Lingonberry Fruit Ethanol Extract Ameliorates DSS-Induced Ulcerative Colitis In Vivo and In Vitro

Ulcerative colitis (UC) is an inflammatory chronic intestinal disease with pathological characteristics, including imbalanced immune function and the overexpression of inflammatory cytokines and mediators. Inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6) were oversecreted in UC condition. Cyclooxygenase (COX)-2 and prostaglandin (PG)E2 were also overexpressed in colon tissue. Lingonberry (LB) (Vaccinium vitis-idaea L.) possesses pharmacological activities, including anti-oxidant, anti-cancer, and anti-obesity effects. To explore LB’s effects on UC, BALB/c mice were administered with 3% (w/v) dextran sulphate sodium (DSS) and LB extract (70% ethanol) orally for nine days. The severity of UC was measured by the change in body weight and colon length. To evaluate LB’s regulatory effect on inflammatory cytokines, the enzyme-linked immunosorbent assay (ELISA) kit was used to measure the inflammatory cytokines in mouse serum. Mouse peritoneal microphages were used to detect LB’s anti-inflammatory effect. The results showed that LB treatment ameliorated less weight loss and longer colon length compared to the DSS-treated group. LB treatment also ameliorated the secretion of inflammatory cytokines. These results indicated that LB has potential as an herbal medicine to treat UC.

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Improved Promotion of M2 Microglial Polarization by Zuogui Jiangtang Jieyu Formulation in Diabetes-Related Depression

10.21203/rs.3.rs-335174/v1 ◽

2021 ◽

Author(s):

xiuli zhang ◽

Dahua Wu ◽

Dandan Li ◽

Jian Liu ◽

Chang Lei ◽

...

Keyword(s):

Inflammatory Cytokines ◽

High Glucose ◽

Neuroprotective Effect ◽

Enzyme Linked Immunosorbent Assay ◽

Mild Stress ◽

Microglial Polarization ◽

M2 Polarization ◽

M1 Polarization

Abstract Background Zuogui Jiangtang Jieyu formulation (ZGJTJY) is a Chinese polyherbal prescription for diabetes-related depression (DD). The mechanism underlying hippocampal M1/M2 polarization in DD and the ZGJTJY treatment effects remain unclear. This study aimed to investigate M1/M2 microglial polarization in the hippocampus of DD rats and HAPI (highly aggressively proliferating immortalized) cells simulating the DD state, as well as to examine the ZGJTJY intervention effects, both in vivo and in vitro. Methods We subjected Sprague Dawley rats to a high-fat diet, streptozotocin, and unpredictable chronic mild stress; subsequently, we orally administered ZGJTJY. HAPI cells were induced using high glucose and corticosterone; subsequently, ZGJTJY-containing serum was added to examine changes in M1/M2 microglial polarization. Moreover, metformin combined with fluoxetine (DMGB/F) was used as a positive drug for evaluating the ZGJTJY intervention. Laser confocal scanning was used to examine the microglial morphology. Further, real-time PCR was used to determine M1 markers (MHCII, iNOS, MCP-1, CD11b), M2 markers (Arg1, Mrc1, Ym1), pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and anti-inflammatory cytokines (IL-4, IL-10). Additionally, an enzyme-linked immunosorbent assay was used to examine inflammatory cytokines. Results There was significant activation of M1 polarization in the hippocampus of DD rats and HAPI cells induced using high glucose and corticosterone. Compared with DMGB/F, ZGJTJY inhibited and promoted M1 and M2 polarization, respectively; moreover, it decreased the M1-to-M2 polarization ratio both in vivo and in vitro. Conclusions The study indicated that hippocampal M1 polarization is crucially involved in DD pathogenesis; moreover, there is a need for further research on the neuroprotective effect of Chinese medicine associated with M2-polarized microglia.

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Tryptanthrin exerts anti-breast cancer effects both in vitro and in vivo through modulating the inflammatory tumor microenvironment

Acta Pharmaceutica ◽

10.2478/acph-2021-0020 ◽

2021 ◽

Vol 71 (2) ◽

pp. 245-266

Author(s):

Qingfang Zeng ◽

Cairong Luo ◽

Junlae Cho ◽

Donna Lai ◽

Xiangchun Shen ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

Colony Formation ◽

Migration And Invasion ◽

Mouse Serum ◽

Enzyme Linked Immunosorbent Assay ◽

Tumor Tissues ◽

Mcf 7

AbstractTryptanthrin is an indole quinazoline alkaloid from the indigo-bearing plants, such as Isatis indigotica Fort. Typically, this natural compound shows a variety of pharmacological activities such as antitumor, antibacterial, anti-inflammatory and antioxidant effects. This study was conducted to assess the antitumor activity of tryptanthrin in breast cancer models both in vitro and in vivo, and to explore the important role of the inflammatory tumor microenvironment (TME) in the antitumor effects of tryptanthrin. Human breast adenocarcinoma MCF-7 cells were used to assess the antitumor effect of tryptanthrin in vitro. MTT assay and colony formation assay were carried out to monitor the antiproliferative effect of tryptanthrin (1.56~50.0 μmol L−1) on inhibiting the proliferation and colony formation of MCF-7 cells, respectively. The migration and invasion of MCF-7 cells were evaluated by wound healing assay and Transwell chamber assay, respectively. Moreover, the 4T1 murine breast cancer model was established to examine the pharmacological activity of tryptanthrin, and three groups with different doses of tryptanthrin (25, 50 and 100 mg kg−1) were set in study. Additionally, tumor volumes and organ coefficients were measured and calculated. After two weeks of tryptanthrin treatment, samples from serum, tumor tissue and different organs from tumor-bearing mice were collected, and the enzyme-linked immunosorbent assay (ELISA) was performed to assess the regulation of inflammatory molecules in mouse serum. Additionally, pathological examinations of tumor tissues and organs from mice were evaluated through hematoxylin and eosin (H&E) staining. The expression of inflammatory proteins in tumor tissues was measured by immunohistochemistry (IHC) and Western blotting. Tryptanthrin inhibited the proliferation, migration and invasion of MCF-7 cells, up-regulated the protein level of E-cadherin, and down-regulated those of MMP-2 and Snail, as suggested by the MCF-7 cell experiment. According to the results from in vivo experiment, tryptanthrin was effective in inhibiting tumor growth, and it showed favorable safety without inducing the fluctuations of body mass and organ coefficient (p > 0.05). In addition, tryptanthrin also suppressed the expression levels of NOS1, COX-2 and NF-κB in mouse tumor tissues, and regulated those of IL-2, IL-10 and TNF-α in the serum of tumor cells-transplanted mice. Tryptanthrin exerted its anti-breast cancer activities through modulating the inflammatory TME both in vitro and in vivo.

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L-Theanine Reduced the Development of Knee Osteoarthritis in Rats via Its Anti-Inflammation and Anti-Matrix Degradation Actions: In Vivo and In Vitro Study

Nutrients ◽

10.3390/nu12071988 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1988 ◽

Cited By ~ 1

Author(s):

Hui Bai ◽

Zhiheng Zhang ◽

Yue Li ◽

Xiaopeng Song ◽

Tianwen Ma ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Quantitative Polymerase Chain Reaction ◽

Hydrolytic Enzyme ◽

Enzyme Linked Immunosorbent Assay ◽

Matrix Degradation ◽

In Vivo Animal Model

The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)β-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1β-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1β-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.

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Efficacy of Pyrus elaeagnifolia subsp. elaeagnifolia in acetic acid–induced colitis model

Open Chemistry ◽

10.1515/chem-2019-0002 ◽

2019 ◽

Vol 17 (1) ◽

pp. 13-22 ◽

Cited By ~ 2

Author(s):

Mert Ilhan ◽

Esra Küpeli Akkol ◽

Hakkı Taştan ◽

Fatma Tuğçe Gürağaç Dereli ◽

Ibrahim Tümen

Keyword(s):

Acetic Acid ◽

Caspase 3 ◽

Folk Medicine ◽

Experimental Colitis ◽

Treated Group ◽

Meoh Extract ◽

Colon Tissue ◽

Snake Bites

AbstractIn Turkish folk medicine, the fruits of Pyrus elaeagnifolia subsp. elaeagnifolia have been used to treat diarrhea and detoxify poisonous snake bites by enlarging the wound. The aim of the study was to confirm the ethnopharmacological usage of the plant using in vivo and in vitro models. Experimental colitis was performed under anesthesia by intrarectal administration of acetic acid in rats, and the extracts were administered orally. The colonic malondialdehyde (MDA), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and nitrite levels, in addition to the myeloperoxidase (MPO) and caspase-3 activities, were measured to determine the effects of the plant extracts. The methanol (MeOH) extract revealed a significant decrease in MPO and caspase-3 levels. The MeOH extract was found to have the highest total tannin content. It was also found to have significant antioxidant (p ˂ 0.01) and anti-inflammatory activities (p ˂ 0.05) in acetic acid induced colitis rat model . According to our results, the present study exhibited a decrease in MDA, nitrite, IL-6, and TNF-α levels in the colon tissue and blood in the MeOH extract treated group. The findings of this study can help in treating various disorders, such as Clostridium difficile infection, irritable bowel syndrome, and inflammatory bowel diseases.

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Alleviation of Ulcerative Colitis Potentially through th1/th2 Cytokine Balance by a Mixture of Rg3-enriched Korean Red Ginseng Extract and Persicaria tinctoria

Molecules ◽

10.3390/molecules25225230 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5230

Author(s):

Evelyn Saba ◽

Yuan Yee Lee ◽

Man Hee Rhee ◽

Sung-Dae Kim

Keyword(s):

Ulcerative Colitis ◽

Mitogen Activated Protein Kinase ◽

Raw 264.7 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Red Ginseng ◽

Korean Red Ginseng ◽

Ginseng Extract ◽

Anti Inflammatory

Ginseng is a vastly used herbal supplement in Southeast Asian countries. Red ginseng extract enriched with Rg3 (Rg3-RGE) is a formula that has been extensively studied owing to its various biological properties. Persicaria tinctoria (PT), belonging to the Polygonaceae family, has also been reported for its anti-inflammatory properties. Ulcerative colitis (UC) is inflammation of the large intestine, particularly in the colon. This disease is increasingly common and has high probability of relapse. We investigated, separately and in combination, the effects of Rg3-RGE and PT using murine exemplary of UC induced by DSS (Dextran Sulfate Sodium). For in vitro and in vivo experiments, nitric oxide assay, qRT-Polymerase Chain Reaction (PCR), Western blot, ulcerative colitis introduced by DSS, Enzyme Linked Immunosorbent Assay (ELISA), and flow cytometry analysis were performed. The results obtained demonstrate that treatment with Rg3-RGE + PT showed synergism to suppress inflammation (in vitro) in RAW 264.7 cells via mitogen-activated protein kinase and nuclear factor κB pathways. Moreover, in C57BL/6 mice, this mixture exhibits strong anti-inflammatory effects in restoring colon length, histopathological damage, pro-inflammatory mediators, and cytokines amount, and decreasing levels of NLRP3 inflammasome (in vivo). Our results recommend that this mixture can be used for the prevention of UC as a prophylactic/therapeutic supplement.

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Extracellular Vesicles of Stem Cells to Prevent BRONJ

Journal of Dental Research ◽

10.1177/0022034520906793 ◽

2020 ◽

Vol 99 (5) ◽

pp. 552-560 ◽

Cited By ~ 4

Author(s):

J. Watanabe ◽

K. Sakai ◽

Y. Urata ◽

N. Toyama ◽

E. Nakamichi ◽

...

Keyword(s):

Stem Cells ◽

Extracellular Vesicles ◽

Inflammatory Cytokines ◽

Bone Marrow Cells ◽

Treated Group ◽

Osteonecrosis Of The Jaw ◽

Oral Epithelium ◽

Stem Cell Markers

Extracellular vesicles (EVs), several tens to hundreds of nanometers in size, are vesicles secreted by cells for intercellular communication. EVs released from mesenchymal stem cells (MSC-EVs) have the potential to treat multiple diseases. This study aimed to determine the effects of MSC-EVs on bisphosphonate-related osteonecrosis of the jaw (BRONJ), whose pathogenesis and treatment are not yet established. To this end, zoledronic acid (ZOL) was administered to bone marrow cells and fibroblasts in vitro. In vivo, a BRONJ model was produced by administering ZOL to rats and extracting teeth. Each MSC-EV-treated and nontreated group was compared histologically and molecularly. In vitro, the nontreated group showed an increased number of β-galactosidase-positive cells and expression of senescence-associated genes p21, pRB and senescence-related inflammatory cytokines. Conversely, MSC-EV administration decreased the number of senescent cells and expression levels of p21, pRB and inflammatory cytokines. In vivo, in the nontreated group, the socket was partially uncovered by the oral epithelium, leaving an exposed bone. Conversely, in the MSC-EV-treated group, the socket was healed. Besides, in the nontreated group, β-galactosidase-positive cells existed in the socket and colocalized with the CD90 and periostin-positive cells. However, there were few β-galactosidase-positive cells in the MSC-EV-treated group. Furthermore, gene expression of stem cell markers Bmi1 and Hmga2 and the vascular endothelial marker VEGF was significantly increased in the MSC-EV-treated group, compared with that in the nontreated group. These results indicate that MSC-EVs prevent ZOL-induced senescence in stem cells, osteoblasts, and fibroblasts and reduce inflammatory cytokines. Furthermore, administration of MSC-EVs prevented senescence of cells involved in wound healing and the spread of chronic inflammation around senescent cells, thereby promoting angiogenesis and bone regeneration and preventing BRONJ.

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A medicinal plant Cudrania tricuspidata ameliorates allergic inflammation in mouse

Journal of Environmental Biology ◽

10.22438/jeb/42/5/mrn-1749 ◽

2021 ◽

Vol 42 (5) ◽

pp. 1213-1220

Author(s):

Y.S. Kim ◽

◽

A.R. Ryu ◽

C.R. Yoon ◽

J.W. Choi ◽

...

Keyword(s):

Nitric Oxide ◽

Allergic Inflammation ◽

Ethanol Extract ◽

Raw 264.7 Cells ◽

Mouse Serum ◽

Enzyme Linked Immunosorbent Assay ◽

Raw 264.7 ◽

Cudrania Tricuspidata ◽

Anti Inflammatory

Aim: This study aims at investigating the effect of ethanol extract of Cudrania tricuspidata twigs on in vitro and in vivo allergic inflammation. Methodology: The ethanol extract of twigs from Cudrania tricuspidata (CTE) was prepared. The effects of CTE on the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in Raw 264.7 cells were examined. 2,4-Dinitrochlorobenzene (DNCB)-induced allergic inflammation model of mouse was constructed for in vivo study. The anti-oxidative, anti-inflammatory and anti-allergic effects of CTE were examined through DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Results: The LPS-induced NO level was significantly reduced by Cudrania tricuspidata application in Raw 264.7 cells. LPS-induced inducible nitric oxide synthase (iNOS) expression was also reduced by CTE, showing CTE’s anti-inflammatory activity. Moreover, CTE reduced DNCB-induced IgE level in the mouse serum. The suppressive effect on the allergic inflammation stimulated by DNCB in the mouse model was investigated in terms of IL-4, IFN-γ, TNF-α level and PAR-2 expression. Interpretation: The ethanol extract of Cudrania tricuspidata twigs can be developed as a potent therapeutics for allergic inflammation.

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In vitro and in vivo anti-inflammatory properties of Mayan propolis

European Journal of Inflammation ◽

10.1177/2058739220935280 ◽

2020 ◽

Vol 18 ◽

pp. 205873922093528

Author(s):

Jorge Xool-Tamayo ◽

Ivan Chan-Zapata ◽

Víctor Ermilo Arana-Argaez ◽

Fabiola Villa-de la Torre ◽

Julio César Torres-Romero ◽

...

Keyword(s):

Inflammatory Cytokines ◽

High Performance ◽

Enzyme Linked Immunosorbent Assay ◽

Thiazolyl Blue Tetrazolium Bromide ◽

Tnf Α ◽

Anti Inflammatory ◽

Main Components ◽

Macrophage Viability

Introduction Propolis has been used traditionally for different human diseases and even recently as dental biomaterials because of its antibacterial, antimycotic, and anti-inflammatory properties. However, a proper correlation between in vitro and in vivo anti-inflammatory properties has not been clearly established. Methods The composition of propolis was determined by high-performance liquid chromatography–ultraviolet mass spectrometry (HPLC-UV-MS). Viability of ethanolic propolis solution was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay on murine macrophages. The anti-inflammatory properties were assessed both in vitro through the enzyme-linked immunosorbent assay (ELISA) quantification of various cytokines and in vivo by induced edemas. Results Chemical analysis showed pinocembrin, pinobanksin-3-O-acetate, and pinobanksin-3-O-propionate as the main components of propolis. Macrophage viability was high (106%) when propolis was used up to 50 µg/mL. ELISA studies showed a reduction in the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) up to 145 pg/mL, 350 pg/mL, and 210 pg/mL, respectively, while the anti-inflammatory cytokines (IL-10 and IL-4) were increased up to 833 pg/mL and 446 pg/mL. Finally, edema was reduced on paw and ear mice by 9% and 22%, respectively. Conclusion Mayan propolis has strong in vitro anti-inflammatory properties without compromising macrophage viability, resulting in a low-to-mild in vivo anti-inflammatory response.

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miR-30a-3p participates in the development of asthma by targeting CCR3

Open Medicine ◽

10.1515/med-2020-0102 ◽

2020 ◽

Vol 15 (1) ◽

pp. 483-491

Author(s):

Xiaobo Li ◽

Binliang Wang ◽

Mao Huang ◽

Xiaomi Wang

Keyword(s):

Inflammatory Response ◽

Peripheral Blood ◽

Specific Ige ◽

Mouse Serum ◽

Enzyme Linked Immunosorbent Assay ◽

Asthmatic Patients ◽

And Migration ◽

Induced Apoptosis

AbstractThis study aimed to investigate the role and relevant mechanism of miR-30a-3p action in asthma. The results of this study revealed that the expression levels of miR-30a-3p were significantly decreased in the peripheral blood of asthmatic patients. In addition, we found that the CC chemokine receptor (CCR3) was a target of miR-30a-3p. Subsequently, an asthma mouse model was established using ovalbumin (OVA). The results showed that the expression of miR-30a-3p and CCR3 was downregulated and upregulated, respectively, in the peripheral blood of asthmatic mice. Enzyme-linked immunosorbent assay (ELISA) in asthmatic mouse serum demonstrated that miR-30a-3p mimic treatment significantly decreased the secretion of OVA-specific IgE, eotaxin-1, interleukin (IL)-5, and IL-4. These results suggested that miR-30a-3p inhibited CCR3 signaling pathway and relieved the inflammatory response against asthma in vivo. Eosinophils have also been implicated in the asthmatic inflammatory response. Therefore, the in vitro effects of miR-30a-3p on eosinophil activity were determined. Findings suggested that miR-30a-3p mimic significantly reduced eosinophil viability and migration and induced apoptosis. In addition, CCR3 and eotaxin-1 downregulation were observed. The aforementioned results were significantly reversed following CCR3 overexpression. This study suggested that miR-30a-3p was involved in asthma by regulating eosinophil activity and targeting CCR3.

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Lactobacillus ruminis Alleviates DSS-Induced Colitis by Inflammatory Cytokines and Gut Microbiota Modulation

Foods ◽

10.3390/foods10061349 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1349

Author(s):

Bo Yang ◽

Mingjie Li ◽

Shuo Wang ◽

R. Paul Ross ◽

Catherine Stanton ◽

...

Keyword(s):

Gut Microbiota ◽

Inflammatory Cytokines ◽

Short Chain Fatty Acids ◽

Colon Tissue ◽

Tnf Α ◽

Lactobacillus Ruminis ◽

Immune Response In Vitro ◽

Pro Inflammatory Cytokines

Lactobacillus ruminis can stimulate the immune response in vitro, but previous studies were only carried out in vitro and the anti-inflammatory effects of L. ruminis needs more in vivo evidences. In this study, the immune regulation and potential mechanisms of L. ruminis was investigated in DSS-induced colitis mice. L. ruminis FXJWS27L3 and L. ruminis FXJSW17L1 relieved the symptoms of colitis, including inhibition of colon shortening and colon tissue damage. L. ruminis FXJWS27L3 significantly reduced the pro-inflammatory cytokines IL-1β, TNF-α, and IL-17, while L. ruminis FXJSW17L1 significantly increased short chain fatty acids in mice feces. Moreover, L. ruminis FXJWS27L3 and L. ruminis FXJSW17L1 treatments significantly increased the gut microbiota diversity and balance the intestine microbiota profiles, which improved the imbalance of intestine microbiota composition to a certain extent. The results showed that L. ruminis can alleviate DSS-induced colitis, which possibly was related to promoting the expression of pro-inflammatory cytokines, up-regulating SCFAs and restoring the imbalance of gut microbiota.

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