RESUMEN
BACKGROUND: Pterospermum rubiginosum has been traditionally used by the tribal inhabitants of Southern India for treating bone fractures and as a local anti-inflammatory agent; however, experimental evidence to support this traditional usage is lacking. The present study aimed to investigate the phytochemical characterization, in silico and in vitro anti-inflammatory evaluation, followed by in vivo toxicological screening of P. rubiginosum methanolic bark extract (PRME). RESULTS: The LCMS evaluation revealed the presence of 80 significant peaks; nearly 50 molecules were identified using the LCMS database. In silico analysis showed notable interactions with inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6). In vitro gene expression study supported the docking results with significant down-regulation of iNOS, IL-6, and IL-10. PRME was administered orally to the SD rats and was found to be non-toxic up to 1000 mg/kg body weight for 14 days. The antioxidant enzymes catalase and sodium dismutase exhibited an increased value in PRME-administered groups, possibly due to the diverse phytochemical combinations in bark extract. CONCLUSIONS: PRME administration significantly downregulated the gene expression of inflammatory markers, such as iNOS, IL-6, and IL-10. The molecular docking analysis of iNOS and IL-6 supports the in vitro study. In vivo toxicological study of PRME in SD rats was found to be non-toxic up to a concentration of 1000 mg/kg body weight for 14 days.
RESUMEN
ATTR amyloidosis is a systemic, debilitating and fatal disease caused by transthyretin (TTR) amyloid accumulation. RNA interference (RNAi) is a clinically validated technology that may be a promising approach to the treatment of ATTR amyloidosis. The vast majority of TTR, the soluble precursor of TTR amyloid, is expressed and synthesized in the liver. RNAi technology enables robust hepatic gene silencing, the goal of which would be to reduce systemic levels of TTR and mitigate many of the clinical manifestations of ATTR that arise from hepatic TTR expression. To test this hypothesis, TTR-targeting siRNAs were evaluated in a murine model of hereditary ATTR amyloidosis. RNAi-mediated silencing of hepatic TTR expression inhibited TTR deposition and facilitated regression of existing TTR deposits in pathologically relevant tissues. Further, the extent of deposit regression correlated with the level of RNAi-mediated knockdown. In comparison to the TTR stabilizer, tafamidis, RNAi-mediated TTR knockdown led to greater regression of TTR deposits across a broader range of affected tissues. Together, the data presented herein support the therapeutic hypothesis behind TTR lowering and highlight the potential of RNAi in the treatment of patients afflicted with ATTR amyloidosis.
Asunto(s)
Neuropatías Amiloides Familiares/terapia , Hígado/metabolismo , Prealbúmina/antagonistas & inhibidores , ARN Mensajero/antagonistas & inhibidores , ARN Interferente Pequeño/administración & dosificación , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/metabolismo , Neuropatías Amiloides Familiares/patología , Animales , Antiinflamatorios no Esteroideos/farmacología , Benzoxazoles/farmacología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Expresión Génica , Humanos , Hígado/patología , Macaca fascicularis , Masculino , Ratones , Ratones Transgénicos , Prealbúmina/genética , Prealbúmina/metabolismo , Interferencia de ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacocinéticaRESUMEN
OBJECTIVE: The aim of this study was to define mental health status of palm plantation farmers in Muar, Johor, Malaysia. MATERIALS AND METHODS: 47 male farmers volunteered to join this study from three rural districts in southern Malaysia. Anthropometric measurements, demographic data including smoking habits and the short form of the Depression-Anxiety-Stress Scales (DASS-21) to assess mental health status were obtained in an interview. RESULTS: Mean and SD age of participants was 30.17 ± 4.86 years. Mean BMI of subjects was 22.86 ± 3.88 kg/m2. Most subjects (76.6%) were smokers. The prevalence of mild to moderate anxiety was 27.7% and Mild to moderate depression was 8.5%. CONCLUSIONS: This study revealed high prevalence of anxiety and smoking in palm plantation workers and that smoking habits can be related to their higher anxiety level.
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Enfermedades de los Trabajadores Agrícolas/epidemiología , Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/epidemiología , Agricultura Forestal , Adulto , Enfermedades de los Trabajadores Agrícolas/psicología , Índice de Masa Corporal , Humanos , Malasia/epidemiología , Masculino , Aceite de Palma , Aceites de Plantas , Pruebas Psicológicas , Riesgo , Fumar/epidemiología , Fumar/psicología , Aislamiento Social , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios , Tolerancia al Trabajo Programado , Adulto JovenRESUMEN
The antibacterial activity of various solvent fractions of Balaguduchi, Dhanadanayanadi and Dasamoolabala was studied against the isolated nosocomial pathogens by in vitro method. The methanol, acetone, choloroform, acetone fractions of test drugs and decoctions exhibited different levels of antibacterial activity from low to very high level against the gram positive and gram -negative bacteria. The zone of inhibition of each fraction of drugs was compared with the standard antibiotics Penicillin and Streptomycin. The present study proves and explains the ability and potency of the extracts of Balaguduchi, Dhanadanayanadi and Dasamoolabala as a preventive measure of secondary infections by bacteria in the hospitalixe patients. Even though, these medicines are prescribed in ayurveda for the different clinical indications, the possible secondary activity is also proved through this study.
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Ethanol extract (ETE) and cold aqueous infusion (CAI) of Vitex leucoxylon leaf were evaluated in a battery of tests to define the activity profile of the plant. CAI depressed SMA, antagonised d-amphetamine stereotypy and oxotremorine tremors, shortened the duration of mice immobility in behavioural 'despair' test and lowered serum total cholesterol level. ETE showed significant inhibition of carrageenin paw oedema and granulation tissue formation in rats. Suppression of acetic acid writhing was observed with both ETE and CAI. LD50 value of ETE was > 3000 mg kg-1 (ip) and that of CAI 1050 (800-1200) mgkg-1.