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Prado VC, Moenke K, Pegoraro NS, Saccol CP, Nogueira-Librelotto DR, Rechia GC, Oliveira SM, Cruz L. Nano-Based Hydrogel for Cutaneous Sesamol Delivery in UVB-Induced Skin Injury. AAPS PharmSciTech 2025; 26:75. [PMID: 40045094 DOI: 10.1208/s12249-025-03071-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 02/18/2025] [Indexed: 05/13/2025] Open
Abstract
Dexamethasone, a glucocorticoid, is used to mitigate UVB radiation-induced skin inflammation. Nevertheless, its continuous use has been linked to adverse effects. Sesamol, a compound with promising pharmacological properties, faces a challenge due to its rapid skin permeation, which limits its effectiveness when administered cutaneously. Consequently, polymeric nanocapsules have emerged as a technological solution to enhance the skin residence time and efficacy of sesamol in topical applications. This study details the preparation of sesamol-loaded ethylcellulose nanocapsule suspensions and evaluates their in vitro cytotoxicity against keratinocyte and fibroblast cell lines using the MTT assay. The results show that while free sesamol reduced the viability of 3T3 fibroblast cells, this cytotoxic effect was mitigated upon nanoencapsulation. In HaCaT cells, only the highest concentration of nanoencapsulated sesamol exhibited a moderate cytotoxic effect. A nano-based hydrogel containing 1 mg/g of sesamol and 2.5% guar gum was formulated for cutaneous application. The hydrogel's pharmacological efficacy was assessed in an in vivo sunburn model induced by UVB light in Swiss mice, demonstrating that the sesamol-loaded nanocapsules significantly attenuated inflammatory responses, as evidenced by a reduction in ear thickness and polymorphonuclear cell infiltration. Furthermore, ex vivo permeation studies on UVB radiation-injured human skin confirmed that nanoencapsulation markedly reduced the permeation rate of sesamol through the skin's layers. The hydrogels were also found to be bioadhesive to human skin. In conclusion, the hydrogel containing sesamol-loaded nanocapsules presents a promising therapeutic approach for treating inflammatory skin conditions, including sunburn.
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Affiliation(s)
- Vinicius Costa Prado
- Laboratório de Tecnologia Farmacêutica, Programa de Pós-Graduação Em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, Rio Grande Do Sul, 97105-900, Brazil
| | - Kauani Moenke
- Laboratório de Tecnologia Farmacêutica, Programa de Pós-Graduação Em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, Rio Grande Do Sul, 97105-900, Brazil
| | - Natháli Schopf Pegoraro
- Programa de Pós-Graduação Em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais E Exatas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande Do Sul, 97105-900, Brazil
| | - Camila Parcianello Saccol
- Laboratório de Tecnologia Farmacêutica, Programa de Pós-Graduação Em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, Rio Grande Do Sul, 97105-900, Brazil
| | - Daniele Rubert Nogueira-Librelotto
- Laboratório de Testes E Ensaios Farmacêuticos In Vitro, Programa de Pós-Graduação Em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, Rio Grande Do Sul, 97105-900, Brazil
| | - Giancarlo Cervo Rechia
- Escola de Medicina, Universidade Franciscana, Santa Maria, Rio Grande Do Sul, 97010-030, Brazil
| | - Sara Marchesan Oliveira
- Programa de Pós-Graduação Em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais E Exatas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande Do Sul, 97105-900, Brazil
| | - Letícia Cruz
- Laboratório de Tecnologia Farmacêutica, Programa de Pós-Graduação Em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, Rio Grande Do Sul, 97105-900, Brazil.
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Santos Filipe M, Cardoso RVC, Ayuso M, Murta D, Díaz-Lanza AM, Rosado C, C S P Pires T, Calhelha RC, Rijo P. Exploring the potential of Hermetia illucens larvae extracts: A promising approach for dermocosmetic formulations. Heliyon 2024; 10:e37395. [PMID: 39296133 PMCID: PMC11409144 DOI: 10.1016/j.heliyon.2024.e37395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 08/30/2024] [Accepted: 09/03/2024] [Indexed: 09/21/2024] Open
Abstract
Globally, the yearly disposal of 1.3 billion tonnes of food raises environmental and public health concerns. Black soldier fly (BSF) larvae present a sustainable solution, converting organic waste into nutrient-rich biomass. The extracted oil from BSF larvae, rich in fatty acids (FA), offers an eco-friendly alternative for the cosmetic industry. In this study, larvae sourced from a Portuguese company were fed olive pomace, a by-product of olive oil production. The lipidic sample extracted revealed a composition high in oleic acid, valuable for cosmetics. Investigating the biological activity of lipid extractions from larvae fed with olive pomace is a novel approach. Notably, the n-hexane ultrasound-assisted extraction method demonstrated potent antioxidant properties, and some extracts displayed antimicrobial activity. Five non-cytotoxic extracts; three with no relevant activity (IC50 from 236 to >400 μg/mL). These findings highlight BSF larvae as an environmentally friendly source of fatty acids, offering promising alternatives for diverse applications.
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Affiliation(s)
- Márcia Santos Filipe
- CBIOS - Universidade Lusófona's Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024, Lisbon, Portugal
- Universidad de Alcalá de Henares. Facultad de Farmacia, Departamento de Ciencias Biomédicas (Área de Farmacología, Nuevos agentes antitumorales, Acción tóxica sobre células leucémicasCtra. Madrid-Barcelona km. 33,600, 28805, Alcalá de Henares, Madrid, Spain
| | - Rossana V C Cardoso
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal
- Laboratório Associado para a Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal
| | - Manuel Ayuso
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal
- Laboratório Associado para a Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal
| | - Daniel Murta
- Ingredient Odyssey SA - EntoGreen, Rua Cidade de Santarém 140, 2005-079, Santarém, Portugal
- CiiEM - Centro de Investigação Interdisciplinar Egas Moniz, Campus Universitário, Caparica, Portugal
| | - Ana María Díaz-Lanza
- Universidad de Alcalá de Henares. Facultad de Farmacia, Departamento de Ciencias Biomédicas (Área de Farmacología, Nuevos agentes antitumorales, Acción tóxica sobre células leucémicasCtra. Madrid-Barcelona km. 33,600, 28805, Alcalá de Henares, Madrid, Spain
| | - Catarina Rosado
- CBIOS - Universidade Lusófona's Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024, Lisbon, Portugal
| | - Tânia C S P Pires
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal
- Laboratório Associado para a Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal
| | - Ricardo C Calhelha
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal
- Laboratório Associado para a Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253, Bragança, Portugal
| | - Patricia Rijo
- CBIOS - Universidade Lusófona's Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024, Lisbon, Portugal
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003, Lisbon, Portugal
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Favarin A, Becker G, Brum ES, Serafini PT, Marquezin LP, Brusco I, Oliveira SM. Topical diosmetin attenuates nociception and inflammation in a ultraviolet B radiation-induced sunburn model in mice. Inflammopharmacology 2024; 32:2295-2304. [PMID: 38907857 DOI: 10.1007/s10787-024-01507-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 06/06/2024] [Indexed: 06/24/2024]
Abstract
Burns are a global health problem and can be caused by several factors, including ultraviolet (UV) radiation. Exposure to UVB radiation can cause sunburn and a consequent inflammatory response characterised by pain, oedema, inflammatory cell infiltration, and erythema. Pharmacological treatments available to treat burns and the pain caused by them include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antimicrobials and glucocorticoids, which are associated with adverse effects. Therefore, the search for new therapeutic alternatives is needed. Diosmetin, an aglycone of the flavonoid diosmin, has antinociceptive, antioxidant and anti-inflammatory properties. Thus, we evaluated the antinociceptive and anti-inflammatory effects of topical diosmetin (0.01, 0.1 and 1%) in a UVB radiation-induced sunburn model in mice. The right hind paw of the anaesthetised mice was exposed only once to UVB radiation (0.75 J/cm2) and immediately treated with diosmetin once a day for 5 days. The diosmetin antinociceptive effect was evaluated by mechanical allodynia and pain affective-motivational behaviour, while its anti-inflammatory activity was assessed by measuring paw oedema and polymorphonuclear cell infiltration. Mice exposed to UVB radiation presented mechanical allodynia, increased pain affective-motivational behaviour, paw oedema and polymorphonuclear cell infiltration into the paw tissue. Topical Pemulen® TR2 1% diosmetin reduced the mechanical allodynia, the pain affective-motivational behaviour, the paw oedema and the number of polymorphonuclear cells in the mice's paw tissue similar to that presented by Pemulen® TR2 0.1% dexamethasone. These findings indicate that diosmetin has therapeutic potential and may be a promising strategy for treating patients experiencing inflammatory pain, especially those associated with sunburn.
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Affiliation(s)
- Amanda Favarin
- Laboratory of Neurotoxicity and Psychopharmacology - Pain Research Group, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Gabriela Becker
- Laboratory of Neurotoxicity and Psychopharmacology - Pain Research Group, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
- Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Evelyne Silva Brum
- Laboratory of Neurotoxicity and Psychopharmacology - Pain Research Group, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
- Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Patrick Tuzi Serafini
- Laboratory of Neurotoxicity and Psychopharmacology - Pain Research Group, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
- Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Lara Panazzolo Marquezin
- Laboratory of Neurotoxicity and Psychopharmacology - Pain Research Group, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Indiara Brusco
- Laboratory of Neurotoxicity and Psychopharmacology - Pain Research Group, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
- Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
- Graduate Program in Environmental Sciences, Community University of Chapecó Region, Chapecó, SC, Brazil
| | - Sara Marchesan Oliveira
- Laboratory of Neurotoxicity and Psychopharmacology - Pain Research Group, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
- Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
- Department of Biochemistry and Molecular Biology, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Av. Roraima 1000, Camobi, Santa Maria, RS, 97105-900, Brazil.
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Marchlewicz M, Polakowska Z, Maciejewska-Markiewicz D, Stachowska E, Jakubiak N, Kiedrowicz M, Rak-Załuska A, Duchnik M, Wajs-Syrenicz A, Duchnik E. Fatty Acid Profile of Erythrocyte Membranes in Patients with Psoriasis. Nutrients 2024; 16:1799. [PMID: 38931154 PMCID: PMC11206573 DOI: 10.3390/nu16121799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 05/28/2024] [Accepted: 06/04/2024] [Indexed: 06/28/2024] Open
Abstract
Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments. Diseases accompanying psoriasis include metabolic and cardiovascular disorders. It has been suggested that inflammation is involved in the development of each of these conditions. The main objective of this study was to analyse the fatty acid profile, including polyunsaturated fatty acids, in the erythrocyte membranes of patients suffering from psoriasis. A total of 58 adult patients of the Department of Skin and Venereal Diseases of the Pomeranian Medical University in Szczecin, suffering from psoriasis, were qualified for this study. The patients had undergone an interview and physical examination, during which the severity of psoriasis was assessed. All patients had their weight and height measured to assess their body mass index (BMI). After 3 months of treatment, biochemical parameters (ALT, AST, total cholesterol) and inflammatory markers (CRP) in the blood were assessed. In addition, the isolation of fatty acids (PUFAs, SFAs, MUFAs) from erythrocyte membranes and the qualitative and quantitative analysis of their profile using a gas chromatograph were carried out. In patients with severe psoriasis requiring systemic treatment, an altered profile of fatty acids in erythrocyte membranes was found, including a significantly lower concentration of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a significantly higher concentration of saturated fatty acids; and a decreased concentration of oleic acid (omega-9), compared to the results obtained in patients with less severe psoriasis receiving topical treatment. In patients with psoriasis and BMI ≥ 25, significantly higher concentrations of AST and ALT in the blood and significantly higher concentrations of pro-inflammatory arachidonic acid in erythrocyte membranes were found. Elevated concentrations of saturated (R = 0.31) and monounsaturated fatty acids (R = 0.29) may correlate with a greater severity of psoriasis.
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Affiliation(s)
- Mariola Marchlewicz
- Department of Dermatology and Venereology, Faculty of Health Sciences, Pomeranian Medical University, 71-210 Szczecin, Poland
| | - Zofia Polakowska
- Department of Aesthetic Dermatology, Faculty of Health Sciences, Pomeranian Medical University, 70-111 Szczecin, Poland
| | | | - Ewa Stachowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland
| | - Natalia Jakubiak
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland
| | - Magdalena Kiedrowicz
- Department of Dermatology and Venereology, Faculty of Health Sciences, Pomeranian Medical University, 71-210 Szczecin, Poland
| | - Aleksandra Rak-Załuska
- Department of Aesthetic Dermatology, Faculty of Health Sciences, Pomeranian Medical University, 70-111 Szczecin, Poland
| | - Michał Duchnik
- Department of General and Vascular Surgery, Public Voivodeship Combined Hospital, 70-891 Szczecin, Poland
| | - Alicja Wajs-Syrenicz
- Department of Dermatology and Venereology, Faculty of Health Sciences, Pomeranian Medical University, 71-210 Szczecin, Poland
| | - Ewa Duchnik
- Department of Aesthetic Dermatology, Faculty of Health Sciences, Pomeranian Medical University, 70-111 Szczecin, Poland
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Pegoraro NS, Gehrcke M, Camponogara C, Fialho MFP, Cruz L, Oliveira SM. The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice. Pharmaceutics 2024; 16:176. [PMID: 38399236 PMCID: PMC10892665 DOI: 10.3390/pharmaceutics16020176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/25/2024] Open
Abstract
Dexamethasone has a high anti-inflammatory efficacy in treating skin inflammation. However, its use is related to the rebound effect, rosacea, purple, and increased blood glucose levels. Nanotechnology approaches have emerged as strategies for drug delivery due to their advantages in improving therapeutic effects. To reduce dexamethasone-related adverse effects and improve the anti-inflammatory efficacy of treatments, we developed nanocarriers containing this corticosteroid and oleic acid. Nanocapsules and nanoemulsion presented dexamethasone content close to the theoretical value and controlled dexamethasone release in an in vitro assay. Gellan gum-based hydrogels were successfully prepared to employ the nanostructured systems. A permeation study employing porcine skin showed that hydrogels containing non-nanoencapsulated dexamethasone (0.025%) plus oleic acid (3%) or oleic acid (3%) plus dexamethasone (0.025%)-loaded nanocapsules provided a higher amount of dexamethasone in the epidermis compared to non-nanoencapsulated dexamethasone (0.5%). Hydrogels containing oleic acid plus dexamethasone-loaded nanocapsules effectively inhibited mice ear edema (with inhibitions of 89.26 ± 3.77% and 85.11 ± 2.88%, respectively) and inflammatory cell infiltration (with inhibitions of 49.58 ± 4.29% and 27.60 ± 11.70%, respectively). Importantly, the dexamethasone dose employed in hydrogels containing the nanocapsules that effectively inhibited ear edema and cell infiltration was 20-fold lower (0.025%) than that of non-nanoencapsulated dexamethasone (0.5%). Additionally, no adverse effects were observed in preliminary toxicity tests. Our study suggests that nanostructured hydrogel containing a reduced effective dose of dexamethasone could be a promising therapeutic alternative to treat inflammatory disorders with reduced or absent adverse effects. Additionally, testing our formulation in a clinical study on patients with skin inflammatory diseases would be very important to validate our study.
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Affiliation(s)
- Natháli Schopf Pegoraro
- Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil; (N.S.P.); (C.C.); (M.F.P.F.)
| | - Mailine Gehrcke
- Graduate Program in Pharmaceutical Sciences, Centre of Health Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil; (M.G.); (L.C.)
| | - Camila Camponogara
- Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil; (N.S.P.); (C.C.); (M.F.P.F.)
| | - Maria Fernanda Pessano Fialho
- Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil; (N.S.P.); (C.C.); (M.F.P.F.)
| | - Letícia Cruz
- Graduate Program in Pharmaceutical Sciences, Centre of Health Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil; (M.G.); (L.C.)
| | - Sara Marchesan Oliveira
- Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil; (N.S.P.); (C.C.); (M.F.P.F.)
- Department of Biochemistry and Molecular Biology, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil
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Ferreira EA, Queiroz LS, Silva Facchini GDF, Guedes MCMR, Macedo GC, de Sousa OV, Da Silva Filho AA. Baccharis dracunculifolia DC (Asteraceae) Root Extract and Its Triterpene Baccharis Oxide Display Topical Anti-Inflammatory Effects on Different Mice Ear Edema Models. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2023; 2023:9923941. [PMID: 37275573 PMCID: PMC10234725 DOI: 10.1155/2023/9923941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 04/25/2023] [Accepted: 05/10/2023] [Indexed: 06/07/2023]
Abstract
B. dracunculifolia is popularly used to treat skin diseases. This work aimed to evaluate the topical anti-inflammatory properties of B. dracunculifolia root extract (BdR) and its major compound baccharis oxide (BOx) on mice ear edema models. BdR was analyzed by GC-MS, and BOx was isolated by chromatographic fractionation. Topical anti-inflammatory activities were determined by using the croton oil, capsaicin, histamine, and phenol-induced mouse ear edema models. N-acetyl-β-D- glucosaminidase (NAG) and myeloperoxidase (MPO) activities, as well as NO dosage and histopathological analyses, were also evaluated. Phytochemical analysis of BdR showed BOx as one of the major constituents. BdR and BOx (both at 0.1, 0.5, and 1.0 mg/ear) significantly reduced croton oil, histamine, and phenol-induced ear edema, while only BOx was effective in reducing capsaicin-induced edema. MPO and NAG activities, as well as NO production, were significantly inhibited by BdR and BOx. Histopathological analysis confirmed the topical anti-inflammatory properties of BdR and BOx. Our findings showed that BdR and BOx demonstrated significant topical anti-inflammatory effects in mouse ear edema induced by different agents, suggesting their possible application on skin inflammatory diseases.
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Affiliation(s)
- Everton Allan Ferreira
- Faculty of Pharmacy, Department of Pharmaceutical Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG 36036-900, Brazil
| | - Lucas Sales Queiroz
- Faculty of Pharmacy, Department of Pharmaceutical Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG 36036-900, Brazil
| | - Gabriella de Faria Silva Facchini
- Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, R. José Lourenço Kelmer s/n, Campus Universitário, 36036-900 Juiz de Fora, MG, Brazil
| | - Maria Clara Machado Resende Guedes
- Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, R. José Lourenço Kelmer s/n, Campus Universitário, 36036-900 Juiz de Fora, MG, Brazil
| | - Gilson Costa Macedo
- Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, R. José Lourenço Kelmer s/n, Campus Universitário, 36036-900 Juiz de Fora, MG, Brazil
| | - Orlando Vieira de Sousa
- Faculty of Pharmacy, Department of Pharmaceutical Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG 36036-900, Brazil
| | - Ademar A. Da Silva Filho
- Faculty of Pharmacy, Department of Pharmaceutical Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG 36036-900, Brazil
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Tan JQ, Zhang L, Xu HX. Garcinia oligantha: A comprehensive overview of ethnomedicine, phytochemistry and pharmacology. JOURNAL OF ETHNOPHARMACOLOGY 2023; 306:116130. [PMID: 36621661 DOI: 10.1016/j.jep.2022.116130] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 12/10/2022] [Accepted: 12/30/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Garcinia oligantha Merr. is an ethnomedicine plant mainly distributed in Guangdong and Hainan, China. It has the effects of heat-clearing and detoxicating, which has been used by local ethnic minorities to treat a variety of diseases, including inflammation, internal heat, toothache and scald. THE AIM OF THE REVIEW This review summarizes and discusses the progress of the chemical compounds and biological activities of G. oligantha that have been studied in recent years to provide the direction for the prospective research and applications of G. oligantha. MATERIALS AND METHODS The relevant literature about G. oligantha was accessible from ancient Chinese medical books and records, theses, as well as major scientific databases such as Google Scholar, PubMed, Web of Science, ScienceDirect, SciFinder, Baidu Scholar and China National Knowledge Infrastructure (CNKI). RESULTS To date, more than 150 chemical compounds were isolated from this plant, including xanthones, volatile oil, fatty acid, benzofurane derivative and biphenyl compounds. Xanthones are the main bioactive compounds that exhibit diverse biological effects, such as antitumor, analgesic, anti-inflammatory, antioxidative, neuroprotective, antimalarial and antibacterial effects, which are consistent with its traditional uses as a folk medicine. Modern pharmacological studies show that these compounds participate in a variety of signaling pathways underlying different pathophysiologies, making them a valuable medicinal resource. CONCLUSION G. oligantha is an ethnomedicine with a long history. However, due to regional and cultural constraints, the popularisation and use of ethnomedicine are still limited. Modern pharmacological and chemical research suggest that G. oligantha contains a variety of bioactive compounds and showed diverse biological functions, which is worthy of comprehensive and in-depth research. This review summarizes and discusses the recent progress in studies on G. oligantha, looking forward to promote further research and sustainable development of folk medicinal plants.
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Affiliation(s)
- Jia-Qi Tan
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, China
| | - Li Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, China.
| | - Hong-Xi Xu
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
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Santa-María C, López-Enríquez S, Montserrat-de la Paz S, Geniz I, Reyes-Quiroz ME, Moreno M, Palomares F, Sobrino F, Alba G. Update on Anti-Inflammatory Molecular Mechanisms Induced by Oleic Acid. Nutrients 2023; 15:nu15010224. [PMID: 36615882 PMCID: PMC9824542 DOI: 10.3390/nu15010224] [Citation(s) in RCA: 70] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 12/23/2022] [Accepted: 12/28/2022] [Indexed: 01/03/2023] Open
Abstract
In 2010, the Mediterranean diet was recognized by UNESCO as an Intangible Cultural Heritage of Humanity. Olive oil is the most characteristic food of this diet due to its high nutraceutical value. The positive effects of olive oil have often been attributed to its minor components; however, its oleic acid (OA) content (70-80%) is responsible for its many health properties. OA is an effective biomolecule, although the mechanism by which OA mediates beneficial physiological effects is not fully understood. OA influences cell membrane fluidity, receptors, intracellular signaling pathways, and gene expression. OA may directly regulate both the synthesis and activities of antioxidant enzymes. The anti-inflammatory effect may be related to the inhibition of proinflammatory cytokines and the activation of anti-inflammatory ones. The best-characterized mechanism highlights OA as a natural activator of sirtuin 1 (SIRT1). Oleoylethanolamide (OEA), derived from OA, is an endogenous ligand of the peroxisome proliferator-activated receptor alpha (PPARα) nuclear receptor. OEA regulates dietary fat intake and energy homeostasis and has therefore been suggested to be a potential therapeutic agent for the treatment of obesity. OEA has anti-inflammatory and antioxidant effects. The beneficial effects of olive oil may be related to the actions of OEA. New evidence suggests that oleic acid may influence epigenetic mechanisms, opening a new avenue in the exploration of therapies based on these mechanisms. OA can exert beneficial anti-inflammatory effects by regulating microRNA expression. In this review, we examine the cellular reactions and intracellular processes triggered by OA in T cells, macrophages, and neutrophils in order to better understand the immune modulation exerted by OA.
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Affiliation(s)
- Consuelo Santa-María
- Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Seville, 41012 Seville, Spain
- Correspondence: (C.S.-M.); (S.L.-E.)
| | - Soledad López-Enríquez
- Departamento de Bioquímica Médica, Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Seville, 41009 Seville, Spain
- Correspondence: (C.S.-M.); (S.L.-E.)
| | - Sergio Montserrat-de la Paz
- Departamento de Bioquímica Médica, Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Seville, 41009 Seville, Spain
| | - Isabel Geniz
- Distrito Sanitario Seville Norte y Aljarafe, Servicio Andaluz de Salud, 41008 Seville, Spain
| | - María Edith Reyes-Quiroz
- Departamento de Bioquímica Médica, Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Seville, 41009 Seville, Spain
| | - Manuela Moreno
- Departamento de Farmacia y Nutrición, Hospital Costa del Sol, 29603 Málaga, Spain
| | - Francisca Palomares
- Departamento de Bioquímica Médica, Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Seville, 41009 Seville, Spain
| | - Francisco Sobrino
- Departamento de Bioquímica Médica, Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Seville, 41009 Seville, Spain
| | - Gonzalo Alba
- Departamento de Bioquímica Médica, Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Seville, 41009 Seville, Spain
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9
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Roy AC, Prasad A, Ghosh I. Phytochemical Profiling of Tupistra nutans Wall. ex Lindl. Inflorescence Extract and Evaluation of Its Antioxidant Activity and Toxicity in Hepatocarcinoma (HepG2) and Fibroblast (F111) Cells. Appl Biochem Biotechnol 2023; 195:172-195. [PMID: 36070165 DOI: 10.1007/s12010-022-04145-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2022] [Indexed: 01/13/2023]
Abstract
Tupistra nutans Wall. ex Lindl. is a medicinal plant found in the Eastern Himalayan region. Besides being used as a folk medicine for pain and high blood sugar, its inflorescence is consumed as a vegetable. However, its medicinal properties have not been proven in vitro and in vivo till now. Therefore, in this study, we reported the phytochemicals present in the methanolic extract of Tupistra nutans Wall. ex Lindl. inflorescence (METNI) and its comparative effect in liver carcinoma HepG2 cells against non-cancerous murine fibroblast F111 cells. Phytochemical profiling by gas chromatography-mass spectrometry (GC-MS) analysis showed that METNI was rich in unsaturated fatty acids, vitamin E, and anticancer compounds like diosgenin, linoleic acid, and palmitoleic acid. METNI was found to have in vitro antioxidant property as determined by DPPH and pyrogallol methods, and UV protection property as investigated by fluorescence-based and spectrophotometric methods. MTT assay revealed METNI caused significantly more cell proliferation inhibition in HepG2 (IC50 = 138 µg/ml) compared to F111 (IC50 = 347 µg/ml) cells. Although in both HepG2 and F111 cells METNI showed significant antioxidant activity, it led to intracellular ROS generation and cell cycle alteration at higher exposure. The obtained results suggest that Tupistra nutans can be a promising application for anticancer drug and skin care product development, but can be harmful if overconsumed.
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Affiliation(s)
- Ashim Chandra Roy
- Biochemistry and Environmental Toxicology Laboratory, Lab. # 103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Abhinav Prasad
- Biochemistry and Environmental Toxicology Laboratory, Lab. # 103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Ilora Ghosh
- Biochemistry and Environmental Toxicology Laboratory, Lab. # 103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
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10
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Pintea A, Vlad RA, Antonoaea P, Rédai EM, Todoran N, Barabás EC, Ciurba A. Structural Characterization and Optimization of a Miconazole Oral Gel. Polymers (Basel) 2022; 14:polym14225011. [PMID: 36433136 PMCID: PMC9692734 DOI: 10.3390/polym14225011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/12/2022] [Accepted: 11/16/2022] [Indexed: 11/22/2022] Open
Abstract
The development of semisolid formulations, gels in particular, has raised the attention of scientists more and more over the last decades. Because of their biocompatibility, hydrophilic nature, and capacity of absorbing large quantities of water, hydrogels are still one of the most promising pharmaceutical formulations in the pharmaceutical industry. The purpose of this study is to develop an optimal formulation capable of incorporating a water-poorly soluble active ingredient such as miconazole used in the treatment of fungal infections with Candida albicans and Candida parapsilosis. A D-optimal design was applied to study the relationship between the formulation parameter and the gel characteristics. The independent parameters used in this study were the Carbopol 940 concentration (the polymer used to obtain the gel matrix), the sodium hydroxide amount, and the presence/absence of miconazole. Ten different dependent parameters (Y1-Y10) were evaluated (penetrometry, spreadability, viscosity, and tangential tension at 1 and 11 levels of speed whilst destructuring and during the reorganization of the gel matrix). The consistency of the gels ranged from 23.2 mm (GO2) to 29.6 mm (GM5). The least spreadable gel was GO7 (1384 mm2), whilst the gel that presented the best spreadability was GO1 (3525 mm2). The viscosity and the tangential stress at the selected levels (1 and 11) varied due to the different compositions of the proposed gels. The gels were also tested for drug content and antifungal activity. All determinations had satisfying results; the drug content was within limits accepted by Ph. Eur. 10 and all formulations containing miconazole exhibited antifungal activity. An optimal formulation with miconazole was attained, consisting of 0.84% Carbopol 940 and 0.32% sodium hydroxide.
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Affiliation(s)
- Andrada Pintea
- Pharmaceutical Technology and Cosmetology Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Robert-Alexandru Vlad
- Pharmaceutical Technology and Cosmetology Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Paula Antonoaea
- Pharmaceutical Technology and Cosmetology Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania
- Correspondence:
| | - Emöke Margit Rédai
- Pharmaceutical Technology and Cosmetology Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Nicoleta Todoran
- Pharmaceutical Technology and Cosmetology Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Enikő-Csilla Barabás
- Cellular Biology and Microbiology Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania
- Department of Laboratory Medicine, Mures, County Hospital, 540136 Targu Mures, Romania
| | - Adriana Ciurba
- Pharmaceutical Technology and Cosmetology Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania
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11
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Locust bean gum-based hydrogel containing nanocapsules for 3,3′-diindolylmethane delivery in skin inflammatory conditions. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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12
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Luo YB, Liu Y, Li Q, Duan H, Luo Z, Yang H, Xu L. Integrating 16S rRNA gene sequencing and metabolomics to evaluate the association between gut microbiota and serum metabolites in patients with myositis. J Appl Microbiol 2022; 133:2547-2559. [PMID: 35858765 DOI: 10.1111/jam.15724] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 07/05/2022] [Accepted: 07/12/2022] [Indexed: 11/30/2022]
Abstract
AIMS Gut microbiota and metabolites have a profound impact on the maintenance of body health. In this study, we assessed the association between gut microbiota and serum metabolite changes in myositis using 16S rRNA gene sequencing and metabolomics to provide new ideas for screening and treating myositis. METHODS AND RESULTS Blood and fecal samples were collected from twenty myositis patients and twenty healthy control subjects. Then, 16S rRNA gene sequencing, enzyme-linked immunosorbent assays, and untargeted metabolomics study were performed to evaluate the relationship between gut microbiota and serum metabolites in patients with myositis. Compared to healthy control subjects, the blood samples from the patients with myositis had elevated levels of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA), and decreased superoxide dismutase (SOD) levels. The increase in Bacteroidota (including Bacteroides and Parabacteroides, but not Prevotella) and the decrease in Firmicutes in the patients were accompanied by functional changes in amino acid and lipid metabolism. The gut microbiota (Bacteroides and Parabacteroides) were negatively correlated with the differential serum metabolites (glutamate and taurine). The differential serum metabolites (glutamate, pyrrolidonecarboxylic acid, and taurine) were also correlated with inflammatory factors (IL-4 and TNF-α) and oxidative stress indexes (MDA and SOD). CONCLUSION Dysbiosis of gut microbiota in patients with myositis was accompanied by changes in inflammatory factors, oxidative stress indexes, and small molecule metabolites in serum. SIGNIFICANCE AND IMPACT OF STUDY Blood and fecal biomarkers could be used for screening myositis.
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Affiliation(s)
- Yue-Bei Luo
- Department of Neurology, Xiangya Hospital, Central South University.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yangtengyu Liu
- Department of Rheumatology & Immunology, Xiangya Hospital, Central South University
| | - Qiuxiang Li
- Department of Neurology, Xiangya Hospital, Central South University
| | - Huiqian Duan
- Department of Neurology, Xiangya Hospital, Central South University
| | - Zhaohui Luo
- Department of Neurology, Xiangya Hospital, Central South University
| | - Huan Yang
- Department of Neurology, Xiangya Hospital, Central South University
| | - Liqun Xu
- Department of Neurology, Xiangya Hospital, Central South University.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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13
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Farag MA, Gad MZ. Omega-9 fatty acids: potential roles in inflammation and cancer management. J Genet Eng Biotechnol 2022; 20:48. [PMID: 35294666 PMCID: PMC8927560 DOI: 10.1186/s43141-022-00329-0] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 03/09/2022] [Indexed: 12/15/2022]
Abstract
Background Omega-9 fatty acids represent one of the main mono-unsaturated fatty acids (MUFA) found in plant and animal sources. They are synthesized endogenously in humans, though not fully compensating all body requirements. Consequently, they are considered as partially essential fatty acids. MUFA represent a healthier alternative to saturated animal fats and have several health benefits, including anti-inflammatory and anti-cancer characters. The main body of the abstract This review capitalizes on the major omega-9 pharmacological activities in context of inflammation management for its different natural forms in different dietary sources. The observed anti-inflammatory effects reported for oleic acid (OA), mead acid, and erucic acid were directed to attenuate inflammation in several physiological and pathological conditions such as wound healing and eye inflammation by altering the production of inflammatory mediators, modulating neutrophils infiltration, and altering VEGF effector pathway. OA action mechanisms as anti-tumor agent in different cancer types are compiled for the first time based on its anti- and pro-carcinogenic actions. Conclusion We conclude that several pathways are likely to explain the anti-proliferative activity of OA including suppression of migration and proliferation of breast cancer cells, as well stimulation of tumor suppressor genes. Such action mechanisms warrant for further supportive clinical and epidemiological studies to confirm the beneficial outcomes of omega-9 consumption especially over long-term intervention.
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Affiliation(s)
- Mohamed A Farag
- Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr El Aini St., P.B, Cairo, 11562, Egypt.
| | - Mohamed Z Gad
- Department of Biochemistry, Faculty of Pharmacy & Biotechnology, The German University in Cairo, Cairo, Egypt
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14
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Differential Metabolomics and Network Pharmacology Analysis of Silkworm Biotransformation between Mulberry Leaves and Silkworm Droppings. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:8819538. [PMID: 34306157 PMCID: PMC8263261 DOI: 10.1155/2021/8819538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 03/29/2021] [Accepted: 06/17/2021] [Indexed: 11/17/2022]
Abstract
Silkworm droppings are the product of mulberry leaves digested by silkworm intestines, which are an important medicinal resource in traditional Chinese medicine (TCM). The contents of total fat, fat acids, crude protein, amino acids, and secondary metabolites of obtained mulberry leaves and silkworm droppings were analyzed by HPLC, GC-MS, and UHPLC-Q-TOF MS. The target genes and enriched pathways related to significantly changed compositions between mulberry leaves and silkworm droppings were analyzed by network pharmacology. High unsaturated C18 : 3 fatty acids were transformed to low unsaturated C18 : 1 from mulberry leaves to silkworm droppings. Only lysine and 17 mini-peptides had significantly higher content in silkworm droppings than in mulberry leaves. There were 36 common target genes or the different compounds between mulberry leaves and silkworm droppings. The main pathways of mulberry leaf were enriched in antivirus and anticancer properties, while the pathways of silkworm droppings were enriched in hormone regulation and signal transduction.
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15
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Camponogara C, Brum ES, Pegoraro NS, Brusco I, Brucker N, Oliveira SM. Diosmetin, a novel transient receptor potential vanilloid 1 antagonist, alleviates the UVB radiation-induced skin inflammation in mice. Inflammopharmacology 2021; 29:879-895. [PMID: 33751333 DOI: 10.1007/s10787-021-00802-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 03/06/2021] [Indexed: 02/07/2023]
Abstract
UVB radiation-mediated inflammation and the oxidative process involve the transient receptor potential vanilloid 1 (TRPV1) channel activation in neuronal and non-neuronal cells. Once diosmetin has been identified as a novel TRPV1 antagonist, we evaluated the action of diosmetin from the inflammatory [ear oedema, myeloperoxidase (MPO) activity, histological changes, and cytokines levels] and oxidative [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and SOD activities] parameters in mice exposed to UVB radiation (0.5 j/cm2). We also verified the action of diosmetin on UVB radiation-induced inflammatory parameters after cutaneous nerve fibers denervation by RTX (50 µg/kg s.c.). The topical treatment with the novel TRPV1 antagonist, diosmetin (1%; 15 mg/ear), reduced ear oedema, MPO activity, and MIP-2 and IL-1β cytokines levels by 82 ± 8%, 59 ± 10%, 40 ± 12%, and 85 ± 9%, respectively. The action of diosmetin on ear oedema and inflammatory cell infiltration was histologically confirmed. Topical diosmetin (1%) also reduced NADPH oxidase activity by 67 ± 10% and reverted SOD activity by 81 ± 13%. After cutaneous nerve fibers denervation using RTX, diosmetin reduced ear oedema, but not the inflammatory cell infiltration in mice exposed to UVB radiation. Diosmetin can be a promising molecule against skin inflammatory disorders as a result of sunburn induced by UVB radiation exposure.
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Affiliation(s)
- Camila Camponogara
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Evelyne S Brum
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Natháli S Pegoraro
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Indiara Brusco
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Natália Brucker
- Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Sara Marchesan Oliveira
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil. .,Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Av. Roraima 1000, Camobi, Santa Maria, RS, 97105-900, Brazil.
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16
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Pegoraro NS, Camponogara C, Cruz L, Oliveira SM. Oleic acid exhibits an expressive anti-inflammatory effect in croton oil-induced irritant contact dermatitis without the occurrence of toxicological effects in mice. JOURNAL OF ETHNOPHARMACOLOGY 2021; 267:113486. [PMID: 33091495 DOI: 10.1016/j.jep.2020.113486] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 10/15/2020] [Accepted: 10/16/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cutaneous inflammatory diseases, such as irritant contact dermatitis, are usually treated with topical corticosteroids, which cause systemic and local adverse effects limiting their use. Thus, the discovery of new therapeutic alternatives able to effectively treat skin inflammatory disorders, without causing adverse effects, is urgently needed. AIM OF THE STUDY To investigate the topical anti-inflammatory effect of oleic acid (OA), a monounsaturated fatty acid, into Pemulen® TR2-based semisolid dosage forms, employing a croton oil-induced irritant contact dermatitis model in mice. MATERIALS AND METHODS Male Swiss mice were submitted to skin inflammation protocols by acute and repeated applications of croton oil. The anti-inflammatory activity of Pemulen® TR2 hydrogels containing OA was evaluated by assessing oedema, inflammatory cell infiltration, and pro-inflammatory cytokine IL-1β levels. The mechanisms of action of OA were evaluated using cytokine IL-1β application or pretreatment with the glucocorticoid antagonist mifepristone. Possible toxic effects of OA were also assessed. RESULTS Pemulen® TR2 3% OA inhibited the acute ear oedema [maximal inhibition (Imax) = 76.41 ± 5.69%], similarly to dexamethasone (Imax = 84.94 ± 2.16%), and also inhibited ear oedema after repeated croton oil application with Imax = 85.75 ± 3.08%, similar to dexamethasone (Imax = 81.03 ± 4.66%) on the day 7 of the experiment. Croton oil increased myeloperoxidase activity, which was inhibited by Pemulen® TR2 3% OA (Imax = 71.37 ± 10.97%) and by 0.5% dexamethasone (Imax = 96.31 ± 3.73%). Pemulen® TR2 3% OA also prevented the increase in pro-inflammatory cytokine IL-1β levels induced by croton oil (Imax = 94.18 ± 12.03%), similar to 0.5% dexamethasone (Imax = 87.21 ± 10.58%). Besides, both Pemulen® TR2 3% OA and 0.5% dexamethasone inhibited IL-1β-induced ear oedema with an Imax of 80.58 ± 2.45% and 77.46 ± 1.92%, respectively. OA and dexamethasone anti-inflammatory effects were prevented by 100% and 91.43 ± 5.43%, respectively, after pretreatment with mifepristone. No adverse effects were related to Pemulen® TR2 3% OA administration. CONCLUSIONS OA demonstrated anti-inflammatory efficacy similar to dexamethasone, clinically used to treat skin inflammatory conditions, without presenting adverse effects.
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Affiliation(s)
- Natháli Schopf Pegoraro
- Graduate Program in Biological Sciences: Biochemistry Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Camila Camponogara
- Graduate Program in Biological Sciences: Biochemistry Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Letícia Cruz
- Graduate Program in Pharmaceutical Sciences, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Sara Marchesan Oliveira
- Graduate Program in Biological Sciences: Biochemistry Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
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17
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Pinzaru I, Tanase A, Enatescu V, Coricovac D, Bociort F, Marcovici I, Watz C, Vlaia L, Soica C, Dehelean C. Proniosomal Gel for Topical Delivery of Rutin: Preparation, Physicochemical Characterization and In Vitro Toxicological Profile Using 3D Reconstructed Human Epidermis Tissue and 2D Cells. Antioxidants (Basel) 2021; 10:antiox10010085. [PMID: 33435216 PMCID: PMC7827235 DOI: 10.3390/antiox10010085] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/07/2021] [Accepted: 01/07/2021] [Indexed: 12/22/2022] Open
Abstract
Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (−27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC50 value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders.
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Affiliation(s)
- Iulia Pinzaru
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania; (I.P.); (I.M.); (C.W.); (L.V.); (C.S.); (C.D.)
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania
| | - Alina Tanase
- Faculty of Dental Medicine, “Victor Babeș” University of Medicine and Pharmacy Timisoara, 9 Revolutiei Bv., Sq., 300041 Timișoara, Romania;
| | - Virgil Enatescu
- Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania;
- Correspondence: (V.E.); (D.C.); Tel.: +40-723-374896 (V.E.); +40-256-494604 (D.C.)
| | - Dorina Coricovac
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania; (I.P.); (I.M.); (C.W.); (L.V.); (C.S.); (C.D.)
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania
- Correspondence: (V.E.); (D.C.); Tel.: +40-723-374896 (V.E.); +40-256-494604 (D.C.)
| | - Flavia Bociort
- Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania;
| | - Iasmina Marcovici
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania; (I.P.); (I.M.); (C.W.); (L.V.); (C.S.); (C.D.)
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania
| | - Claudia Watz
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania; (I.P.); (I.M.); (C.W.); (L.V.); (C.S.); (C.D.)
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania
| | - Lavinia Vlaia
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania; (I.P.); (I.M.); (C.W.); (L.V.); (C.S.); (C.D.)
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania
| | - Codruta Soica
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania; (I.P.); (I.M.); (C.W.); (L.V.); (C.S.); (C.D.)
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania
| | - Cristina Dehelean
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania; (I.P.); (I.M.); (C.W.); (L.V.); (C.S.); (C.D.)
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania
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Abdelalim LR, Elnaggar YSR, Abdallah OY. Oleosomes Encapsulating Sildenafil Citrate as Potential Topical Nanotherapy for Palmar Plantar Erythrodysesthesia with High Ex vivo Permeation and Deposition. AAPS PharmSciTech 2020; 21:310. [PMID: 33164131 DOI: 10.1208/s12249-020-01862-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Accepted: 10/24/2020] [Indexed: 12/19/2022] Open
Abstract
Palmar plantar erythrodysesthesia (PPE) is a commonly reported skin toxicity of chemotherapeutic agents that significantly affects patients' quality of life. PPE is described as inflammation, swelling, and even cracks and ulcers in the skin of palms and soles of the feet. Conventional treatment includes topical creams, analgesics, or corticosteroids. However, serious cases are not responding to these medications. PPE has been reported to cause drug cessation or dose reduction if not properly treated. Sildenafil citrate (SC) has a well-documented activity in wound healing through improving blood supply to the affected area. However, SC has poor physicochemical properties limiting its transdermal permeation and deposition. This research endeavored to elaborate novel vesicular system with natural components, phospholipids and oleic acid, loaded with sildenafil citrate for topical management of PPE. Sildenafil-loaded oleosomes were prepared using modified ethanol injection method. Optimized oleosomes had nanometric particle size (157.6 nm), negative zeta potential (- 85.2 mv), and high entrapment efficiency (95.56%). Ex vivo studies on human skin revealed that oleosomes displayed 2.3-folds higher permeation and 4.5-folds more deposition through the human skin compared to drug suspension. Results endorsed SC oleosomes as suitable topical treatment of PPE providing ameliorated sildenafil permeability in addition to acting as a reservoir for gradual release of the drug. Graphical abstract.
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Camponogara C, Brum ES, Pegoraro NS, Brusco I, Rocha FG, Brandenburg MM, Cabrini DA, André E, Trevisan G, Oliveira SM. Neuronal and non-neuronal transient receptor potential ankyrin 1 mediates UVB radiation-induced skin inflammation in mice. Life Sci 2020; 262:118557. [PMID: 33035578 DOI: 10.1016/j.lfs.2020.118557] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 09/23/2020] [Accepted: 09/28/2020] [Indexed: 01/05/2023]
Abstract
AIMS Neuronal and non-neuronal TRPA1 channel plays an active role in the pathogenesis of several skin inflammatory diseases. Although a recent study identified the TRPA1 channel activation upon UVB exposure, its role in inflammatory, oxidative, and proliferative processes underlying UVB radiation-induced sunburn was not yet fully understood. We evaluated the TRPA1 channel contribution in inflammatory, oxidative, and proliferative states on skin inflammation induced by UVB radiation in mice. MAIN METHODS TRPA1 role was evaluated from inflammatory (ear edema, myeloperoxidase, and N-acetyl-β-D-glycosaminidase activities, histological changes, and cytokines levels), proliferative (epidermal hyperplasia, PCNA, and TRPA1 levels), and oxidative (reactive oxygen intermediates measure, H2O2 quantification, and NADPH oxidase activity) parameters caused by UVB radiation single (0.5 J/cm2) or repeated (0.1 J/cm2) exposure. We verified the contribution of non-neuronal and neuronal TRPA1 on UVB radiation-induced inflammatory parameters using RTX-denervation (50 μg/kg s.c.). KEY FINDINGS TRPA1 blockade by the selective antagonist Lanette® N HC-030031 reduced all parameters induced by UVB radiation single (at concentration of 1%) or repeated (at concentration of 0.1%) exposure. We evidenced an up-regulation of the TRPA1 protein after UVB radiation repeated exposure, which was blocked by topical Lanette® N HC-030031 (0.1%). By RTX-denervation, we verified that non-neuronal TRPA1 also interferes in some inflammatory parameters induction. However, cutaneous nerve fibers seem to be most needed in the development of UVB radiation-induced inflammatory processes. SIGNIFICANCE We propose the TRPA1 channel participates in the UVB radiation-induced sunburn in mice, and it could be a promising therapeutic target to treat skin inflammatory disorders.
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Affiliation(s)
- Camila Camponogara
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Evelyne S Brum
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Natháli S Pegoraro
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Indiara Brusco
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Fernanda G Rocha
- Graduate Program in Pharmacology, Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil
| | - Margareth M Brandenburg
- Graduate Program in Pharmacology, Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil
| | - Daniela A Cabrini
- Graduate Program in Pharmacology, Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil
| | - Eunice André
- Graduate Program in Pharmacology, Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil
| | - Gabriela Trevisan
- Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Sara Marchesan Oliveira
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
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