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1.
Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500621

RESUMO

Jellyfish venom is a rich source of bioactive proteins and peptides with various biological activities including antioxidant, antimicrobial and antitumor effects. However, the anti-proliferative activity of the crude extract of Rhopilema nomadica jellyfish venom has not been examined yet. The present study aimed at the investigation of the in vitro effect of R. nomadica venom on liver cancer cells (HepG2), breast cancer cells (MDA-MB231), human normal fibroblast (HFB4), and human normal lung cells (WI-38) proliferation by using MTT assay. The apoptotic cell death in HepG2 cells was investigated using Annexin V-FITC/PI double staining-based flow cytometry analysis, western blot analysis, and DNA fragmentation assays. R. nomadica venom displayed significant dose-dependent cytotoxicity on HepG2 cells after 48 h of treatment with IC50 value of 50 µg/mL and higher toxicity (3:5-fold change) against MDA-MB231, HFB4, and WI-38 cells. R. nomadica venom showed a prominent increase of apoptosis as revealed by cell cycle arrest at G2/M phase, upregulation of p53, BAX, and caspase-3 proteins, and the down-regulation of anti-apoptotic Bcl-2 protein and DNA fragmentation. These findings suggest that R. nomadica venom induces apoptosis in hepatocellular carcinoma cells. To the best of the authors' knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest of R. nomadica jellyfish venom.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Venenos de Cnidários/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Cifozoários/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo
2.
Drug Deliv ; 28(1): 1150-1165, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34121561

RESUMO

The objective of this paper is to confine piperine, a poor oral bioavailable herbal drug into bile salt based nano vesicles for improving its aqueous solubility, hence, its therapeutic activity. Piperine-loaded bilosomes were fabricated adopting thin film hydration technique according to 32.21 full factorial design to investigate the impact of different formulation variables on the characters of bilosomes: entrapment efficiency (EE%), particle size, and % of drug released post 8 h (Q8hr). The selected optimum formula was F2 (enclosing 1% bile salt, brij72 as a surfactant, and ratio of surfactant:cholesterol was 9:1) with desirability value 0.801, exhibiting high EE% (97.2 ± 0.8%) nanosized spherical vesicles (220.2 ± 20.5 nm) and Q8hr (88.2%±5.6). The superiority of the optimized formula (F2) over the drug suspension was revealed via ex vivo permeation study, also pharmacokinetic study denoted to the boosted oral bioavailability of piperine-loaded bilosome compared to piperine suspension. Moreover, antiviral activity and safety margin of F2 was significantly higher than that of the drug suspension. The ability of piperine to interact with the key amino acids in the receptor binding domain 4L3N as indicated by its docking configuration, rationalized its observed activity. Furthermore, F2 significantly reduce oxidant markers, inflammatory cytokines in MERS-CoV-infected mice. Hence, bilosomes can be considered as a carrier of choice for piperine with potential antiviral and anti-inflammatory activities.


Assuntos
Alcaloides , Benzodioxóis , Ácidos e Sais Biliares/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Piperidinas , Alcamidas Poli-Insaturadas , Administração Oral , Alcaloides/administração & dosagem , Alcaloides/farmacocinética , Animais , Antivirais/administração & dosagem , Antivirais/farmacocinética , Benzodioxóis/administração & dosagem , Benzodioxóis/farmacocinética , Disponibilidade Biológica , Inibidores das Enzimas do Citocromo P-450/administração & dosagem , Inibidores das Enzimas do Citocromo P-450/farmacocinética , Liberação Controlada de Fármacos , Lipossomos , Camundongos , Simulação de Acoplamento Molecular , Nanoestruturas , Piperidinas/administração & dosagem , Piperidinas/farmacocinética , Plantas Medicinais , Alcamidas Poli-Insaturadas/administração & dosagem , Alcamidas Poli-Insaturadas/farmacocinética , Tensoativos/farmacocinética
3.
Environ Sci Pollut Res Int ; 28(14): 18134-18145, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33405105

RESUMO

Alzheimer's disease (AD) is characterized by alterations in monoamines, oxidative stress, and metabolic dysfunctions. We aim to assess the therapeutic impacts of roots or leaf extract from Urtica dioica (UD; stinging nettle) against scopolamine (SCOP)-induced memory dysfunction, amnesia, and oxidative stress in rats. Spatial memory was assessed by Y maze test. Tissue analyses of norepinephrine (NE), dopamine (DA), serotonin (5-HT), malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH, GSSG), AMP, ADP, and ATP were assessed by HPLC. mRNA levels of Tau and Hsp70 were estimated by PCR. UD extracts particularly nettle root (NR) significantly normalized the SCOP-induced memory deficits even more potent than sermion (SR) and donepezil (DON). Similarly, NR had potent therapeutic impacts on the levels of cortical and hippocampal monoamines e.g. DA, NE, and 5-HT. SCOP induced a dramatic oxidative stress as measured by MDA, NO, and GSSG levels; however, UD extracts showed significant anti-oxidative stress impacts. Additionally, UD extracts restored ATP levels and reduced the levels of AMP and ADP compared to SCOP-treated rats. Furthermore, cortical Tau and hippocampal Hsp70 were modulated by UD extracts particularly NR compared to the SCOP group. In conclusion, UD extracts particularly roots have potential therapeutic impacts against SCOP-induced neuroinflammatory and/or Alzheimer-like phenotype in rats.


Assuntos
Urtica dioica , Animais , Malondialdeído , Estresse Oxidativo , Extratos Vegetais , Ratos , Escopolamina
4.
Molecules ; 25(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321768

RESUMO

In this study, we evaluated the inflammatory responses induced by aluminum silicate (AS) cytotoxicity in rat lungs. The prophylactic effect of propolis extract was evaluated in 60 adult male albino rats. The rats were divided into six groups: (1) a normal, healthy control group; (2) a normal group fed with 200 mL of propolis extract/Kg; (3) a low-dose positive control group injected with 5 mg/kg of AS; (4) a treated group given propolis and a low dose of AS; (5) a high-dose positive control group injected with 20 mg/kg of AS; and (6) a treated group given propolis with a high-dose of AS. At the end of the two-month experiment, the rats' lungs were removed. For each pair of lungs, one portion was subjected to biochemical analysis and the other underwent hematoxylin and eosin (H&E) staining in order to study its histology. The rats that received AS doses displayed significant disorders in their antioxidant contents as well as in their enzymatic activities and their histopathological structures revealed severe damage to their lung tissues. Upon the rats being treated with propolis, the enzymatic and antioxidant contents improved and partial improvements in the lung structures appeared, including minimized congestion, a reduced hemorrhage of blood vessels and preserved bronchioles, alveolar ducts, and alveoli. The prophylactic effectiveness of propolis extract on the cytotoxicity of AS, owing to the antioxidant properties of propolis, were studied.


Assuntos
Silicatos de Alumínio/química , Antioxidantes/química , Antioxidantes/farmacologia , Pulmão/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Própole/química , Animais , Biomarcadores , Imuno-Histoquímica , Pulmão/metabolismo , Pulmão/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos
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