precise mechanisms remain unclear. Methods: An in vivo model of lung injury has been constructed by intratracheal infusion of lipopolysaccharide (LPS). The number of neutrophils and the phagocytosis of apoptotic neutrophils were observed by Diff- Quick method. Lung injury was observed by HE staining .BALF cells were counted by hemocytometer and concentrations of protein plus inflammatory factors were measured with a BCA test kit. During in vitro experiments, RAW264.7 cells were pretreated with UTI (1000 and 5000U/ mL), stained with CellTrackerTM Green B0DIPYTM and HL60 cells added with UV-induced apoptosis and PKH26 Red staining. The expression of ERK5\Mer related proteins was detected by western blot and immunofluorescence.Results: An in vivo model of lung injury has been constructed by intratracheal infusion of lipopolysaccharide (LPS). UTI treatment enhanced the phagocytotic effect of mouse alveolar macrophages on neutrophils, alleviated lung lesions, decreased the pro-inflammatory factor and total protein content of BALF and increased levels of anti-inflammatory factors. in vitro experiments ，UTI enhanced the phagocytosis of apoptotic bodies by RAW264.7 cells in a dose-dependent manner. Increased expression levels of ERK5 and Mer by UTI were shown by Western blotting and immunofluorescence.Conclusions: UTI mediated the activation of the ERK5/Mer signaling pathway, enhanced phagocytosis of neutrophils by macrophages and improved lung inflammation. The current study indicates potential new clinical approaches for accelerating the recovery from lung inflammation.

scholarly journals Hordenine Protects Against Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiyue Zhang ◽  
Li Du ◽  
Jinrong Zhang ◽  
Chunyan Li ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Protein Kinase ◽  
Lung Injury ◽  
Biological Activities ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Anti Inflammatory

Acute lung injury (ALI) is a respiratory disease that leads to death in severe cases. Hordenine (Hor), a barley-derived natural product, has various biological activities, including anti-inflammatory, and anti-oxidation activities. We investigated the effect of Hor on lipopolysaccharide-induced ALI and its potential mechanism. The anti-inflammatory effects of Hor were detected using in vivo and in vitro models by enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blotting, and molecular docking simulations. Hor inhibited increases in the levels of inflammatory factors both in vivo and in vitro, and its anti-inflammatory effect inhibited activation of protein kinase B, nuclear factor-κB, and mitogen-activated protein kinase signaling. Hor alleviated lipopolysaccharide-induced ALI by inhibiting inflammatory cytokine increases in vivo and in vitro and shows potential for preventing inflammatory disease.

scholarly journals Perilla Leaf Extract (PLE) Attenuates COPD Airway Inflammation via the TLR4/Syk/PKC/NF-κB Pathway In Vivo and In Vitro

2022 ◽  
Vol 12 ◽  
Author(s):  
Jiqiao Yuan ◽  
Xuyu Li ◽  
Nan Fang ◽  
Ping Li ◽  
Ziqian Zhang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Airflow Limitation ◽  
Interleukin 4 ◽  
Inflammatory Factors ◽  
Chronic Obstructive ◽  
Potential Mechanism ◽  
Tnf Α ◽  
Anti Inflammatory

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease characterized by persistent airflow limitation but still lacking effective treatments. Perilla frutescens (L.) Britt., an important traditional medicinal plant with excellent antioxidant and anti-inflammatory properties, is widely used for the treatment of respiratory disease in China. However, its protective activity and mechanism against COPD airway inflammation have not been fully studied. Here, the anti-inflammatory effects of the PLE were investigated, and its underlying mechanisms were then elucidated. The presented results suggested a notable effect of the PLE on airway inflammation of COPD, by significantly ameliorating inflammatory cell infiltration in lung tissue, lessening leukocytes (lymphocytes, neutrophils, and macrophages) and inflammatory mediators (interleukin 4 (IL-4), IL-6, IL-17A, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α)) in the bronchoalveolar lavage fluid (BALF) of cigarette smoke (CS)/lipopolysaccharide (LPS)-induced COPD mice in vivo and inhibiting the production of inflammatory factors (nitric oxide (NO), IL-6, and TNF-α) and intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells in vitro. For further extent, PLE treatment significantly suppressed the expression and phosphorylation of TLR4, Syk, PKC, and NF-κB p65 in vivo and their mRNA in vitro. Subsequently, by co-treating with their inhibitors in vitro, its potential mechanism via TLR4/Syk/PKC/NF-κB p65 signals was disclosed. In summary, the obtained results indicated a noteworthy effective activity of the PLE on COPD inflammation, and partly, the TLR4/Syk/PKC/NF-κB p65 axis might be the potential mechanism.

scholarly journals Amla (Emblica officinalisGaertn.) extract inhibits lipopolysaccharide-induced procoagulant and pro-inflammatory factors in cultured vascular endothelial cells

2013 ◽  
Vol 110 (12) ◽  
pp. 2201-2206 ◽  
Author(s):  
Theertham Pradyumna Rao ◽  
Takayuki Okamoto ◽  
Nobuyuki Akita ◽  
Tatsuya Hayashi ◽  
Naomi Kato-Yasuda ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Inflammatory Factors ◽  
Target Cells ◽  
Fruit Extract ◽  
Leucocyte Adhesion ◽  
Anti Inflammatory

Amla (Emblica officinalisGaertn.) has been used for many centuries in traditional Indian Ayurvedic formulations for the prevention and treatment of many inflammatory diseases. The present study evaluated the anti-inflammatory and anticoagulant properties of amla fruit extract. The amla fruit extract potentially and significantly reduced lipopolysaccharide (LPS)-induced tissue factor expression and von Willebrand factor release in human umbilical vein endothelial cells (HUVEC)in vitroat clinically relevant concentrations (1–100 μg/ml). In a leucocyte adhesion model of inflammation, it also significantly decreased LPS-induced adhesion of human monocytic cells (THP-1) to the HUVEC, as well as reduced the expression of endothelial-leucocyte adhesion molecule-1 (E-selectin) in the target cells. In addition, thein vivoanti-inflammatory effects were evaluated in a LPS-induced endotoxaemia rat model. Oral administration of the amla fruit extract (50 mg/kg body weight) significantly decreased the concentrations of pro-inflammatory cytokines, TNF-α and IL-6 in serum. These results suggest that amla fruit extract may be an effective anticoagulant and anti-inflammatory agent.

scholarly journals Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

2021 ◽  
Vol 12 ◽  
Author(s):  
Huan Xia ◽  
Yitong Liu ◽  
Guiyang Xia ◽  
Yi Liu ◽  
Sheng Lin ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Stage ◽  
Critical Role ◽  
Isoquinoline Alkaloid ◽  
Inflammatory Factors ◽  
Skin Wound Healing ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Macrophages play a critical role in innate and adaptive immunity, and the regulation of macrophage function in inflammatory disease treatment has been widely studied. Litsea cubeba is an important Chinese medicinal plant used for the treatment of inflammatory diseases. However, the inflammatory bioactive ingredients in L. cubeba and underlying molecular mechanisms are poorly understood. Herein, we first obtained and elucidated a novel isoquinoline alkaloid, Litcubanine A (LA), from L. cubeba. An in vitro study indicated that LA could significantly inhibit LPS-induced activation of inflammatory macrophages via the NF-κB pathway, leading to the decrease of inflammatory factors including iNOS, TNF-α, and IL-1β. Moreover, LA showed an inhibiting effect on the expression of NO in macrophages by directly binding to iNOS protein. Molecular simulation docking also demonstrated that active LA created an interaction with GLU 371 residue of iNOS via attractive charge derived from the N→O group, revealing its highly selective inhibition toward iNOS. By using the IκK inhibitor and iNOS inhibitor, these two regulatory targets of LA on inflammatory macrophages were verified in vitro. Finally, by using a caudal fin resection model in zebrafish larvae, and the skin wound healing model in mice, we proved in vivo that LA down-regulated the secretion of local inflammatory factors by inhibiting macrophage recruitment and activation at the early stage of the injury. Collectively, our study demonstrated that the novel isoquinoline alkaloid LA suppresses LPS-induced activation of inflammatory macrophages by modulating the NF-κB pathway, suggesting that inflammatory macrophage activation pathway is an effective target for inflammation treatment, and LA is a new pharmacophore for the development of novel and effective anti-inflammatory agents to regulate local macrophages.

scholarly journals DJ-1 Regulates Microglial Polarization Through P62-Mediated TRAF6/IRF5 Signaling in Cerebral Ischemia-Reperfusion

2020 ◽  
Vol 8 ◽  
Author(s):  
Tingting Wang ◽  
Na Zhao ◽  
Li Peng ◽  
Yumei Li ◽  
Xiaohuan Huang ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Macrophage Polarization ◽  
Specific Inhibitor ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Inflammatory Factors ◽  
Microglial Polarization ◽  
Anti Inflammatory

The polarization of microglia/macrophage, the resident immune cells in the brain, plays an important role in the injury and repair associated with ischemia-reperfusion (I/R). Previous studies have shown that DJ-1 has a protective effect in cerebral I/R. We found that DJ-1 regulates the polarization of microglial cells/macrophages after cerebral I/R and explored the mechanism by which DJ-1 mediates microglial/macrophage polarization in cerebral I/R. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were used to simulate cerebral I/R in vivo and in vitro, respectively. DJ-1 siRNA and the DJ-1-based polypeptide ND13 were used to produce an effect on DJ-1, and the P62-specific inhibitor XRK3F2 was used to block the effect of P62. Enhancing the expression of DJ-1 induced anti-inflammatory (M2) polarization of microglia/macrophage, and the expression of the anti-inflammatory factors IL-10 and IL-4 increased. Interference with DJ-1 expression induced pro-inflammatory (M1) polarization of microglia/macrophage, and the expression of the proinflammatory factors TNF-α and IL-1β increased. DJ-1 inhibited the expression of P62, impeded the interaction between P62 and TRAF6, and blocked nuclear entry of IRF5. In subsequent experiments, XRK3F2 synergistically promoted the effect of DJ-1 on microglial/macrophage polarization, further attenuating the interaction between P62 and TRAF6.

scholarly journals Protocatechuic aldehyde from Salvia miltiorrhiza exhibits an anti-inflammatory effect through inhibiting MAPK signalling pathway

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shuang Wu ◽  
Qingyu Wang ◽  
Jinquan Wang ◽  
Baoyu Duan ◽  
Qihe Tang ◽  
...  
Keyword(s):  
Salvia Miltiorrhiza ◽  
Inflammatory Factors ◽  
Histopathological Analysis ◽  
Mapk Signalling Pathway ◽  
Aerial Parts ◽  
Protocatechuic Aldehyde ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Background The aerial parts of Salvia miltiorrhiza, which was considered to be the waste part and discarded during the root harvest, is rich in protocatechuic aldehyde (PAI). This study investigated the health-promoting effects of extracts and PAI from the aerial parts of Salvia miltiorrhiza, including its anti-inflammatory effects and the underlying mechanisms of action in vitro and in vivo. Method Purification of the sample paste of Salvia miltiorrhiza was accomplished using HPLC analysis. TheMTT (Methylthiazolyldiphenyl-tetrazolium bromide) assay was employed to determine the cell viability. The production of inflammatory factors was detected by ELISA assays. The histopathological analysis was used to analyse the lungs and livers of mice treated with PAI. Western blot was performed to reveal the mechanism of PAI in anti-inflammatory. Results The extracts and PAI from the aerial parts of Salvia miltiorrhiza inhibited TNF-α, IL-6 production and promoted the production of IL-10 in vivo in mice and in vitro in the macrophage cell line RAW264.7. NF-κB and MAPKs kinase phosphorylation were also suppressed by PAI in vivo and in vitro, indicating that PAI exhibited an anti-inflammatory effect. Conclusion These findings suggest that the aerial parts of Salvia miltiorrhiza extract may serve as potential protective agents for inflammatory.

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