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1.
Phytother Res ; 34(7): 1556-1569, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32022345

RESUMO

Malaria is one of the life-threatening parasitic diseases that is endemic in tropical areas. The increased prevalence of malaria due to drug resistance leads to a high incidence of mortality. Drug discovery based on natural products and secondary metabolites is considered as alternative approaches for antimalarial therapy. Herbal medicines have advantages over modern medicines, including fewer side effects, cost-effectiveness, and affordability encouraging the herbal-based drug discovery. Several naturally occurring, semisynthetic, and synthetic antimalarial medications are on the market. For example, chloroquine is a synthetic medication for antimalarial therapy derived from quinine. Moreover, artemisinin, and its derivative, artesunate with sesquiterpene lactone backbone, is an antimalarial agent originated from Artemisia annua L. A. annua traditionally has been used to detoxify blood and eliminate fever in China. Although the artemisinin-based combination therapy against malaria has shown exceptional responses, the limited medicinal options demand novel therapeutics. Furthermore, drug resistance is the cause in most cases, and new medications are proposed to overcome the resistance. In addition to conventional therapeutics, this review covers some important genera in this area, including Artemisia, Cinchona, Cryptolepis, and Tabebuia, whose antimalarial activities are finely verified.


Assuntos
Antimaláricos/uso terapêutico , Artemisia/química , Cinchona/química , Cryptolepis/química , Malária/tratamento farmacológico , Plantas Medicinais/química , Tabebuia/química , Antimaláricos/farmacologia , Humanos
2.
Prep Biochem Biotechnol ; 49(1): 38-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30735094

RESUMO

Single-chain fragment variable (scFv) antibodies are antibody fragments consist of variable domains of full antibodies known to retain antigen binding properties while having much lower molecular weights granting some beneficial properties to them. In our previous study, three phage particles each displaying an individual scFv antibody (i.e. J43, J44, and J48) were identified as tumor necrosis factor alpha (TNF-α) binders. The current study aimed to produce previously identified anti-TNF-α scFv antibodies and to investigate their abilities to bind and inhibit TNF-α biological effect. The estimated free energy of folding determined using spectrofluorimetry method for the prepared scFv proteins was in the range of 6.35-12.45 kJ mol-1 indicating their proper folding in the solution. In ELISA experiment, the produced scFvs showed an appropriate affinity towards TNF-α with Kd values in the range of 0.5-2.18 µM. They also inhibited the TNF-α-induced cytotoxicity on L929 cells with sub-micromolar IC50 values (0.12 and 0.73 µM for J44 and J48, respectively). Molecular docking studies showed that J44 could mimic adalimumab interactions with TNF-α, confirming its relatively high TNF-α inhibitory effect compared to J43 and J48. It seems that the findings in the current study can be useful for designing more potent anti-TNF-α antibodies.


Assuntos
Simulação por Computador , Anticorpos de Cadeia Única/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Concentração Inibidora 50 , Camundongos , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Reação em Cadeia da Polimerase , Espectrometria de Fluorescência , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologia
3.
Sci Rep ; 14(1): 2692, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302508

RESUMO

Artemisia absinthium has long been used traditionally as an anti-microbial and antioxidant agent. Various biologically active secondary metabolites, including phenolic compounds such as gallic acid and p-coumaric acid, have been reported from the species. In addition, growing the plants under in vitro conditions enriched with elicitors is a cost-effective approach to enhance secondary metabolite production. This paper examined microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC) effects on morphological characteristics, phenolic compounds, antioxidant activity, and volatile oil content of A. absinthium. The treated shoots with various concentrations of MCC and NCC were subjected to spectrophotometric, GC-MS, and LC-MS analysis. FESEM-EDX, TEM, XRD, and DLS methods were applied to characterize MCC and NCC properties. Morphological findings revealed that the stem length, dry, and fresh weights were improved significantly (P ≤ 0.05) under several MCC and NCC concentrations. Some treatments enhanced gallic and p-coumaric acid levels in the plant. Although 1.5 g/L of MCC treatment showed the highest antioxidant activity, all NCC treatments reduced the antioxidant effect. The findings suggest that both MCC and NCC, at optimized concentrations, could be exploited as elicitors to improve the secondary metabolite production and morphological properties.


Assuntos
Antioxidantes , Artemisia absinthium , Ácidos Cumáricos , Antioxidantes/metabolismo , Artemisia absinthium/química , Artemisia absinthium/metabolismo , Celulose/química , Fenóis/metabolismo
4.
Iran J Basic Med Sci ; 25(3): 364-371, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35656178

RESUMO

Objectives: The current study's objectives were to obtain different extracts and essential oils of Symphytum kurdicum and Symphytum asperrimum and to determine the chemical composition, as well as to evaluate free radical scavenging activity (IC50) and minimum bactericidal concentration (MBC), and the effect of liposomal formulation on antimicrobial properties. Materials and Methods: Air-dried powdered aerial parts of S. kurdicum and S. asperrimum were used. The antioxidant and antibacterial properties, essential oil compositions, total phenol, and flavonoid contents of different fractions were determined by DPPH test, disk diffusion assay, gas chromatography-mass spectrometry, Folin-ciocalteu reagent, and colorimetric assay method, respectively. The film hydration method was used to fabricate nanoparticles. Results: GC-MS analysis indicated that hexafarnesyl acetone was a major essential oil component. n-butanol and ethyl acetate extracts of S. kurdicum had the highest anti-oxidant activity. Extracts of both plants showed antimicrobial activity. The extracts' maximum inhibition zones against Staphylococcus epidermidis were established. A particle size analyzer detected the formulation size of 140 nm. The optimum formulation of liposomes contains the ratio of 75 mg lecithin, 25 mg cholesterol, and 50 mg herbal extract. Despite the nanoparticles' appropriate particle size, the liposomal extract's antimicrobial effect was lower than that of the free form. Conclusion: Our findings demonstrated that extracts have significant antibacterial and anti-oxidant activities, attributed to their bioactive constituents.

5.
Iran J Pharm Res ; 18(2): 759-771, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531059

RESUMO

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine which plays crucial roles in pathogenesis of inflammatory diseases. The current study aimed to investigate the binding abilities of I44 and I49 domain antibodies to TNF-α. The dAbs were expressed in bacterial expression system and purified by affinity chromatography using Ni-sepharose column. The expression and purity of the proteins were evaluated using western blotting and SDS-PAGE techniques, respectively. ELISA experiment showed that I44 and I49 dAbs bind to TNF-α with the binding constants (Kd) of 5.18 ± 1.41 and 2.42 ± 0.55 µM, respectively. The inhibitory effect of dAbs on TNF-α biological effect was determined in MTT assay in which I44 and I49 prevented TNF-α cell cytotoxicity with IC50 values of 6.61 and 3.64 µM, respectively. The identified anti-TNF-α dAbs could bind to and inhibit TNF-α activity. The dAbs activities can be attributed to their ability to establish hydrogen bonds as well as hydrophobic contacts with TNF-α. The results of the current study can pave the way for further structural studies in order to introduce new more potent anti-TNF-α antibodies.

6.
Curr Res Transl Med ; 67(2): 72-75, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30723056

RESUMO

H syndrome is a rare monogenic autosomal recessive disease with characteristic cutaneous findings and multisystem involvement. The aim of this study is to present an Iranian patient with H syndrome and to describe a novel frameshift mutation in SLC29A3 gene. The patient was diagnosed with a few small areas of hyperpigmentation and accompanying hypertrichosis in the lumbar area of her back. Her clinical phenotypes included short stature, hepatosplenomegaly, facial widespread bilateral telangiectatic lesions, bilateral hypertrophy of the parotid gland, upper extremity flexion contracture, elevated inflammatory markers (ESR, CRP) and diabetes mellitus. The identification of a novel homozygous frameshift mutation (c.307_308delTT, p.F103Ter) in SLC29A3 gene, together with the characteristic clinical manifestations of H syndrome, provided accurate diagnosis for this patient.


Assuntos
Anormalidades Múltiplas/genética , Mutação da Fase de Leitura , Hiperpigmentação/genética , Hipertricose/genética , Proteínas de Transporte de Nucleosídeos/genética , Anormalidades Múltiplas/patologia , Pré-Escolar , Feminino , Homozigoto , Humanos , Hiperpigmentação/complicações , Hiperpigmentação/patologia , Hipertricose/complicações , Hipertricose/patologia , Irã (Geográfico) , Mastocitose Cutânea/complicações , Mastocitose Cutânea/genética , Mastocitose Cutânea/patologia , Síndrome
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