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

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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Pulsed Electromagnetic Field Inhibits Synovitis via Enhancing the Efferocytosis of Macrophages

BioMed Research International ◽

10.1155/2020/4307385 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Junjie Ouyang ◽

Bin Zhang ◽

Liang Kuang ◽

Peng Yang ◽

Xiaolan Du ◽

...

Keyword(s):

Medial Meniscus ◽

Current Data ◽

Pulsed Electromagnetic Field ◽

Western Blot Assay ◽

Anti Inflammatory ◽

Pulsed Electromagnetic ◽

Underlying Mechanisms ◽

Pemf Treatment ◽

Inflammatory Effect

Synovitis plays an important role in the pathogenesis of arthritis, which is closely related to the joint swell and pain of patients. The purpose of this study was to investigate the anti-inflammatory effects of pulsed electromagnetic fields (PEMF) on synovitis and its underlying mechanisms. Destabilization of the medial meniscus (DMM) model and air pouch inflammation model were established to induce synovitis in C57BL/6 mice. The mice were then treated by PEMF (pulse waveform, 1.5 mT, 75 Hz, 10% duty cycle). The synovitis scores as well as the levels of IL-1β and TNF-α suggested that PEMF reduced the severity of synovitis in vivo. Moreover, the proportion of neutrophils in the synovial-like layer was decreased, while the proportion of macrophages increased after PEMF treatment. In addition, the phagocytosis of apoptotic neutrophils by macrophages (efferocytosis) was enhanced by PEMF. Furthermore, the data from western blot assay showed that the phosphorylation of P38 was inhibited by PEMF. In conclusion, our current data show that PEMF noninvasively exhibits the anti-inflammatory effect on synovitis via upregulation of the efferocytosis in macrophages, which may be involved in the phosphorylation of P38.

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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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Machaerium hirtum (Vell.) Stellfeld Alleviates Acute Pain and Inflammation: Potential Mechanisms of Action

Biomolecules ◽

10.3390/biom10040590 ◽

2020 ◽

Vol 10 (4) ◽

pp. 590 ◽

Cited By ~ 2

Author(s):

Juliana Agostinho Lopes ◽

Vinícius Peixoto Rodrigues ◽

Marcelo Marucci Pereira Tangerina ◽

Lucia Regina Machado da Rocha ◽

Catarine Massucato Nishijima ◽

...

Keyword(s):

Transient Receptor Potential ◽

Antinociceptive Effect ◽

Folk Medicine ◽

Receptor Potential ◽

Experimental Models ◽

Transient Receptor Potential Channels ◽

Anti Inflammatory ◽

Potential Channels ◽

Inflammatory Effect

Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as “jacaranda de espinho” or “espinheira santa nativa” is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, l-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE2) showed involvement of the COX pathway, based on observed decreases in PGE2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, β-amyrin, allantoin, apigenin-7-methoxy-6-C-β-d-glucopyranoside, and apigenin-6-C-β-d-glucopyranosyl-8-C-β-d-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE2 levels.

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The Anti-Inflammatory Activity of HMGB1 A Box Is Enhanced When Fused with C-Terminal Acidic Tail

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/915234 ◽

2010 ◽

Vol 2010 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

Wei Gong ◽

Yingru Zheng ◽

Fan Chao ◽

Yuan Li ◽

Zhizhen Xu ◽

...

Keyword(s):

Fusion Proteins ◽

Inflammatory Diseases ◽

Inflammatory Activity ◽

In Vivo Experiments ◽

Specific Antagonist ◽

Proinflammatory Activity ◽

Anti Inflammatory ◽

Inflammatory Effect

HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence(Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box.

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In vivo anti-inflammatory, antipyretic, analgesic activity and in vitro anti-proliferative activity of aqueous methanolic extract of Euphorbia granulata Forssk

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-021-00184-9 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Mohsin Ahmad Ghauri ◽

Liaqat Iqbal ◽

Ali Raza ◽

Uzma Hayat ◽

Naveel Atif ◽

...

Keyword(s):

Plant Extract ◽

Mtt Assay ◽

Proliferative Activity ◽

Methanol Extract ◽

Folk Medicine ◽

Aqueous Methanol ◽

Whole Plant ◽

Anti Inflammatory

Abstract Background Naturally occurring substances of plant origin have long been used in folk medicine for curing various ailments including fever, pain, and inflammation etc. After careful evaluation on scientific bases, a large number of those substances provides cheaper alternative to currently used synthetic or semi-synthetic agents. Thus, with an aim of discovering alternative medicine for treatment of such ailments, current study was carried out. Euphorbia granulata Forssk. had long been used as a therapeutic agent against various morbid conditions, e.g., anthelmintic, snake bite, scorpion sting, purgative, and diuretic, and as blood purifying agent in folk medicine. The purpose of the current study was to determine the extended therapeutic use of Euphorbia granulata Forssk. based upon scientific evaluation, to explore the potential of its anti-proliferative, analgesic, antipyretic, and anti-inflammatory activities while using an aqueous methanol extract of the whole plant. Results In vivo study was performed on female rats of specie Rattus norvegicus weighing (100–150 g). Anti-inflammatory activity of the plant extract was calculated against using carrageenan induced paw edema. Analgesic potential both central and peripheral was assessed by using Eddy’s hot plate method and acetic acid-induced writhing model, respectively. The antipyretic potential was appraised using brewer’s yeast suspension, injected under the nape of the neck, and body temperature was measured using a digital thermometer. The plant extract strengths used for in vivo experiments were 50 mg, 100 mg, and 200 mg/kg (diluted in normal saline) and were administered through intra-peritoneal route. MTT assay was performed to estimate in vitro anti-proliferative potential. For this assay, a serial dilution of the plant extract was used with 100 μg/ml as the highest concentration. In vivo results demonstrated that plant extract at dose strength of 200 mg/kg, showed significant (p* < 0.05) anti-inflammatory, analgesic, and antipyretic activities. In case of MTT assay, however, no significant anti-proliferative activity (p > 0.05) was observed up to 100 μg/ml dose strength. Conclusion It can be concluded that aqueous methanol extract of Euphorbia granulata (whole plant) have shown significant anti-inflammatory, analgesic, and anti-pyretic activity in animal model. Therefore it can be a potential candidate, as a therapeutic alternative against treatment of algesia, pyrexia, and inflammation of various pathological origin. However, the plant extract did not demonstrate any significant anti-proliferation activity at doses used in this study.

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Potential Anti-inflammatory Sesquiterpene Lactones from Eupatorium lindleyanum

Planta Medica ◽

10.1055/s-0043-117742 ◽

2017 ◽

Vol 84 (02) ◽

pp. 123-128 ◽

Cited By ~ 10

Author(s):

Fang Wang ◽

Huanhuan Zhong ◽

Shiqi Fang ◽

Yunfeng Zheng ◽

Cunyu Li ◽

...

Keyword(s):

Sesquiterpene Lactones ◽

Folk Medicine ◽

2D Nmr ◽

In Vitro Assays ◽

Raw 264.7 Cells ◽

Therapeutic Effects ◽

In Vivo Experiments ◽

Anti Inflammatory

Abstract Eupatorium lindleyanum has traditionally been used as folk medicine in Asian countries for its therapeutic effects on tracheitis and tonsillitis. Investigation of the anti-inflammatory active constituents from E. lindleyanum led to the isolation of two novel sesquiterpene lactones, named eupalinolide L (1) and eupalinolide M (2), and seven known sesquiterpene lactones (3–9). The structures and configurations of the new compounds were determined on the basis of spectroscopic analysis, especially 2D NMR techniques. In vivo experiments showed that the sesquiterpenes fraction significantly reduced mouse ear edema induced by xylene (18.6%, p < 0.05). In in vitro assays, compounds 1–9 showed excellent anti-inflammatory activities, as they lowered TNF-α and IL-6 levels in lipopolysaccharide-stimulated murine macrophage RAW 264.7 cells (p < 0.001). The above results suggest that the sesquiterpene lactones from E. lindleyanum can be developed as novel potential natural anti-inflammatory agents.

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

Journal of Nutrition & Food Sciences ◽

10.4172/2155-9600.1000653 ◽

2018 ◽

Vol 08 (01) ◽

Cited By ~ 3

Author(s):

Yulia Solomonov ◽

Nurit Hadad ◽

Rachel Levy

Keyword(s):

Mouse Model ◽

Carnosic Acid ◽

Anti Inflammatory ◽

Inflammatory Effect

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Anti-Inflammatory Effect of Homo- and Heterodimers of Natural Enkephalinase Inhibitors in Experimental Colitis in Mice

Molecules ◽

10.3390/molecules25245820 ◽

2020 ◽

Vol 25 (24) ◽

pp. 5820

Author(s):

Małgorzata Sobocińska ◽

Maciej Salaga ◽

Jakub Fichna ◽

Elżbieta Kamysz

Keyword(s):

Mouse Model ◽

Human Plasma ◽

Experimental Colitis ◽

Neutral Endopeptidase ◽

Myeloperoxidase Activity ◽

Anti Inflammatory ◽

Enkephalinase Inhibitors ◽

Inflammatory Effect

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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