Activation of cholinergic anti-inflammatory pathway contributes to the protective effects of 100% oxygen inhalation on zymosan-induced generalized inflammation in mice.

BACKGROUND: The 100% oxygen inhalation has been demonstrated to have a protective effect on mice with zymosan-induced generalized inflammation. However, the underlying mechanism is largely unknown. The present study was designed to explore the role of the cholinergic anti-inflammatory pathway in this animal model. METHODS: Oxygen inhalation was given to mice at 4 and 12 h after zymosan injection. One group of mice underwent vagotomy 7 d before zymosan injection. The other two groups of mice either received nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine, or α7 nicotinic acetylcholine receptor (α7nAChR) antagonist methyllycaconitine 30 min before oxygen was given. RESULTS: The 100% oxygen treatment significantly decreased the serum level of TNF-α and increased the serum level of IL-10. The pathologic changes of the heart, lung, liver, and kidney were attenuated, as well as the dysfunction of liver and kidney. The 7-d survival rate of zymosan-challenged mice was also improved. Conversely, all these protective effects caused by pure oxygen treatment were abolished in those animals that received anti-cholinergic treatments. CONCLUSIONS: The cholinergic anti-inflammatory pathway may be involved in the 100% oxygen protective mechanism against zymosan-induced generalized inflammation in mice.

Effects of intraoperative dexmedetomidine with intravenous anesthesia on postoperative emergence agitation/delirium in pediatric patients undergoing tonsillectomy with or without adenoidectomy: A CONSORT-prospective, randomized, controlled clinical trial.

Postoperative emergence agitation/delirium (POED) is a common complication in pediatric surgery patients, which increases the risk of developing postoperative airway obstruction and respiratory depression. This study aims to investigate the safety and efficacy of intraoperative infusion of dexmedetomidine (DEX) and its effects on POED in pediatric patients undergoing tonsillectomy with or without adenoidectomy.Sixty patients scheduled for tonsillectomy with or without adenoidectomy, aged 2 to 8 years, were randomly allocated into 2 groups (n = 30). Pediatric patients in the group DEX received intravenous (IV) DEX 1 µg/kg over 10 minutes, followed by 0.5 µg/kg/h continuous infusion, and the same volume of 0.9% saline was administrated in the group control. Anesthesia was maintained with target-controlled infusion (TCI) of propofol and remifentanyl. Intraoperative heart rate (HR), noninvasive blood pressure (NIBP), blood oxygen saturation (SPO2), recovery time, and extubation time were recorded. Pain level was evaluated using the objective pain score (OPS), pediatric anesthesia emergence delirium (PAED) scale and Cole 5-point scale (CPS) was used to evaluate POED when patients at 0, 5, 15 minutes, and then at intervals of 15 minutes for 60 minutes after parents arrival at postanesthesia care unit (PACU).The results showed that intraoperative HR was significantly lower in group DEX (P <0.05), mean diastolic and systolic NIBP was not statistically different between groups. Time to wake and time to extubation were lengthened in group DEX as compared with group control (P <0.05). OPS and CPS were lower in group DEX at 15, 30, and 45 minutes time points (P <0.05); however, there were no significantly differences in the PAED score at different time points in the PACU.The present data suggested that intraoperative infusion of dexmedetomidine combined with intravenous anesthetics can provide satisfactory intraoperative conditions for pediatric patients undergoing tonsillectomy with or without adenoidectomy, without adverse hemodynamic effects, though the lower incidence of POED was not observed.

[Study on chemical constituents from Opuntia dillenii].

OBJECTIVE: To study the chemical composition of Opuntia dillenii. METHOD: Many kinds of chromatography methods were used in the isolation procedure, while the structures of isolated compounds were determined on the aids of NMR and MS spectral analysis. RESULT: A new compound, together with five known compounds, was isolated form the 80% ethanolic extract of its stems. CONCLUSION: The new compound was characterized as opuntioside. Four compounds were obtained for the first from the genus Opuntia, and they were daucosterol, p-hydroxybenzoicacid, L-(-)-malic acid, (E)-ferulic acid. Opuntiol was also separated for the first from the plant.

[The isolation and identification of a new alpha-pyrone from Opuntia dillenii].

AIM: To study the chemical composition of Opuntia dillenii Haw. METHODS: Many kinds of chromatography methods were used to separate the chemical constituents. Their structures were determined by NMR and MS spectral analysis. RESULTS: A new compound, together with five known compounds, were isolated from the 80% ethanolic extract of the stems. CONCLUSION: The new compound was identified as 4-ethoxyl-6-hydroxymethyl-alpha-pyrone. Compounds 1, 3, 4 and 5 were obtained for the first time from the genus of Opuntia, and they were: 3-O-methyl isorhamnein, 1-heptanecanol, vanillic acid, isorhamnetin-3-O-beta-D-rutinoside. Ruin was isolated from this plant for the first time.

[Study on the chemical constituents of the roots of commercial ginseng].

OBJECTIVE: To isolate and elucidate the constituents from the roots of Commercial Ginseng. METHOD: Column chromatography and HPLC were used to isolate chemical constituents. Physico-chemical characters and spectr-oscopic analysis were employed for structural identification. RESULT: Sixteen compounds were identified as: notoginsenoside-R2(1), ginsenoside-Rg2(2), 20 (R)-Rg2 (3), ginsenoside-Rg1 (4), -Rf(5), -Re(6), -Rd(7), -Rc(8), -Rb1(9), -Rb2(10), -Rb3(11), -Ra3(12), -Ra2(13), -Ra1 (14), notoginsenoside-R4(15) and ginsenoside -Ro(16). CONCLUSION: Compound 1 was obtained from the plant for the first time.

ß2-adrenergic receptor antagonist butoxamine partly abolishes the protection of 100% oxygen treatment against zymosan-induced generalized inflammation in mice.

We have demonstrated that 100% oxygen inhalation is beneficial to zymosan-induced generalized inflammation, and reactive oxygen species may be involved in the protection of oxygen treatment. Other investigators suggest that reactive oxygen species may modulate the sympathetic nervous system activity and ß2-adrenergic receptor (ß2AR)-mediated pathway. Moreover, studies have demonstrated that ß2AR agonists are beneficial to sepsis. Therefore, we assessed the effects of ß2AR antagonist butoxamine on the protection of oxygen treatment against zymosan-induced generalized inflammation in mice. Mice were given oxygen treatment by exposure to 100% oxygen for 3 h starting at 4 and 12 h after zymosan injection, respectively. In the mortality study, survival was monitored for 7 days after zymosan injection in mice. At 24 h after zymosan injection, mice were killed, and blood sample and organs were harvested for analysis. We observed that 100% oxygen treatment prevented the abnormal changes in organ histopathology, lactate dehydrogenase and C-reactive protein in serum, inflammatory cytokines in serum and tissue, and arterial blood gas analysis and improved the survival rate in zymosan-challenged mice. We found that pretreatment with ß2AR antagonist butoxamine partly abolished the protection of 100% oxygen inhalation. We also showed that zymosan induced the increase in serum 3'-5'-cyclic adenosine monophosphate (cAMP) and the decrease in tissue cAMP. However, oxygen treatment increased the cAMP levels in both serum and tissue, which were partly abolished by pretreatment with butoxamine. Thus, 100% oxygen inhalation may protect against zymosan-induced generalized inflammation in mice partly through activation of ß2AR pathway and subsequently enhance cAMP levels in both serum and tissue.

Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release.

Despite recent advances in antibiotic therapy and intensive care, sepsis is still considered to be the most common cause of death in intensive care units. Excessive production of reactive oxygen species plays an important role in the pathogenesis of sepsis. Recently, it has been suggested that molecular hydrogen (H2) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radicals (*OH, the most cytotoxic reactive oxygen species) and effectively protects against organ damage induced by I/R. Therefore, we hypothesized that H2 treatment had a beneficial effect on sepsis. In the present study, we found that H2 inhalation starting at 1 and 6 h after cecal ligation and puncture (CLP) or sham operation significantly improved the survival rate of septic mice with moderate or severe CLP in a concentration- and time-dependent manner. Furthermore, moderate or severe CLP mice showed significant multiple organ damage characterized by the increases of lung myeloperoxidase activity, wet-to-dry weight ratio, protein concentration in bronchoalveolar lavage, serum biochemical parameters, and organ histopathologic scores at 24 h after CLP operation, which was significantly attenuated by 2% H2 treatment. In addition, we found that the beneficial effects of H2 treatment on sepsis and sepsis-associated organ damage were associated with the decreased levels of oxidative product, increased activities of antioxidant enzymes, and reduced levels of high-mobility group box 1 in serum and tissue. Thus, H2 inhalation may be an effective therapeutic strategy for patients with sepsis.

Hydrogen gas improves survival rate and organ damage in zymosan-induced generalized inflammation model.

Sepsis/multiple organ dysfunction syndrome is the leading cause of death in critically ill patients. Recently, it has been suggested that hydrogen gas (H2) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radical (•OH, the most cytotoxic reactive oxygen species). We have found that H2 inhalation significantly improved the survival rate and organ damage of septic mice with moderate or severe cecal ligation and puncture. In the present study, we investigated the effects of 2% H2 treatment on survival rate and organ damage in zymosan (ZY)-induced generalized inflammation model. Here, we found that 2% H2 inhalation for 60 min starting at 1 and 6 h after ZY injection, respectively, significantly improved the 14-day survival rate of ZY-challenged mice from 10% to 70%. Furthermore, ZY-challenged mice showed significant multiple organ damage characterized by the increase in serum biochemical parameters (aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine), as well as lung, liver, and kidney histopathological scores at 24 h after ZY injection, which was significantly attenuated by 2% H2 treatment. In addition, we found that the beneficial effects of H2 treatment on ZY-induced organ damage were associated with the decreased levels of oxidative product, increased activities of antioxidant enzyme, and reduced levels of early and late proinflammatory cytokines in serum and tissues. In conclusion, this study provides evidence that H2 treatment protects against multiple organ damages in ZY-induced generalized inflammation model, suggesting the potential use of H2 as a therapeutic agent in the therapy of conditions associated with inflammation-related multiple organ dysfunction syndrome.

Ginsenoside Rg8, a new dammarane-type triterpenoid saponin from roots of Panax quinquefolium.

A new dammarane-type triterpenoid saponin, ginsenoside Rg(8) (1), was isolated from the roots of Panax quinquefolium, along with five known saponins, (20E)-ginsenoside F(4) (2), ginsenosides Rh(1) (3), Rg(2) (4), F(1) (5), and (20R)-ginsenoside Rh(1) (6). The structure of ginsenoside Rg(8) (1) was determined to be (3beta,6alpha,12beta,20E)-24,25-epoxy-3,12,23-trihydroxydammar-20(22)-en-6-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranoside by various spectroscopic analyses. Among the known saponins, (20E)-ginsenoside F(4) (2) and ginsenoside F(1) (5) were first reported from the title plant.

Complete 1H and 13C NMR assignments of two phytosterols from roots of Piper nigrum.

Using modern NMR techniques, including DQF-COSY, NOESY, HETCOR and HMBC, the full assignments of all 1H and 13C chemical shifts were made for stigmastane-3,6-dione and stigmast-4-ene-3,6-dione, isolated from the roots of Piper nigrum (Piperaceae). Their stereochemistry was resolved by a combination of 2D NOESY data and analysis of coupling constants. The two compounds were isolated from the genus Piper for the first time.

A novel biflavonoid from roots of Glycyrrhiza uralensis cultivated in China.

A novel biflavonoid named licobichalcone was isolated from the roots of Glycyrrhiza uralensis cultivated in China, along with twelve known compounds, including five chalcones, two isoflavones, two flavanones, two flavones and one pterocarpan. Their structures were respectively elucidated on the basis of chemical and spectroscopic evidence.

New amide alkaloids from the roots of Piper nigrum.

Seven new amide alkaloids, named N-isobutyl-4-hexanoyl-4-hydroxypyrrolidin-1-one (1), (+/-)-erythro-1-(1-oxo-4,5-dihydroxy-2E-decaenyl)piperidine (2), (+/-)-threo-1-(1- oxo-4,5-dihydroxy-2E-decaenyl)piperidine (3), (+/-)-threo-N-isobutyl-4,5-dihydroxy-2E-octaenamide (4), 1-(1,6-dioxo-2E,4E-decadienyl)piperidine (5), 1-[1-oxo-3(3,4-methylenedioxy-5-methoxyphenyl)-2Z-propenyl]piperidine (6), and 1-[1-oxo-5(3,4-methylenedioxyphenyl)-2Z,4E-pentadienyl]pyrrolidine (7), were isolated from the roots of Piper nigrum, together with 32 known amides. Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence.