A sesquiterpenoid from Ligularia pleurocaulis modulated macrophages polarisation through TLR4 pathway.

An eremophilane-type sesquiterpenoid (EPS), 3-oxo-eremophila-1,7(11)-dien-12,8ß-olide, has been isolated from anti-inflammatory folk herbs, Ligularia pleurocaulis. The aim of present study is to explore protective effects of EPS on lipopolysaccharide (LPS)-induced inflammatory responses in acute lung injury (ALI). EPS treatments (40 and 80 mg/kg) significantly ameliorated LPS-stimulated pathological changes in lungs. Furthermore, in vivo and in vitro mechanism studies suggest that EPS exerts its protective effects on LPS-induced ALI by regulating macrophage polarisation via suppression of TLR4/MyD88-mediated MAPK and NF-κB signaling pathways, and EPS may be useful for the prevention on ALI in the clinical setting.

Mogroside IIIE Attenuates LPS-Induced Acute Lung Injury in Mice Partly Through Regulation of the TLR4/MAPK/NF-κB Axis via AMPK Activation.

Acute lung injury (ALI) often leads to high mortality, and there is as yet no effective drug treatment. The present study aimed to investigate protective effects of mogroside IIIE (MGIIIE, a cucurbitane-type triterpenoid from Siraitia grosvenorii Fruits) in experimental ALI and its underlying mechanism. MGIIIE (1, 10 0r 20 mg/kg) was orally administered for 1 h before a single intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg). MGIIIE treatment dose-dependently suppressed pulmonary oedema, pro-inflammatory mediators (IL-1ß, IL-6, TNF-α and HMGB1) release and higher MPO activity in lung tissues induced by LPS challenge. Molecular researches showed that mogroside IIIE (20 mg/kg) not only increased the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) but suppressed the over-expression of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In addition, MGIIIE also inhibited the activation of MAPKs and nuclear factor κB (NF-κB) signalling in lung tissues from LPS-challenged mice. Similar antiinflammatory effects of MGIIIE were obtained in LPS-treated macrophages. Compound C (a pharmacological AMPK inhibitor) obviously reversed the antiinflammatory effect of MGIIIE in LPS-induced ALI mice. Taken together, AMPK activation plays a crucial role in the antiinflammatory effects of MGIIIE in LPS-induced ALI by down-regulating TLR4/MAPK/NF-κB signalling pathways. Copyright © 2017 John Wiley & Sons, Ltd.

An Active Drimane-Type Lactone from Polygonum jucundum Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice Through TLR4-MAPKs Signaling Pathway.

The herbs of Polygonum jucundum Lindex. (Polygonaceae) is a traditional Chinese medicine for inflammatory diseases. 2α-Hydroxyl-3ß-angeloylcinnamolide (HAC), a drimane-type sesquiterpenoid, was the major active compound of the ethanol extract of P. jucundum which inhibited the production of inflammatory mediators. However, the biological mechanism of HAC for anti-inflammatory activity has not been reported. In the current study, we investigated whether HAC could suppress the production of inflammatory mediators in lipopolysaccharide (LPS)-induced acute lung injury in mice (ALI) through downregulation of Toll-like receptor 4 (TLR4) and activations of mitogen-activated protein kinases (MAPKs) and inducible protein nitric oxide synthase (iNOS). Moreover, our data indicated that HAC inhibits the overexpression of iNOS and TLR4 in LPS-treated RAW264.7, and also inhibits MAPK signal. These findings suggest that HAC shows anti-inflammatory effects in ALI mice through suppressing TLR4-mediated MAPK pathway in activated macrophages. In addition, six derivatives of HAC obtained by structure modification were investigated for their inhibitory effects on the production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), suggesting that the acetylation could increase the inhibition of HAC on TNF-α release in LPS-treated RAW264.7 cells. In summary, all these results showed that HAC may be a potential anti-inflammatory lead compound for the treatment of acute lung injury.

Protective role of rhapontin in experimental pulmonary fibrosis in vitro and in vivo.

BACKGROUND: Pulmonary fibrosis is a scaring process related to chronic lung injury of all causes. The treatment options for pulmonary fibrosis are very limited. Rhapontin has anti-inflammatory effect and anti-proliferative activity which is widely distributed in the medicinal plants of Rheum genus in China. However, the anti-fibrotic activities of rhapontin have not been previously investigated. METHODS: The effect of rhapontin on TGF-ß1-mediated extracellular matrix (ECM) deposition in primary lung fibroblast (PLF) cells, on TGF-ß1 secretion in LPS-stimulated human THP-1 derived macrophages in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo. Fibrotic mice were induced by intratracheal instillation of bleomycin, and then treated with rhapontin (25, 50, or 100mg/kg/day) or prednisone (6.5mg/kg/day, positive drug) for 2weeks. RESULTS: In TGF-ß1 stimulated PLFs, treatment with rhapontin resulted in a reduction of ECM with a decrease in Lox2 and p-Smad2/3. In LPS activated macrophages, treatment with rhapontin reduced TGF-ß1 production. However, in vitro the attenuated ECM deposition and inflammatory response by rhapontin were closely associated with AMPK activation, and these suppression of rhapontin were significantly abolished by the AMPK inhibitor. Treatment with rhapontin for 2weeks resulted in an amelioration of the BLM-induced pulmonary fibrosis in rats with a lower Lox2, whereas a higher AMPK expression, with reductions of the pathological score, collagen deposition, TGF-ß1, α-SMA, Lox2, and HIF-1α expressions in lung tissues at fibrotic stage at 100mg/kg. CONCLUSION: In summary, rhapontin reversed ECM, as well as Lox2 proliferation in vitro and prevented pulmonary fibrosis in vivo by modulating AMPK activation and suppressing the TGF-ß/Smad pathway.

Immunosuppressive C21 steroidal glycosides from the root of Cynanchum atratum.

Six new C21 steroidal glycosides (1-6) and one dideoxysaccharide (7), named atratcynosides A-F and atratcynose A, were isolated from the 80% ethanol extract of the root of Cynanchum atratum, together with three known compounds (8-10). The structures of the new compounds were determined on the basis of extensive spectral analyses and qualitative chemical methods. All compounds were subjected to detect the immunosuppressive activities by an in vitro model of concanavalin A-induced proliferation of T-lymphocytes from mice. Compounds 1-3 showed significant immunosuppressive activities in dose-dependent manners with the IC50 values from 3.3 to 7.0 µM. Moreover, the structure-activity relationship of the steroidal glycosides on the immunosuppression was analyzed.

Clinical curative effect of fuzi-cake-separated moxibustion for preventing dysuria after operation for lower limb fracture.

OBJECTIVE: To assess the clinical curative effect of fuzi-cake-separated moxibustion at Zhongji (CV 3) and Guanyuan (CV 4) for preventing dysuria after internal fixation of lower limb fractures. METHODS: Sixty patients conforming to the inclusion standards were randomly divided into a treatment group (n = 30) and a control group (n = 30). Fuzi-cake-separated moxibustion was performed at Guanyuan (CV 4) and Zhongji (CV 3), 20 min at a time, twice a day, for 3 days before operation in the treatment group. No fuzi-cake-separated moxibustion was performed in the control group. After treatment, the score for symptoms of first urination, urinary time, urinary volume, 24 h remaining urinary volume, incidence of uroschesis, and rate of controlling dysuria were compared to evaluate the curative effect of preventing post-operative dysuria. RESULTS: The score for symptoms of first urination, 24 h remaining urinary volume (maximum 120 mL vs 250 ml, and less than 10 ml in 24 cases vs 15 cases), and the rate of controlling dysuria (83.34% vs 30%) were significantly better (P < 0.05, P < 0.05, and P < 0.001, respectively) in the treatment compared with the control group. There was no statistical difference (P > 0.05) between the two groups in first post-operative urinary time, urinary volume, or incidence of 24 h uroschesis. CONCLUSION: Fuzi-cake-separated moxibustion at Zhongji (CV 3) and Guanyuan (CV 4) can better prevent post-operative dysuria, effectively promote the functional restoration of the urinary bladder, and control the incidence of post-operative dysuria.

[Effect of down-regulation of GAT-1 on analgesic action of oxysophoridine].

OBJECTIVE: To study the effect of GABA transporter (GAT-1) on the analgesic action of oxysophoridine (OSR) in the central nervous system of mice. METHOD: Hot plate test was used to observe and analyze the effect of gamma aminobutyric acid and the inhibitor of GAT-1 (NO-711) on the analgesic action of oxysophoridine. Real time RT-PCR was used to investigate the influence of OSR on the expression of GAT-1 mRNA induced by formalin in spinal cord and brain of mice. RESULT: Both GABA (2.0 mg x kg(-1), icv) and NO-711(0.125 mg x kg(-1), icv) enhanced the analgesic action of OSR (32.0 mg x kg(-1), iv) in the hot plate test, and the latencies was markedly increased (P < 0.05, P < 0.01). OSR (500.0 mg x kg(-1), iv) significantly inhibited the expression of GAT-1 mRNA induced by formalin (P < 0.05). CONCLUSION: GAT-1 was involved in the analgesia effect of OSR and the down-regulation of GAT-1 mRNA enhanced the analgesic effect.

[Studies on analgesic effects and sites of oxymatrine-carbenoxolone sodium complex].

OBJECTIVE: To study the analgesic effects and sites of oxymatrine-carbenoxolone sodium complex (OCSC). METHOD: Adopting formalin test, warm water tail-flick test and intracerebroventricularly (icv) injection to observe the analgesic effects of OCSC in mice. RESULT: Intraperitoneally injecting (ip) OCSC (75, 150 mg x kg(-1)) remarkedly inhibited the pain of mice in the formalin test and prolonged latent phases of tail-shrinking of mice, icy OCSC (1.875, 3.75, 7.5 mg x kg(-1)) significantly prolonged latent phases of tail-shrinking of mice, it had dose-dependent effect with concentration. CONCLUSION: The result indicated that OCSC has obvious analgesic effects and its mechanism may be involved in central nervous system (CNS).