scholarly journals A Synthetic Cell-Penetrating Heparin-Binding Peptide Derived from BMP4 with Anti-Inflammatory and Chondrogenic Functions for the Treatment of Arthritis

2020 ◽  
Vol 21 (12) ◽  
pp. 4251
Author(s):  
Da Hyeon Choi ◽  
Dongwoo Lee ◽  
Beom Soo Jo ◽  
Kwang-Sook Park ◽  
Kyeong Eun Lee ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Combined Treatment ◽  
Therapeutic Effects ◽  
Heparin Binding ◽  
Rheumatic Arthritis ◽  
Binding Peptide ◽  
Human Knee ◽  
Synthetic Cell ◽  
Cell Penetrating ◽  
Anti Inflammatory

We report dual therapeutic effects of a synthetic heparin-binding peptide (HBP) corresponding to residues 15–24 of the heparin binding site in BMP4 in a collagen-induced rheumatic arthritis model (CIA) for the first time. The cell penetrating capacity of HBP led to improved cartilage recovery and anti-inflammatory effects via down-regulation of the iNOS-IFNγ-IL6 signaling pathway in inflamed RAW264.7 cells. Both arthritis and paw swelling scores were significantly improved following HBP injection into CIA model mice. Anti-rheumatic effects were accelerated upon combined treatment with Enbrel® and HBP. Serum IFNγ and IL6 concentrations were markedly reduced following intraperitoneal HBP injection in CIA mice. The anti-rheumatic effects of HBP in mice were similar to those of Enbrel®. Furthermore, the combination of Enbrel® and HBP induced similar anti-rheumatic and anti-inflammatory effects as Enbrel®. We further investigated the effect of HBP on damaged chondrocytes in CIA mice. Regenerative capacity of HBP was confirmed based on increased expression of chondrocyte biomarker genes, including aggrecan, collagen type II and TNFα, in adult human knee chondrocytes. These findings collectively support the utility of our cell-permeable bifunctional HBP with anti-inflammatory and chondrogenic properties as a potential source of therapeutic agents for degenerative inflammatory diseases.

scholarly journals Allium sativum L. (Garlic) Role in Osteoarthritis: A Systematic Review of Clinical Trials

2021 ◽  
Vol 11 (4) ◽  
pp. 12104-12119
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Side Effects ◽  
Allium Sativum ◽  
Inflammatory Diseases ◽  
Control Group ◽  
Therapeutic Effects ◽  
Inflammatory Factor ◽  
Anti Inflammatory ◽  
Over Time

Osteoarthritis is a chronic degenerative disease involving the joints and bones, causing their degradation over time. Inflammation, pain, and stiffness in joints are indicators of the disease. Pharmacotherapy cannot always be efficient and may cause side effects. So, adjuncts such as complementary herbs have become of note. Garlic is a herb well-known for its various therapeutic effects such as anti-bacterial, anti-hypertension, antioxidant and anti-inflammatory effects. Due to garlic's widespread use, studying its effects and mechanisms on inflammatory diseases such as osteoarthritis has been noteworthy. We searched Science Direct, Pubmed, Cochrane, and Google Scholar databases for all articles published until October 2020, based on PRISMA. Searched keywords were the following: [(garlic and arthritis), (garlic and osteoarthritis), (Garlic and OA), (Allium sativum and arthritis), (Allium sativum and osteoarthritis), (Allium sativum and OA)]. The results showed garlic, and its constituents have remarkable effects on improving OA symptoms through antioxidant and anti-inflammatory pathways. Our review shows that groups receiving garlic as a treatment showed a significant reduction in pain and inflammatory factor levels and an improved physical function instead of the control group.

scholarly journals Hydrogen, a Novel Therapeutic Molecule, Regulates Oxidative Stress, Inflammation, and Apoptosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Tian ◽  
Yafang Zhang ◽  
Yu Wang ◽  
Yunxi Chen ◽  
Weiping Fan ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Ischemia Reperfusion Injury ◽  
Inflammatory Diseases ◽  
Biological Effects ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Mitochondrial Energy Metabolism ◽  
Wide Range ◽  
Anti Inflammatory

Molecular hydrogen (H2) is a colorless and odorless gas. Studies have shown that H2 inhalation has the therapeutic effects in many animal studies and clinical trials, and its application is recommended in the novel coronavirus pneumonia treatment guidelines in China recently. H2 has a relatively small molecular mass, which helps it quickly spread and penetrate cell membranes to exert a wide range of biological effects. It may play a role in the treatment and prevention of a variety of acute and chronic inflammatory diseases, such as acute pancreatitis, sepsis, respiratory disease, ischemia reperfusion injury diseases, autoimmunity diseases, etc.. H2 is primarily administered via inhalation, drinking H2-rich water, or injection of H2 saline. It may participate in the anti-inflammatory and antioxidant activity (mitochondrial energy metabolism), immune system regulation, and cell death (apoptosis, autophagy, and pyroptosis) through annihilating excess reactive oxygen species production and modulating nuclear transcription factor. However, the underlying mechanism of H2 has not yet been fully revealed. Owing to its safety and potential efficacy, H2 has a promising potential for clinical use against many diseases. This review will demonstrate the role of H2 in antioxidative, anti-inflammatory, and antiapoptotic effects and its underlying mechanism, particularly in coronavirus disease-2019 (COVID-19), providing strategies for the medical application of H2 for various diseases.

scholarly journals Elucidation of the Anti-Inflammatory Mechanisms of Bupleuri and Scutellariae Radix Using System Pharmacological Analyses

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xia Shen ◽  
Zhenyu Zhao ◽  
Hao Wang ◽  
Zihu Guo ◽  
Benxiang Hu ◽  
...  
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Active Components ◽  
Scutellariae Radix ◽  
Combined Application ◽  
Anti Inflammatory ◽  
Bupleuri Radix

Objective. This study was aimed at elucidating the molecular mechanisms underlying the anti-inflammatory effect of the combined application of Bupleuri Radix and Scutellariae Radix and explored the potential therapeutic efficacy of these two drugs on inflammation-related diseases. Methods. After searching the databases, we collected the active ingredients of Bupleuri Radix and Scutellariae Radix and calculated their oral bioavailability (OB) and drug-likeness (DL) based on the absorption-distribution-metabolism-elimination (ADME) model. In addition, we predicted the drug targets of the selected active components based on weighted ensemble similarity (WES) and used them to construct a drug-target network. Gene ontology (GO) analysis and KEGG mapper tools were performed on these predicted target genes. Results. We obtained 30 compounds from Bupleuri Radix and Scutellariae Radix of good quality as indicated by ADME assays, which possess potential pharmacological activity. These 30 ingredients have a total of 121 potential target genes, which are involved in 24 biological processes related to inflammation. Conclusions. Combined application of Bupleuri Radix and Scutellariae Radix was found not only to directly inhibit the synthesis and release of inflammatory cytokines, but also to have potential therapeutic effects against inflammation-induced pain. In addition, a combination therapy of these two drugs exhibited systemic treatment efficacy and provided a theoretical basis for the development of drugs against inflammatory diseases.

Biological Responses to Hydrogen Molecule and its Preventive Effects on Inflammatory Diseases

2020 ◽  
Vol 26 ◽  
Author(s):  
Ikuroh Ohsawa
Keyword(s):  
Oxidative Stress ◽  
Hydroxyl Radical ◽  
Inflammatory Diseases ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Therapeutic Effects ◽  
Ophthalmic Surgery ◽  
Protective Function ◽  
Oxidation Of H2 ◽  
Anti Inflammatory

: Because multicellular organisms do not have hydrogenase, H2 has been considered to be biologically inactive in these species, and enterobacteria to be largely responsible for the oxidation of H2 taken into the body. However, we showed previously that inhalation of H2 markedly suppresses brain injury induced by focal ischemia–reperfusion by buffering oxidative stress. Although the reaction constant of H2 with hydroxyl radical in aqueous solution is two to three orders of magnitude lower than that of conventional antioxidants, we showed that hydroxyl radical generated by the Fenton reaction reacts with H2 at room temperature without a catalyst. Suppression of hydroxyl radical by H2 has been applied in ophthalmic surgery. However, many of the anti-inflammatory and other therapeutic effects of H2 cannot be completely explained by its ability to scavenge reactive oxygen species. H2 administration is protective in several disease models, and preculture in the presence of H2 suppresses oxidative stress-induced cell death. Specifically, H2 administration induces mitochondrial oxidative stress and activates Nrf2; this phenomenon, in which mild mitochondrial stress leaves the cell less susceptible to subsequent perturbations, is called mitohormesis. Based on these findings, we conclude that crosstalk between antioxidative stress pathways and the anti-inflammatory response is the most important molecular mechanism involved in the protective function of H2 , and that regulation of the immune system underlies H2 efficacy. For further medical applications of H2 , it will be necessary to identify the biomolecule on which H2 first acts.

scholarly journals Polyphenolic Maqui Extract as a Potential Nutraceutical to Treat TNBS-Induced Crohn’s Disease by the Regulation of Antioxidant and Anti-Inflammatory Pathways

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1752
Author(s):  
Tamara Ortiz ◽  
Federico Argüelles-Arias ◽  
Matilde Illanes ◽  
Josefa-María García-Montes ◽  
Elena Talero ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Body Weight Loss ◽  
Trinitrobenzene Sulfonic Acid ◽  
Therapeutic Effects ◽  
Transmural Inflammation ◽  
Microscopic Damage ◽  
Anti Inflammatory

Nutraceuticals include a wide variety of bioactive compounds, such as polyphenols, which have been highlighted for their remarkable health benefits. Specially, maqui berries have shown great antioxidant activity and anti-inflammatory effects on some inflammatory diseases. The objectives of the present study were to explore the therapeutic effects of maqui berries on acute-phase inflammation in Crohn’s disease. Balb/c mice were exposed to 2,4,6-trinitrobenzene sulfonic acid (TNBS) via intracolonic administration. Polyphenolic maqui extract (Ach) was administered orally daily for 4 days after TNBS induction (Curative Group), and for 7 days prior to the TNBS induction until sacrifice (Preventive Group). Our results showed that both preventive and curative Ach administration inhibited body weight loss and colon shortening, and attenuated the macroscopic and microscopic damage signs, as well as significantly reducing transmural inflammation and boosting the recovery of the mucosal architecture and its muco-secretory function. Additionally, Ach promotes macrophage polarization to the M2 phenotype and was capable of down-regulating significantly the expression of inflammatory proteins COX-2 and iNOS, and at the same time it regulates the antioxidant Nrf-2/HO-1 pathway. In conclusion, this is the first study in which it is demonstrated that the properties of Ach as could be used as a preventive and curative treatment in Crohn’s disease.

Molecular mechanisms of the glucocorticoid receptor in steroid therapy – lessons from transgenic mice

2012 ◽  
Vol 3 (3) ◽  
pp. 241-253 ◽  
Author(s):  
Sabine Hübner ◽  
Jan Tuckermann
Keyword(s):  
Side Effects ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Pathological Condition ◽  
Cell Types ◽  
Therapeutic Effects ◽  
Gene Promoters ◽  
Inflammatory Conditions ◽  
Anti Inflammatory ◽  
And Function

AbstractGlucocorticoids (GCs) are potent anti-inflammatory agents that are used to treat chronic inflammatory diseases, allergic conditions, and some cancers. However, their therapeutic effects are hampered by severe side effects, such as muscle weakness, insulin resistance, fat redistribution, and osteoporosis. GCs act on many cell types that express the GC receptor (GR) via several modes of action. One of them includes GR homodimers recognizing binding sequences in the DNA of gene promoters. Another mode involves the modulation of other DNA-bound transcription factors via dimer-independent mechanisms. To what extent these mechanisms contribute to GC-mediated effects is currently being elucidated from analyses of mice with conditional and function-selective mutations of the GR and is summarized in this review. Whether GR homodimerization or its monomer activity is decisive in the therapeutic effectiveness and associated side effects of GCs for the treatment of inflammatory conditions depends on the type of the pathological condition. Thus, the classic criterion for selective GR modulators, discrimination between GR dimer- and GR monomer-dependent protein-protein interaction, will not help in any condition to avoid side effects and maintain anti-inflammatory activity. Rather, novel criteria for selective GR modulators have to be defined that take into consideration the tissue-specific mechanisms of the GR to achieve optimized anti-inflammatory therapies with reduced side effects. In the case of avoiding osteoporosis as a side effect, a first example of such optimized compounds can be provided.

scholarly journals Anti-Inflammatory and Antimicrobial Volatile Oils: Fennel and Cumin Inhibit Neutrophilic Inflammation via Regulating Calcium and MAPKs

2021 ◽  
Vol 12 ◽  
Author(s):  
Michal Korinek ◽  
Heba Handoussa ◽  
Yi-Hong Tsai ◽  
You-Ying Chen ◽  
Meng-Hua Chen ◽  
...  
Keyword(s):  
Mediterranean Diet ◽  
Inflammatory Diseases ◽  
Formyl Peptide Receptor ◽  
Mass Spectrometry Analysis ◽  
Human Neutrophils ◽  
Therapeutic Effects ◽  
Volatile Oils ◽  
Foeniculum Vulgare ◽  
The Mediterranean ◽  
Anti Inflammatory

Neutrophilic inflammatory diseases, such as chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), or psoriasis, exert a huge burden on the global health system due to the lack of safe and effective treatments. Volatile oils from terrestrial plants showed impressive therapeutic effects against disorders of the skin, digestive system, lungs, liver, metabolism, and nervous system. However, their effect on the immune system and neutrophil function is still elusive. Fennel, cumin, marjoram, lavender, caraway, and anise are the common nutraceuticals that are widely used in the Mediterranean diet. The volatile oils of these herbs were screened for various biological activities, including anti-inflammatory, anti-allergic, antimicrobial, and antiviral effects. Several oils showed anti-inflammatory and antimicrobial potential. Fennel (Foeniculum vulgare) and cumin (Cuminum cyminum) fruits' volatile oils significantly suppressed the activation of human neutrophils, including respiratory burst and the degranulation induced by formyl peptide receptor agonists fMLF/CB and MMK1 in the human neutrophils (IC50, 3.8–17.2 µg/ml). The cytotoxic effect and free-radical scavenging effects (ABTS, DPPH) of these oils did not account for the observed effects. Both fennel and cumin volatile oils significantly shortened calcium influx recovery time and inhibited phosphorylation of mitogen-activated protein kinases (p38, JNK, and ERK) expression. The gas chromatography–mass spectrometry analysis of these oils revealed the presence of estragole and cuminaldehyde as the major components of fennel and cumin volatile oils, respectively. Our findings suggested that cumin and fennel, common in the Mediterranean diet, hold the potential to be applied for the treatment of neutrophilic inflammatory diseases.

scholarly journals Hepatosplenic Protective Actions of Spirulina platensis and Matcha Green Tea Against Schistosoma mansoni Infection in Mice via Antioxidative and Anti-inflammatory Mechanisms

2021 ◽  
Vol 8 ◽  
Author(s):  
Amany M. Ramez ◽  
Ehab Kotb Elmahallawy ◽  
Gehad E. Elshopakey ◽  
Amira A. Saleh ◽  
Samar M. Moustafa ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Green Tea ◽  
Spirulina Platensis ◽  
Combined Treatment ◽  
Infected Group ◽  
Antioxidant Systems ◽  
Control Group ◽  
High Morbidity ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Schistosomiasis, a major parasitic illness, has high morbidity and negative financial effects in subtropical and tropical countries, including Egypt. The present study investigated the therapeutic effects of Spirulina platensis (SP) and matcha green tea (MGT) in Schistosoma mansoni-infected mice combined with tracing their possible antioxidant and anti-inflammatory impacts and their protective potency. A total of 60 Swiss albino mice were randomly allocated into six groups (n = 10): control group (CNT, received normal saline); SP–MGT group [received oral SP (3 g/kg bodyweight/day) plus MGT (3 g/kg bodyweight/day)]; S. mansoni group (infected with S. mansoni cercariae, 100 ± 10/mouse, using the tail immersion method); SP-infected group (infected with S. mansoni and received oral SP); MGT-infected group (received oral MGT after S. mansoni infection); and SP–MGT-infected group (received combined treatment of SP and MGT after S. mansoni infection). Treatment with SP and MGT started 4 weeks after S. mansoni infection and ended 10 weeks after. SP and MGT treatment (SP-infected and MGT-infected groups) and the combined treatment (SP–MGT-infected group) minimized the hepatic damage induced by S. mansoni; circulating alanine aminotransferase and aspartate transaminase decreased, and total protein, albumin, and globulin serum levels increased. The serum level of malondialdehyde significantly declined, and catalase, glutathione peroxidase, superoxide dismutase, and total antioxidant capacity increased in SP-infected, MGT-infected, and SP–MGT-infected groups compared with the infected group. Co-administration of SP and MGT reduced serum cytokine levels (tumor necrosis factor-alpha, interferon-gamma, and interleukin-13) and increased interleukin-10 levels after S. mansoni infection compared with the infected group. Moreover, treatment with SP and/or MGT decreased the number of granulomas in hepatic and splenic tissues compared with the infected group. Collectively, our results suggest that combined SP and MGT treatment is effective for S. mansoni infection. Liver and spleen tissue alterations were improved, the antioxidant systems were stimulated, and the inflammatory response was suppressed. Further research is recommended to investigate the mechanisms of the combined SP and MGT treatment effects to facilitate the development of novel therapies against this disease.

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