Antioxidant and Anti-Inflammatory Activity of Citrus Flavanones Mix and Its Stability after In Vitro Simulated Digestion

Recently, several studies have highlighted the role of Citrus flavanones in counteracting oxidative stress and inflammatory response in bowel diseases. The aim of study was to identify the most promising Citrus flavanones by a preliminary antioxidant and anti-inflammatory screening by in vitro cell-free assays, and then to mix the most powerful ones in equimolar ratio in order to investigate a potential synergistic activity. The obtained flavanones mix (FM) was then subjected to in vitro simulated digestion to evaluate the availability of the parent compounds at the intestinal level. Finally, the anti-inflammatory activity was investigated on a Caco-2 cell-based model stimulated with interleukin (IL)-1β. FM showed stronger antioxidant and anti-inflammatory activity with respect to the single flavanones, demonstrating the occurrence of synergistic activity. The LC-DAD-ESI-MS/MS analysis of gastric and duodenal digested FM (DFM) showed that all compounds remained unchanged at the end of digestion. As proof, a superimposable behavior was observed between FM and DFM in the anti-inflammatory assay carried out on Caco-2 cells. Indeed, it was observed that both FM and DFM decreased the IL-6, IL-8, and nitric oxide (NO) release similarly to the reference anti-inflammatory drug dexamethasone.

Download Full-text

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

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210913113522 ◽

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.

Download Full-text

Reduction of Inflammation and Colon Injury by a Spearmint Phenolic Extract in Experimental Bowel Disease in Mice

Medicines ◽

10.3390/medicines6020065 ◽

2019 ◽

Vol 6 (2) ◽

pp. 65 ◽

Cited By ~ 2

Author(s):

Rosa Direito ◽

João Rocha ◽

Ana Lima ◽

Maria Margarida Gonçalves ◽

Maria Paula Duarte ◽

...

Keyword(s):

Inflammatory Activity ◽

Colon Injury ◽

Mentha Spicata ◽

Inflammation Model ◽

Bowel Diseases ◽

Phenolic Extract ◽

Anti Inflammatory ◽

Ht 29

Background: Inflammatory Bowel Diseases (IBD) encompasses both Crohn’s Disease and Ulcerative Colitis, known to be connected to an enlarged risk for developing colorectal cancer (CRC). Spearmint (Mentha spicata L.) is a Mediterranean plant used as an aromatic agent, and studies have mainly focused on the essential oil suggesting an anti-inflammatory activity. This work aimed to perform a preliminary screening of the in vivo anti-inflammatory effects of a spearmint phenolic extract in an acute inflammation model, in a chronic inflammation model of colitis, and also study the effects in vitro on a colon cancer model. Methods: Spearmint extract was administered to rats of a paw oedema model (induced by carrageenan) and to mice from a TNBS-induced colitis model in parallel with studies using HT-29 CRC cells. Results: Administration of the extract led to reduced paw inflammation, reduction of colon injury and inflammation, with attenuation of histological markers, and reduction of iNOS expression. It repressed the in vitro movement of HT-29 cells in a wound healing assay. Conclusions: These findings suggest that spearmint extract exhibits acute and chronic anti-inflammatory activity and is able to inhibit migration of cancer cells, suggesting a potential role in the supplementary therapy of IBD patients.

Download Full-text

Probiotic yeast Kluyveromyces marxianus CIDCA 8154 shows anti-inflammatory and anti-oxidative stress properties in in vivo models

Beneficial Microbes ◽

10.3920/bm2015.0066 ◽

2016 ◽

Vol 7 (1) ◽

pp. 83-93 ◽

Cited By ~ 10

Author(s):

D.E. Romanin ◽

S. Llopis ◽

S. Genovés ◽

P. Martorell ◽

V.D. Ramón ◽

...

Keyword(s):

Oxidative Stress ◽

Kluyveromyces Marxianus ◽

Intestinal Inflammation ◽

In Vivo Models ◽

Benzene Sulfonic Acid ◽

Bowel Diseases ◽

Probiotic Yeast ◽

Anti Inflammatory

Inflammatory bowel diseases (IBDs) are complex affections with increasing incidence worldwide. Multiple factors are involved in the development and maintenance of the symptoms including enhanced oxidative stress in intestinal mucosa. The conventional therapeutic approaches for IBDs are based on the use anti-inflammatory drugs with important collateral effects and partial efficacy. In the present work we tested the anti-inflammatory capacity of Kluyveromyces marxianus CIDCA 8154 in different models. In vitro, we showed that the pretreatment of epithelial cells with the yeast reduce the levels of intracellular reactive oxygen species. Furthermore, in a murine model of trinitro benzene sulfonic acid-induced colitis, yeast-treated animals showed a reduced histopathological score (P<0.05) and lower levels of circulating interleukin 6 (P<0.05). The capacity to modulate oxidative stress in vivo was assessed using a Caenorhabditis elegans model. The yeast was able to protect the nematodes from oxidative stress by modulating the SKN-1 transcription factor trough the DAF-2 pathway. These results indicate that K. marxianus CIDCA 8154 could control the intestinal inflammation and cellular oxidative stress. Deciphering the mechanisms of action of different probiotics might be useful for the rational formulation of polymicrobial products containing microorganisms targeting different anti-inflammatory pathways.

Download Full-text

Intestinal Anti-Inflammatory Activity of Terpenes in Experimental Models (2010–2020): A Review

Molecules ◽

10.3390/molecules25225430 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5430

Author(s):

Maria Elaine Araruna ◽

Catarina Serafim ◽

Edvaldo Alves Júnior ◽

Clelia Hiruma-Lima ◽

Margareth Diniz ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Biological Activities ◽

Structural Diversity ◽

Experimental Models ◽

New Drugs ◽

Inflammatory Activity ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Anti Inflammatory

Inflammatory bowel diseases (IBDs) refer to a group of disorders characterized by inflammation in the mucosa of the gastrointestinal tract, which mainly comprises Crohn’s disease (CD) and ulcerative colitis (UC). IBDs are characterized by inflammation of the intestinal mucosa, are highly debilitating, and are without a definitive cure. Their pathogenesis has not yet been fully elucidated; however, it is assumed that genetic, immunological, and environmental factors are involved. People affected by IBDs have relapses, and therapeutic regimens are not always able to keep symptoms in remission over the long term. Natural products emerge as an alternative for the development of new drugs; bioactive compounds are promising in the treatment of several disorders, among them those that affect the gastrointestinal tract, due to their wide structural diversity and biological activities. This review compiles 12 terpenes with intestinal anti-inflammatory activity evaluated in animal models and in vitro studies. The therapeutic approach to IBDs using terpenes acts basically to prevent oxidative stress, combat dysbiosis, restore intestinal permeability, and improve the inflammation process in different signaling pathways.

Download Full-text

Anti-inflammatory activity of CD44 antibodies in murine immune thrombocytopenia is mediated by Fcγ receptor inhibition

Blood ◽

10.1182/blood.2020009497 ◽

2021 ◽

Author(s):

Peter Alan Albert Norris ◽

Gurleen Kaur ◽

Ramsha Khan ◽

Guangheng Zhu ◽

Heyu Ni ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Mechanistic Explanation ◽

Inflammatory Activity ◽

Receptor Inhibition ◽

Inflammatory Mechanism ◽

Igg Binding ◽

Anti Inflammatory

Monoclonal IgG antibodies to CD44 (anti-CD44) are anti-inflammatory in numerous murine autoimmune models but the mechanisms are poorly understood. Anti-CD44 anti-inflammatory activity shows complete therapeutic concordance with intravenous immunoglobulin (IVIg) in treating autoimmune disease models, making anti-CD44 a potential IVIg alternative. In murine immune thrombocytopenia (ITP), there is currently no mechanistic explanation for anti-CD44 activity although anti-CD44 ameliorates disease similarly to IVIg. Here we demonstrate a novel anti-inflammatory mechanism of anti-CD44 that explains disease amelioration by anti-CD44 in murine ITP. Macrophages treated with anti-CD44 in vitro had dramatically suppressed phagocytosis through FcγRs in two separate systems of IgG-opsonized platelets and erythrocytes. Phagocytosis inhibition by anti-CD44 was mediated by blockade of the FcγR IgG binding site without changing surface FcγR expression. Anti-CD44 of different subclasses revealed that FcγR blockade was specific to receptors that could be engaged by the respective anti-CD44 subclass, and Fc-deactivated anti-CD44 variants lost all FcγR-inhibiting activity. In vivo, anti-CD44 functioned analogously in the murine passive ITP model and protected mice from ITP when thrombocytopenia was induced through an FcγR that could be engaged by the CD44 antibody's subclass. Consistent with FcγR blockade, Fc-deactivated variants of anti-CD44 were completely unable to ameliorate ITP. Together, anti-CD44 inhibits macrophage FcγR function and ameliorates ITP consistent with an FcγR blockade mechanism. Anti-CD44 is a potential IVIg alternative and may be of particular benefit in ITP due to the significant role of FcγRs in human ITP pathophysiology.

Download Full-text

Prickly Pear Betalain-Rich Extracts as New Promising Strategy for Intestinal Inflammation: Plant Complex vs. Main Isolated Bioactive Compounds

Frontiers in Pharmacology ◽

10.3389/fphar.2021.722398 ◽

2021 ◽

Vol 12 ◽

Author(s):

A. Smeriglio ◽

C. De Francesco ◽

M. Denaro ◽

D. Trombetta

Keyword(s):

Bioactive Compounds ◽

Intestinal Inflammation ◽

Prickly Pear ◽

Synergistic Activity ◽

Dry Extract ◽

Promising Strategy ◽

Food Dyes ◽

Anti Inflammatory

Recently, many studies have highlighted the health effects of betalains beyond their use as food dyes. The present study investigated betalain-rich extracts with different colors and their main bioactive compounds in order to provide first evidence as a new promising strategy for intestinal inflammation management. Prickly pear betalain–rich extracts, obtained by a QuEChERS method, have been characterized by LC-DAD-ESI-MS/MS analysis. The potential role of betanin, indicaxanthin, and prickly pear extracts in counteracting the antioxidant and anti-inflammatory events was evaluated by several in vitro cell-free and cell-based assays. Indicaxanthin and betanin represent the most abundant compounds (≥22.27 ± 4.50 and 1.16 ± 0.17 g/100 g dry extract, respectively). Prickly pear extracts showed the strongest antioxidant and anti-inflammatory activities with respect to the pure betalains both on in vitro cell-free and cell-based assays, demonstrating the occurrence of synergistic activity, without any cytotoxicity or alteration of the barrier systems. The release of reactive oxygen species (ROS) and key inflammatory markers (IL-6, IL-8, and NO) was strongly inhibited by both betalains and even more by prickly pear extracts, which showed a similar and sometimes better profile than the reference compounds trolox and dexamethasone in counteracting the IL-1β–induced intestinal inflammation.

Download Full-text

Combination Effect of Three Main Constituents From Sarcandra glabra Inhibits Oxidative Stress in the Mice Following Acute Lung Injury: A Role of MAPK-NF-κB Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2020.580064 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chun-Ping Liu ◽

Jian-Xing Liu ◽

Jiangyong Gu ◽

Fang Liu ◽

Jin-Hua Li ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Raw 264.7 Cells ◽

Anti Inflammatory ◽

Model C ◽

Raw264.7 Macrophage

Caffeoylquinic acids, coumarins and dicaffeoyl derivatives are considered to be three kinds of the most abundant bioactive components in Sarcandra glabra, an anti-inflammatory herb mainly found in Southern Asia. The combined anti-inflammatory effect of three typical constituents C + R + I (chlorogenic acid + rosmarinic acid + isofraxidin) from this plant has been investigated. The result implies that targeting the MAPK-NF-κB pathway would be one of the major mechanisms involved, using LPS stimulated RAW 264.7 cells as in vitro model and LPS-induced acute lung injury in mice as in vivo model. C + R + I can significantly suppress the levels of nitric oxide (NO), pro-inflammatory cytokines, and inhibit iNOS and COX-2 expression in LPS-treated RAW264.7 macrophage cells. Western blot analysis showed that C + R + I suppressed phosphorylation of NF-κB and MAPK, including phosphorylation of p65-NF-κB, IKB, ERK, JNK and P38. Besides, C + R + I suppressed MPO protein expression, but promoted SOD and HO-1 expression, and the related targets for C, R, and I were also predicted by molecular docking. This indicated that C + R + I could alleviate oxidative stress induced by LPS, which were further verified in the in vivo model of mice with acute lung injury through the measurement of corresponding inflammatory mediators and the analysis of immunehistochemistry.

Download Full-text

Terminalia ferdinandiana, a traditional medicinal plant of Australia, alleviates hydrogen peroxide induced oxidative stress and inflammation, in vitro

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2019-0008 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Mridusmita Chaliha ◽

Yasmina Sultanbawa

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Medicinal Plant ◽

Mammalian Cells ◽

Cell Types ◽

Inflammatory Activity ◽

Ros Production ◽

Anti Inflammatory ◽

Terminalia Ferdinandiana

AbstractBackgroundOxidative stress and inflammation are the underlying factors in many chronic debilitating diseases and commonly intertwined. Terminalia ferdinandiana is a traditional medicinal plant, endemic to Australia and is a rich source of many bioactive phytochemicals such as ellagic acid (EA) with known antioxidant capacity.MethodsWe investigated the in vitro antioxidant and anti-inflammatory activity of an aqueous food grade EA enriched (EAE) extract of T. ferdinandiana. Caco-2 and KERTr cell lines were treated with EAE or pure EA (used as reference control), followed by the exposure to hydrogen peroxide (H2O2). Levels of reactive oxygen species (ROS) production and gene expression of molecular markers associated with oxidative stress and inflammation were monitored.ResultsSignificant reduction in ROS production was observed in both cell types treated with 100 or 200 µg/mL EA or EAE. Treatment of cells with EAE or EA showed upregulation of mRNA expression of the antioxidative gene superoxide dismutase (SOD)-2 and downregulated the expression of inducible nitric oxide synthase (iNOS), soluble cell adhesion molecule (sICAM), and cyclooxygenase (COX)-2. Neither EAE nor EA had any effect on the constitutively expressed COX1.ConclusionsThe antioxidant and anti-inflammatory activity of T. ferdinandiana extract on mammalian cells exposed to H2O2 suggests the potential of using this traditional medicinal plant in preventing oxidative damage and inflammation related diseases.

Download Full-text