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Acne vulgaris, a prevalent skin condition, arises from an imbalance in skin flora, fostering bacterial overgrowth. Addressing this issue, clindamycin molecularly imprinted polymeric nanoparticles (Clin-MIP) loaded onto polyurethane nanofiber scaffolds were developed for acne treatment. Clin-MIP was synthesized via precipitation polymerization using methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), and azoisobutyronitrile (AIBN) as functional monomers, crosslinkers, and free-radical initiators, respectively. MIP characterization utilized Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) before being incorporated into polyurethane nanofibers through electrospinning. Further analysis involved FTIR, scanning electron microscopy (SEM), in vitro release studies, and an ex vivo study. Clin-MIP showed strong antibacterial activity against S. aureus, with inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.39 and 6.25 µg/mL, respectively. It significantly dropped the bacterial count from 1 × 108 to 39 × 101 CFU/mL in vivo and has bactericidal activity within 180 min of incubation in vitro. The pharmacodynamic and histopathology studies revealed a significant decrease in infected animal skin inflammation, epidermal hypertrophy, and congestion upon treatment with Clin-MIP polyurethane nanofiber and reduced pro-inflammatory cytokines (NLRP3, TNF-α, IL-1ß, and IL-6) conducive to acne healing. Consequently, the recently created Clin-MIP polyurethane nanofibrous scaffold. This innovative approach offers insight into creating materials with several uses for treating infectious wounds caused by acne.
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Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.
Assuntos
Althaea , Quitosana , Diabetes Mellitus , Nanopartículas Metálicas , Óxido de Zinco , Humanos , Animais , Ratos , Óxido de Zinco/química , Quitosana/química , Althaea/metabolismo , Interleucina-6 , Fator de Necrose Tumoral alfa , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Cicatrização , Anti-Inflamatórios/farmacologia , Inflamação , Flores , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
Purpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results: Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.
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Antralina , Psoríase , Humanos , Animais , Camundongos , Antralina/farmacologia , Antralina/uso terapêutico , Ciclosporina/farmacologia , Fosfolipídeos , Ceramidas/farmacologia , Administração Cutânea , Psoríase/tratamento farmacológico , Psoríase/patologia , Pele , Modelos Animais de DoençasRESUMO
AIM: PI3K/AKT/GSK-3ß/ß-catenin signaling pathway is a triggering factor for epithelial to mesenchymal transition (EMT) which plays a pivotal role in the pathogenesis of endometriosis. Parthenolide is a sesquiterpene lactone extract that has anti-inflammatory, analgesic and anticancer properties. Hence, we investigated the effect of parthenolide against EMT in the endometrial tissue implants and immortalized epithelial endometriotic cell lines 12Z. MAIN METHODS: Twenty- four female Rats with surgically induced endometriosis were treated with parthenolide (2, 4 mg/kg), for 4 weeks. Endometriotic cell line 12Z was used to identify the effect of parthenolide on the wound healing, cellular migration and invasion properties of endometriotic cells. KEY FINDINGS: Parthenolide decreased the endometriotic implant tissue expression of total PI3K, PI3K-p85, p-AKT, p/total AKT, p-GSK-3ß, P/total GSK-3ß, and nß-catenin, as well as increased E-cadherin and decreased vimentin mRNA expression. Parthenolide upregulated PTEN immunoreactivity as well as the endometriotic tissue caspase-3, caspase-9, BAX levels while reducing Bcl2 level. Additionally, parthenolide decreased endometriotic tissue implants surface area and histopathological score of the epithelial growth. SIGNIFICANCE: Our findings showed that parthenolide in a dose dependent manner inhibited PI3K/AKT/GSK-3ß/nß-catenin cascade via enhancement of PTEN with subsequent inhibition of EMT evidenced by elevation of the epithelial marker, E-cadherin and reduction of mesenchymal marker, vimentin, of the endometriotic implants in addition to reversal of invasion and migration properties of epithelial endometriotic cell lines. These findings provide a valuable therapeutic approach for treatment of endometriosis.
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Endometriose , Sesquiterpenos , Humanos , Ratos , Feminino , Animais , beta Catenina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Transição Epitelial-Mesenquimal , Vimentina/metabolismo , Endometriose/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Caderinas/metabolismo , Sesquiterpenos/farmacologia , Movimento Celular , PTEN Fosfo-Hidrolase/metabolismoRESUMO
Liver fibrosis is a health challenge requiring alternative therapeutic approaches. Cilostazol is a selective phosphodiesterase-3 inhibitor and possesses antioxidant, anti-inflammatory and antifibrotic properties. Sirtuin 1 (SIRT1) is a member of the silent information regulator 2 family. Cilostazol upregulates SIRT1 expression. Cilostazol protects against the cholestatic liver insults caused by bile duct obstruction. Involvement of SIRT1 pathway in this protective effect has not been studied yet. So, we hypothesized that SIRT1 signaling may have a role in cilostazol protective effects against bile duct ligation-induced liver damages. Rats were subjected to common bile duct ligation then treated with cilostazol (9 mg/kg or 27 mg/kg) in the presence or absence of specific SIRT1 inhibitor EX527. Cilostazol improved liver function, reduced inflammation, enhanced antioxidant status, ameliorated cholestatic liver injury and upregulated hepatic SIRT1. However, these protective effects were abrogated by EX527, suggesting that SIRT1 signaling may have a role in these effects. In conclusion, cilostazol in a dose-dependent way produced hepatoprotective effects via anti-inflammatory, antioxidant, antifibrotic effects which were mediated, in part, through SIRT1 upregulation.
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Cilostazol/farmacologia , Ducto Colédoco/cirurgia , Fígado/lesões , Fígado/patologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Ácidos e Sais Biliares/sangue , Biomarcadores/metabolismo , Carbazóis/farmacologia , Cilostazol/antagonistas & inibidores , Cilostazol/uso terapêutico , Colágeno Tipo IV/sangue , Citocinas/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hidroxiprolina/metabolismo , Ligadura/efeitos adversos , Fígado/efeitos dos fármacos , Masculino , Oxirredução/efeitos dos fármacos , Ratos , Ratos Wistar , Sirtuína 1/antagonistas & inibidores , Fator de Transcrição RelA/metabolismo , Fator de Crescimento Transformador beta1/sangue , Regulação para Cima/efeitos dos fármacosRESUMO
Peripheral nervous system neurotoxicity is the most problematic complication of cisplatin treatment. In this study, we have addressed the possible neuroprotective effect of canagliflozin on cisplatin-induced peripheral neurotoxicity in rats. Rats were randomly allocated into the following: control (vehicle) group, received hydhroxypropyl methyl cellulose; cisplatin group, injected cisplatin 2 mg/kg intraperitoneal, twice a week for 5 consecutive weeks; canagliflozin-cisplatin of received canagliflozin, 10 mg/kg/day by gavage and cisplatin in the same schedule like cisplatin group. Thermal nociception and rotarod performance were assessed. Malondialdehyde (MDA), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), and caspase 3 were determined in serum. Hematoxylin and eosin (H&E) and immunohistochemical stained sciatic nerve sections were examined. Cisplatin induced thermal hypoalgesia and decreased rotarod performance as well as GSH serum level while increased MDA, TNF-α, and caspase-3 serum levels with atrophy and fragmentation of the nerve fibers with decreased expression of myelin basic protein. Canagliflozin prevented thermal hypoalgesia and improved rotarod performance with increment in GSH serum level while decreased MDA, TNF-α, and caspase-3 levels as well as prevented fragmentation of the nerve fibers and enhanced myelin basic protein expression in relation to cisplatin group. Canagliflozin attenuates the neurotoxic effect of cisplatin through anti-inflammatory and anti-oxidant actions as well as inhibition of apoptosis.
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Anti-Inflamatórios/uso terapêutico , Canagliflozina/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos , Apoptose/efeitos dos fármacos , Canagliflozina/farmacologia , Caspase 3/sangue , Cisplatino , Glutationa/sangue , Masculino , Malondialdeído/metabolismo , Síndromes Neurotóxicas/sangue , Doenças do Sistema Nervoso Periférico/sangue , Substâncias Protetoras/farmacologia , Ratos Wistar , Fator de Necrose Tumoral alfa/sangueRESUMO
Elevated blood glucose and insulin resistance are triggering factors for non-alcoholic steatohepatitis (NASH). We investigated the effects of the Sodium Glucose co-Transporter 2 (SGLT2) inhibitor canagliflozin on NASH development in rats with type 2 diabetes mellitus as well as the possible underlying mechanisms and for the first time the effect of canagliflozin on the hepatic zinc-α2-glycoprotein (ZAG) levels. Rats were treated with nicotinamide and streptozotocin to reduce the insulin secretory capacity then fed high fat diet for 8 weeks. The diabetic high fat diet rats were divided into three groups; untreated group, canagliflozin 10â¯mg/kg treated group and canagliflozin 20â¯mg/kg treated group during this period. The elevated blood glucose and glycated haemoglobin (HbA1c) levels in the diabetic high fat diet rats were significantly reduced by canagliflozin. Moreover, the diabetic high fat diet induced NASH development as evidenced by liver weight gain, hepatic lipid accumulation and low hepatic ZAG expression as well as increased serum alanine aminotransferase; all these changes were reversed in rats treated with canagliflozin. Additionally, canagliflozin succeeded to upregulate the hepatic ZAG levels in both normal and diabetic high fat fed rats, lower the serum and hepatic inflammatory cytokines levels as well as lower the serum caspase-3 levels and enhanced hepatic Bcl-2 expression. Also, canagliflozin attenuated hepatic oxidative stress and elevated the antioxidant enzymes activity as well as the total antioxidant capacity. All these effects of canagliflozin were dose dependant. CONCLUSION: SGLT2 inhibitor-canagliflozin- has beneficial effects in treatment of NASH associated with diabetes mellitus.
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Canagliflozina/farmacologia , Proteínas de Transporte/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Glicoproteínas/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Regulação para Cima/efeitos dos fármacos , Adipocinas , Alanina Transaminase/sangue , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Caspase 3/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Jejum/sangue , Hemoglobinas Glicadas/metabolismo , Insulina/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangueRESUMO
Doxorubicin (Dox)-induced cardiotoxicity constitutes the major adverse effect that limited its use. We investigated the possible protective effects of liraglutide on Dox-induced cardiotoxicity in rats. Rats were divided into the following groups: control group rats received normal saline [1 ml/kg, intraperitoneal (i.p.)]; doxorubicin group rats received doxorubicin (1.25 mg/kg, i.p.), four times per week for 4 weeks; and liraglutide group rats received doxorubicin (1.25 mg/kg, i.p.) four times per week for 4 weeks then received liraglutide (100 µg/kg, i.p) daily for 4 weeks. At the end of the study, animals were sacrificed and serum creatine kinase-MB (CK-MB) and troponin I levels were determined. Malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and caspase-3 levels of the heart were determined. Cardiac AMPK, phosphorylated-Akt, tissue growth factor-ß1 (TGF-ß1), and GSK3-ß levels of the heart were determined. Hematoxylin and eosin (H&E) stained sections form the heart were examined as well as immunohistochemical sections for detection of Bcl-2 expression. Dox treatment increased serum level of troponin I and CK-MB while decreased SOD activity, decreased AMPK, and p-Akt cardiac levels with increased in MDA, IL-6, TNF-α,GSK-3b, TGFB1, and caspase-3 levels in the heart with inflammation and necrosis in cardiac histopathology with decreased Bcl-2. Treatment with liraglutide decreased troponin I and CK-MB while increased SOD activity, AMPK, p-Akt with decrements in MDA, IL-6, TNF-α, GSK-3ß, TGF-ß1, and caspase-3 levels with attenuation of inflammation and necrosis while increased Bcl-2 expression. Liraglutide may thus represent a new clinical tool for the treatment of Dox-induced cardiotoxicity.