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Ischemic stroke is divided into acute, subacute and convalescent phases according to the time of onset. Clinically, Mailuoning oral liquid (MLN O) is a traditional Chinese patent medicine for treating ischemic stroke. Previous studies have shown that MLN O could prevent acute cerebral ischemia-reperfusion. However, its underlying mechanism remains unclear. To investigate the relationship between neuroprotection and apoptosis for clarifying MLN O mechanism in the recovery phase of ischemic stroke. We imitated stroke using middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro models. The infarct volume, neurological deficit scores, HE staining, Nissl staining, TUNEL staining, immunohistochemistry, and Western blot were correspondingly performed to find pathological changes and detect neuronal apoptosis in rat cerebral cortex. The contents of LDH, Cyt-c, c-AMP and BDNF in rat plasma and cerebral cortex were detected by ELISA. Cell viability was measured by CCK8 assay. Cell morphology, Hoechst 33342 staining and Annexin-V-Alexa Fluor 647/PI staining were performed to assess neuronal apoptosis. The expression levels of proteins were evaluated by western blotting. MLN O obviously reduced brain infarct volume and neurological deficit scores in MCAO rats. MLN O inhibited inflammatory cell infiltration and neuronal apoptosis, but promoted gliosis, neuronal survival, and neuroprotection in the cortical region of MCAO rats. Additionally, MLN O decreased the amount of LDH and cytochrome c , while increasing the expression of c-AMP in the plasma and ischemic cerebral cortex of MCAO rats, and promoting the expression of BDNF in the cortical tissue of MCAO rats. Besides, MLN O improved cell viability, restored cell morphology, while attenuating cell damage, inhibiting neuronal apoptosis following OGD/R in PC-12 cells. Moreover, MLN O inhibited apoptosis by suppressing the expression of pro-apoptotic-associated proteins, including Bax, cytochrome c , Cleaved caspase 3 and HIF-1α, whereas accelerating the expression of Bcl-2 in vivo and in vitro. Furthermore, MLN O inhibited the activity of AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR), but activated the signaling pathway of cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) in MCAO rats and OGD/R-stimulated PC-12 cells. These results demonstrated that MLN O inhibited AMPK/mTOR to affect apoptosis associated with mitochondria, leading to improve CREB/BDNF-mediated neuroprotection in the recovery period of ischemic stroke in vivo and in vitro. [Display omitted] • Mailuoning oral liquid reverses AICAR-mediated pro-apoptosis and anti-neuroprotection. • AICAR could promote mitochondrial pathway of apoptosis by activating AMPK/mTOR. • AICAR could inhibit neuroprotection via inactivating CREB/BDNF. • AMPK/mTOR influences CREB/BDNF in convalescent ischemic stroke for the first time. [ABSTRACT FROM AUTHOR]

Suhuang antitussive capsule (SH capsule), a typical traditional Chinese medicines (TCMs) compound, is widely used for the treatment of post-infectious cough (PIC) in the clinic. Our previous studies have demonstrated that SH capsule possesses significant ameliorative effects on cough variant asthma (CVA), sputum obstruction and airway remodeling. This study is designed to investigate the ameliorative effects and potential mechanisms of SH capsule on PIC in mice. To establish the PIC model, ICR mice were induced by lipopolysaccharide (LPS) (3 mg/kg) once, followed by cigarettes smoke (CS) exposure for 30 min per day for 30 days. Mice were intragastrically (i.g.) administrated with SH capsule at the doses of 3.5, 7, 14 g/kg each day for 2 weeks since the 24th day. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA) and histological analysis were used to investigate the effects of SH capsule on PIC mice. Quantitative-polymerase chain reaction (Q-PCR) and western blotting were conducted to evaluate the levels of mRNA and proteins associated with Aryl hydrocarbon receptor (AhR)–NF–E2-related factor 2 (Nrf2) pathway. Superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) assays were performed to evaluate the oxidative stress. A549 cells were used to investigate the ameliorative effects of SH capsule in vitro. SH capsule effectively diminished the number of coughs and extended coughs latencies in PIC mice. The airway inflammation was alleviated by decreasing the expression levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Moreover, SH capsule dose-dependently activated AhR-Nrf2 pathway and induced the nuclear translocation in vitro and in vivo. Besides, SH capsule significantly increased the levels of SOD, GSH and T-AOC in mice. Our study demonstrates that SH capsule ameliorates airway inflammation-associated PIC in mice through activating AhR-Nrf2 pathway and consequently alleviating inflammatory responses and oxidative stress. [Display omitted] • Suhuang antitussive capsule significantly ameliorated cough symptoms and pulmonary histological damage in mice. • Suhuang antitussive capsule down-regulated the expressions of inflammatory mediators in vitro and in vivo. • Suhuang antitussive capsule exerted the ameliorative effect on post-infectious cough mice via activating AhR-Nrf2 pathway. • AhR-Nrf2 pathway may be exploited as a novel therapeutic target for post-infectious cough. [ABSTRACT FROM AUTHOR]