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1.
Nutrients ; 16(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38613012

RESUMO

Aging-associated hepatic fatty acid (FA) oxidation dysfunction contributes to impaired adaptive thermogenesis. 5-Heptadecylresorcinol (AR-C17) is a prominent functional component of whole wheat and rye, and has been demonstrated to improve the thermogenic capacity of aged mice via the regulation of Sirt3. However, the effect of AR-C17 on aging-associated hepatic FA oxidation dysfunction remains unclear. Here, 18-month-old C57BL/6J mice were orally administered with AR-C17 at a dose of 150 mg/kg/day for 8 weeks. Systemic glucose and lipid metabolism, hepatic FA oxidation, and the lipolysis of white adipose tissues (WAT) were measured. The results showed that AR-C17 improved the hepatic FA oxidation, and especially acylcarnitine metabolism, of aged mice during cold stimulation, with the enhancement of systemic glucose and lipid metabolism. Meanwhile, AR-C17 improved the WAT lipolysis of aged mice, promoting hepatic acylcarnitine production. Furthermore, the adipose-specific Sirt3 knockout mice were used to investigate and verify the regulation mechanism of AR-C17 on aging-associated hepatic FA oxidation dysfunction. The results showed that AR-C17 failed to improve the WAT lipolysis and hepatic FA oxidation of aged mice in the absence of adipose Sirt3, indicating that AR-C17 might indirectly influence hepatic FA oxidation via regulating WAT Sirt3. Our findings suggest that AR-C17 might improve aging-associated hepatic FA oxidation dysfunction via regulating adipose Sirt3.


Assuntos
Carnitina/análogos & derivados , Resorcinóis , Sirtuína 3 , Animais , Camundongos , Camundongos Endogâmicos C57BL , Obesidade , Metabolismo dos Lipídeos , Envelhecimento , Glucose , Camundongos Knockout , Ácidos Graxos
2.
J Drugs Dermatol ; 23(3): 192-194, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38443116

RESUMO

Plaque psoriasis is a chronic, immune-mediated, cutaneous, and systemic inflammatory dermatosis. Its pathogenesis involves the dysregulation of the interleukin (IL)-23/IL-17 signaling pathway. There are a range of treatment options available, encompassing topical agents, biologics, oral systemic therapy, and phototherapy. The utility of combination treatment has also been described and is a budding field of research. Here we describe the first case of adult severe generalized plaque psoriasis treated with once-daily oral deucravacitinib 6 mg combined with tapinarof cream 1% applied once daily. To our knowledge, the combination of these agents has not yet been described in the literature. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.8091.


Assuntos
Compostos Heterocíclicos , Psoríase , Estilbenos , Adulto , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Terapia Combinada , Resorcinóis , Emolientes
3.
J Ethnopharmacol ; 328: 118060, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38521429

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoporosis (OP) is a metabolic disorder characterized by disrupted osteoclastic bone resorption and osteoblastic bone formation. Curculigo orchioides Gaertn has a long history of application in traditional Chinese and Indian medicine for treating OP. Orcinol gentiobioside (OGB) is a principal active constituent derived from Curculigo orchioides Gaertn and has been shown to have anti-OP activity. However, the therapeutic efficacy and mechanism of OGB in modulating osteoclastic bone resorption remain undefined. AIM OF THE STUDY: To evaluate the effect of OGB on the formation, differentiation and function of osteoclasts derived from bone marrow macrophages (BMMs), and further elucidate the underlying action mechanism of OGB in OP. MATERIALS AND METHODS: Osteoclasts derived from BMMs were utilized to evaluate the effect of OGB on osteoclast formation, differentiation and bone resorption. Tartrate-resistant acid phosphatase (TRAP) staining and activity assays were conducted to denote the activity of osteoclasts. Osteoclast-related genes and proteins were determined by RT-PCR and Western blotting assays. The formation of the F-actin ring was observed by confocal laser microscopy, and bone resorption pits were observed by inverted microscopy. The target of OGB in osteoclasts was predicted by using molecular docking and further verified by Cellular Thermal Shift Assay (CETSA) and reversal effects of the target activator. The apoptosis of osteoclasts was analyzed by flow cytometry, and autophagic flux in osteoclasts was determined by confocal laser microscopy. RESULTS: OGB inhibited osteoclast formation and differentiation, osteoclast-related genes and proteins expression, F-actin ring formation, and bone resorption activity. Molecular docking and CETSA analysis demonstrated that OGB exhibited good affinity for c-Jun N-terminal Kinase 1 (JNK1). In addition, OGB induced apoptosis and inhibited autophagy in osteoclasts, and the JNK agonist anisomycin reversed the increase in apoptosis and inhibition of autophagy induced by OGB in osteoclasts. CONCLUSION: OGB inhibited osteoclastogenesis by promoting apoptosis and diminishing autophagy via JNK1 signaling.


Assuntos
Reabsorção Óssea , Osteogênese , Resorcinóis , Humanos , Actinas/metabolismo , Simulação de Acoplamento Molecular , Células Cultivadas , Osteoclastos , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Apoptose , Autofagia , Ligante RANK/farmacologia , Ligante RANK/metabolismo , Diferenciação Celular
4.
J Drugs Dermatol ; 23(2): 23-28, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306128

RESUMO

Atopic dermatitis (AD) is a chronic relapsing–remitting disease with a multifactorial etiology involving epidermal barrier and immunologic dysfunction. Topical therapies form the mainstay of AD treatment, but options are limited by adverse effects and restrictions on application site, duration, and extent of use. Tapinarof (VTAMA; Dermavant Sciences, Inc.) is a first-in-class, non-steroidal, topical aryl hydrocarbon receptor (AhR) agonist approved for the treatment of plaque psoriasis. AhR is a ligand-dependent transcription factor with wide-ranging roles, including regulation of homeostasis and immune response in skin cells. AhR expression and signaling are altered in many inflammatory skin diseases, and clinical trials with tapinarof have validated AhR as a therapeutic target capable of delivering significant efficacy. Tapinarof cream 1% once daily demonstrated efficacy versus vehicle in adults and adolescents with AD and is being investigated in the ADORING trials for the treatment of AD in adults and children down to 2 years of age. J Drugs Dermatol. 2024;23(2):23-28.  doi:10.36849/JDD.8026.


Assuntos
Dermatite Atópica , Estilbenos , Humanos , Dermatite Atópica/tratamento farmacológico , Receptores de Hidrocarboneto Arílico/agonistas , Resorcinóis , Pele
5.
Planta Med ; 90(4): 316-332, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387478

RESUMO

Concerns about health hazards associated with the consumption of trans-delta-8-tetrahydrocannabinol products were highlighted in public health advisories from the U. S. Food and Drug Administration and U. S. Centers for Disease Control and Prevention. Simple and rapid quantitative methods to determine trans-delta-8-tetrahydrocannabinol impurities are vital to analyze such products. In this study, a gas chromatography-flame ionization detection method was developed and validated for the determination of delta-8-tetrahydrocannabinol and some of its impurities (recently published) found in synthesized trans-delta-8-tetrahydrocannabinol raw material and included olivetol, cannabicitran, Δ 8-cis-iso-tetrahydrocannabinol, Δ 4-iso-tetrahydrocannabinol, iso-tetrahydrocannabifuran, cannabidiol, Δ 4,8-iso-tetrahydrocannabinol, Δ 8-iso-tetrahydrocannabinol, 4,8-epoxy-iso-tetrahydrocannabinol, trans-Δ 9-tetrahydrocannabinol, 8-hydroxy-iso-THC, 9α-hydroxyhexahydrocannabinol, and 9ß-hydroxyhexahydrocannabinol. Validation of the method was assessed according to the International Council for Harmonization guidelines and confirmed linearity with R2 ≥ 0.99 for all the target analytes. The limit of detection and limit of quantitation were 1.5 and 5 µg/mL, respectively, except for olivetol, which had a limit of detection of 3 µg/mL and a limit of quantitation of 10 µg/mL. Method precision was calculated as % relative standard deviation and the values were less than 8.4 and 9.9% for the intraday precision and inter-day precision, respectively. The accuracy ranged from 85 to 118%. The method was then applied to the analysis of 21 commercially marketed vaping products claiming to contain delta-8-tetrahydrocannabinol. The products analyzed by this method have various levels of these impurities, with all products far exceeding the 0.3% of trans-Δ 9-tetrahydrocannabinol limit for hemp under the Agriculture Improvement Act of 2018. The developed gas chromatography-flame ionization detection method can be an important tool for monitoring delta-8-tetrahydrocannabinol impurities in commercial products.


Assuntos
Dronabinol , Dronabinol/análogos & derivados , Resorcinóis , Vaping , Dronabinol/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Cromatografia Gasosa
7.
Chem Biodivers ; 21(3): e202301900, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38282171

RESUMO

The emergence of multi-drug-resistant microbial strains spurred the search for antimicrobial agents; as a result, two distinct approaches were combined: four in vitro studies and four corresponding molecular docking investigations. Antituberculosis, anti-methicillin-resistant Staphylococcus aureus (anti-MRSA), antifungal, and larvicidal activities of the crude extract, two fractions, and seven isolated compounds from Aspergillus terreus derived from Morus alba roots were explored. The isolated compounds (5 butyrolactones and 2 orsellinic acid derivatives) showed potent to moderate antitubercular activity with MIC values ranging from 1.95 to 62.5 µg/mL (compared to isoniazid, 0.24 µg/mL) and promising anti-MRSA potential with inhibition zone diameters ranging from 8 to 25 mm. Additionally, the in silico study proved that the isolated compounds bind to the two corresponding proteins' active sites with high to moderate -(C-Docker interaction energies) and stable interactions. The isolated compounds displayed antifungal activities against different fungal strains at diverse degrees of activity, among them compound (8"S,9")-dihydroxy-dihydrobutyrolactone I eliciting the best antifungal activity. Meanwhile, all isolated compounds, fractions, and the crude extract demonstrated extremely selective potent to moderate activity against Cryptococcus neoformans. The isolated five butyrolactone derivatives could develop potential mosquito larvicidal agents as a result of promising docking outcomes in the larval enzyme carboxylesterase.


Assuntos
Anti-Infecciosos , Aspergillus , Staphylococcus aureus Resistente à Meticilina , Morus , Resorcinóis , Animais , Antifúngicos/farmacologia , Simulação de Acoplamento Molecular , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Fungos , Misturas Complexas , Antibacterianos/farmacologia , Antibacterianos/química
8.
Int J Biol Macromol ; 258(Pt 2): 129132, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171433

RESUMO

Adhesives are used extensively in the wood industry. As resource and environmental issues become increasingly severe, the development of green and sustainable biomass-based adhesives has attracted increasing attention. In this work, a green wood adhesive is developed from poly(vinyl alcohol) and lignin with molecular designs of lignin extending beyond those in nature. The lignin undergoes extraction from corncob residue, aldehydration, and phenolisation (phenol, resorcinol, and catechol) to significantly increase the phenolic hydroxyl groups (over 7.92 mmol/g), which has the effect of enhancing the hydrogen bonding force between the adhesive and the wood, thereby greatly improving adhesive performance. Compared with pure PVA, polyphenol lignin-containing PVA showed improved adhesion strength and hydrophobicity. PVA/resorcinol-lignin has the significantly improved wood lap shear strength (6.27 MPa, 77.6 % improvement) and hydrophobicity (almost 100 % increase in wet shear strength). This research not only provides a green and high-performance alternative raw material for wood adhesives but also broadens the path for large-scale application of biomass.


Assuntos
Lignina , Polifenóis , Polifenóis/análise , Lignina/química , Álcool de Polivinil , Adesivos/química , Madeira/química , Fenóis/química , Metanol , Cloreto de Polivinila , Resorcinóis
9.
Ann Pharmacother ; 58(1): 76-85, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37076998

RESUMO

OBJECTIVE: This article reviews the efficacy and safety of 1% tapinarof cream for plaque psoriasis. DATA SOURCES: A literature search was conducted from August 2022 to February 2023. The terms tapinarof, VTAMA, benvitimod, GSK2894512, DMVT-505, and WBI-1001 were queried in PubMed. ClinicalTrials.gov was searched to identify ongoing or unpublished studies. STUDY SELECTION AND DATA EXTRACTION: All clinical trials written in English and relevant to pharmacology, efficacy, and safety were included. DATA SYNTHESIS: In two 12-week phase III clinical trials, disease severity assessed by a Physician's Global Assessment (PGA) score of clear or almost clear and a 2-point PGA improvement was 35.4% and 40.2% at week 12 in the 2 trials, respectively. In the 40-week, open-label extension trial, the efficacy and safety results were similar: 40.9% of patients achieved a PGA of 0 at least once during the trial, and 58.2% of patients with PGA ≥ 2 achieved PGA 0/1 at least once. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Tapinarof is a topical aryl hydrocarbon receptor agonist and a first-in-class, potentially promising treatment for plaque psoriasis recently approved by the U.S. Food and Drug Administration. CONCLUSION: Compared with placebo, tapinarof may be an effective and safe topical treatment for mild to severe plaque psoriasis. Head-to-head trials to compare the efficacy and adverse effect profile of tapinarof to other topical treatments are still needed, as are investigation in patients with recent or current use of phototherapy or biologic or nonbiologic systemics. Cost and adherence to treatment may be barriers for treatment efficacy.


Assuntos
Psoríase , Estilbenos , Humanos , Resorcinóis/uso terapêutico , Estilbenos/uso terapêutico , Resultado do Tratamento , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença
10.
Nat Protoc ; 19(2): 313-339, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040980

RESUMO

The tail-to-head terpene (THT) cyclization is a biochemical process that gives rise to many terpene natural product skeletons encountered in nature. Historically, it has been difficult to achieve THT synthetically without using an enzyme. In this protocol, a hexameric resorcin[4]arene capsule acts as an artificial enzyme mimic to carry out biomimetic THT cyclizations and related carbocationic rearrangements. The precursor molecule bears a leaving group (usually an alcohol or acetate group) and undergoes the THT reaction in the presence of the capsule catalyst and HCl as a cocatalyst. Careful control of several parameters (including water content, amount of HCl cocatalyst, temperature and solvent) is crucial to successfully carrying out the reaction. To facilitate the application of this unique capsule-catalysis methodology, we therefore developed a very detailed procedure that includes the preparation and analysis of all reaction components. In this protocol, we describe how to prepare two different terpenes: isolongifolene and presilphiperfolan-1ß-ol. The two procedures differ in the water content required for efficient product formation, and thus exemplify the two common use cases of this methodology. The influence of other crucial reaction parameters and means of precisely controlling them are described. A commercially available substrate, nerol, can be used as simple test substrate to validate the reaction setup. Each synthetic procedure requires 5-7 d, including 1-5 h of hands-on time. The protocol applies to the synthesis of many complex terpene natural products that would otherwise be difficult to access in synthetically useful yields.


Assuntos
Biomimética , Resorcinóis , Terpenos , Terpenos/química , Ciclização , Água , Catálise
11.
Int J Biol Macromol ; 257(Pt 2): 128578, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38048928

RESUMO

Properties of paraoxon, such as poor water solubility, low rate of natural decomposition, ability to accumulate in soil and wastewater, lead to the fact that paraoxon is found in various agricultural products and textiles. In this regard, the search for effective ways of paraoxon degradation becomes an extremely urgent problem, which can be solved by creating catalysts by mimicking paraxonase. In this work, a complex of physicochemical methods was used to study the supramolecular interactions of sodium alginate, which has a calcium-binding ability similar to paraxonase, with viologen calix[4]resorcinol and to reveal the nature of the intermolecular interactions between them resulting in the spontaneous formation of nanoparticles. Before proceeding to the investigation of the binding ability of obtained nanoparticles to paraoxon, the encapsulating effect of nanoparticles on a number of model substrates of different solubility (doxorubicin hydrochloride, quercetin and oleic acid) was studied. The kinetics of paraoxon hydrolysis reaction using these nanoparticles was studied at room temperature in an aqueous medium by spectrophotometric method. The rate of this reaction increases with increasing concentration of stable nanoparticles having hydrophobic domains that ensure paraoxon immobilization. The results obtained allow considering the supramolecular polysaccharide/calixarene system as an effective biomimetic catalyst.


Assuntos
Alginatos , Paraoxon , Paraoxon/química , Hidrólise , Temperatura , Resorcinóis
12.
Contact Dermatitis ; 90(3): 245-252, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37987093

RESUMO

BACKGROUND: Monitoring of adverse events induced by cosmetics performed by health authorities, known as cosmetovigilance, has been relied on the collection of case notifications. OBJECTIVES: We aimed to show how a contact dermatitis registry can contribute to the cosmetovigilance of emerging allergens. We used the example of phenylethyl resorcinol, an infrequent allergen with only 6 previous cases reported in Europe and Japan since 2013. METHODS: A systematic search in the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC) database was performed to identify patients with positive patch test to phenylethyl resorcinol or cosmetics that contains it between June 2018 and January 2023. We collected the main clinical features of these patients and compared them with those of patients recorded in the registry with similar epidemiological features. RESULTS: Thirteen patients with positive patch test to phenylethyl resorcinol were identified. All the patients were women with a mean age of 42 years (range 32-59) and their lesions were mainly in the face. CONCLUSION: Assessing the importance of infrequent allergens based solely on a case series is difficult. Multicentre registries facilitate the collection of cases and provide appropriate background information for new allergens.


Assuntos
Compostos Benzidrílicos , Cosméticos , Dermatite Alérgica de Contato , Resorcinóis , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Espanha/epidemiologia , Estudos Retrospectivos , Cosméticos/efeitos adversos , Testes do Emplastro/efeitos adversos , Sistema de Registros
13.
J Invest Dermatol ; 144(3): 509-519.e7, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37734479

RESUMO

Tight junctions are involved in skin barrier functions. In this study, the expression of CLDN1, CLDN4, and OCLN was found to decrease in skin lesions of atopic dermatitis by bioinformatics analysis. Immunohistochemistry staining in skin specimens from 12 patients with atopic dermatitis and 12 healthy controls also showed decreased CLDN1, CLDN4, and OCLN expression in atopic dermatitis lesions. In vitro studies showed that IL-4 and IL-13 downregulated CLDN1, CLDN4, and OCLN expression in HaCaT cells as well as CLDN4 and OCLN expression in human primary keratinocytes. This effect, which was mediated through the Jak-signal transducer and activator of transcription 6 signaling pathway, increased paracellular flux of 4-kDa dextran. Benvitimod, a new drug for atopic dermatitis, upregulated CLDN4 and OCLN through the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator pathway. Benvitimod induced nuclear translocation of NRF2 and reduced production of ROS in keratinocytes, thus inhibiting IL-4-/IL-13-induced CLDN1 downregulation and signal transducer and activator of transcription 6 phosphorylation. These results indicate that T helper 2 cytokines are involved in tight junction impairment, and benvitimod can inhibit these effects.


Assuntos
Dermatite Atópica , Interleucina-13 , Resorcinóis , Estilbenos , Humanos , Interleucina-13/metabolismo , Dermatite Atópica/patologia , Junções Íntimas/metabolismo , Interleucina-4/farmacologia , Interleucina-4/metabolismo , Fosforilação , Fator de Transcrição STAT6/metabolismo , Queratinócitos/metabolismo , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Translocador Nuclear Receptor Aril Hidrocarboneto/farmacologia
14.
Exp Dermatol ; 33(1): e14862, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37350230

RESUMO

Tapinarof is an aryl hydrocarbon receptor (AHR) ligand which is used to treat plaque psoriasis in adults. However, the underlying mechanism is not yet fully understood. In this study, we applied two of the most studied psoriasis mouse models: topical application of imiquimod (IMQ) and subcutaneous injection of IL-23. Although both models successfully induced psoriasis-like lesions in mice, tapinarof had a completely opposite effect on the two models. Tapinarof decreased the expression of multiple essential cytokines involved in the pathological IL-23/IL-17/IL-22 axis and ameliorated IMQ-induced psoriatic dermatitis, inhibiting keratinocyte proliferation and abnormal differentiation. However, in the IL-23-injection-model, tapinarof instead aggravated the disease. Here, tapinarof increased epidermal thickness and differentiated epidermal dysplasia in mice. Our data suggest that tapinarof may have different effects on varied types of psoriasis.


Assuntos
Psoríase , Estilbenos , Animais , Camundongos , Imiquimode , Psoríase/metabolismo , Resorcinóis/efeitos adversos , Interleucina-23 , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
15.
J AOAC Int ; 107(1): 46-51, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-37831814

RESUMO

BACKGROUND: Its broad applicability and capacity to separate numerous components in a single chromatographic run led to the initial recognition of reversed-phase (RP)-HPLC as an analytical technique. OBJECTIVE: The objective of this study was to create a straightforward and reliable method for accurately and precisely measuring the amount of tapinarof in both the topical formulation and the active pharmaceutical ingredient. Additionally, a robust HPLC assay was developed specifically for analyzing the topical formulation. METHODS: In this study, chromatographic analysis was conducted using a Kromosil C18 column with dimensions of 250 × 4.6 mm and a particle size of 5 microns. The mobile phase consisted of a phosphate buffer and methanol in a ratio of 100:900 (v/v). The flow rate was set at 1.0 mL/min, with an injection volume of 10 µL and a run time of 6 min using isocratic elution. UV detection was performed at a wavelength of 313 nm, and the temperature was maintained at 30°C. The analysis showed well-separated peaks with a high number of theoretical plates, a low tailing factor, and consistent retention time. Validation of the method was conducted, and all validation parameters were found to be within the acceptable limits. RESULTS: A method that is simple, accurate, and precise has been developed to estimate the amount of tapinarof in a topical formulation and active pharmaceutical ingredient. The optimized method involved the use of a column temperature set at 30°C, 90% methanol as the mobile phase, and a flow rate of 1.0 mL/min. The retention time for tapinarof was determined to be 2.88 min. The method exhibited linearity in the concentration range of 5 to 30 µg/mL (with an R2 value greater than 0.999) for tapinarof. CONCLUSION: The topical formulated cream and active pharmaceutical ingredient showed more than 90% dissolution within 5 min. The method developed in this study utilized photo diode array (PDA) for peak integrity and purity confirmation, making it suitable for the quantification of tapinarof in both topical formulations and active pharmaceutical ingredients. HIGHLIGHTS: The method was validated and can be recommended for routine analysis in QC laboratories.


Assuntos
Estilbenos , Metanol/química , Resorcinóis , Cromatografia Líquida de Alta Pressão/métodos
17.
Expert Rev Clin Immunol ; 20(4): 327-337, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38117596

RESUMO

INTRODUCTION: Plaque psoriasis, a chronic immune-mediated skin disorder, is characterized by well-demarcated erythematous plaques with silvery scales. This condition stems from complex interactions between genetic predisposition, immune dysregulation, and environmental triggers. Tapinarof downregulates the cytokine IL-17, diminishes the inflammatory infiltrate, and provides antioxidant properties while enhancing the expression of skin barrier proteins. AREAS COVERED: This review begins by assessing tapinarof's mechanism in treating plaque psoriasis. Subsequently, it examines the effectiveness and safety of tapinarof 1% cream in adult patients. EXPERT OPINION: Tapinarof 1% cream, which works by activating the aryl hydrocarbon receptor, is an FDA-approved treatment for adult plaque psoriasis. This therapy introduces a novel, nonsteroidal method for addressing inflammation and skin barrier issues, potentially serving as an alternative to conventional treatments. The once-daily, convenient cream formulation and favorable safety profile may enhance patient adherence, which is often poor with topical treatments. Tapinarof also maintains disease clearance for a mean of 4 months after treatment cessation.


Assuntos
Psoríase , Estilbenos , Adulto , Humanos , Psoríase/tratamento farmacológico , Administração Tópica , Resorcinóis/uso terapêutico , Estilbenos/uso terapêutico , Doença Crônica , Resultado do Tratamento
18.
J Manag Care Spec Pharm ; 29(12-a Suppl): S1-S13, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38051146

RESUMO

Plaque psoriasis is a chronic, immunemediated skin disease characterized by scaly, erythematous, pruritic plaques. The effects of psoriasis are often debilitating and stigmatizing, significantly impacting patients' physical and psychological well-being and quality of life. Current guideline-recommended psoriasis therapies (topicals, oral systemics, and biologics) have substantial limitations that include overall efficacy, safety, tolerability, sites of application, disease severity, and duration and extent of body surface area treated. Due to these limitations, psoriasis treatment regimens often require combination therapy, especially for moderate to severe disease, leading to increased treatment burden. Psoriasis is also associated with increased indirect costs (eg, reduced work productivity), leading to greater total costs expenditures. Thus, more effective, safe, well-tolerated, and cost-effective therapeutic options are needed. Tapinarof cream 1% once daily is a first-in-class, nonsteroidal, topical aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration in 2022 for the treatment of plaque psoriasis in adults. Tapinarof cream has been evaluated in plaque psoriasis, including 2 pivotal phase 3 trials (NCT03956355 and NCT03983980) and a long-term extension trial (NCT04053387). These trials demonstrated high rates of complete skin clearance with tapinarof cream, durable effects while on treatment (a lack of tachyphylaxis for up to 52 weeks), an approximately 4-month remittive effect off therapy after achieving complete clearance and stopping treatment (ie, duration during which psoriasis does not recur off therapy), and no rebound effects after cessation of therapy. According to the US Food and Drug Administration-approved prescribing information, tapinarof may be used to treat plaque psoriasis of any severity and in any location, has no restrictions on duration of use or extent of total body surface area treated, and has no contraindications, warnings, precautions, or drug-drug interactions. Tapinarof cream is thus an efficacious, well-tolerated, steroid-free topical option that addresses many of the limitations of current recommended therapies. Here we review current knowledge on the physical, psychological, and financial burdens of plaque psoriasis and identify how the clinical profile of tapinarof cream can address key treatment gaps important in the management of plaque psoriasis and patient quality of life. In this article, we aim to assist pharmacists and other managed care practitioners by providing an evidence-based overview of tapinarof cream to support patient-centric decision-making.


Assuntos
Psoríase , Receptores de Hidrocarboneto Arílico , Adulto , Humanos , Receptores de Hidrocarboneto Arílico/uso terapêutico , Qualidade de Vida , Psoríase/tratamento farmacológico , Resorcinóis/uso terapêutico , Resultado do Tratamento
19.
Sci Rep ; 13(1): 22771, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123653

RESUMO

In recent years, concerns about the presence of pharmaceutical compounds in wastewater have increased. Various types of residues of tetracycline family antibiotic compounds, which are widely used, are found in environmental waters in relatively low and persistent concentrations, adversely affecting human health and the environment. In this study, a resorcinol formaldehyde (RF) aerogel was prepared using the sol-gel method at resorcinol/catalyst ratio of 400 and resorcinol/water ratio of 2 and drying at ambient pressure for removing antibiotics like minocycline. Next, RF aerogel was modified with graphene and to increase the specific surface area and porosity of the modified sample and to form the graphene plates without compromising the interconnected porous three-dimensional structure of the aerogel. Also, the pores were designed according to the size of the minocycline particles on the meso- and macro-scale, which bestowed the modified sample the ability to remove a significant amount of the minocycline antibiotic from the aqueous solution. The removal percentage of the antibiotic obtained by UV-vis spectroscopy. Ultimately, the performance of prepared aerogels was investigated under various conditions, including adsorbent doses (4-10 mg), solution pHs (2-12), contact times of the adsorbent with the adsorbate (3-24 h), and initial concentration of antibiotic (40-100 mg/l). The results from the BET test demonstrated that the surface area of the resorcinol formaldehyde aerogel sample, which included 1 wt% graphene (RF-G1), exhibited an augmentation in comparison to the surface area of the pure aerogel. Additionally, it was noted that the removal percentage of minocycline antibiotic for both the unmodified and altered samples was 71.6% and 92.1% at the optimal pH values of 4 and 6, respectively. The adsorption capacity of pure and modified aerogel for the minocycline antibiotic was 358 and 460.5 mg/g, respectively. The adsorption data for the modified aerogel was studied by the pseudo-second-order model and the results obtained from the samples for antibiotic adsorption with this model revealed a favorable fit, which indicated that the chemical adsorption in the rapid adsorption of the antibiotic by the modified aerogel had occurred.


Assuntos
Antibacterianos , Grafite , Minociclina , Antibacterianos/isolamento & purificação , Formaldeído , Grafite/química , Minociclina/isolamento & purificação , Resorcinóis , Água/química
20.
J Agric Food Chem ; 71(47): 18375-18384, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37962857

RESUMO

5-Heptadecylresorcinol (AR-C17), as the most important active monomer, is found in large quantities in wheat and triticale and plays a variety of health benefits, such as antidiabetic, anti-inflammatory, and antitumor. However, the low bioavailability of AR-C17 due to its low water solubility restricts its application. Moreover, the transport mechanism of AR-C17 is not fully understood. Here, we showed that the transport of AR-C17 in vitro was time- and concentration-dependent, and relatively higher temperature and lower pH obviously promoted the transport of AR-C17. Besides, transporters, especially P-glycoprotein (P-gp), markedly affected the transport of AR-C17 as well. Quercetin, a natural synergist in triticale bran (TB), was confirmed as an inhibitor of P-gp to promote the transport of AR-C17 in this study, and the bioavailability of AR-C17 reached the highest when the concentration ratio of quercetin to AR-C17 was 1:1.


Assuntos
Quercetina , Resorcinóis , Quercetina/farmacologia , Quercetina/metabolismo , Resorcinóis/farmacologia , Disponibilidade Biológica
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