Withania somniferashows a protective effect in monocrotaline-induced pulmonary hypertension

Abstract

Context: Withania somnifera (Linn.) Dunal (Solanaceae), a clinically used herbal drug in Ayurveda, shows potent antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective effects. However, the efficacy of W. somnifera in pulmonary hypertension (PH), a cardiopulmonary disorder, remains unexplored. Objective: The present study investigates the effect of W. somnifera root powder on monocrotaline (MCT)-induced PH in rats. Materials and methods: In preventive studies, W. somnifera root powder (50 and 100 mg/kg/d, p.o.) was administered from day 1 following single administration of MCT (60 mg/kg, s.c.) in Sprague-Dawley (SD) rats. After 35 d, right ventricular pressure (RVP) was measured in anesthetized rats. Various physical markers of right ventricular hypertrophy (RVH) were measured in isolated hearts. Markers of endothelial function, inflammation, and oxidative stress were estimated in lung homogenate. Vasoreactivity of pulmonary arteries was also studied. In therapeutic treatment, W. somnifera (50 and 100 mg/kg/d, p.o.) was administered from day 21 to 35 post-MCT administration. Results: Preventive treatment with 50 and 100 mg/kg W. somnifera significantly reduced the RVP (32.18 ± 1.273 mm Hg and 29.98 ± 1.119 mm Hg, respectively, versus 42.96 ± 1.789 mm Hg of MCT) and all markers of RVH in MCT-challenged rats. There was an improvement in inflammation, oxidative stress and endothelial dysfunction, and attenuation of proliferative marker and apoptotic resistance in lungs. Therapeutic treatment with W. somnifera (100 mg/kg) also reduced RVP and RVH. Discussion: This study demonstrated that W. somnifera significantly protected against MCTinduced PH due to its antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective properties.

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

“…The major constituent in Ashwaganda, identified as Withaferin A, itself is an inhibitor of HMG-CoA, angiotensinogen-converting enzyme, (Ravindran et al, 2015b) can lower total cholesterol, triglycerides, higher HDL/LDL ratios (Shukla et al, 2014) and reduce severity or incidence of myocardial infarction, (Khalil et al, 2015) stroke (Ahmad et al, 2015, Raghavan and Shah, 2015, Sood et al, 2015) and hypertension. (Kaur et al, 2015) As far as glial cells, little has been investigated, but it has been reported that Withaferin A has potential in treatment of glioblastoma multiforme (Chang et al, 2016) with possible future therapies to target brain tumors (Kataria et al, 2015). …”

Inhibition of fatty acid synthase is protective in pulmonary hypertension

“…Pulmonary vascular remodelling, which includes thickening of pulmonary vasculature, plays an important role in PH (Kaur et al , ). Histopathological studies of lungs of MCT‐treated rats showed pulmonary vascular remodelling in our study.…”

“…Following the measurement of the RVP, animals were killed; the wall of the RV, left ventricular (LV) wall and ventricular septum (S) were separated from the rats’ hearts. The Fulton index (RV/LV + S), a marker of hypertrophy, was determined (Kaur et al , 2015a,b).…”

“…The functionality of the pulmonary artery endothelium was checked by obtaining an acetylcholine (300 nM–3 mM)‐induced relaxation response in PE (1 μM)‐preconstricted pulmonary rings. The relaxant responses of acetylcholine were plotted as a % of relaxation (Kaur et al , ).…”

Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis

“…Its primary bioactive compound (Withaferin A) directly inhibits β1-adrenergic receptors, HMG-CoA, angiotensinogen-converting enzyme, total cholesterol, triglycerides, low density lipoprotein and elevation of protective high density lipoproteins and endogenous antioxidant systems [86, 87]. In animal models, WS prevents isoproterenol induced myocardial infarction, stroke distal middle cerebral artery occlusion and monocrotaline induced pulmonary hypertension in rats [88–91]. With respect to the immune system, WS can attenuate mitogen induced T/B-cell activation, secretion of Th1 and Th2 cytokines and inhibit NF-κB nuclear translocation in lymphocytes [92].…”