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

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.

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P006 3D Multicellular intestine-on-a-chip model for disease modelling and drug discovery

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.135 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S132-S133

Author(s):

G Lo Sasso ◽

L Gijzen ◽

D Marescotti ◽

E Naumovska ◽

E Raineri ◽

...

Keyword(s):

Barrier Function ◽

Intestinal Inflammation ◽

The Body ◽

Collagen I ◽

Epithelial Barrier ◽

Human Intestine ◽

In Vivo Models ◽

Anti Inflammatory

Abstract Background One of the major functions of the human intestine is to provide a protective epithelial barrier between the body and digestive environment. Additionally, the interplay of commensal microbes of the gut microbiome with the gut tissue and host immune system significantly contributes to intestinal homeostasis. Crohn’s disease and ulcerative colitis, collectively referred to as inflammatory bowel diseases, are both associated with increased permeability of the epithelial barrier and dysregulated immune response. Great efforts have been made to develop both in vitro and in vivo models of the human intestine in order to understand the development and underlying pathogenesis of IBD. These efforts have provided valuable insights into multiple aspects of the disease. However, none of these models has been able to capture the complexity and multifactorial nature of IBD. Animal models generally fail to accurately predict the efficacy and toxicity of novel compounds in human tissues, while in vitro human intestinal models developed on porous membranes within Transwell inserts fail to accurately recapitulate and mimic key aspects of the in vivo situation. Methods Here, we present the development and characterisation of a 3D multicellular perfused intestine-on-a-chip model in a microfluidic platform, the OrganoPlate®, and its application for investigating intestinal inflammation. The model described here comprises a coculture of Caco-2 and mucus-secreting HT29-MTX cells in the top compartment of the chip and a coculture of immune-competent cells THP-1 and MUTZ-3 in the bottom compartment, lining a collagen-I ECM in the middle. Results We show that the Caco-2 and HT29-MTX coculture form confluent and polarised tubular structures against the collagen-I ECM in the OrganoPlate®, with a stable barrier function over time as well as the capability to secrete mucus. By exposing the cultures to TNFα and/or IL-1β, we were able to induce an inflammatory state, characterised by cytokine release (IL-8) and a decrease in trans-epithelial electrical resistance. Finally, we proved the applicability of the model in screening anti-inflammatory compounds by its reversibility. Using a well-known anti-inflammatory drug, TPCA-1, we were able to prevent cytokine-induced inflammation. This result was evident from the decreased secretion of IL-8 and retention of barrier function in treated cultures, similar to that observed in untreated cultures. Conclusion Overall, this complex 3D multicellular perfused intestine-on-a-chip model provides the versatile modularity of mimicking key features of intestinal inflammation and can, therefore, further support drug screening efforts and provide a platform for personalised medicine.

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A Review on Opuntia Species and its Chemistry, Pharmacognosy, Pharmacology and Bioapplications

Current Nutrition & Food Science ◽

10.2174/1573401316666200220092414 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1227-1244

Author(s):

Dharmendra Kumar ◽

Pramod K. Sharma

Keyword(s):

Human Consumption ◽

In Vivo Models ◽

Sugar Amino Acids ◽

Opuntia Species ◽

Therapeutic Uses ◽

Anti Inflammatory ◽

Online Library ◽

Different Parts

Background:: Opuntia species, locally known as prickly pear was used for various purposes as food, medicine, beverage, source of dye and animal food. Many studies have revealed its pharmacology activity from time to time. This review is a collection of chemistry, pharmacognosy, pharmacology and bioapplications of the cactus family. Methods: Many sources were used to collect information about Opuntia species such as Pub med, Google scholar, Agris, science direct, Embase, Merk index, Wiley online library, books and other reliable sources. This review contains studies from 1812 to 2019. Results: The plants from the cactus family offer various pharmacological active compounds including phenolic compounds, carotenoids, betalains, vitamins, steroids, sugar, amino acids, minerals and fibers. These bioactive compounds serve various pharmacological activities such as anticancer, antiviral, anti-diabetic, Neuroprotective, anti-inflammatory, antioxidant, Hepatoprotective, antibacterial, antiulcer and alcohol hangover. According to various studies, Opuntia species offer many bioapplications such as fodder for animal, soil erosion, prevention, human consumption and waste water decontamination. Finally, different parts of plants are used in various formulations that offer many biotechnology applications. Conclusion: Different parts of Opuntia plant (fruits, seeds, flowers and cladodes) are used in various health problems which include wound healing, anti-inflammatory and urinary tract infection from ancient times. Nowadays, researches have extended several pharmacological and therapeutic uses of Opuntia species as discussed in this review. Many in-vitro and in-vivo models are also discussed in this review as the proofs of research findings. Various research gaps have been observed in current studies that require attention in the future.

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Phytochemical Analysis of Anti-Inflammatory and Antioxidant Effects of Mahonia aquifolium Flower and Fruit Extracts

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/2879793 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 13

Author(s):

Andra-Diana Andreicut ◽

Alina Elena Pârvu ◽

Augustin Cătălin Mot ◽

Marcel Pârvu ◽

Eva Fischer Fodor ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

Stress Index ◽

Tnf Alpha ◽

Phytochemical Analysis ◽

Anti Inflammatory ◽

Mahonia Aquifolium ◽

Antioxidant Effects

Oxidative stress and inflammation are interlinked processes. The aim of the study was to perform a phytochemical analysis and to evaluate the antioxidant and anti-inflammatory activities of ethanolic Mahonia aquifolium flower (MF), green fruit (MGF), and ripe fruit (MRF) extracts. Plant extract chemical composition was evaluated by HLPC. A DPPH test was used for the in vitro antioxidant activity. The in vivo antioxidant effects and the anti-inflammatory potential were tested on a rat turpentine oil-induced inflammation, by measuring serum nitric oxide (NOx) and TNF-alpha, total oxidative status (TOS), total antioxidant reactivity (TAR), oxidative stress index (OSI), 3-nitrothyrosine (3NT), malondialdehyde (MDA), and total thiols (SH). Extracts were administrated orally in three dilutions (100%, 50%, and 25%) for seven days prior to inflammation. The effects were compared to diclofenac. The HPLC polyphenol and alkaloid analysis revealed chlorogenic acid as the most abundant compound. All extracts had a good in vitro antioxidant activity, decreased NOx, TOS, and 3NT, and increased SH. TNF-alpha was reduced, and TAR increased only by MF and MGF. MDA was not influenced. Our findings suggest that M. aquifolium has anti-inflammatory and antioxidant effects that support the use in primary prevention of the inflammatory processes.

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Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific XPO1 translation in epithelial cells

Gut ◽

10.1136/gutjnl-2020-322566 ◽

2021 ◽

pp. gutjnl-2020-322566

Author(s):

Ane Olazagoitia-Garmendia ◽

Linda Zhang ◽

Paula Mera ◽

Julie K Godbout ◽

Maialen Sebastian-DelaCruz ◽

...

Keyword(s):

Intestinal Inflammation ◽

Autoimmune Disorder ◽

Intestinal Cell ◽

In Vivo Models ◽

Knock Out ◽

New Therapeutic Approaches ◽

Intestinal Cell Line ◽

Environment Characteristic

ObjectivesCoeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a strict, lifelong gluten free diet. Human leucocyte antigen (HLA) genes and several non-HLA regions have been associated with the genetic susceptibility to CD, but their role in the pathogenesis of the disease is still essentially unknown, making it complicated to develop much needed non-dietary treatments. Here, we describe the functional involvement of a CD-associated single-nucleotide polymorphism (SNP) located in the 5’UTR of XPO1 in the inflammatory environment characteristic of the coeliac intestinal epithelium.DesignThe function of the CD-associated SNP was investigated using an intestinal cell line heterozygous for the SNP, N6-methyladenosine (m6A)-related knock-out and HLA-DQ2 mice, and human samples from patients with CD.ResultsIndividuals harbouring the risk allele had higher m6A methylation in the 5’UTR of XPO1 RNA, rendering greater XPO1 protein amounts that led to downstream nuclear factor kappa B (NFkB) activity and subsequent inflammation. Furthermore, gluten exposure increased overall m6A methylation in humans as well as in in vitro and in vivo models.ConclusionWe identify a novel m6A-XPO1-NFkB pathway that is activated in CD patients. The findings will prompt the development of new therapeutic approaches directed at m6A proteins and XPO1, a target under evaluation for the treatment of intestinal disorders.

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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.

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Vascular Dysfunction Induced by Mercury Exposure

International Journal of Molecular Sciences ◽

10.3390/ijms20102435 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2435 ◽

Cited By ~ 4

Author(s):

Tetsuya Takahashi ◽

Takayoshi Shimohata

Keyword(s):

Oxidative Stress ◽

Vascular Dysfunction ◽

Brain Parenchyma ◽

Transport Systems ◽

Mehg Exposure ◽

In Vivo Models ◽

The Central Nervous System ◽

The Brain

Methylmercury (MeHg) causes severe damage to the central nervous system, and there is increasing evidence of the association between MeHg exposure and vascular dysfunction, hemorrhage, and edema in the brain, but not in other organs of patients with acute MeHg intoxication. These observations suggest that MeHg possibly causes blood–brain barrier (BBB) damage. MeHg penetrates the BBB into the brain parenchyma via active transport systems, mainly the l-type amino acid transporter 1, on endothelial cell membranes. Recently, exposure to mercury has significantly increased. Numerous reports suggest that long-term low-level MeHg exposure can impair endothelial function and increase the risks of cardiovascular disease. The most widely reported mechanism of MeHg toxicity is oxidative stress and related pathways, such as neuroinflammation. BBB dysfunction has been suggested by both in vitro and in vivo models of MeHg intoxication. Therapy targeted at both maintaining the BBB and suppressing oxidative stress may represent a promising therapeutic strategy for MeHg intoxication. This paper reviews studies on the relationship between MeHg exposure and vascular dysfunction, with a special emphasis on the BBB.

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Modulatory effect of Syzygium aromaticum and Pelargonium graveolens on oxidative stress and inflammation

10.1101/362426 ◽

2018 ◽

Author(s):

Ilias Marmouzi ◽

El Mostafa Karym ◽

Rachid Alami ◽

Meryem El Jemli ◽

Mourad Kharbach ◽

...

Keyword(s):

Oxidative Stress ◽

Essential Oils ◽

Toxic Effect ◽

Tetrahymena Pyriformis ◽

Syzygium Aromaticum ◽

Minimal Risk ◽

Pelargonium Graveolens ◽

Anti Inflammatory

AbstractBackgroundTherapy combination is defined as disease treatment with two or more medication to acheive efficacy with lower doses or lower toxicity. Regarding its reported toxicities and efficacy, the Essential Oils (EOs) from Syzygium aromaticum (SA) and Pelargonium graveolens (PG) were combined for in vitro and in vivo assays and toxicities.MethodsThe Essential Oils and mixture were tested for in vivo/in vitro antioxidant and anti-inflammatory activities. The assays included the animal model of acute inflammation (carrageenan model), the protective effect on H2O2/Sodium nitroprissude induced stress in Tetrahymena pyriformis, and the in vitro antioxidant assays.ResultsThe chemical analysis of the investigated Oils has lead to the identification of Eugenol (74.06%), Caryophyllene (11.52%) and Carvacrol acetate (7.82%) as the major element in SA; while PG was much higher in Citronellol (30.77%), 10-epi-γ-Eudesmol (22.59%), and Geraniol (13.95%). In our pharmacological screening of samples, both Oils demonstrated good antioxidant effects. In vivo investigation of the antioxidant activity in the protozoa model (T. pyriformis) demonstrated a lesser toxic effect of EOs mixture with no significant differences when oxidative stress markers and antioxidant enzymes (MDA, SOD and CAT) were evaluated. On the other hand the in vivo model of inflammatory response to carrageenan demonstrated a good inhibitory potential of both EOs. The EOs Mixture demonstrated equivalent bioactivity with lower toxic effect and minimal risk for each compound.ConclusionsThe results from this study indicate that EOs mixture from SA and PG demonstrated promising modulatory antioxidant/anti-inflammatory effect, which suggest an efficient association for therapy.

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Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

International Journal of Molecular Sciences ◽

10.3390/ijms221910822 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10822

Author(s):

Agata Winiarska ◽

Monika Knysak ◽

Katarzyna Nabrdalik ◽

Janusz Gumprecht ◽

Tomasz Stompór

Keyword(s):

Oxidative Stress ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Kidney Injury ◽

Organ Protection ◽

In Vivo Models ◽

Diabetic Kidney ◽

And Oxidative Stress

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) antagonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R antagonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.

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Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

Pharmaceuticals ◽

10.3390/ph14121248 ◽

2021 ◽

Vol 14 (12) ◽

pp. 1248

Author(s):

Muhammad Waleed Baig ◽

Humaira Fatima ◽

Nosheen Akhtar ◽

Hidayat Hussain ◽

Mohammad K. Okla ◽

...

Keyword(s):

In Silico ◽

Therapeutic Potential ◽

In Vivo Studies ◽

Metabolic Reaction ◽

Datura Innoxia ◽

In Vivo Models ◽

Immobility Time ◽

Anti Inflammatory

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

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