Fermented Cordyceps Powder Attenuates Inflammation and Pulmonary Arterioles Remodeling by Inhibiting p38 MAPK/NF-κB Signaling Pathway in Hypoxic Pulmonary Hypertension Rats

Abstract

Background Pulmonary hypertension (PH) is a pulmonary vascular disease caused by a variety of causes and has a poor prognosis. Hypoxic pulmonary hypertension (HPH) is one of the types of PH. Cordyceps sinensis could treat a variety of lung diseases; its pharmacological active ingredients mainly include cordycepin, nucleosides, cordyceps polysaccharides, sterols, and amino acids. Fermented cordyceps powder (FCP) is an alternative to C. sinensis. In order to investigate the effect of FCP on HPH in rats, we established the HPH rat model. Materials and Methods Forty-two male Sprague–Dawley (SD) rats were randomly divided into a control group, hypoxia group, hypoxia + FCP (0.1 g.kg−1.d−1), hypoxia + FCP (0.2 g.kg−1.d−1), hypoxia + FCP (0.4 g.kg−1.d−1), and hypoxia + sildenafil (30 mg.kg−1.d−1) group. Except for the control group, the other five groups of rats were fed in the hypobaric chamber. The corresponding dose was given by intragastric administration, once a day, for 28 days. The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured; hematological parameters white blood cells (WBC), neutrophils (Neu), Lymphocytes (Lym), monocytes (Mon), red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), and platelets (PLT) levels were detected; serum levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA); the morphological changes of pulmonary arterioles were observed by hematoxylin and eosin (H&E) staining, and the vascular remodeling indexes, vessel wall thickness as a percentage of vascular outer diameter (WT%), vascular wall area as a percentage of total vessel area (WA%), and lumen area as a percentage of the total vascular area (LA%) were calculated; the protein expression levels of IL-1β, IL-6, p-p38, p38, p-IκBα, IκBα, p-p65, and p65 were determined by western blotting. Results FCP could significantly downregulate mPAP, improve pulmonary arteriole remodeling, and reduce the serum levels of IL-1β and IL-6 in HPH rats. In addition, FCP downregulated the protein levels of IL-1β, IL-6, p-p38, p-IκBα, and p-p65. Conclusion FCP could alleviate mPAP and vascular remodeling in HPH rats. Its mechanism could be through inhibiting the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway and by downregulating the expression of inflammatory factors. Our study might provide a research basis for the therapeutic potential of FCP in HPH.