Ginsenoside Compound K attenuates Pulmonary Arterial Hypertension.
Abstract
Background: An important pathogenic mechanism in the development of
pulmonary arterial hypertension (PAH) is hypothesized to be the
pulmonary vascular remodeling, in which cancer-like pulmonary arterial
smooth muscle cells (PASMCs) proliferation and perivascular inflammation
play an important role. Ginsenoside compound K (G-CK) exhibits
anticancer and anti-inflammation properties. However, whether or not
G-CK could protect against PAH in rats is still unknown. Objective: The
aim was to investigate whether or not G-CK attenuates PAH, if so, to
elucidate the molecular mechanisms underlying its effects. Methods and
Results: we established PAH rat models by left pneumonectomy combined
with monocrotaline, and PAH rats were treated G-CK in the prevention (on
7 th day) and reversal group (on 21th day) respectively. The weekly body
weight, the survival rate, mean pulmonary arterial pressure and right
ventricle hypertrophy index of prevention group and reversal group
improved to varying degrees. Hematoxylin and eosin and elastic Van
Gieson staining of lung tissue showed that the increased of wall
thickness, vescular occlusion score and the degree of neointimal
proliferation in the model group were mitigated by G-CK.
Immunohistochemical analysis of Ki67 and α-smooth muscle actin showed
that G-CK suppressed proliferation of PASMCs and muscularization
compared with model group. Moreover, G-CK inhibited NF-κB/Nod-like
receptor family pyrin domain containing 3 (NLRP3) inflammasome
signalling and reduced IL-18, TNF‐α, IL‐6, and IL‐1β in lung tissue by
western blot.