Penehyclidine hydrochloride ameliorates renal ischemia reperfusion-stimulated lung injury in mice by activating Nrf2 signaling

Introduction: Penehyclidine hydrochloride (PHC) is an anticholinergic with anti-inflammatory and anti-oxidation activities. PHC displayed protectivity against renal ischemia reperfusion (RIR) injury. Nevertheless, the precise protectivity of PHC on RIR-induced lung injury remains unknown. Methods: We examined the effects of PHC on RIR-induced lung injury and investigated the underlying mechanism. We induced RIR in mice and administrated PHC to RIR mice. Kidney function was monitored by measuring the blood urea nitrogen (BUN) and creatinine level in serum. We evaluated the lung injury, myeloperoxidase (MPO) activity in lung, pro-inflammatory cytokine level, and oxidative markers in serum and lung tissues. We tested the expression level of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) in lung of RIR mice after PHC treatment. Finally, we evaluated the effects of PHC in RIR Nrf2-/- mice. Results: PHC greatly downregulated the serum levels of BUN, creatinine, IL-6, NO, malondialdehyde (MDA), and matrix metalloproteinase-2. PHC also ameliorated the lung injury, decreased the MPO activity, and suppressed production of IL-6, TNF-α, IFN-γ, MDA, and O2-, while it promoted production of superoxide dismutase (SOD) and catalase (CAT) in lung. PHC improved the production of Nrf2 and HO-1. Conclusion: The protectivity of PHC was absent in Nrf2-/- mice. PHC ameliorated RIR-induced lung injury through Nrf2 pathway.

Penehyclidine Hydrochloride Has the Function of Lung Protection for Acute Lung Injury in Rat Models:A Systemic Review and Meta-analysis

ObjectiveThis systematic review and meta-analysis aims to review the effects of penehyclidine hydrochloride (PHC) on acute lung injury in animal models. MethodsPubMed, Embase, CNKI were searched for collecting the randomized controlled trials(RCTs) on the effects of penehyclidine hydrochloride on acute lung injury in rat models from inception to July 1, 2021. We used Cochrane evaluating quality and RevMan 5.3 software performing Meta-analysis.(lung W/D ratio、PaO2/FiO2、SOD、MPO activity、IL-6 and TNF-α) ResultsOur search including 11 studies in 3 databases. Meta-analysis showed that, Compared with the acute lung injury model group, the PHC treatment group: lung W/D ratio[MD=-1.29，95%CI（-1.94，-0.64），P＜0.01]、PaO2/FiO2[MD=1.73，95%CI（0.01，3.45），P＜0.01]、SOD[MD=7.05，95%CI（5.58，8.52），P＜0.000,01]、IL-6 [MD=-1.03，95%CI（-1.29，-0.77），P＜0.0001]、IL-6 [MD=-3.35，95%CI（-5.29，-1.40），P＜0.001]and TNF-α[MD=-2.17，95%CI（-3.27，-1.07），P＜0.0001].Conclusionspenehyclidine hydrochloride has the function of lung protection in acute lung injury and provides a new therapy for future clinical treatment.

Health Informatics of Doxofylline Combined with Penehyclidine Hydrochloride on Pulmonary Inflammation in Chronic Obstructive Pulmonary Disease Based on ANOVA Statistical Analysis

Objective: This study evaluated the effect of doxofylline combined with penehyclidine hydrochloride on the pulmonary inflammatory response during mechanical ventilation in chronic obstructive pulmonary disease (COPD), as well as to identify the effects of JNK/SAPK signaling pathway in this inflammatory response. Methods: The COPD model can be constructed by exposing it to cigarette smoke and injections of lipopolysaccharide into the airway. Rats were selected randomly for treatment with doxofylline, penehyclidine hydrochloride, a combination of these two drugs. The control Group received no drug treatment. The date were processed using ANOVA statistical analysis. Results: In all rats, the lung tissue was pathologically characteristic of COPD. Peak airway pressure, the wet/dry weight of lungs, and degrees of TNF-α, IL-10, malondialdehyde, JNK, and p-JNK decreased; while IL-10 and superoxide dismutase levels increased (p < 0.05) in all Groups having received drug treatment (p < 0.05) when compared to control. The combination of penehyclidine hydrochloride with doxofylline had a stronger effect on all of these metrics than either drug alone (p < 0.05). Conclusion: Based on health informatics, This study suggests that the combination of penehyclidine hydrochloride with doxofylline can promote the recovery and maintenance of immune homeostasis in mechanically ventilated COPD rats, and that the underlying mechanism may be is influenced by downregulation of the JNK/SAPK signaling pathway.

Cholinergic receptor blockers affect the protective effect of Angong Niuhuang pill on neurologic deficits and intestinal injury in intracerebral hemorrhage mice

Stroke is a devastating disease, intracerebral hemorrhage (ICH) is a devastating subtype. This study aimed to investigate whether cholinergic receptors participate in the process of Angong Niuhuang Pill (ANP) improving neurological function and relieving intestinal injury in ICH mice. The mice were treated with ANP, cholinergic receptor blockers, atropine (ATR), penehyclidine hydrochloride (PHC) or methyllycaconitine (MLA). Male CD-1 mice were randomly divided into 9 groups, Sham, ICH, ANP (0.2 g/kg), ANP plus ATR, ANP plus PHC, ANP plus MLA, ATR, PHC, MLA. ICH model is made by collagenase VII injection (0.075 U). ANP (0.2 g/kg) was administered by gavage after 30 min of ICH. MLA, ATR, PHC was given at 15 min after ICH. Neurological function was evaluated by Garcia test. Intestinal injury was observed by histological analysis. Endotoxin (ET) was measured by enzyme-linked immunosorbent assay. Compared to the Sham group, the score of Garcia test in the ICH significantly decreased. ANP increased significantly the score of ICH mice. ANP also ameliorated the intestinal injury caused by ICH. Cholinergic receptor blockers reversed partially the improvement of neurological function and intestinal injury by ANP. ANP attenuates the neurological deficits and intestinal injury in ICH mice and the protective effect of ANP may be involved in the regulation of the cholinergic system.

Chest X-ray Image Analysis and Penehyclidine Hydrochloride Postconditioning Influence of Lung Ischemia Reperfusion Injury

Purpose: We analyze chest X-ray diagnosis results of patients undergoing cardiopulmonary bypass heart surgery in intensive care unit (ICU). In our previous study, we found that penehyclidine hydrochloride (PHC) preconditioning pretects lung function and reduced the apoptosis. Although preconditioning is effective, this clinical treatment is often given only when symptoms appear, when postconditioning is easier to administer. In this study, after confirming the lung condition via medical image analysis, we aimed to look the effect of high-dose penehyclidine hydrochloride postconditioning in lung after I/R in rats, and the apoptosis mechanisms involved. Methods: Chest X-ray was taken in 256 adult patients under cardiopulmonary bypass with heart syurery. Medical image analysis was preliminarily performed, the diagnostic results were analyzed. Rats were subjected to ischemia in left lung 45 min, and then 2 h reperfusion, and treated with PHC. We then observed the effects of PHC on the following: lung function, lung injury, oxidative stress, rate of apoptosis of lung cells, apoptosis-related proteins, and the p38 MAPK pathway. Results: Analysis results of chest X-ray suggest multiple pulmonary complications after cardiopulmonary bypass heart surgery. The laboratory results showed that high-dose penehyclidine hydrochloride postconditioning significantly protected lung function, reduced oxidative stress and apoptosis of the lungs caused by reperfusion, and inhibited activation of the p38 MAPK pathway. Conclusion: Analysis results of chest X-ray show multiple pulmonary complications after cardiopulmonary bypass heart surgery. This study suggests that high-dose penehyclidine hydrochloride can treat lung I/R injury.

Effect of penehyclidine hydrochloride on IL-6, TNF-α, HIF- 1α and oxidative stress in lung tissue of young rats with acute lung injury

Purpose: To investigate the effect of penehyclidine hydrochloride (PHC) on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α), and oxidative stress levels in lung tissues of acute lung injury (ALI) neonatal rats.Methods: 40 male Sprague-Dawley (SD) rats were assigned to model, low-dose PHC, high-dose PHC, and control groups (n = 10). Levels of IL-6, TNF-α and HIF-1α were evaluated by enzyme-linked immunosorbent assay (ELISA). Pulmonary lesions were determined histologically using H&E staining.Results: The lung tissue levels of IL-6, TNF-α and HIF-1α were significantly higher in model rats than in control rats, and significantly lower in PHC-treated rats than in model group, with decrease in levels as PHC dose increased (p < 0.05). The lung tissue activity of MPO and level of MDA in model rats were significantly higher than those in control rats, but significantly lower in the lung tissues of the two PHC groups than in the model group; decrease in levels occurred as PHC dose increased (p < 0.05).Conclusion: PHC decreases the lung and serum levels of IL-6, TNF-α and HIF-1α in a rat model of ALI, and mitigates pulmonary oxidative stress and lung tissue damage. Thus, penehyclidine hydrochloride may be useful to mitigate ALI-induced damage in patients. However, further studies and clinical trials are required to ascertain this Keywords: Penehyclidine hydrochloride, Alveolar septum, Acute lung injury, Inflammatory cells, IL-6, TNF-α, HIF-1α, Oxidative stress