Fen Luo

Protective activity of salidroside against ethanol-induced gastric ulcer via the MAPK/NF-κB pathway in vivo and in vitro.

Salidroside (Sal) is a traditional Chinese medicine with various pharmacological effects. The present study aimed to investigate the protective effect of Sal on ethanol-induced acute gastric ulcer and H2O2-induced gastric epithelial cell damage. 0.2 ml ethanol and 400 μM H2O2 were applied to establish a gastric ulcer model in vivo and in vitro respectively. The production of interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor (TNF)-α was analyzed, as well as myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD). MTT assay was used to detect cell viability. In addition, MAPK/NF-κB signal pathway-related proteins p-ERK, p-JNK, p-p38, p-IκBα and p-NF-κBp65 were analyzed to determine the underlying protective mechanism. Downstream genes such as cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and leukotrienes B4 (LTB4) were also measured. Obtained data indicated that Sal inhibited the overproduction of pro-inflammatory cytokines and enhanced antioxidant activity. Collectively, it is assumed that Sal could alleviate ethanol-induced acute gastric ulcer and H2O2-induced gastric epithelial cell damage through the MAPK/NF-κB pathway.

Salidroside ameliorates cognitive impairment in a d-galactose-induced rat model of Alzheimer’s disease

The purpose of the present study was to investigate possible preventive effects of salidroside (sal) on a rat model of Alzheimers disease and to explore its possible mechanism. Sub-acute aging was induced in male SD rats by subcutaneous injection of d-gal (120mg/kg) for 42 days, and the rats were treated with sal (20, 40mg/kg) or normal saline for 28 days after 14 days of d-gal injection. Morris water maze (MWM) test and step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in hippocampus were assayed by enzyme-linked immunosorbent assay (ELISA) to assess the anti-inflammatory effect of sal. Further, we estimated the expression levels of thioredoxin (Trx), thioredoxin interacting protein (Txnip/vitamin D3 up-regulated protein/thioredoxin binding protein-2), Bax, Bcl-2, caspase-9 and related-proteins of nuclear factor kappa B (NF-κB) signaling pathway by western blot assay. It showed that administration of sal significantly attenuated all the d-gal-induced changes in the hippocampus, including cognitive impairment and neuroinflammation. These analytical results provides evidence that sal can improve cognitive capacity by inhibiting neuroinflammation and affecting apoptosis-related proteins in hippocampus.

Esculetin attenuates lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice.

Esculetin is one of the major bioactive compounds of Cichorium intybus L. The main purpose of the present study was to investigate the effects and possible underlying mechanism of esculetin (Esc) on lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice. Mice were pretreatment with esculetin (Esc, 20, 40mg/kg, intragastric administration) and a positive control drug fluoxetine (Flu, 20mg/kg, intragastric administration) once daily for 7 consecutive days. At the 7th day, LPS (0.83mg/kg) was intraperitoneal injection 30min after drug administration. Higher dose (40mg/kg) of esculetin and fluoxetine significantly decreased immobility time in TST and FST. There was no significant effect on locomotor activity in mice by the drugs. Esculetin significantly reduced LPS-induced elevated levels of pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum and hippocampus. Esculetin attenuated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression by inhibiting nuclear factor-κB (NF-κB) pathway in hippocampus. In addition, neuroprotection of esculetin was attributed to the upregulations of Brain derived neurotrophic factor (BDNF) and phosphorylated tyrosine kinase B (p-TrkB) protein expression in hippocampus. The obtained results demonstrated that esculetin exhibited antidepressant-like effects which might be related to the inhibition of NF-κB pathway and the activation of BDNF/TrkB signaling.

Cardioprotective effects of salidroside on myocardial ischemia–reperfusion injury in coronary artery occlusion-induced rats and Langendorff-perfused rat hearts

BACKGROUND/OBJECTIVES The current study was designed to investigate the protective role of salisroside on rats through the study of energy metabolism homeostasis and inflammation both in ex vivo and in vivo. METHODS Energy metabolism homeostasis and inflammation injury were respectively assessed in global ischemia of isolated hearts and coronary artery ligated rats. RESULTS Excessive release of cardiac enzymes and pro-inflammatory cytokines was inhibited by salidroside in coronary artery occlusion-induced rats. ST segment was also restored with the treatment of salidroside. Triphenyltetrazolium chloride staining (TTC) staining and pathological analysis showed that salidroside could significantly alleviate myocardial injury in vivo. Accumulated data in ex vivo indicated that salidroside improved heart function recovery, which was reflected by enhanced myocardial contractility and coronary flow in isolated hearts. The contents of ATP and glycogen both in ex vivo and in vivo were restored by salidroside compared with those in the model group. Besides, the expressions of p-AMPK, PPAR-α and PGC-1α in rats and isolated hearts subjected to salidroside were significantly elevated, while the levels of p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were dramatically reduced by salidroside. CONCLUSIONS The present study comprehensively elaborated the protective effects of salidroside on myocardial injury and demonstrated that AMPK/PGC-1α and AMPK/NF-κB signaling cascades were implicated in the myocardial ischemia-reperfusion injury (I/R) model.

Liujunzi Tang, a famous traditional Chinese medicine, ameliorates cigarette smoke-induced mouse model of COPD

ETHNOPHARMACOLOGICAL RELEVANCE Liujunzi Tang is a traditional herbal medicine widely used in East Asia and clinically applied to treat Phlegm-Heat Syndrome. The purpose of the present study was to investigate the protective effects of Liujunzi Tang on cigarette smoke-induced (CS) mouse model of chronic obstructive pulmonary disease (COPD) and explore its potential molecular mechanism. MATERIALS AND METHODS The mice received 1h of cigarette smoke for 8 weeks. The serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were tested by biochemical methods. Histopathological alteration was observed by hematoxylin-eosin (H&E) staining. Additionally, the expressions of nuclear transcription factor-κB (NF-κBp65) and (inhibitor of NF-κB)IκB-α were determined by western blot and immunohistochemistry analysis. RESULTS Liujunzi Tang enhanced the activities of antioxidant enzymes and attenuated the levels of lipid oxidative production, meanwhile significantly inhibited the generations of inflammatory cytokines by inhibiting the phosphorylation of IκB-α and NF-κB. CONCLUSION Our findings indicated that Liujunzi Tang exhibited the protective effect on cigarette smoke-induced COPD mice by anti-inflammatory and anti-oxidative properties through the inhibition of NF-κB activation.

Salidroside alleviates cigarette smoke-induced COPD in mice

The present study was to evaluate the effects of salidroside (Sal) on CS (cigarette smoke)-induced COPD in mice and explore its underlying mechanisms. 50 male ICR mice were randomly assigned to five groups: control group, CS group, CS+dexamethasone (2mg/kg) group, CS+salidroside (20mg/kg) group and CS+salidroside (40mg/kg) group. The COPD mice were induced by CS exposure for 8 weeks. The results of H&E staining demonstrated that Sal alleviated CS-induced pathological injury in lungs. Besides, Sal increased the activities of superoxide dismutase (SOD), reduced the content of malondialdehyde (MDA) in serum. Sal also inhibited the generations of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum and lungs. Furthermore, the administration of Sal significantly inhibited the protein levels of MAPK/NF-κB pathway in CS-induced mice. Our findings showed that Sal might effectively ameliorate the progression of COPD via MAPK/NF-κB pathway.

Umbelliferone attenuates lipopolysaccharide-induced acute lung injury linked with regulation of TLRs–MyD88 and RIP140/NF-κB signaling pathways

Umbelliferone (Umb), isolated from the chloroform fraction of Potentilla evestita, exerts a variety of pharmacological activities. The aim of the present study was to evaluate the protective effects and possible mechanisms of Umb on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice were randomly divided into five groups: control group, LPS group, LPS + dexamethasone (Dex, 2 mg kg−1) group, LPS + Umb (20 mg kg−1) group, and LPS + Umb (Umb, 40 mg kg−1) group. Umb and Dex were orally administered 15 min before the intra-tracheal (IT) administration of LPS. 6 h later, the mice were sacrificed. The lung tissues and bronchoalveolar fluid (BALF) were prepared for further analysis. Our results showed that pretreatment with Umb prior to the LPS challenge significantly decreased the lung W/D weight ratio, total leukocyte number and neutrophil percentage in the BALF. Umb also reduced pulmonary MPO activity and alleviated histopathological alteration. Besides, the contents of inflammatory cytokines including interleukin (IL)-6, interleukin (IL)-1β and tumor neurosis factor (TNF)-α were also found to be significantly inhibited by Umb in BALF. Furthermore, the expressions of TLR2, TLR4, MyD88, receptor-interacting protein 140 (RIP140), RelA, CBP, nuclear factor kappa B (NF-κB), caspase-9, caspase-3, Bax in lung tissues were inhibited and Bcl-2 expression was increased in the LPS + Umb group. These results showed that administration of Umb could attenuate LPS-induced ALI, possibly via the anti-inflammatory and anti-apoptotic activities through the TLRs–MyD88 and RIP140/NF-κB pathway.