[Glabridin reduces lipopolysaccharide-induced lung injury in rats by inhibiting p38 mitogen activated protein kinase/extracellular regulated protein kinases signaling pathway].

Objective: To investigate whether glabridin has a beneficial effect on lipopolysaccharide (LPS) induced acute respiratory distress syndrome (ARDS) in rats, and to explore the possible underlying mechanisms. Methods: Thirty-two Wistar rats were randomly assigned into control group, model group (LPS group), glabridin group (GLA group), and ulinastatin group (UTI group), with 8 rats in each group. ARDS rat model was reproduced by intraperitoneal injection of LPS (10 mg/kg). The rats in the control group received an equal volume of normal saline at the same times. The rats in GLA group were gavaged by glabridin (30 mg/kg). The rats in UTI group were injected ulinastatin (20 000 U/kg). Animals were sacrificed 12 hours after LPS challenge. Plasma and lung tissue samples were collected. Histopathological evaluation, lung wet/dry (W/D)ratio, tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase(SOD)were analyzed. Immunohistochemical method was used to detect the protein expression of p38MAPK and ERK. Western blot method was used to detect the changes of p38 mitogen activated protein kinase (p-p38MAPK) and phosphorylated extracellular regulated protein kinases (pERK) protein expression in lung tissues. Result: In the control groups, lung tissue showed a normal structure and clear pulmonary alveoli under a light microscope. In the model group, ARDS characters such as extensive thickening of the alveolar wall, significant infiltration of inflammatory cells, demolished structure of pulmonary alveoli, and hemorrhage were found. In the GLA and UTI treatment group, these pathological changes in lung were markedly alleviated compare with LPS-induced ARDS group. Compared with control groups, lung W/D ratio, TNF-α and IL-18 in plasma, and lung MDA, NO levels in lung homogenates of the LPS group were increased significantly, while the lung SOD levels of the LPS group were decreased. Compared with the LPS group, lung W/D ratio, TNF-α and IL-18 in plasma , and lung MDA, NO levels in lung homogenates of the GLA group and UTI group were decreased significantly, while the lung SOD levels of the GLA and ulinastatin groups were increased [TNF-α(µg/L): 51.7±10.3 vs 105.7±30.5, IL-18(µg/L): 37.9±13.9 vs 49.2±14.5, MDA (nmol/mgprot): 2.87±0.62 vs 3.81±0.42, NO(µmol/L): 18.96±0.79 vs 28.58±2.51, SOD(U/mgprot): 115.5±15.2 vs 75.9±14.0, all P<0.05]. Immunohistochemistry showed that the positive expressions of p38MAPK and ERK in cytoplasm and nucleus of the glabridin and ulinastatin treatment group were significantly lower than those of the model group. Western blot showed that compared with the control group, the p-p38MAPK and pERK protein expression in LPS group were significantly increased. And the glabridin and ulinastatin inhibited the protein expressions compared with model group. Conclusion: Traditional Chinese medicine glabridin significantly ameliorated the lung injury induced by LPS in rats via reducing inflammation which caused by the inhibition of p38MAPK and ERK signaling pathway and antioxidant effect.

Alcohol and high fat induced chronic pancreatitis: TRPV4 antagonist reduces hypersensitivity.

The pathogenesis of pain in chronic pancreatitis is poorly understood, and its treatment can be a major clinical challenge. Surgical and other invasive methods have variable outcomes that can be unsatisfactory. Therefore, there is a great need for further discovery of the pathogenesis of pancreatitis pain and new therapeutic targets. Human and animal studies indicate a critical role for oxidative stress and activation of transient receptor potential (TRP) cation channel subfamily members TRPV1 and TRPA1 on pancreatic nociceptors in sensitization mechanisms that result in pain. However, the in vivo role of transient receptor potential cation channel subfamily V member 4 (TRPV4) in chronic pancreatitis needs further evaluation. The present study characterized a rat alcohol/high fat diet (AHF)-induced chronic pancreatitis model with hypersensitivity, fibrotic pathology, and fat vacuolization consistent with the clinical syndrome. The rats with AHF-induced pancreatitis develop referred visceral pain-like behaviors, i.e. decreased hindpaw mechanical thresholds and shortened abdominal and hindpaw withdrawal latency to heat. In this study, oxidative stress was characterized as well as the role of TRPV4 in chronic visceral hypersensitivity. Lipid peroxidase and oxidative stress were indicated by increased plasma thiobarbituric acid reactive substances (TBARS) and diminished pancreatic manganese superoxide dismutase (MnSOD). The secondary sensitization associated with AHF-induced pancreatitis was effectively alleviated by the TRPV4 antagonist, HC 067047. Similarity of the results to those with the peripherally restricted µ-opiate receptor agonist, loperamide, suggested TRPV4 channel activated peripheral sensitization. This study using a reliable model that provides pre-clinical correlates of human chronic pancreatitis provides further evidence that TRPV4 channel is a potential therapeutic target for treatment of pancreatitis pain.

A rat knockout model implicates TRPC4 in visceral pain sensation.

Acute and chronic pain resulting from injury, surgery, or disease afflicts >100 million Americans each year, having a severe impact on mood, mental health, and quality of life. The lack of structural and functional information for most ion channels, many of which play key roles in the detection and transmission of noxious stimuli, means that there remain unidentified therapeutic targets for pain management. This study focuses on the transient receptor potential canonical subfamily 4 (TRPC4) ion channel, which is involved in the tissue-specific and stimulus-dependent regulation of intracellular Ca²âº signaling. Rats with a transposon-mediated TRPC4-knockout mutation displayed tolerance to visceral pain induced by colonic mustard oil (MO) exposure, but not somatic or neuropathic pain stimuli. Moreover, wild-type rats treated with a selective TRPC4 antagonist (ML-204) prior to MO exposure mimicked the behavioral responses observed in TRPC4-knockout rats. Significantly, ML-204 inhibited visceral pain-related behavior in a dose-dependent manner without noticeable adverse effects. These data provide evidence that TRPC4 is required for detection and/or transmission of colonic MO visceral pain sensation. In the future, inhibitors of TRPC4 signaling may provide a highly promising path for the development of first-in-class therapeutics for this visceral pain, which may have fewer side effects and less addictive potential than opioid derivatives.

[Investigation on growth and development of Tussilago farfara L. in Beijing].

OBJECTIVE: To provide a scientific basis for the introduction and harvest of T. farfara in Beijing. METHOD: Random sampling in late growing period. RESULT: T. farfara reached the peak of vegetation growth in early September and concurrently began its reproductive growth. During this period its bud and rhizome began to form and develop and kept growing until the period of freezing weather. CONCLUSION: There are two optimum the times for reaping T. farara bud: one is around the fifteenth day before the period of freezing weather, and the other is around the tenth day after the thawing season in the next year.

[Effect of storage methods on breaking seed dormancy of Trollius chinensis Bge].

OBJECTIVE: Exploring the best seed storage method for Trollius chinensis. METHOD: Different temperatures were applied to the seed storage in wet sand and dry sand, and the embryo-endosperm ratio and germination rate were inspected. RESULT: The dormancy of T. chinensis seeds could only be broken in lower temperatures. The newly collected seeds set out to germinate after 75 days of storage at 5-6 degrees C when the embryo-endosperm ratio reached 47%, and the time of seed germination varied with the length of storage time before low-temperature treatment. CONCLUSION: The best storage method for the seed of T. chinensis is keeping it in dry for 6-8 months with an additional 1 month of low-temperature treatment to follow.

[Inhibition of protein kinase C by stilbenoids].

The effect of 15 stilbenoids on protein kinase C (PKC) was studied in order to search for naturally occurring PKC inhibitors. All these compounds were isolated from Chinese medicines. Three oligomeric stilbenes from Caragana sinica, alpha-viniferin, kobophenol A and miyabenol C, were shown to intensely inhibit the activity of partially purified rat brain PKC with IC50 values of 62.5, 52.0, and 27.5 mumol.L-1, respectively. Kinetic analyses revealed that that inhibition was noncompetitive. The other compounds also showed the effect. Monomer stilbenes exhibited PKC inhibitory activity at higher mumol.L-1 concentrations than oligomeric stilbenes. Whenever they are methylated or acetylated perfectly, the inhibition weakens or disappears.

Lunar phases, myocardial infarction and hemorrheological character. A Western medical study combined with appraisal of the related traditional Chinese medical theory.

Lunar phases and their connections with acute myocardial infarction (AMI) and hemorrheological character (HCh) are studied with the lunar calendar (LC) instead of the solar calendar. AMI onset is maximal on the 1st day of the LC month, decreasing with an obvious trough around the 15th day. After the 15th day, occurrence increases gradually. The end and beginning of the lunar months show sharp peaks of AMI incidence. This study shows also that HCh variations have similar LC monthly rhythms. Our investigation demonstrates the correctness of traditional Chinese medical theory. This monthly rhythm forecasts the onset of AMI peaks and contributes to the secondary prevention of coronary heart disease (CHD).