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

Molecules ◽  
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.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

scholarly journals Sorbaria kirilowii Ethanol Extract Exerts Anti-Inflammatory Effects In Vitro and In Vivo by Targeting Src/Nuclear Factor (NF)-κB

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 741 ◽  
Author(s):  
Jiwon Jang ◽  
Jong Sub Lee ◽  
Young-Jin Jang ◽  
Eui Su Choung ◽  
Wan Yi Li ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Inflammatory Activity ◽  
No Production ◽  
Nuclear Factor ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Inflammation is a fundamental process for defending against foreign antigens that involves various transcriptional regulatory processes as well as molecular signaling pathways. Despite its protective roles in the human body, the activation of inflammation may also convey various diseases including autoimmune disease and cancer. Sorbaria kirilowii is a plant originating from Asia, with no anti-inflammatory activity reported. In this paper, we discovered an anti-inflammatory effect of S. kirilowii ethanol extract (Sk-EE) both in vivo and in vitro. In vitro effects of Sk-EE were determined with lipopolysaccharide (LPS)-stimulated RAW264.7 cells, while ex vivo analysis was performed using peritoneal macrophages of thioglycollate (TG)-induced mice. Sk-EE significantly reduced the nitric oxide (NO) production of induced macrophages and inhibited the expression of inflammation-related cytokines and the activation of transcription factors. Moreover, treatment with Sk-EE also decreased the activation of proteins involved in nuclear factor (NF)-κB signaling cascade; among them, Src was a prime target of Sk-EE. For in vivo assessment of the anti-inflammatory effect of Sk-EE, HCl/EtOH was given by the oral route to mice for gastritis induction. Sk-EE injection dose-dependently reduced the inflammatory lesion area of the stomach in gastritis-induced mice. Taking these results together, Sk-EE exerts its anti-inflammatory activity by regulating intracellular NF-κB signaling pathways and also shows an authentic effect on reducing gastric inflammation.

scholarly journals Pro-Inflammatory Cytokines at Ultra-Low Dose Exert Anti-Inflammatory Effect In Vitro: A Possible Mode of Action Involving Sub-Micron Particles?

Dose-Response ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 155932582096172
Author(s):  
Ilaria Floris ◽  
Thorsten Rose ◽  
Juan Antonio Collado Rojas ◽  
Kurt Appel ◽  
Camille Roesch ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Mode Of Action ◽  
Inflammatory Diseases ◽  
Resistive Pulse ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are pro-inflammatory cytokines involved in acute and chronic inflammatory diseases. Indeed, immunotherapy blocking these 2 cytokines has been developed. Micro-immunotherapy (MI) also uses ultra-low doses (ULD) of pro-inflammatory cytokines, impregnated on lactose-sucrose pillules, to counteract their overexpression. The study has been conducted with 2 objectives: examine the anti-inflammatory effect in vitro and the capacity of 2 unitary medicines, TNF-α (27 CH) and IL-1β (27 CH), to reduce the secretion of TNF-α in human primary monocytes and THP-1 cells differentiated with phorbol-12-myristate-13-acetate, after lipopolysaccharide (LPS) exposure; then, investigate the presence of particles possibly containing starting materials using tunable resistive pulse sensing technique. The results show that the unitary medicines, tested at 3 pillules concentrations (5.5, 11 and 22 mM), have reduced the secretion of TNF-α in both models by about 10−20% vs. vehicle control, depending on concentration. In this exploratory study, particles (150−1000 nm) have been detected in MI ULD-impregnated pillules and a hypothesis for MI medicines mode of action has been proposed. Conscious that more evaluations are necessary, authors are cautious in the conclusions because the findings described in the study are still limited, and future investigations may lead to different hypothesis.

scholarly journals Toxicity and Anti-inflammatory Activities of an Extract of the Eleutherine bulbosa Rhizome on Collagen Antibody-induced Arthritis in a Mouse Model

2018 ◽  
Vol 13 (7) ◽  
pp. 1934578X1801300
Author(s):  
Pham Thi Bich Hanh ◽  
Do Thi Thao ◽  
Nguyen Thi Nga ◽  
Ngo Thi Phuong ◽  
Le Ngoc Hung ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ethanol Extract ◽  
Serum Levels ◽  
Negative Control ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Beneficial Effects ◽  
Anti Inflammatory

As a continuation of our interest in the anti-inflammatory activities of Vietnamese plants, we searched for novel anti-inflammatory agents in Eleutherine bulbosa and evaluated the anti-inflammatory effects of an ethanol extract of the rhizome of E. bulbosa (EBE) on lipopolysaccharide-stimulated RAW 264.7 macrophages in vitro and in a collagen antibody-induced arthritic (CAIA) mouse model in vivo. Treatment of the CAIA mice with EBE decreased the incidence of arthritis, especially at a dose of 1000 mg/kg body weight. A significant ( P<0.05) decrease in the arthritis score was seen after high-dose EBE treatment between days 10 and 14 in comparison with the negative control. The serum levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10 in the mice were measured using commercial ELISA kits. The results suggest that an ethanol extract of the E. bulbosa rhizome has beneficial effects on inflammatory cytokine regulation in an experimental CAIA model.

Anti-inflammatory effect of an Ayurveda polyherbal topical application and exploration of its mechanism of action

2017 ◽  
Vol 2 (06) ◽  
Author(s):  
Sitaram Ahalya ◽  
B. A. Venkatesh ◽  
R. Vijayasarathi ◽  
Tirumalapura Vijayanna Shalini
Keyword(s):  
Topical Application ◽  
Inflammatory Activity ◽  
Polyherbal Formulation ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Ear Oedema ◽  
Inflammatory Effect

Background: Topical application of herbs is one of the recommended treatment modalities for Osteoarthritis (OA) in Ayurveda (Indian system of medicine). The current study intended to evaluate the anti-inflammatory effect of a polyherbal powder used as Upanaha (poultice) for OA by in vitro and in vivo techniques. Materials and Methods: The polyherbal formulation Upanaha Choornam (UC) was sourced from Vaidyaratnam Oushadhasala (P) Ltd., Thrissur, India. Changes in the secretion of TNF-α and NO and expression of Cox-2 genes were evaluated by semi quantitative PCR activity to establish anti-inflammatory action in vitro. Macrophages and connective tissue of mice were used as media for the former two experiments and only macrophages for the latter. In vivo anti–inflammatory activity was evaluated by TPA induced ear oedema in Swiss Albino mice (n=24), divided into 4 groups as Group I - saline treatment, Group II - Indomethacin treatment, and Groups III and IV treated with 30% and 60% of UC respectively. Results: In the in vitro study, UC at 1000 µg/ml and 500 µg/ml upregulated the COX-2 level by 0.08 and 0.03 folds respectively as compared to control. Release of TNF-α, and NO in LPS-induced RAW cells were significantly inhibited in a dose dependent manner. The TPA induced ear oedema significantly reduced in Groups III and IV (F=1250, p less than 0.001) Conclusion: The current study demonstrates the safety and anti-inflammatory activity of a polyherbal formulation Upanaha Choornam as a topical application. This indicates the potential of select herbs in managing degenerative conditions like OA.

In Vitro and in Vivo Therapeutics of β-Thujaplicin on Lps-Induced Inflammation in Macrophages and Septic Shock in Mice

2012 ◽  
Vol 25 (1) ◽  
pp. 39-48 ◽  
Author(s):  
M-F. Shih ◽  
L-Y. Chen ◽  
P-J. Tsai ◽  
J-Y. Cherng
Keyword(s):  
Septic Shock ◽  
Mortality Rate ◽  
Molecular Mechanisms ◽  
No Production ◽  
Active Constituent ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Effect

β-thujaplicin, an active constituent from Chamaecyparis obtusa, has been shown to have acaricidal and antimicrobial effects. Very few studies have focused on the potential of the anti-inflammatory effect of β-thujaplicin. Moreover, its capability of inhibiting inflammatory mediators e.g. TNF-α gene transcription, nitric oxide (NO) and prostaglandin E2, remains unknown. Besides those molecular mechanisms behind the anti-inflammatory effect of β-thujaplicin, solid proof of its effectiveness in vivo has not yet been studied. In our study, in vitro effects of β-thujaplicin were verified on RAW 264.7 macrophages which were stimulated by LPS. Indomethacin was used as a positive control. The inducible NO production after stimulation was measured by Griess reagent. PGE2, IL-6 and TNF-α were measured by ELISA methods. Protein expressions of iNOS, COX2, and NF-κB were evaluated by Western blotting. Septic ICR mice were administered 20 mg/kg of LPS and then the mortality rate was monitored. Within the concentration range which was devoid of cytotoxicty, β-thujaplicin exhibited a clear dose-dependent inhibition on LPS-induced NO production. Furthermore, β-thujaplicin inhibited LPS-induced PGE2, IL-6, and TNF-α production as well as iNOS, COX2, and NF-κB protein expression more substantially potent than indomethacin. In agreement with the in vitro study, β-thujaplicin was shown to be effective in vivo for inhibiting LPS-induced NO and TNF-α production and a significant decrease in mortality rate of mice suffering from septic shock was observed. This study demonstrates the potential of β-thujaplicin in treatment of inflammation and sepsis. These effects occur through an efficient blockage of TNF-α and iNOS production, β-thujaplicin efficacy is comparable to that of indomethacin thus it can be a substitution but bear less depletion of PGE2, making this compound very promising in clinical applications.

scholarly journals Adipose Stem Cell-Derived Exosomes Exert a Synergic Anti-Inflammatory Effect with Glucocorticoids and Override Their Detrimental Effects on Rotator Cuff Tendons

2021 ◽  
Author(s):  
Xuancheng Zhang ◽  
Ang Li ◽  
Kang Han ◽  
He Zhang ◽  
Xiaoqiao Huangfu ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Inflammatory Cytokines ◽  
Cellular Proliferation ◽  
In Vivo Studies ◽  
Degradative Enzymes ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Abstract Background: Glucocorticoids (GCs) injections are commonly used to relieve pain and improve function in patients with multiple shoulder disability, they cause detrimental effects on the rotator cuff tendons. Adipose stem cell-derived exosomes (ASC-Exos) reportedly recover impaired tendon matrix metabolism by maintaining tissue homeostasis. It is unclear whether additional ASC-Exos treatment overrides the detrimental effects of GCs without interfering with their anti-inflammatory effects.Methods: The in vitro studies included inflammatory analysis and cytoprotective analysis. In the inflammatory analysis, rat raw cells were treated with saline, GCs, or GCs + ASC-Exos and evaluated regarding cellular proliferation, migration, and secretion of inflammatory-related cytokines. In the cytoprotective analysis, rat tenocytes were treated with saline, GCs, or GCs + ASC-Exos and evaluated regarding cellular proliferation, migration, senescence, apoptosis, and transcription of tenocytic genes. In the in vivo studies, a subacromial injection of saline, GCs, or GCs + ASC-Exos was performed in a chronic injured-intact rotator cuff rat model. Histological and biomechanical analysis were performed 1 week to evaluate the protective effect of ASC-Exos against GCs-induced detriments on injured-intact in rotator cuffs.Results: In the in vitro inflammatory analysis, GCs treatment significantly decreased the proliferation, migration, and secretion of pro-inflammatory cytokines in raw cells, and increased the secretion of anti-inflammatory cytokines; additional ASC-Exos treatment further significantly decreased the secretion of pro-inflammatory cytokines and increased the secretion of anti-inflammatory cytokines, while restoring GCs-suppressed cellular proliferation and migration. In the in vitro cytoprotective analysis, GCs treatment significantly decreased the proliferation, migration, and transcription of tenocytic matrix molecules of tenocytes, and significantly increased their senescence, apoptosis, and transcription of ROS and tenocytic degradative enzymes; additional ASC-Exos treatment significantly improved the GCs-suppressed cellular proliferation, migration, and transcription of tenocytic matrix molecules, transcription of tenocytic degradative enzyme inhibitors, and significantly decreased the GCs-induced cell senescence, apoptosis, and transcription of ROS and tenocytic degradative enzymes. In the in vivo studies, an additional ASC-Exos injection restored the impaired histological and biomechanical properties owing to GCs administration.Conclusion: ASC-Exos may exert a stronger anti-inflammatory effect in combination with GCs, and override their detrimental effects on the rotator cuff.

GH-releasing peptide-2 administration prevents liver inflammatory response in endotoxemia

2008 ◽  
Vol 294 (1) ◽  
pp. E131-E141 ◽  
Author(s):  
Miriam Granado ◽  
Ana Isabel Martín ◽  
María López-Menduiña ◽  
Asunción López-Calderón ◽  
M. Angeles Villanúa
Keyword(s):  
Receptor Agonist ◽  
Serum Levels ◽  
Ghrelin Receptor ◽  
Nonparenchymal Cells ◽  
Tnf Α ◽  
Igf I ◽  
Ghrelin Receptor Agonist ◽  
Anti Inflammatory ◽  
Inflammatory Effect

It has been reported that growth hormone (GH)-releasing peptide-2 (GHRP-2), a ghrelin receptor agonist, has an anti-inflammatory effect. We investigated whether this GH secretagogue attenuates liver injury in LPS-treated rats. Wistar rats were simultaneously injected (ip) with LPS (1 mg/kg) and/or GHRP-2 (100 μg/kg). Serum levels of aspartate and alanine transaminases were measured as an index of liver damage. Circulating nitrites/nitrates and hepatic IGF-I and TNF-α were evaluated as possible mediators of GHRP-2 actions. LPS increased serum levels of transaminases and nitrites/nitrates. Moreover, LPS increased hepatic TNF-α and decreased hepatic IGF-I mRNAs. GHRP-2 administration attenuated the effects of LPS on transaminases, nitrites/nitrates, TNF-α, and IGF-I in vivo. This GHRP-2 effect does not seem to be due to modifications in food intake, since fasting did not modify serum levels of transaminases, serum nitrites/nitrates, and hepatic TNF-α mRNA both in vehicle rats and in LPS-injected rats. To elucidate whether GHRP-2 is acting directly on the liver, cocultures of hepatocytes and nonparenchymal cells and monocultures of isolated hepatocytes were incubated with LPS and GHRP-2. The ghrelin receptor agonist prevented an endotoxin-induced increase in transaminases and nitrite/nitrate release as well as in TNF-α mRNA and increased IGF-I mRNA from cocultures of hepatocytes and nonparenchymal cells, but not from monocultures. In summary, these data indicate that GHRP-2 has a protective effect on the liver in LPS-injected rats that seems to be mediated by IGF-I, TNF-α, and nitric oxide. Our data also suggest that the anti-inflammatory effect of GHRP-2 in the liver is exerted on nonparenchymal cells.

scholarly journals Celastrol alleviates LPS-induced inflammation in BMDMs and acute lung injury in mice via inhibition of p-38 MAPK/MK2 signaling

2021 ◽  
Vol 19 ◽  
pp. 205873922110205
Author(s):  
Zhengxu Chen ◽  
Xinyi Yang ◽  
Lu Zhang ◽  
Man Li ◽  
Lei Sun ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
P38 Mapk ◽  
Lavage Fluid ◽  
Lung Edema ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Objective: Celastrol is a compound extracted from a medicinal plant Tripterygium wilfordii which has a broad-spectrum anti-inflammatory effect in traditional medicine. However, the effect of celastrol on acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is still unknown. Methods: We reported that celastrol alleviated LPS-induced acute lung injury by H&E staining, MPO activity and the expression of cytokines in broncho-alveolar lavage fluid. The effect of celastrol on bone marrow-derived macrophages (BMDMs) after LPS treatment was measured by ELISA and Western blotting. Results: In vivo, celastrol reduced the LPS-induced lung edema and MPO activity of lung tissue. Furthermore, the production of inflammatory cytokines IL-6, TNF-α, and KC in bronchoalveolar lavage was reduced. In vitro, upon treatment of LPS, celastrol dose-dependently inhibited the expression of iNOS in BMDMs. Meanwhile, the expression of IL-6, TNF-α, and KC in BMDMs were also inhibited by celastrol treatment. Furthermore, we found that celastrol attenuated the phosphorylation of p38 MAPK and MK2, and inhibited the interaction between p38 MAPK and MK2. Conclusion: Our data indicate that celastrol has an anti-inflammatory effect on LPS-induced inflammatory response in vivo and in vitro, suggesting celastrol is a promising compound for the treatment of ALI and ARDS.

scholarly journals In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosangela Montanaro ◽  
Alessio D’Addona ◽  
Andrea Izzo ◽  
Carlo Ruosi ◽  
Vincenzo Brancaleone
Keyword(s):  
Inflammatory Markers ◽  
In Vitro Study ◽  
Inos Expression ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

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