Different Concentrations of Notoginsenoside Rg1 Attenuate Hypoxic and Hypercapnia Pulmonary Hypertension by Reducing the Expression of ERK in Rat PASMCs

Pulmonary arterial hypertension (PAH) is a serious disease which is characterized by increased vascular resistance and pressure. We have previously hypothesized that panax notoginseng saponins (PNS) might attenuate pulmonary vasoconstriction under hypoxia and hypercapnia condition. This study aims to investigate the effect of notoginsenoside Rg1, a main ingredient of PNS, with various concentrations (8, 40, 100 mg/L, respectively) on extracellular signal regulated kinase (ERK1/2) signaling pathway in pulmonary arterial smooth muscle cells (PASMCs). In addition, PASMCs were randomly divided into six groups: SD rat under normoxic condition as control group (N group), hypoxia hypercapnia group (H group), DMSO control group (HD group), Rg1-treatment groups (RgLRgM and RgH group). Western-blot and RT-PCR were used to test the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA. This study provided the evidence that the expression of p-ERK protein and the expression of ERK1 mRNA and ERK2 mRNA in HD group and H group were obviously higher than that in N group (P < 0.01), Whereas the level of ERK1/2 mRNA in Rg1-treatment groups was significantly lower than that in HD group and H group (P < 0.01), and the proper concentration of Rg1 is 40 mg/L. These results suggested that notoginsenoside Rg1 can attenuate pulmonary vasoconstriction which may lead to HHPV through reducing the expression of ERK1/2.

Notoginsenoside R₁Attenuates Hypoxia and Hypercapnia-Induced Vasoconstriction <i>In Vitro</i>by Reducing the Expression of p38

Notoginsenoside R1, the main active ingredient of Panax notoginseng saponins (PNS), has been proposed to play fatal roles in the development of hypoxic hypercapnia-induced pulmonary vasoconstriction (HHPV). Subsequently, pulmonary arterial smooth muscle cells (PASMCs) lead to pulmonary vascular system remodeling and chronic pulmonary disease in the development of HHPV. Despite considerable studies have contributed to pulmonary disease, the mechanism of how Notoginsenoside R1 affects HHPV remains unclear. In this view, we will discuss the effect of notoginsenoside R1 by investigating the expression of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in PASMCs under hypoxia and hypercapnia condition. The third order PASMCs of Sprague Dawley (SD) rats were cultured with various concentrations (8, 40, 100 mg/L, respectively) of Notoginsenoside R1. Our data showed that the protein and mRNA expression levels of p-38 MAPK were higher in hypoxic hypercapnia group compared with hypoxic DMSO and normoxia control groups (p 1 treatment groups, the level of p-p38 MAPK protein and p38 MAPK mRNA were significantly decreased with different degrees (p 1 treatment may contribute to attenuate HHPV via decreasing the protein and mRNA expression levels of p-38 MAPK.

Major ascaroside pheromone component asc-C5 influences reproductive plasticity among isolates of the invasive species pinewood nematode

Pheromones are communication chemicals and regulatory signals used by animals and represent unique tools for organisms to mediate behaviors and make“decisions”to maximize their fitness.Phenotypic plasticity refers to the innate capacity of a species to tolerate a greater breadth of environmental conditions across which it adapts to improve its survival,reproduction,and fitness.The pinewood nematode,Bursaphelenchus xylophilus,an invasive nematode species,was accidentally introduced from North America into Japan,China,and Europe;however,few studies have investigated its pheromones and phenotypic plasticity as a natural model.Here,we demonstrated a novel phenomenon,in which nematodes under the condition of pheromone presence triggered increased reproduction in invasive strains(JP1,JP2,CN1,CN2,EU1,and EU2),while it simultaneously decreased reproduction in native strains(US1 and US2).The bidirectional effect on fecundity,mediated by presence/absence of pheromones,is henceforth termed pheromone-regulative reproductive plasticity(PRRP).We further found that synthetic ascaroside asc-C5(ascr#9),the major pheromone component,plays a leading role in PRRP and identified 2 candidate receptor genes,Bxydaf-38 and Bxysrd-10,involved in perceiving asc-C5.These results suggest that plasticity of reproductive responses to pheromones in pinewood nematode may increase its fitness in novel environments following introduction.This opens up a new perspective for invasion biology and presents a novel strategy of invasion,suggesting that pheromones,in addition to their traditional roles in chemical signaling,can influence the reproductive phenotype among native and invasive isolates.In addition,this novel mechanism could broadly explain,through comparative studies of native and invasive populations of animals,a potential underlying factor behind of the success of other biological invasions.