scholarly journals The Anti-Inflammatory and Anti-Pruritus Mechanisms of Huanglian Jiedu Decoction in the Treatment of Atopic Dermatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yubin Xu ◽  
Saizhen Chen ◽  
Lingling Zhang ◽  
Guirong Chen ◽  
Jinguang Chen
Keyword(s):  
Atopic Dermatitis ◽  
Protein Expression ◽  
Transient Receptor Potential ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Lymphocyte Activation ◽  
Receptor Potential ◽  
Histamine H4 Receptor ◽  
Cell Percentage ◽  
Anti Inflammatory

Atopic dermatitis (AD) is a common chronic skin disease driven by a T-cell-mediated immune response, with inflammation and pruritus being its main clinical manifestations. Huanglian Jiedu decoction (HLJDT), which is an ancient Chinese medicine herbal formula derived from Wai-Tai-Mi-Yao, is a potentially effective treatment for AD. We aimed to clarify the anti-inflammatory and anti-pruritus mechanisms of HLJDT in AD treatment. We performed immunohistochemistry, Western blotting, reverse transcriptase-polymerase chain reaction, Luminex-based direct multiplex immunoassay, enzyme-linked immunosorbent assays, and flow cytometry to address the abovementioned aims. HLJDT significantly reduced clinical symptoms and ear swelling in AD-like mice by inhibiting the production of cytokines [histamine, interleukin (IL)-3, IL-4, IL-5, IL-13, IL-17A, IL-31, and IL-33], substance P (SP), transient receptor potential cation channel subfamily V member 1 (TRPV-1), and gastrin-releasing peptide (GRP). Additionally, HLJDT significantly suppressed the protein expression levels and positive cell percentage of CD28, CD80, CD86, CD207, CD326, MHCII, and OX40 in the lymphoid nodes. Moreover, HLJDT significantly suppressed mRNA and protein expression of tyrosine–protein kinase (JAK1), histamine H4 receptor, and IL-4Rα, as well as the protein expression of GRP, SP, and TRPV-1 in the root ganglion. Our findings indicate that HLJDT can treat AD by regulating the antigen presentation function of dendritic cells, weakening T-lymphocyte activation, and subsequently exerting anti-inflammatory and anti-pruritus effects.

scholarly journals Intractable Itch in Atopic Dermatitis: Causes and Treatments

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 229
Author(s):  
Yoshie Umehara ◽  
Chanisa Kiatsurayanon ◽  
Juan Valentin Trujillo-Paez ◽  
Panjit Chieosilapatham ◽  
Ge Peng ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Atopic Dermatitis ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Clinical Problem ◽  
Transient Receptor Potential Channels ◽  
Protease Activated Receptors ◽  
H1 Antihistamines ◽  
Potential Channels

Itch or pruritus is the hallmark of atopic dermatitis and is defined as an unpleasant sensation that evokes the desire to scratch. It is also believed that itch is a signal of danger from various environmental factors or physiological abnormalities. Because histamine is a well-known substance inducing itch, H1-antihistamines are the most frequently used drugs to treat pruritus. However, H1-antihistamines are not fully effective against intractable itch in patients with atopic dermatitis. Given that intractable itch is a clinical problem that markedly decreases quality of life, its treatment in atopic dermatitis is of high importance. Histamine-independent itch may be elicited by various pruritogens, including proteases, cytokines, neuropeptides, lipids, and opioids, and their cognate receptors, such as protease-activated receptors, cytokine receptors, Mas-related G protein-coupled receptors, opioid receptors, and transient receptor potential channels. In addition, cutaneous hyperinnervation is partly involved in itch sensitization in the periphery. It is believed that dry skin is a key feature of intractable itch in atopic dermatitis. Treatment of the underlying conditions that cause itch is necessary to improve the quality of life of patients with atopic dermatitis. This review describes current insights into the pathophysiology of itch and its treatment in atopic dermatitis.

Hydrogen sulfide modulates IL-6/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity

2019 ◽  
Vol 39 (1) ◽  
pp. 77-85 ◽  
Author(s):  
AA Fouad ◽  
HM Hafez ◽  
AAH Hamouda
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nuclear Factor Κb ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Stat3 Pathway ◽  
Anti Inflammatory ◽  
Apoptotic Effects

Methotrexate (MTX) is a commonly used anticancer and immunosuppressive agent. However, MTX can induce hepatotoxicity due to oxidative stress, inflammation, and apoptosis. Hydrogen sulfide (H2S), the endogenous gaseous molecule, has antioxidant, anti-inflammatory, and anti-apoptotic effects. The present work explored the probable protective effect of H2S against MTX hepatotoxicity in rats and also the possible mechanisms underlying this effect. MTX was given at a single intraperitoneal (i.p.) dose of 20 mg/kg. Sodium H2S (56 µmol /kg/day, i.p.), as H2S donor, was given for 10 days, starting 6 days before MTX administration. H2S significantly reduced serum alanine aminotransferase, hepatic malondialdehyde, interleukin 6, nuclear factor κB p65, cytosolic cytochrome c, phosphorylated signal transducer and activator of transcription 3, and Bax/Bcl-2 ratio and significantly increased hepatic total antioxidant capacity and endothelial nitric oxide synthase (eNOS) in rats received MTX. In addition, H2S minimized the histopathological injury and significantly decreased the expression of STAT3 in liver tissue of MTX-challenged rats. The effects of H2S were significantly antagonized by administration of glibenclamide as KATP channel blocker, Nω-nitro-l-arginine, as eNOS inhibitor, or ruthenium red, as transient receptor potential vanilloid 1 (TRPV1) antagonist. It was concluded that H2S provided significant hepatoprotection in MTX-challenged rats through its antioxidant, anti-inflammatory, anti-apoptotic effects. These effects are most probably mediated by the ability of H2S to act as IL-6/STAT3 pathway modulator, KATP channel opener, eNOS activator, and TRPV1 agonist.

scholarly journals Neuropathophysiology, Genetic Profile, and Clinical Manifestation of Mucolipidosis IV—A Review and Case Series

2020 ◽  
Vol 21 (12) ◽  
pp. 4564 ◽  
Author(s):  
Aleksandra Jezela-Stanek ◽  
Elżbieta Ciara ◽  
Karolina M. Stepien
Keyword(s):  
Transient Receptor Potential ◽  
Clinical Manifestations ◽  
Case Series ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Facial Dysmorphism ◽  
Genetic Profile ◽  
Lysosomal Storage ◽  
Psychomotor Delay ◽  
Severe Intellectual Disability

Mucolipidosis type IV (MLIV) is an ultra-rare lysosomal storage disorder caused by biallelic mutations in MCOLN1 gene encoding the transient receptor potential channel mucolipin-1. So far, 35 pathogenic or likely pathogenic MLIV-related variants have been described. Clinical manifestations include severe intellectual disability, speech deficit, progressive visual impairment leading to blindness, and myopathy. The severity of the condition may vary, including less severe psychomotor delay and/or ocular findings. As no striking recognizable facial dysmorphism, skeletal anomalies, organomegaly, or lysosomal enzyme abnormalities in serum are common features of MLIV, the clinical diagnosis may be significantly improved because of characteristic ophthalmological anomalies. This review aims to outline the pathophysiology and genetic defects of this condition with a focus on the genotype–phenotype correlation amongst cases published in the literature. The authors will present their own clinical observations and long-term outcomes in adult MLIV cases.

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

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 590 ◽  
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.

Intracellular calcium handling in ventricular myocytes from mdx mice

2007 ◽  
Vol 292 (2) ◽  
pp. H846-H855 ◽  
Author(s):  
Iwan A. Williams ◽  
David G. Allen
Keyword(s):  
Heart Failure ◽  
Protein Expression ◽  
Transient Receptor Potential ◽  
Ventricular Myocytes ◽  
Clinical Symptoms ◽  
Disease Process ◽  
Calcium Handling ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Age Related

Duchenne muscular dystrophy (DMD) is a lethal degenerative disease of skeletal muscle, characterized by the absence of the cytoskeletal protein dystrophin. Some DMD patients show a dilated cardiomyopathy leading to heart failure. This study explores the possibility that dystrophin is involved in the regulation of a stretch-activated channel (SAC), which in the absence of dystrophin has increased activity and allows greater Ca2+ into cardiomyocytes. Because cardiac failure only appears late in the progression of DMD, we examined age-related effects in the mdx mouse, an animal model of DMD. Ca2+ measurements using a fluorescent Ca2+-sensitive dye fluo-4 were performed on single ventricular myocytes from mdx and wild-type mice. Immunoblotting and immunohistochemistry were performed on whole hearts to determine expression levels of key proteins involved in excitation-contraction coupling. Old mdx mice had raised resting intracellular Ca2+ concentration ([Ca2+]i). Isolated ventricular myocytes from young and old mdx mice displayed abnormal Ca2+ transients, increased protein expression of the ryanodine receptor, and decreased protein expression of serine-16-phosphorylated phospholamban. Caffeine-induced Ca2+ transients showed that the Na+/Ca2+ exchanger function was increased in old mdx mice. Two SAC inhibitors streptomycin and GsMTx-4 both reduced resting [Ca2+]i in old mdx mice, suggesting that SACs may be involved in the Ca2+-handling abnormalities in these animals. This finding was supported by immunoblotting data, which demonstrated that old mdx mice had increased protein expression of canonical transient receptor potential channel 1, a likely candidate protein for SACs. SACs may play a role in the pathogenesis of the heart failure associated with DMD. Early in the disease process and before the onset of clinical symptoms increased, SAC activity may underlie the abnormal Ca2+ handling in young mdx mice.

Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as Emerging Target for Novel Analgesics and Anti-Inflammatory Agents

2010 ◽  
Vol 53 (14) ◽  
pp. 5085-5107 ◽  
Author(s):  
Pier Giovanni Baraldi ◽  
Delia Preti ◽  
Serena Materazzi ◽  
Pierangelo Geppetti
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Anti Inflammatory ◽  
Transient Receptor

Diet-induced obesity alters dural CGRP release and potentiates TRPA1-mediated trigeminovascular responses

Cephalalgia ◽  
2016 ◽  
Vol 37 (6) ◽  
pp. 581-591 ◽  
Author(s):  
Balázs Marics ◽  
Barna Peitl ◽  
Angelika Varga ◽  
Kitti Pázmándi ◽  
Attila Bácsi ◽  
...  
Keyword(s):  
Protein Expression ◽  
Transient Receptor Potential ◽  
Fasting Blood Glucose ◽  
Receptor Potential ◽  
Primary Headache ◽  
Headache Disorder ◽  
Chemical Exposure ◽  
Receptor Activation ◽  
Trigeminal Ganglia ◽  
Cgrp Release

Background Clinical studies suggest a link between obesity and the primary headache disorder migraine. In our study we aimed to reveal the effect of obesity on meningeal nociceptor function in rats receiving a high-fat, high-sucrose diet. Methods Transient receptor potential ankyrin 1 (TRPA1) receptor activation-induced changes in meningeal blood flow, release of calcitonin gene-related peptide (CGRP) from trigeminal afferents and TRPA1 protein expression in the trigeminal ganglia were measured in control and obese rats. Metabolic parameters of the animals were assessed by measuring glucose and insulin homeostasis as well as plasma cytokine concentrations. Results The present experiments revealed an enhanced basal and TRPA1 receptor agonist-induced CGRP release from meningeal afferents of obese insulin-resistant rats and an attenuated CGRP release to potassium chloride. Obesity was also associated with an augmented vasodilatation in meningeal arteries after dural application of the TRPA1 agonist acrolein, a reduction in TRPA1 protein expression in the trigeminal ganglia and elevations in circulating proinflammatory cytokines IL-1β and IL-6 in addition to increased fasting blood glucose and insulin concentrations. Conclusions Our results suggest trigeminal sensitisation as a mechanism for enhanced headache susceptibility in obese individuals after chemical exposure of trigeminal nociceptors.

scholarly journals Abundance of TRPC6 protein in glomerular mesangial cells is decreased by ROS and PKC in diabetes

2011 ◽  
Vol 301 (2) ◽  
pp. C304-C315 ◽  
Author(s):  
Sarabeth Graham ◽  
Yves Gorin ◽  
Hanna E. Abboud ◽  
Min Ding ◽  
Duck Yoon Lee ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Protein Expression ◽  
Transient Receptor Potential ◽  
Cultured Cells ◽  
Mesangial Cells ◽  
Receptor Potential ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells

The present study was performed to investigate the underlying mechanism, particularly the roles of reactive oxygen species (ROS) and protein kinase C (PKC), in the diabetes-induced canonical transient receptor potential 6 (TRPC6) downregulation. We found that high glucose (HG) significantly reduced TRPC6 protein expression in cultured mesangial cells (MCs). TRPC6 protein was also significantly reduced in the glomeruli but not in the heart or aorta isolated from streptozotocin-induced diabetic rats. In the cultured MCs, H2O2 suppressed TRPC6 protein expression in a dose- and time-dependent manner, which emulated the HG effect. Catalase as well as superoxide dismutase were able to prevent the inhibitory effect of HG on TRPC6. The antioxidant effect observed in cultured cells was also observed in diabetic rats treated with tempol for 2 wk, which exhibited a preservation of TRPC6 in the glomeruli. Specific knockdown of Nox4, a component of NADPH oxidase, increased TRPC6 protein expression. Furthermore, the PKC activator phorbol 12-myristate 13-acetate (PMA), but not its analog 4α-phorbol 12, 13-didecanoate (4α-PDD), suppressed TRPC6 expression, and this PMA effect was not affected by catalase. Moreover, Gö6976, but not LY333531, attenuated the negative effect of HG on TRPC6 expression. Gö6976 also inhibited H2O2 effect on TRPC6. Furthermore, either knockdown of TRPC6 or HG treatment significantly decreased ANG II-stimulated MC contraction, and the HG-impaired MC contraction was rescued by overexpression of TRPC6. These results suggest that hyperglycemia in diabetes downregulated TRPC6 protein expression in MCs through a NADPH oxidase Nox4-ROS-PKC pathway, proving a mechanism for impaired MC contraction in diabetes.

scholarly journals Clinical manifestations of childhood asthma persisting until the age of seven

2016 ◽  
Vol 44 (1) ◽  
pp. 1
Author(s):  
Rini Asterina ◽  
Sjawitri P Siregar ◽  
Bambang Madiyono ◽  
Bambang Supriyatno
Keyword(s):  
Allergic Rhinitis ◽  
Atopic Dermatitis ◽  
Childhood Asthma ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Persistent Asthma ◽  
Cigarette Smoke Exposure ◽  
Atopic Diseases ◽  
Inclusion Criteria

Background Asthma is a chronic illness commonly found in chil-dren. We aimed to find out the clinical manifestations of childhoodasthma persisting until the age of seven and the influencing factors.Methods A review was performed at the outpatient clinic of theDepartment of Child Health Cipto Mangunkusumo Hospital Jakarta,from January 1992 to December 2001, on children with asthmawho still had symptoms until the age of seven.Results During the period of 10 years, there were 322 childrenwith clinical symptoms of asthma persisting until the age of 7. Onehundred and forty-six (45.3%) met the inclusion criteria, consistingof 75 (51.4%) boys and 71 (48.6%) girls. The average age was11.7 years. There were 101 (69.2%) patients with rare episodicasthma, 26.0% with frequent episodic asthma, and 4.8% with per-sistent asthma. Age of onset was mostly beyond 3 year-old (51%).Besides asthma, atopic diseases noted in these patients were al-lergic rhinitis in 85 (58.2%) and atopic dermatitis in 42 (28.8%).Logistic regression found that cigarette smoke exposure (adjustedOR 4.72, 95%CI 2.05;10.87, p=0.000), allergic rhinitis (adjustedOR 3.44, 95%CI 1.40;8.45, p=0.007), and atopic dermatitis (ad-justed OR 2.37, 95%CI 1.01;5.72, p=0.048) had significant asso-ciation with the degree of asthma.Conclusion Of 146 children who still had asthma until the age ofseven, there were 69% with rare episodic asthma, 26% with fre-quent episodic asthma, and 4.8% with persistent asthma. Factorspresumably influencing this manifestations were cigarette smokeexposure, allergic rhinitis, and atopic dermatitis

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