The Combined Anti-Inflammatory Effect of Astaxanthin, Lyc-O-Mato and Carnosic Acid In Vitro and In Vivo in a Mouse Model of Peritonitis

Background: the pharmacological treatment and/or maintenance of remission in inflammatory bowel diseases (IBDs) is currently one of the biggest challenges in the field of gastroenterology. Method: our aim was the synthesis of homo- and heterodimers of natural enkephalinase inhibitors (opiorphin; sialorphin; spinorphin) and the in vitro characterization of their effect on the degradation of enkephalin by neutral endopeptidase (NEP) and stability in human plasma. We investigated the in vivo heterodimer of Cys containing analogs of sialorphin and spinorphin (peptide X) in a mouse model of colitis. The extent of inflammation was evaluated based on the microscopic score; macroscopic score; ulcer score, colonic wall thickness, colon length and quantification of myeloperoxidase activity. Results: we showed that the homo- and heterodimerization of analogs of sialorphin, spinorphin and opiorphin containing Cys residue at the N-terminal position resulted in dimeric forms which in vitro exhibited higher inhibitory activity against NEP than their parent and monomeric forms. We showed that peptide X was more stable in human plasma than sialorphin and spinorphin. Peptide X exerts potent anti-inflammatory effect in the mouse model of colitis. Conclusion: we suggest that peptide X has the potential to become a valuable template for anti-inflammatory therapeutics for the treatment of gastrointestinal (GI) tract inflammation.

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Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽

10.3390/molecules26092529 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2529

Author(s):

Haeyeop Kim ◽

Woo Seok Yang ◽

Khin Myo Htwe ◽

Mi-Nam Lee ◽

Young-Dong Kim ◽

...

Keyword(s):

Ethanol Extract ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Tnf Α ◽

Anti Inflammatory ◽

Related Proteins ◽

Pro Inflammatory Cytokines ◽

Inflammatory Effect

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

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TAK1/AP-1-Targeted Anti-Inflammatory Effects of Barringtonia augusta Methanol Extract

Molecules ◽

10.3390/molecules26103053 ◽

2021 ◽

Vol 26 (10) ◽

pp. 3053

Author(s):

Anh Thu Ha ◽

Mi-Yeon Kim ◽

Jae Youl Cho

Keyword(s):

Mouse Model ◽

Methanol Extract ◽

Folk Medicine ◽

Activator Protein 1 ◽

Western Blot Assay ◽

In Vivo Experiments ◽

Chemokine Ligand ◽

Anti Inflammatory ◽

Inflammatory Effect

Barringtonia augusta methanol extract (Ba-ME) is a folk medicine found in the wetlands of Thailand that acts through an anti-inflammatory mechanism that is not understood fully. Here, we examine how the methanol extract of Barringtonia augusta (B. augusta) can suppress the activator protein 1 (AP-1) signaling pathway and study the activities of Ba-ME in the lipopolysaccharide (LPS)-treated RAW264.7 macrophage cell line and an LPS-induced peritonitis mouse model. Non-toxic concentrations of Ba-ME downregulated the mRNA expression of cytokines, such as cyclooxygenase and chemokine ligand 12, in LPS-stimulated RAW264.7 cells. Transfection experiments with the AP-1-Luc construct, HEK293T cells, and luciferase assays were used to assess whether Ba-ME suppressed the AP-1 functional activation. A Western blot assay confirmed that C-Jun N-terminal kinase is a direct pharmacological target of Ba-ME action. The anti-inflammatory effect of Ba-ME, which functions by β-activated kinase 1 (TAK1) inhibition, was confirmed by using an overexpression strategy and a cellular thermal shift assay. In vivo experiments in a mouse model of LPS-induced peritonitis showed the anti-inflammatory effect of Ba-ME on LPS-stimulated macrophages and acute inflammatory mouse models. We conclude that Ba-ME is a promising anti-inflammatory drug targeting TAK1 in the AP-1 pathway.

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472 Anti-inflammatory actions of phosphatidyl glycerol and its precursor glycerol in vitro and in an in vivo mouse model of psoriasis

Journal of Investigative Dermatology ◽

10.1016/j.jid.2017.02.491 ◽

2017 ◽

Vol 137 (5) ◽

pp. S81

Author(s):

V. Choudhary ◽

V. Custer ◽

I. Kaddour-Djebbar ◽

W.B. Bollag

Keyword(s):

Mouse Model ◽

Phosphatidyl Glycerol ◽

Anti Inflammatory

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Natural populations of Galphimia spp. attenuates peripheral and central inflammation

10.21203/rs.3.rs-315697/v1 ◽

2021 ◽

Author(s):

Reinier Gesto-Borroto ◽

Gabriela Meneses ◽

Alejandro Espinosa-Cerón ◽

Guillermo Granados ◽

Jacquelynne Cervantes-Torres ◽

...

Keyword(s):

Systemic Inflammation ◽

Natural Populations ◽

Inflammatory Activity ◽

Medicinal Species ◽

Methanolic Extracts ◽

Nitrite Production ◽

Anti Inflammatory ◽

Inflammatory Effect

Abstract The genus Galphimia is widely distributed in Mexico, and is represented by 22 species, including medicinal species. The sedative and anti-inflammatory effects of galphimines produced by the species Galphimia glauca have been documented. Formerly, molecular studies using DNA barcodes demonstrated that nine populations botanically classified as Galphimia glauca belong to four different species of the genus Galphimia, and that only one exhibited the sedative properties; however, all the collected species showed anti-inflammatory activity. Other bioactive compounds like quercetin, galphins, galphimidins and glaucacetalins have been identified from methanolic extracts of plants botanically classified as Galphimia glauca. The aim of this work was to determine the anti-inflammatory activity of methanolic extracts of nine collected Galphimia spp. populations grown in Mexico. The possible modes of action were analyzed by evaluating the inhibition of LPS-induced inflammation processes both in vitro and in vivo. The nine populations were evaluated by an in vitro model using RAW 264.7 murine macrophage cells, and two populations (a galphimine-producing and a non-galphimine-producing population) were selected for the in vivo experiments of systemic inflammation and neuroinflammation in mice. Results suggest that an anti-inflammatory in vitro effect was present in all the studied populations, evidenced by the inhibition of nitrite production. An inhibitory systemic inflammation in mice was exerted by the two analyzed populations. In the neuroinflammation model, the anti-inflammatory effect was demonstrated in methanolic extract of the non-galphimine-producing population. For the populations of Galphimia spp. studied herein, the anti-inflammatory effect could not be correlated to the presence of galphimines.

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In vitro antihemolytic effect, in vivo anti inflammatory and In vitro antioxidant activity of Anchusa azurea Mill

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/1871523020666211201162917 ◽

2021 ◽

Vol 20 ◽

Author(s):

Boussoualim Naouel ◽

Trabsa Hayat ◽

Krache Imane ◽

Ouhida Soraya ◽

Arrar Lekhmissi ◽

...

Keyword(s):

Methanolic Extract ◽

Folk Medicine ◽

Oxidative Degradation ◽

Negative Control ◽

Dependent Manner ◽

Anti Inflammatory ◽

Β Carotene ◽

Inflammatory Effect

Background: Anchusa azurea Mill. (AA) is a medicinal plant largely used traditionally in folk medicine in Algeria, it is locally named: hamham. It is effective in the treatment of various diseases. Objectives: The aim of the present study is to determine the antioxidant, anti-inflammatory and anti-hemolytic effects of phenolic fractions from Anchusa azurea Mill. Methods: In this study, various extracts from Anchusa azurea Mill. (AA) using solvents with increasing polarity were prepared. The quantification of polyphenols and flavonoids was determined. The anti-radical activity of the different extracts was evaluated using DPPH and by measuring the inhibition of the oxidative degradation of β-carotene. The In vitro antihemolytic effect of the plant extracts is determined (CrE, ChE, AcE and AqE). For each extract, four concentrations were tested: 10.59, 21.18, 42.37, 84.74 µg/ml. Vitamin C is used as a standard. Free-radical attack was measured by measuring the HT50 (Half-Hemolysis Time). The anti-inflammatory effect using PMA on mice of the methanolic extract (CrE) was evaluated. Results: The quantification of polyphenols and flavonoids showed that ethyl acetate extract (AcE) contains a higher amount of polyphenols. However, chloroform extract (ChE) presents a higher amount of flavonoids. AcE showed an important scavenging activity using the DPPH radical (IC50= 68.35 µg/ml). The results showed that AcE also exhibited very great inhibition on the oxidation of β-carotene/linoleic acid (84.33%). All extracts increased the HT50 values (Half-Hemolysis Time) in a dose-dependent manner. The three highest concentrations (21.18, 42.37 and 84.74 µg / ml) of ChE caused a very significant delay (p ≤ 0.001) of hemolysis compared to the negative control and the positive control "VIT C". The anti-inflammatory effect using PMA on mice showed that the methanolic extract (CrE) of AA reduced the weight of the ear edema. Conclusions: This plant has a strong pharmacological power, which supports its traditional medicinal use.

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In Vitro and In Vivo Anti-Inflammatory Activity of the Rhizomes of Globba pendula Roxb

Natural Product Communications ◽

10.1177/1934578x211055907 ◽

2021 ◽

Vol 16 (10) ◽

pp. 1934578X2110559

Author(s):

Le Minh Ha ◽

Ngo Thi Phuong ◽

Nguyen Thi Thu Hien ◽

Pham Thi Tam ◽

Do Thi Thao ◽

...

Keyword(s):

Ethyl Acetate ◽

Ethyl Acetate Extract ◽

Inhibitory Effect ◽

Potential Effect ◽

Inflammatory Activity ◽

No Production ◽

Anti Inflammatory ◽

Inflammatory Effect

In this study, we aimed at evaluating in vitro and in vivo anti-inflammatory activity of various extracts of the rhizomes of Globba pendula Roxb. Three extracts ( n-hexane, ethyl acetate, and water) were screened for their inhibitory effect on NO production by lipopolysaccharide-stimulated RAW 264.7 macrophages. The ethyl acetate extract of G. pendula rhizomes (EGP) showed a potential effect with an IC50 value of 32.45 µg/mL. For in vivo study, the ethyl acetate extract was further investigated for its anti-inflammatory effect using collagen antibody-induced arthritic mice (CAIA). The level of arthritis in experimental mice significantly reduced ( P < .05) after treatment with EGP at a dose of 500 mg/kg body weight (b.w.). This study also revealed that EGP is orally non-toxic. Ethyl p-methoxy cinamate was identified as the main constituent of EGP, which may result in its anti-inflammatory effect.

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Betulinic Acid-Azaprostanoid Hybrids: Synthesis and Pharmacological Evaluation as Anti-inflammatory Agents

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/1871523018666190426152049 ◽

2020 ◽

Vol 19 (3) ◽

pp. 254-267

Author(s):

Tatyana S. Khlebnicova ◽

Yuri A. Piven ◽

Fedor A. Lakhvich ◽

Iryna V. Sorokina ◽

Tatiana S. Frolova ◽

...

Keyword(s):

Cell Lines ◽

Betulinic Acid ◽

Inflammatory Diseases ◽

Toxic Agent ◽

Analgesic Effects ◽

Low Toxic ◽

Anti Inflammatory ◽

Inflammatory Effect

Background: Prevention and treatment of chronic inflammatory diseases require effective and low-toxic medicines. Molecular hybridization is an effective strategy to enhance the biological activity of new compounds. Triterpenoid scaffolds are in the focus of attention owing to their anti-inflammatory, antiviral, antiproliferative, and immunomodulatory activities. Heteroprostanoids have different pleiotropic effects in acute and chronic inflammatory processes. Objective: The study aimed to develop structurally new and low toxic anti-inflammatory agents via hybridization of betulinic acid with azaprostanoic acids. Methods: A series of betulinic acid-azaprostanoid hybrids was synthesized. The synthetic pathway included the transformation of betulin via Jones' oxidation into betulonic acid, reductive amination of the latter and coupling obtained by 3β-amino-3-deoxybetulinic acid with the 7- or 13-azaprostanoic acids and their homo analogues. The hybrids 1-9 were investigated in vivo on histamine-, formalin- and concanavalin A-induced mouse paw edema models and two models of pain - the acetic acid-induced abdominal writhing and the hotplate test. The hybrids were in vitro evaluated for cytotoxic activity on cancer (MCF7, U- 87 MG) and non-cancer humane cell lines. Results: In the immunogenic inflammation model, the substances showed a pronounced anti-inflammatory effect, which was comparable to that of indomethacin. In the models of the exudative inflammation, none of the compounds displayed a statistically significant effect. The hybrids produced weak or moderate analgesic effects. All the agents revealed low cytotoxicity on human immortalized fibroblasts and cancer cell lines compared with 3β- amino-3-deoxybetulinic acid and doxorubicin. Conclusion: The results indicate that the principal anti-inflammatory effect of hybrids is substantially provided with the triterpenoid scaffold and in some cases with the azaprostanoid scaffold, but the latter makes a significant contribution to reducing the toxicity of hybrids. Hybrid 1 is of interest as a potent low toxic agent against immune-mediated inflammation.

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