Anti-inflammatory activity of the antiallergic drug 7-[4-(4-benzhydrylpiperazinyl-1)butyl]-3-methylxanthine succinate (theoritin)

2021 ◽  
Vol 18 (2) ◽  
pp. 20-31
Author(s):  
Igor S. Gushchin ◽  
Kirill L. Kryshen ◽  
Andrei B. Bondarenko
Keyword(s):  
Proinflammatory Cytokines ◽  
Allergic Inflammation ◽  
Clinical Importance ◽  
Test Scheme ◽  
Cytotoxic Action ◽  
H1 Receptor ◽  
Reference Drug ◽  
H1 Antihistamines ◽  
Antiallergic Drug ◽  
Anti Inflammatory

BACKGROUND: Many antagonists of histamine (H1) receptor, in addition to antihistamine action, suppress allergic inflammation by inhibiting the formation and secretion of proinflammatory cytokines. The new antiallergic drug benzhydrylpiperazinyl butylmethylxanthine succinate (theoritin), which has an antihistamine activity comparable to the known second generation H1-antihistamines, surpasses them in the ability to suppress the allergic inflammatory reaction, which allows this drug to have additional anti-inflammatory properties associated with the inhibition of the formation of proinflammatory cytokines. AIM: This study aimed to determine the effect of theoritin on the induced release of proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)- in cell culture in comparison with the action of the inverse agonist of H1 receptor cetirizine and a known inflammation inhibitor glucocorticosteroid dexamethasone. MATERIALS AND METHODS: U937 cells differentiated toward macrophage-like cells were used. Cytotoxicity of the substances used was assessed in the methyltetrazolium test at different incubation times (up to 24 h). Cells were stimulated with lipopolysaccharide (LPS). The tested compounds (theoritin and cetirizine) were evaluated at concentrations from 0.001 to 100 M and dexamethasone at 10 M was tested when added to cells 1 h before (prophylactic effect) or 1 h after (therapeutic effect) the addition of LPS. The presence of IL-6, IL-8, and TNF in the supernatants was determined by enzyme immunoassay. RESULTS: For cetirizine and theoritin, no cytotoxic action was found in the tested concentrations and time points. Dexamethasone inhibited the formation of IL-6 and TNF to the initial level and IL-8 to 50%60%. Theoritin led to a significant concentration-dependent decrease in the LPS-induced production of IL-6, IL-8, and TNF, and at a concentration of 100 M, the effect of theoritin was comparable with that of dexamethasone at a concentration of 10 M. The prophylactic test scheme for theoritin was more effective in suppressing LPS-induced production of proinflammatory cytokines than the curative one. The described effect of theoritin on LPS-induced production of proinflammatory cytokines exceeded that of the reference drug cetirizine. CONCLUSION: In addition to its antihistaminic action, theoritin, a new antiallergic agent, inhibits LPS-induced production of proinflammatory cytokines, which may be of clinical importance in suppressing allergic inflammation.

scholarly journals Inhibition of Proinflammatory Cytokines in Cutibacterium acnes-Induced Inflammation in HaCaT Cells by Using Buddleja davidii Aqueous Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Anh Thu Nguyen ◽  
Ki-young Kim
Keyword(s):  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Treatment Options ◽  
Mapk Signaling ◽  
Cytokine Expression ◽  
Proinflammatory Cytokine Expression ◽  
Cutibacterium Acnes ◽  
Anti Inflammatory ◽  
New Treatment ◽  
Hacat Keratinocyte

Acne is an inflammatory skin disorder; although some anti-inflammatory medicines for treating acne are available in a market, they have considerable side effects; therefore, new treatment options are needed. In the present study, among the 16 aqueous extracts of plants collected from Jeju Island in Korea which are used to test anti-inflammatory activity, B. davidii showed the strong decline of the proinflammatory cytokine expression against the inflammatory process caused by C. acnes in Human HaCaT keratinocyte cells. B. davidii downregulated the expression of 57% of COX-2, 41% of iNOS, and proinflammatory cytokines 29% of TNF-α, 32% of IL-1β, 21% of IL-6, and 35% of IL-8. Furthermore, B. davidii inhibited NF-κB and MAPK signaling cascades in keratinocytes that activated by toll-like receptor 2 (TLR-2) in response to C. acnes. Given those results, B. davidii is a potential agent to reduce the proinflammatory cytokine expression against C. acnes-induced inflammation and might provide an alternative to the current medications.

scholarly journals The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3701
Author(s):  
Salah E. M. Eltom ◽  
Ahmed A. H. Abdellatif ◽  
Hamzah Maswadeh ◽  
Mohsen S. Al-Omar ◽  
Atef A. Abdel-Hafez ◽  
...  
Keyword(s):  
Oral Administration ◽  
Standard Procedure ◽  
P Value ◽  
Skin Thickness ◽  
Paw Edema ◽  
Reference Drug ◽  
Struthio Camelus ◽  
Anti Inflammatory ◽  
Nano Emulsion ◽  
Inflammatory Effect

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.

Ozone Therapy Alleviates Monosodium Urate Induced Acute Gouty Arthritis in Rats Through Inhibition of NLRP3 Inflammasome

2021 ◽  
Vol 16 ◽  
Author(s):  
Doaa M. Abdullah ◽  
Soad L. Kabil
Keyword(s):  
Gouty Arthritis ◽  
Antioxidant Defense System ◽  
Albino Rats ◽  
Monosodium Urate ◽  
Ozone Therapy ◽  
Reference Drug ◽  
Acute Gouty Arthritis ◽  
Beneficial Effects ◽  
Anti Inflammatory ◽  
Domain 3

Background: Gout is a metabolic disease strictly related to hyperuricemia. The associated intense inflammation and pain are triggered by the deposited monosodium urate crystals (MSU) in joints. The principal therapeutic strategies of gout involve the control of hyperuricemia and anti-inflammatory medications. Objectives: This study aimed to investigate the possible beneficial effects of ozone therapy, a well-known antioxidant, and an immunomodulation, on gouty arthritis and the underlying mechanisms. Methods : Acute gouty arthritis was induced in male albino rats via MSU crystals intra-articular injection in the ankle joint. The gouty arthritic rats received pre-treatment with ozone, colchicine (as a reference drug), or combination. Results : The obtained results of ozone therapy showed obvious reduction in the degree of ankle edematous swelling, pro-inflammatory cytokines, lipid peroxidation, the nucleotide binding oligomerization domain like receptor containing pyrin domain 3 (NLRP3), procaspase-1, caspase-1, interleukin-1β synovial tissue levels with enhancement of antioxidant defense system. Additionally, ozone therapy significantly attenuated the histological derangements in gouty arthritic rats. Conclusion : This study suggests that ozone is able to treat gouty arthritis and reducing synovial injury through an anti-inflammatory effect as well as antioxidant activity.

scholarly journals Inhibitory effect of AD-1590, a non-steroidal anti-inflammatory drug, on allergic inflammation in mice and rats.

1988 ◽  
Vol 92 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Hideo NAKAMURA ◽  
Satoru MOTOYOSHI ◽  
Katsumi ISHII ◽  
Toshiaki KADOKAWA
Keyword(s):  
Allergic Inflammation ◽  
Inhibitory Effect ◽  
Inflammatory Drug ◽  
Anti Inflammatory

scholarly journals Plasma levels of melatonin, certain cytokines and placental growth factor at non-pharmacological correction of pineal function in pregnant women with intrauterine growth restriction

2020 ◽  
Vol 8 (2) ◽  
Author(s):  
A. Berbets ◽  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Pineal Gland ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Placental Growth Factor ◽  
Placental Insufficiency ◽  
Tnf Α ◽  
Anti Inflammatory

The pineal gland produces the important hormone melatonin, the level of which in the blood of pregnant women decreases in case of placental insufficiency. The effect of dysfunction of the pineal gland on the immune system of pregnant women and on the angiogenic activity of the placenta during pregnancy remains insufficiently studied. Objective: to establish the effect of our method of non-drug correction of function of pineal gland on the state of the cytokine part of the immune system and on the synthesis of placental growth factor (PlGF) in pregnant women with placental insufficiency manifesting as fetal intrauterine growth restriction (IUGR). Material and methods. 46 pregnant women with IUGR at 30-36 weeks of gestation were examined. The group was divided into two subgroups: with non-drug correction of the pineal gland function (n = 25) and without correction (n = 21). The method of correction included a set of measures of following of lighting regimen, activity and sleep for 14 days. The control group consisted of 20 women with uncomplicated pregnancy. Levels of melatonin, PlGF, TNF-α, IL-1β, IL-6, IL-4, IL-10 were determined in the venous blood by enzyme-linked immunosorbent assay. Results. It was established that the concentration of melatonin in the blood of pregnant women with IUGR was significantly reduced, as well as the concentration of PlGF (p < 0.01). Significant changes were also found in pregnant women with placental insufficiency, namely, increased concentrations of proinflammatory cytokines, such as TNF-α (p < 0.05), IL-1-β (p < 0.001) and IL-6 (p < 0.05), comparing to healthy pregnant women. Also, in the group of pregnant women with IUGR the levels of anti-inflammatory cytokines IL-4 (p <0.001) and IL-10 (p < 0.001) were elevated in comparison to the control group. After application of the developed complex of non-drug correction of pineal gland function, the concentration of melatonin in the blood of pregnant women in the subgroup of correction increased significantly, comparing to the subgroup without correction (p < 0.001), as well as the level of PlGF (p < 0.05). Also, significantly lower levels of proinflammatory cytokines TNF-α, IL-1-β and IL-6 were observed in pregnant women in the subgroup of correction (p < 0.01). Regarding anti-inflammatory cytokines, under the influence of the developed complex of measures there was a decrease in the level of IL-4 and an increase in the level of IL-10 (p < 0.01). Conclusions. When the measures, aimed at non-drug correction of function of pineal gland, are applied in pregnant women with placental insufficiency, manifested as IUGR, the following changes are observed: increased of plasma levels of melatonin and placental growth factor, decreased of levels of proinflammatory cytokines. We suggest that the pineal gland exerts its effect on the immune system through melatonin, which moderates the activity of pro- and anti-inflammatory cytokines, thereby reducing the influence of inflammation on placental tissue, what results in increasing of concentrations of placental growth factor in the blood of pregnant women.

scholarly journals Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later

2021 ◽  
Vol 118 (15) ◽  
pp. e2014464118
Author(s):  
Jill M. Goldstein ◽  
Justine E. Cohen ◽  
Klara Mareckova ◽  
Laura Holsen ◽  
Susan Whitfield-Gabrieli ◽  
...  
Keyword(s):  
Sex Differences ◽  
Functional Connectivity ◽  
Proinflammatory Cytokines ◽  
Brain Activity ◽  
In Utero ◽  
Anterior Cingulate ◽  
Hippocampal Activity ◽  
Brain Circuitry ◽  
Anti Inflammatory ◽  
In Utero Development

Stress is associated with numerous chronic diseases, beginning in fetal development with in utero exposures (prenatal stress) impacting offspring’s risk for disorders later in life. In previous studies, we demonstrated adverse maternal in utero immune activity on sex differences in offspring neurodevelopment at age seven and adult risk for major depression and psychoses. Here, we hypothesized that in utero exposure to maternal proinflammatory cytokines has sex-dependent effects on specific brain circuitry regulating stress and immune function in the offspring that are retained across the lifespan. Using a unique prenatal cohort, we tested this hypothesis in 80 adult offspring, equally divided by sex, followed from in utero development to midlife. Functional MRI results showed that exposure to proinflammatory cytokines in utero was significantly associated with sex differences in brain activity and connectivity during response to negative stressful stimuli 45 y later. Lower maternal TNF-α levels were significantly associated with higher hypothalamic activity in both sexes and higher functional connectivity between hypothalamus and anterior cingulate only in men. Higher prenatal levels of IL-6 were significantly associated with higher hippocampal activity in women alone. When examined in relation to the anti-inflammatory effects of IL-10, the ratio TNF-α:IL-10 was associated with sex-dependent effects on hippocampal activity and functional connectivity with the hypothalamus. Collectively, results suggested that adverse levels of maternal in utero proinflammatory cytokines and the balance of pro- to anti-inflammatory cytokines impact brain development of offspring in a sexually dimorphic manner that persists across the lifespan.

scholarly journals Synthesis, Characterization and Acute Anti-inflammatory Evaluation of New Mefenamic Acid Derivatives Having 4-Thiazolidinone Nucleus

2019 ◽  
Vol 28 (1) ◽  
pp. 138-146
Author(s):  
Mustafa H. Ali Alsafi ◽  
Muthanna S. Farhan
Keyword(s):  
Side Effects ◽  
Mefenamic Acid ◽  
Paw Edema ◽  
Compound I ◽  
Reference Drug ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Derivatives Of ◽  
Cox 1 ◽  
Inflammatory Effect

Mefenamic acid (MA) is one of the non-steroidal anti-inflammatory drugs, it is widely used probably due to having both anti-inflammatory and analgesic activity, the main side effects of mefenamic acid include gastrointestinal tract (GIT) disturbance mainly diarrhea, peptic ulceration, and gastric bleeding. The analgesic effects of NSAIDs are probably linked to COX-2 inhibition, while COX-1 inhibition is the major cause of this classic adverse effects. Introduction of thiazolidinone may lead to the increase in the bulkiness leads to the preferential inhibition of COX-2 rather than COX-1 enzyme. The study aimed to synthesize derivatives of mefenamic acid with more potency and to decrease the drug's potential side effects, new series of 4-thiazolidinone derivatives of mefenamic acid were synthesized IVa-g. The synthetic procedures for target compounds and their intermediates are designed to be as follows: acylation of secondary amine of mefenamic acid by chloroacetylchloride to produce compound (I), then reaction between compound (I) and hydrazine hydrate to form hydrazine derivative of mefenamic acid (compound II). After that, Schiff base formation by addition of seven benzaldehyde derivatives and finally, cyclization in presence of thioglycolic acid to form 4-thiazolidinone heterocyclic ring. The characterization of the titled compounds has been established on the basis of their spectral FTIR, 1HNMR data, and by measurements of their physical properties. In vivo acute anti-inflammatory effect of the synthesized compounds was evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug produced significant reduction of paw edema with respect to the effect of dimethyl sulfoxide 10%v/v (control group). Compound IVe showed more potent effect than mefenamic acid at 240-300 min, while at time 300 min, compounds IVa and IVd exhibit more potent anti-inflammatory effect than mefenamic acid (50mg/kg, i.p.) as they reduced paw edema significantly more than mefenamic acid at mentioned intervals (p<0.05) . On the other hand compound IVc exhibited lower anti-inflammatory effect.

scholarly journals Scientific Evaluation of anti-inflammatory potential of Macrotyloma uniflorum seeds extracts

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1883-1888
Author(s):  
Anandarajagopal K ◽  
Abdullah Khan ◽  
Sugalia S ◽  
Bama Menon ◽  
Tan Ching Siang ◽  
...  
Keyword(s):  
Antioxidant Properties ◽  
Water Extract ◽  
Ethanol Extract ◽  
Inflammatory Activity ◽  
Leguminous Plant ◽  
Paw Edema ◽  
Reference Drug ◽  
Macrotyloma Uniflorum ◽  
Phenolic Constituents ◽  
Anti Inflammatory

Phytochemicals possessing the antioxidant properties naturally present in food attract a greater interest to healthcare researchers due to their desirable health effects on human health as they can be explored for protection against oxidative deterioration. Macrtotyloma uniflorum is a leguminous plant belonging to the family Fabaceae and commonly known as Horse gram. Aqueous and ethanol extracts of seeds of Macrotyloma uniflorum were evaluated for their anti-inflammatory effects using the scientific protocol on experimental rats. Extraction was carried out using the cold maceration method, and the anti-inflammatory activity was evaluated using a digital plethysmometer in the experimental rats injected with carrageenan to produce paw edema. Preliminary phytochemical studies confirmed the presence of various bioactive compounds such as alkaloids, glycosides, carbohydrates, proteins and amino acids, terpenoids, tannins, and phenolic compounds in both extracts while flavonoids were found only in ethanol extract. Both extracts of M. uniflorum seeds (200 mg/ml) significantly (p<0.01) reduced the paw edema volume induced by carrageenan. The ethanol extract of M. uniflorum seeds exhibited more potent anti-inflammatory activity than water extract, that might be due to the presence of flavonoids in ethanol extract. The activity of the extracts was compared with diclofenac sodium (10mg/kg b.wt.) as a reference drug. From the results, it may be suggested that the antioxidative potential of phenolic constituents and flavonoids is the primary factors for the anti-inflammatory activity of M. uniflorum seeds extracts.

scholarly journals CURRENT CONCEPTS OF ATOPIC DERMATITIS IN CHILDREN: PROBLEMS AND PROSPECTS

2019 ◽  
Vol 20 (2) ◽  
pp. 99-107
Author(s):  
Galina I. Smirnova
Keyword(s):  
Atopic Dermatitis ◽  
Immune Responses ◽  
Proinflammatory Cytokines ◽  
Genetic Predisposition ◽  
Allergic Inflammation ◽  
Skin Lesions ◽  
Current Understanding ◽  
Epidermal Barrier ◽  
Barrier Integrity ◽  
Atopic Skin

There are presented modern data describing the current understanding of the pathogenesis of atopic dermatitis (AD): a genetic predisposition to atopy, disruptions of epidermal barrier integrity and a cascade of immune responses, contributing allergic inflammation in the skin. There are both described several mechanisms of acute and chronic phases of AD, the main directions of pathogenetically substantiated treatment of AD in children and indicated the prospects of new preparations specific blockers of proinflammatory cytokines involved in the development of AD - crisaborole, apremilast, dupilumab, lebrikizumab, tralokinumab, tezepelumab. There is especially presented in details external therapy of atopic skin lesions in children with the use of means of modern dermatological cosmetics.

Sign in / Sign up

Export Citation Format

Share Document