RESUMO
Chrysin (5,7-dihydroxyflavone) has many pharmacological properties including anti-inflammatory actions. The objective of this study was to evaluate the anti-arthritic activity of chrysin and to compare its effect with the non-steroidal anti-inflammatory agent, piroxicam, against complete Freund's adjuvant (CFA)-induced arthritis in a pre-clinical model in rats. Rheumatoid arthritis was induced by injecting CFA intra-dermally in the sub-plantar region of the left hind paw of rats. Chrysin (50 and 100 mg/kg) and piroxicam (10 mg/kg) were given to rats with established arthritis. The model of arthritis was characterized using an index of arthritis, with hematological, biological, molecular, and histopathological parameters. Treatment with chrysin significantly reduced the arthritis score, inflammatory cells, erythrocyte sedimentation rate, and rheumatoid factor. Chrysin also reduced the mRNA levels of tumor necrosis factor, nuclear factor kappa-B, and toll-like recepter-2 and increased anti-inflammatory cytokines interleukin-4 and -10, as well as the hemoglobin levels. Using histopathology and microscopy, chrysin reduced the severity of arthritis in joints, infiltration of inflammatory cells, subcutaneous inflammation, cartilage erosion, bone erosion, and pannus formation. Chrysin showed comparable effects to piroxicam, which is used for the treatment of rheumatoid arthritis. The results showed that chrysin possesses anti-inflammatory and immunomodulatory effects that make it a potential drug for the treatment of arthritis.
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Nimbolide is an active constituent of Azadirachta indica and is known for its anti-inflammatory, anti-oxidant, immune-modulatory, and anti-cancer effects. Few studies suggest that nimbolide treatment influences the responses to rheumatoid arthritis, but the underlying molecular mechanisms involved are not yet well established. Therefore, the present study was designed to determine the effect of nimbolide on expression regulation of toll-like receptors to attenuate rheumatoid arthritis. The rheumatoid arthritis model was established by injecting complete Freund's adjuvant (CFA) intra-dermally into the sub-plantar region of the left hind paw of rats. Nimbolide (20 mg/kg) and piroxicam (10 mg/kg) were given to arthritic rats. Rats treated with nimbolide showed a significant reduction in inflammatory cells, rheumatoid factor, ESR, and improved the body weight. The results indicated that nimbolide possesses the capacity to attenuate rheumatoid arthritis by downregulating toll-like receptors, IL-17, IL-23, HSP70, and IFN-γ expression levels. Nimbolide treatment showed significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to piroxicam, which is a standard non-steroidal anti-inflammatory drug used for the treatment of rheumatoid arthritis. It can be concluded that nimbolide can be considered as a potential candidate for therapeutic targeting of the toll-like receptors pathway in rheumatoid arthritis.
Assuntos
Artrite Experimental , Artrite Reumatoide , Ratos , Animais , Adjuvante de Freund/efeitos adversos , Piroxicam/efeitos adversos , Artrite Experimental/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Transdução de Sinais , Artrite Reumatoide/tratamento farmacológico , Antioxidantes/uso terapêuticoRESUMO
Industrial waste is mainly responsible for accumulating Zn (II) in the soil, which needs to be removed to avoid its bioaccumulation and hazardous effects on the environment. In a recent study, the potential of the RY12 strain was evaluated as a biosorbent of Zn (II) ions in an aqueous medium. Different microbiological techniques like biochemical, molecular characterization, and 16S rRNA gene sequencing were used for the identification of RY12. The impact of different parameters such as the initial zinc ion concentration, pH, temperature, and the removal of other metals such as manganese, lead, cobalt, silver, copper, mercury, and chromium was also evaluated on the reduction of Zn (II). Fourier Transform Infrared spectroscopy (FTIR) was also carried out to investigate the role of cellular surfaces in the sorption of Zn+2 ions. Both biochemical and phylogenetic analyses established that strain RY12 Pseudomonas sp. capable of reducing Zn+2 up to 89% at 28°C (pH = 6.5; initial Zn+2 concentration = 200 mg/L). The FTIR analysis revealed that the bacterial cell wall's amino, carboxyl, and phosphate groups were involved in the reaction with Zn (II). Our findings suggest that Pseudomonas sp. RY12 is a proficient bacterium for removing zinc from industrial waste and could be a valuable bioremediation agent.
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BACKGROUND AND OBJECTIVE: Psoriasis is a chronic skin disease with 2-4% of prevalence worldwide conferring a major burden on health systems. It is assumed that the prevalence might increase due to climatic change and deterioration of protective ozone barrier. With the chances of increasing prevalence, newer and specific treatment options need to be explored. Skin is a constant target of oxidative stress owing to continuous exposure to ultraviolet radiations. Oxidative stress is considered to have a central role in dermatological diseases, including psoriasis. This study was designed to explore the role of Humanin analogue (S14-G HNG) as an important anti oxidant for psoriasis like condition in BALB/c mice as till date the commomly used drugs for this disease are corticosteroids which have a dissatisfactory adverse effect profile in terms of chronic use. METHODOLOGY: Imiquimod 5% was used to induce Psoriasis like condition in mice, and the role of HNG was assessed through the histological examination, protein expressions and markers of oxidative stress. Two doses (low and high) of HNG were used and results were compared with an established drug methylprednisolone. KEY RESULT: Significant improvement was seen on histology, PASI scoring, protein expression and oxidative stress by the use of intraperitoneal injections of S14-G HNG and the results were comparable to those obtained through peritoneal injections of methylprednisolone. CONCLUSION: S14G-HNG can be considered as a suitable option for treatment of Psoriasis after clinical trials and it might prove to have lesser side effects as compared to other drugs employed for the treatment of psoriasis being an innate anti oxidant and anti apoptotic compound.
Assuntos
Antioxidantes , Psoríase , Animais , Antioxidantes/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular , Metilprednisolona/uso terapêutico , Camundongos , Psoríase/tratamento farmacológicoRESUMO
Human immunodeficiency virus (HIV) infection is fast becoming widespread in the world with 37.7 million people living with HIV in 2020. Antiretroviral therapy involving chemical drugs has declined acquired immunodeficiency syndrome (AIDS)-related mortality and improved the life quality of AIDS/HIV sufferers. However, the emergence of drug resistance and side effects are the main obstacles for the long-term use of these chemicals as antiretroviral therapy. Recently, a lot of emphasis is being put on finding naturally occurring drug candidates that show activity against HIV and can be potentially used as antiretroviral therapy. In this study, different medicinal plants, Pistacia khinjuk, Teucrium stocksianum, Uncaria tomentosa, Pistacia integerrima, Trigonella gharuensis, and Artocarpus lakoocha, were explored for their anti-HIV potential. Syncytium and p24 assays were performed to determine antiviral activity, while the MTT assay was used to determine cytotoxicity. Results showed that extracts from all six plants inhibited HIV replication in vitro. Also, extracts from Pistacia khinjuk, Teucrium stocksianum, Uncaria tomentosa, and Pistacia integerrima showed low cytotoxicity with a 50% cytotoxicity concentration value of >200 µM. Results of this study indicate that there is potential in these natural extracts to become candidate drugs to be used as complementary and alternative medicine for HIV infection.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , HIV-1 , Plantas Medicinais , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Pseudoephedrine (substituted phenethylamine) is well known as psychotic and bronchodilator. Numerous studies on phenethylamine derivatives indicated that these agents have the potential to abolish inflammatory responses in the non-biological and biological systems. These facts provided the basis to conduct a study on pseudoephedrine to explore its therapeutics in Complete Freund's Adjuvant (CFA)-induced arthritis. Furthermore, existing treatment approaches for RA associated with limited effect on chronic immunological models. Real-time polymerase chain reaction (q-PCR) was performed to execute the expression of pro and anti-inflammatory cytokines in treated and non-treated arthritic rats. These findings were further co investigate by histological observations. The paw volume, paw diameter, weight variations and arthritic score were determined at specific days throughout the experiment of 28 days. Pseudoephedrine at all doses significantly (p < 0.001) suppressed the expression of PGE2, TNF-α, IL-1ß and IL-6. Moreover, pseudoephedrine (20 and 40 mg/kg) caused significant augmentation of IL-4 and IL-10. Similarly, the drug expressed a significant anti-arthritic effect by reducing the paw volume, paw diameter and arthritic score. Similarly, it also reverts the reduction in body weight of arthritic rats at all above-mentioned doses. These findings supported the anti-arthritic potential of pseudoephedrine and recommended it for clinical trials.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Citocinas/antagonistas & inibidores , Pseudoefedrina/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/química , Antirreumáticos/farmacologia , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Adjuvante de Freund , Interleucina-10/agonistas , Interleucina-10/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/metabolismo , Interleucina-4/agonistas , Interleucina-4/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Fenetilaminas/química , Fenetilaminas/farmacologia , Fenetilaminas/uso terapêutico , Pseudoefedrina/química , Pseudoefedrina/farmacologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Unfortunately, the 4th author name was incorrectly published in the original publication.
RESUMO
Amlodipine, a second-generation calcium channel blocker, exhibits documented anti-inflammatory potential. Thereby, present investigation was accomplished with an aim to explore anti-arthritic potential of amlodipine, giving a second chance to an existing drug. For validation of anti-arthritic potential of amlodipine, some in vitro models comprised of bovine serum albumin- and egg albumin-induced protein denaturation along with membrane stabilization of red blood cell was being conducted. In vivo models comprised of formaldehyde-provoked acute arthritis and CFA-instigated chronic arthritic. Paw edema, arthritic index, body weight alterations, biochemical and hematological parameters, and ankle joint histological and radiographic investigations were appraised. Moreover, RT-PCR was conducted to evaluate the levels of several inflammatory markers. Molecular docking was being conducted targeting TNF-α, IL-1ß and IL-6 to establish the correlation between experimental and theoretical results. Amlodipine provides significant protection against denaturation being provoked by heating egg albumin and BSA along with stabilizing membrane of red blood cell, thereby proving in vitro anti-arthritic effect. A significant (p < 0.001) reduction in paw swelling was being observed with amlodipine in case of formaldehyde-instigated arthritis especially at the dose of 20 mg/kg. In case of CFA-provoked arthritis, reduction in paw volume and arthritic score while preservation of body weight loss and normal hematological and biochemical parameters in comparison to arthritic control were being manifested by amlodipine at the dose of 20 mg/kg. Gene expression level of TNF-α, IL-6 and IL-1ß was significantly reduced by amlodipine while an increase in expression level of IL-4 and IL-10 was evident in animals treated with piroxicam and amlodipine. Molecular docking analysis demonstrated strong binding interaction of amlodipine with TNF-α, IL-6 and IL-1ß thus providing a good correlation between experimental and theoretical results. Thus, current study is suggestive that amlodipine exhibits strong anti-arthritic potential and thus can be considered as a candidate for drug repurposing as anti-arthritic agent.