Combination of pseudoephedrine and emodin ameliorates LPS-induced acute lung injury by regulating macrophage M1/M2 polarization through the VIP/cAMP/PKA pathway

Abstract

Background Acute lung injury (ALI) is an acute multifactorial infectious disease induced by trauma, pneumonia, shock, and sepsis. This study aimed to investigate the protective effects of pseudoephedrine and emodin combined treatment in experimental ALI, as well as the mechanisms underlying the regulation of inflammation and pulmonary edema via the VIP/cAMP/PKA pathway. Methods The wistar rats were randomly divided into fifteen groups (n = 5). Rats in each group were given intragastric administration 1 h before LPS injection. Those in the control and LPS groups were given intragastric administrations of physiological saline, rats in other groups were given intragastrically administered of differential dose therapeutic agents. The rats in the LPS and treatment groups were then injected intraperitoneally with LPS (7.5 mg/kg) to induce ALI. After being treated with pseudoephedrine and emodin for 12 h, all animals were sacrifice. Anal temperatures were taken on an hourly basis for 8 h after LPS injection. Pathological examination of lung specimen was performed by H&E staining. Cytokines (IL-1β, TNF-α, IL-6, iNOS, IL-10, Arg-1, CD86, CD206, F4/80, VIP) in lung tissue were assayed by ELISA and immunofluorescence. The expression of VIP, CAMP, AQP-1, AQP-5, p-PKA, PKA, p-IκBα, IκBα, p-p65, p65, p-P38, P38, p-ERK1/2, ERK1/2, p-JNK1/2, JNK1/2 protein in lung was determined by western blotting. Results After rats being treated with pseudoephedrine + emodin, reduced of fever symptoms. The contents of inflammatory cytokines (IL-1β, TNF-α, IL-6, iNOS) were decreased and anti-inflammatory cytokines (IL-10, Arg-1) were significantly increased in serum. Pseudoephedrine + emodin treatment effectively promoted VIP cAMP and p-PKA protein expression in lung tissues, and significantly inhibited NF-κB, MAPK phosphorylation, Pseudoephedrine + emodin treatment can inhibit M1 polarization and promoted M2 polarization via the VIP/cAMP/PKA signaling pathway. Conclusions The combination of Pseudoephedrine and emodin was effective in ameliorating LPS-induced ALI in rats by inducing VIP/cAMP/PKA signaling. Inhibiting the NF-κB, MAPK inflammatory pathway, relief of pulmonary edema suppressing macrophage M1 polarization, and promoting macrophage M2 polarization.

Network pharmacological prediction and molecular docking analysis of the combination of Atractylodes macrocephala Koidz. and Paeonia lactiflora Pall. in the treatment of functional constipation and its verification

“…21,22 Meanwhile, F2, AQP expression is closely related to AC, 27 cAMP, 28,29 and PKA. 30,31 The adenylyl cyclase (AC)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling system is the best postreceptor signal transduction system. 32 The expression of cAMPmediated AQP channels and the expression of G(salpha) were closely connected.…”

Helicobacter pylori promotes inflammatory factor secretion and lung injury through VacA exotoxin-mediated activation of NF-κB signaling

“…For the immunofluorescence assay, sections of lung tissue were incubated first with anti-p65 NF-κB antibody (Abcam, Cambridge, MA, USA; 1:100) and then with secondary antibody (Abcam; 1:3000) at 37°C for 1 h, after which they were counterstained with DAPI [ 17 ]. Samples were observed under a fluorescence microscope (Olympus CX23, Tokyo, Japan).…”

“…For Western blotting, total protein was separated by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride membranes (Millipore, Atlanta, GA, USA) [ 17 ]. After washing and blocking, the membranes were incubated with primary antibodies against VacA (sc-32,746, Santa Cruz Biotechnology, Santa Cruz, CA, USA, 1:500), p65 NF-κB (ab32536, 1:5000), p-p65 NF-κB (ab76302, 1:1000), and GAPDH (ab8245; Abcam, 1:10,000).…”

LGALS2 and EGR1: markers of endometriosis for predictive, preventive and personalized medicine

“…The medication pseudoephedrine is widely used to treat sinusitis and bronchial asthma [55]. It lowers mast cell and CD4+ cell infiltration and inhibits the release of serum inflammation-related factors such as TNF-, IL-1, IL-4, IL-6, IL-13, IL-33, TSLP, and IL-23) and neutrophil migratory factors in a mouse model of atopic dermatitis (CCL2 and MMP-9) [56]. Unknown is the association between Pseudoephedrine and EM, and it is hypothesized that EM's phenotype may be improved by a transformative interaction with macrophages.…”