Chunhua Ma

Anti-inflammatory effects of water extract of Taraxacum mongolicum hand.-Mazz on lipopolysaccharide-induced inflammation in acute lung injury by suppressing PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE Taraxacum mongolicum Hand.-Mazz is a famous medicinal plant in China, has been listed in the Pharmacopoeia of the Peoples Republic of China and used to treat infection, fever, upper respiratory tract infection, pneumonia, and other infectious diseases. This study aims to evaluate the possible mechanisms responsible for the anti-inflammation effects of water extract of T. mongolicum Hand.-Mazz (WETMHM) on lipopolysaccharide (LPS)-induced inflammatory in acute lung injury. MATERIALS AND METHODS Female BALB/c mice were randomly divided into five groups with 10 mice in each group: (1) control group (saline), (2) LPS group, (3) LPS+dexamethasone (LPS+Dex, 2mg/kg, administered by gavage), (4) LPS+WETMHM (5 g/kg, administered by gavage), (5) LPS+WETMHM (10 g/kg, administered by gavage). The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity were assayed by SOD and MPO kits, respectively. The levels of inflammation mediators including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were assayed by an enzyme-linked immunosorbent assay method. Pathological changes of lung tissues were observed by hematoxylin and eosin (HE) staining. The levels of P-PI3K, PI3K, P-Akt, Akt, P-mTOR and mTOR were measured by Western blotting. RESULTS The data showed that treatment with the WETMHM inhibited LPS-induced inflammation: (1) WETMHM attenuated inflammation cell numbers in the BALF, (2) decreased protein levels of lung PI3K/Akt/mTOR, and (3) improved SOD activity and (4) inhibited MPO activity; (5) histological studies demonstrated that WETMHM substantially inhibited LPS-induced neutrophils in lung tissue. CONCLUSION The results indicated that the WETMHM had a protective effect on LPS-induced ALI in mice.

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.

Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice.

The present study aimed to determine the protective effects and the underlying mechanisms of curcumin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and curcumin (50 mg/kg, 100 mg/kg, 200 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright-Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Treg/Th17 cytokines were measured by enzyme-linked immunosorbent assay, Treg cells and Th17 cells were evaluated by flow cytometry (FCM). Our study demonstrated that curcumin inhibited OVA-induced increases in eosinophil count; interleukin (IL)-17A level were recovered in bronchoalveolar lavage fluid increased IL-10 level in bronchoalveolar lavage fluid. Histological studies demonstrated that curcumin substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry (FCM) studies demonstrated that curcumin remarkably inhibited Th17 cells and significantly increased Treg cells. The results in vivo show ovalbumin-induced significantly broke Treg/Th17 balance; curcumin treatments markedly attenuated the inflammatory in asthma model by regulating Treg/Th17 balance. Our findings support the possible use of curcumin as a therapeutic drug for patients with allergic asthma.

Immunoregulatory effects of glycyrrhizic acid exerts anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4(+)CD25(+)Foxp3+ regulatory T cells in ovalbumin-sensitized mice.

ETHNOPHARMACOLOGICAL RELEVANCE Glycyrrhizic acid (GA) is the main bioactive ingredient of licorice (Glycyrrhiza glabra), and has been found to be associated with multiple therapeutic properties. AIM OF THE STUDY In this study, we investigated immunoregulatory effects of glycyrrhizic acid on anti-asthmatic effects and underlying mechanisms. MATERIALS AND METHODS Asthma model was established by ovalbumin-induced. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg) and GA (10 mg/kg, 20 mg/kg, 40 mg/kg). Airway resistance (Raw) were measured by the forced oscillation technique, histological studies were evaluated by The hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was evaluated by Flow Cytometry (FCM), the forkhead/winged helix transcription factor (Foxp3) was evaluated by western blotting. RESULTS Our study demonstrated that, compared with model group, GA inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4, IL-5, IL-13 levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-γ level in bronchoalveolar lavage fluid; histological studies demonstrated that GA substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue compared with model group. Flow cytometry studies demonstrated that GA substantially enhanced Tregs compared with model group. CONCLUSION These findings suggest that GA may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

Anti‐asthmatic Effects of Baicalin in a Mouse Model of Allergic Asthma

The aim of the study was to investigate the anti‐asthmatic effects of baicalin (BA) and the possible mechanisms. Asthma model was established by ovalbumin (OVA) intraperitoneal injection. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and BA (10 mg/kg, 20 mg/kg, 40 mg/kg). Airway resistance (RI) and lung compliance (Cdyn) were measured, histological studies were evaluated by the hematoxylin and eosin staining, Th1/Th2, OVA‐specific serum, and BALF IgE levels and Th17 cytokines were evaluated by enzyme‐linked immunosorbent assay, and Th17 cells was evaluated by flow cytometry (FCM). Our study demonstrated that BA inhibited OVA‐induced increases in RI and eosinophil count; interleukin (IL)‐4, IL‐17A levels, and Cdyn were recovered and increased IFN‐γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that BA substantially inhibited OVA‐induced eosinophilia in lung tissue and airway tissue. FCM studies demonstrated that BA substantially inhibited Th17 cells. These findings suggest that BA may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma. Copyright

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.

Anti-ulcerogenic effect of Zuojin Pill against ethanol-induced acute gastric lesion in animal models

ETHNOPHARMACOLOGICAL RELEVANCE Zuojin Pill (ZJP), a traditional Chinese medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and Tetradium ruticarpum (A. Juss.) Hartley in the ratio of 6:1 (w/w). In this study, ZJP was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in mice. MATERIALS AND METHODS 50 mice were assigned to 5 groups: groups 1 and 2 were given distilled water orally. Group 3 was administered omeprazole 20mg/kg, groups 4 and 5 were given ZJP (1g/kg, 2g/kg, respectively). After an additional hour, the mice in groups 2-5 received ethanol (0.2ml/kg) orally while group 1 received distilled water instead. Mice were killed after 4h and their serum and stomachs subjected to further studies. The superoxidase dismutase (SOD) activities and malondialdehyde (MDA) level in serum were assayed by SOD and MDA kits, respectively. The myeloperoxidase (MPO) activities in stomachs were assayed by MPO kit. The levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum were assayed by enzyme-linked immunosorbent assay method (ELISA). Pathological changes were observed by hematoxylin-eosin (HE) staining. The levels of nuclear factor-кBp65 (NF-кBp65), P-NF-кBp65, P-IкBα, IкBα, P-IKKα, IKKα, P-IKKβ, IKKβ in stomachs were assayed by western blot. RESULTS The data showed that treatment with the ZJP markedly attenuated MPO, MDA, TNF-α, IL-6, IL-1βand increased SOD; and ZJP also decreased protein levels of P-NF-кBp65, P-IкBα, P-IKKαand P-IKKβin gastric stomachs. CONCLUSION It was concluded that ZJP may represents a potential therapeutic option to reduce the risk of gastric ulceration and the gastroprotective activity of ZJP might contribute in adjusting the inflammatory cytokine by regulating the NF-кB signaling pathway.

Venenum Bufonis induces rat neuroinflammation by activiating NF-κB pathway and attenuation of BDNF

ETHNOPHARMACOLOGICAL RELEVANCE Venenum Bufonis (VB), also called toad venom, has been widely used in clinic as a cardiotonic, anohyne and antineoplastic agents both in China and other Asian countries. However, its neurotoxicity and cardiotoxicity limit its wide clinical application. Compared with extensive attention attracted with cardiotoxicity, the toxic effect of VB on Central Nervous System (CNS) is much less studied. AIM OF THE RESEARCH This study was performed to examine the neurotoxicity caused by VB on Sprague Dawley (SD) rats, then to clarify the mechanism in vivo by investigating its action on the neuroinflammation which possibly attributed to the activation of nuclear factor κB (NF-κB) pathway and the attenuation of brain-derived neurotrophic factor (BDNF). MATERIALS AND METHODS Rats administrated with 0.5% carboxymethyl cellulose sodium salt (CMC-Na) aqueous solution and VB (100mg/kg, 200mg/kg and 400mg/kg) were sacrificed at 2h, 4h, 6h, 8h, 24h and 48h. The brain level of neurotransmitters and their corresponding receptors, pro-inflammatory cytokines, BDNF/TrkB and NF-κB pathway-related proteins were examined, respectively. RESULTS VB administration induced severe neurologic damage and neuroinflammation, as indicated by the disordered 5-hydroxytryptamine (5-HT), dopamine (DA) and their corresponding receptors, together with the over production of inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). VB also notably promoted the expression of p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ and down-regulated the expression of BDNF and TrkB. CONCLUSION This study demonstrates that VB triggers neurotoxicity which probably is induced by neuroinflammation via activating of NF-κB pathway and attenuating the expression of BDNF.

TXNIP/TRX/NF-κB and MAPK/NF-κB pathways involved in the cardiotoxicity induced by Venenum Bufonis in rats

Venenum Bufonis (VB) is a widely used traditional medicine with serious cardiotoxic effects. The inflammatory response has been studied to clarify the mechanism of the cardiotoxicity induced by VB for the first time. In the present study, Sprague Dawley (SD) rats, were administered VB (100, 200, and 400 mg/kg) intragastrically, experienced disturbed ECGs (lowered heart rate and elevated ST-segment), increased levels of serum indicators (creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and serum interleukin (IL-6, IL-1β, TNF-α) at 2 h, 4 h, 6 h, 8 h, 24 h, and 48 h, which reflected that an inflammatory response, together with cardiotoxicity, were involved in VB-treated rats. In addition, the elevated serum level of MDA and the down-regulated SOD, CAT, GSH, and GPx levels indicated the appearance of oxidative stress in the VB-treated group. Furthermore, based on the enhanced expression levels of TXNIP, p-NF-κBp65, p-IκBα, p-IKKα, p-IKKβ, p-ERK, p-JNK, and p-P38 and the obvious myocardial degeneration, it is proposed that VB-induced cardiotoxicity may promote an inflammatory response through the TXNIP/TRX/NF-κB and MAPK/NF-κB pathways. The observed inflammatory mechanism induced by VB may provide a theoretical reference for the toxic effects and clinical application of VB.

Puerarin attenuates airway inflammation by regulation of eotaxin-3.

Puerarin is an isoflavonoid isolated from the root of the plant Pueraria lobata and has been used as a prescribed drug in China for the treatment of many diseases in the clinical practice. The present study aimed to determine the protective effects and the underlying mechanisms of puerarin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg), and puerarin (10 mg/kg, 20 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright-Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Th1/Th2 cytokines were measured by enzyme-linked immunosorbent assay, eotaxin-3 was evaluated by western blotting. Our study demonstrated that, compared with model group, puerarin inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4, IL-5, IL-13 levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-γ level in bronchoalveolar lavage fluid; histological studies demonstrated that puerarin substantially inhibited OVA-induced eosinophilia in lung tissue compared with model group. Western blotting studies demonstrated that puerarin substantially inhibited eotaxin-3 compared with model group. Our findings support puerarin can prevent some signs of allergic asthma in the mouse model.