An acute herb-drug interaction of Magnoliae Officinalis Cortex with methotrexate via inhibiting multidrug resistance-associated protein 2.

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

Two curcumin analogs inhibited the function and protein expression of breast cancer resistance protein: in vitro and in vivo studies.

1. Two curcumin analogs, (1E,6E)-1,7-bis(3,5-diethyl-4-hydroxyphenyl)hepta-1,6-diene-3,5- dione (N17) and its prodrug ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2,6-diethyl-4,1- phenylene)bis(3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate) (N17'), were evaluated as breast cancer resistance protein (BCRP) inhibitors.2. MDCKII-BCRP and MDCKII-WT were used to evaluate the modulation effects of N17 and N17' on BCRP and to explore the relevant mechanism. Sprague-Dawley rats were orally administered rosuvastatin (ROS), a probe substrate of BCRP, without and with N17' (100 mg/kg) to investigate the effect of N17' on ROS pharmacokinetics.3. In cell studies, N17 and N17' were substrates of BCRP, and they decreased the activity and protein expression of BCRP. In rat study, N17' increased the systemic exposure of ROS by 218% (p = 0.058).4. N17 and N17' are potential BCRP inhibitors and will be promising candidates for overcoming the BCRP-mediated multidrug resistance.

Cranberry Ingestion Modulated Drug Transporters and Metabolizing Enzymes: Gefitinib Used as a Probe Substrate in Rats.

Cranberry, a polyphenol-rich functional food, is commonly used for the prophylaxis of urinary tract infections. Gefitinib, an anticancer agent clinically prescribed to treat non-small-cell lung cancer, is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and metabolized mainly by cytochrome P450 (CYP) 3A4 and CYP2D6. This study used gefitinib as a probe substrate to investigate the modulation of cranberry on P-gp, BCRP, CYP3A4 and CYP2D6. Rats were administered gefitinib with and without 5.0 g/kg of cranberry as juice (CJ). The concentration of gefitinib in serum was determined by LC-MS/MS. The results showed that CJ significantly increased the Cmax and AUC0-t of gefitinib by 28% and 55%, respectively. Mechanism studies indicated that CJ activated P-gp, and cranberry metabolites (CM) inhibited CYP2D6. Moreover, the protein level of P-gp in rat enterocytes was decreased, whereas that in hepatocytes was increased. In addition, the protein levels of BCRP, CYP3A4 and CYP2D6 in enterocytes and hepatocytes were decreased. In conclusion, CJ ingestion affected the activities and protein levels of P-gp, BCRP, CYP3A4 and CYP2D6.

Polyimidazolyl acetate ionic liquid grafted on cellulose filter paper as thin-film extraction phase for extraction of non-steroidal anti-inflammatory drugs from water.

Recently, pharmaceuticals and personal care products in the water environment exhibited potential risks to both human and aquatic organisms. In order to improve the sensitivity and accuracy of pharmaceutical detection, the polyimidazolyl acetate ionic liquid was synthesized by Radziszewski reaction and coated on cellulose filter papers as a thin-film extraction phase for extraction of non-steroidal anti-inflammatory drugs from water. The attenuated total reflection-infrared spectrometry, thermogravimetric analysis, and scanning electron microscope analyses demonstrated that the polyimidazolyl acetate ionic liquid was successfully prepared and attached to the surface of the cellulose filter paper through chemical bonding. The adsorption capacity of the homemade thin-film extraction material for the four non-steroidal anti-inflammatory drugs was greater than 8898 ng/cm2 under the optimum conditions, and the desorption rate was over 90%. Then, a paper-based thin-film extraction phase-high-performance liquid chromatography-tandem mass spectrometry method was established for the extraction of non-steroidal anti-inflammatory drugs in water. This method provided limits of detection and limits of quantification were in the range of 0.02-0.15 and 0.17-0.50 µg/L, respectively. Hence, the obtained thin-film extraction phase showed excellent recovery and reproducibility for the target non-steroidal anti-inflammatory drugs with carboxyl groups from water.

Magnolol and Honokiol Inhibited the Function and Expression of BCRP with Mechanism Exploration.

Breast cancer resistance protein (BCRP), one of the ATP-binding cassette (ABC) transporters, was associated with the multidrug resistance (MDR) of chemotherapy. Magnolol (MN) and honokiol (HK) are major bioactive polyphenols of Magnolia officinalis. This study investigated the effects of MN and HK on the function and expression of BCRP for the purpose of developing BCRP inhibitor to overcome MDR. Cell lines including MDCKII-BCRP and MDCKII-WT were used for evaluating the function and expression of BCRP. The results showed that MN (100-12.5 µM) and HK (100-12.5 µM) significantly decreased the function of BCRP by 80~12% and 67~14%, respectively. In addition, MN and HK were verified as substrates of BCRP. Furthermore, MN and HK reduced the protein expression of BCRP, and inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K). In conclusion, both MN and HK decreased the function and expression of BCRP via EGFR/PI3K signaling pathway. Therefore, both compounds were promising candidates for reversing the MDR of chemotherapy.

One-Step Preparation of Chitosan-Based Magnetic Adsorbent and Its Application to the Adsorption of Inorganic Arsenic in Water.

Chitosan is a kind of biodegradable natural polysaccharide, and it is a very promising adsorber material for removing metal ions from aqueous solutions. In this study, chitosan-based magnetic adsorbent CMC@Fe3O4 was synthesized by a one-step method using carboxymethyl chitosan (CMC) and ferric salts under relatively mild conditions. The Fe3O4 microspheres were formed and the core-shell structure of CMC@Fe3O4 was synthesized in the meantime, which was well characterized via SEM/TEM, XRD, VSM, FT-IR, thermo gravimetric analysis (TGA), XPS, size distribution, and zeta potential. The effects of initial arsenic concentration, pH, temperature, contact time, and ionic strength on adsorption quantity of inorganic arsenic was studied through batch adsorption experiments. The magnetic adsorbent CMC@Fe3O4 displayed satisfactory adsorption performance for arsenic in water samples, up to 20.1 mg/g. The optimal conditions of the adsorption process were pH 3.0, 30-50 °C, and a reaction time of 15 min. The adsorption process can be well described by pseudo-second-order kinetic model, suggesting that chemisorption was main rate-controlling step. The Langmuir adsorption model provided much higher correlation coefficient than that of Freundlich adsorption model, indicating that the adsorption behavior is monolayer adsorption on the surface of the magnetic adsorbents. The above results have demonstrated that chitosan-based magnetic adsorbent CMC@Fe3O4 is suitable for the removal of inorganic arsenic in water.

Effect of remote ischemic preconditioning among donors and recipients following pediatric liver transplantation: A randomized clinical trial.

BACKGROUND: Studies suggested that remote ischemic preconditioning (RIPC) may effectively lessen the harmful effects of ischemia reperfusion injury during organ transplantation surgery. AIM: To investigate the protective effects of RIPC on living liver donors and recipients following pediatric liver transplantation. METHODS: From January 2016 to January 2019 at Renji Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, 208 donors were recruited and randomly assigned to four groups: S-RIPC group (no intervention; n = 55), D-RIPC group (donors received RIPC; n = 51), R-RIPC group (recipients received RIPC, n = 51) and DR-RIPC group (both donors and recipients received RIPC; n = 51). We primarily evaluated postoperative liver function among donors and recipients and incidences of early allograft dysfunction, primary nonfunction and postoperative complications among recipients. RESULTS: RIPC did not significantly improve alanine transaminase and aspartate aminotransferase levels among donors and recipients or decrease the incidences of early allograft dysfunction, primary nonfunction, and postoperative complications among recipients. Limited protective effects were observed, including a lower creatinine level in the D-RIPC group than in the S-RIPC group on postoperative day 0 (P < 0.05). However, no significant improvements were found in donors who received RIPC. Furthermore, RIPC had no effects on the overall survival of recipients. CONCLUSION: The protective effects of RIPC were limited for recipients who received living liver transplantation, and no significant improvement of the prognosis was observed in recipients.

Sleep Problems Influence Emotional/Behavioral Symptoms and Repetitive Behavior in Preschool-Aged Children With Autism Spectrum Disorder in the Unique Social Context of China.

Sleep disturbances are common in people with autism spectrum disorder (ASD), but research on this topic is still limited in China. In the current study, we evaluated the prevalence of sleep problems in preschool-aged children with ASD and to examine the correlations between sleep disturbances and emotional/behavioral symptoms and repetitive behavior in the unique social context of China. This study recruited 475 preschool-aged children aged 3-6 years old, including 252 children with ASD (mean age 5.13 ± 1.15, 80.6% male) and 223 age-matched typically developing (TD) children (mean age 5.12 ± 0.97, 74.9% male). The parents of all children completed a sociodemographic questionnaire and the Childhood Sleep Habits Questionnaire. The parents of 114 ASD children completed the Strengths and Difficulties Questionnaire (SDQ) and the Repetitive Behavioral Questionnaire-2 (RBQ-2). The prevalence of sleep problems in preschool-aged children with ASD in this study was 81.7%, which was higher than that in TD children (61.0%). The scores for bedtime resistance, sleep anxiety, sleep duration, parasomnias, and sleep onset delay in the ASD group were significantly higher than those in the TD group (t=-7.664, P=0.000; t=-10.477, P=0.000; t=-4.133, P=0.000; Z=-3.916, P=0.000; Z=-7.093, P=0.000; respectively). Sleep onset delay explained 17.3% of the variance (adjusted R2 = 0.173) in the total SDQ score of children with ASD, and bedtime resistance explained a large proportion of total RBQ-2 score variance (adjusted R2 = 0.206). The high rate of sleep disturbances in preschool-aged children with ASD emphasizes the importance of screening for sleep problems in this population. Attention should also be directed toward formulating good sleep hygiene practices for preschool-aged children in the particular social context and cultural setting of China.

The Griffiths Development Scales-Chinese (GDS-C): A reliable and valid neurodevelopmental assessment tool in children with ASD aged 3-8 years old in Tianjin, China.

BACKGROUND: The reliability and validity of the Griffiths Development Scales-Chinese (GDS-C) for autistic children in China are unknown. Thus, it is urgent to verify the instrument's reliability and validity in this population. The aim of the study was to explore whether the GDS-C is reliable and valid for assessing neurodevelopment in autistic children. METHOD: This study included 296 autistic children and 141 typically developing children from 3 to 8 years of age in China. The reliability of the scale was estimated based on its internal consistency, test-retest reliability and interrater reliability. The validity of the scale was calculated based on the construct validity, discriminate validity and criterion validity. Receiver operating characteristic curves were used to calculate the general quotients (GQs) corresponding to the diagnostic classification within the Childhood Autism Rating Scale (CARS) scores. RESULTS: This study shows sufficient reliability (Cronbach's alpha = 0.957; test-retest reliability = 0.945 for the whole scale and 0.830-0.919 for the subscales; interrater reliability = 0.925 for the whole scale and 0.796-0.919 for the subscales). The results also provide good support for the validity of the GDS-C. In the discriminant analysis, 85.5% of the children in the autistic sample were correctly classified. The cutoff value for distinguishing autistic children from normal children within the CARS scale corresponds to a GQ of 84.83, and that for distinguishing severely autistic children from mild or moderately autistic children corresponds to a GQ of 66.60. CONCLUSION: Our findings suggest that the GDS-C may be a valid and reliable tool for assessing the neurodevelopment of autistic children.

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice.

Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF-α, IL-1ß, and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF-κB activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds-adenosine and N6-(2-hydroxyethyl) adenosine (HEA)-inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro. Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation.

Rosiglitazone ameliorates tissue plasminogen activator-induced brain hemorrhage after stroke.

OBJECTIVE: Delayed thrombolytic therapy with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier (BBB) breakdown after ischemic stroke and lead to catastrophic hemorrhagic transformation (HT). Rosiglitazone(RSG), a widely used antidiabetic drug that activates peroxisome proliferator-activated receptor-γ (PPAR-γ), has been shown to protect against cerebral ischemia through promoting poststroke microglial polarization toward the beneficial anti-inflammatory phenotype. However, whether RSG can alleviate HT after delayed tPA treatment remains unknown. In this study, we sort to examine the role of RSG on tPA-induced HT after stroke. METHODS AND RESULTS: We used the murine suture middle cerebral artery occlusion (MCAO) models of stroke followed by delayed administration of tPA (10 mg/kg, 2 hours after suture occlusion) to investigate the therapeutic potential of RSG against tPA-induced HT. When RSG(6 mg/kg) was intraperitoneally administered 1 hour before MCAO in tPA-treated MCAO mice, HT in the ischemic territory was significantly attenuated 1 day after stroke. In the tPA-treated MCAO mice, we found RSG significantly mitigated BBB disruption and hemorrhage development compared to tPA-alone-treated stroke mice. Using flow cytometry and immunostaining, we confirmed that the expression of CD206 was significantly upregulated while the expression of iNOS was down-regulated in microglia of the RSG-treated mice. We further found that the expression of Arg-1 was also upregulated in those tPA and RSG-treated stroke mice and the protection against tPA-induced HT and BBB disruption in these mice were abolished in the presence of PPAR-γ antagonist GW9662 (4 mg/kg, 1 hour before dMCAO through intraperitoneal injection). CONCLUSIONS: RSG treatment protects against BBB damage and ameliorates HT in delayed tPA-treated stroke mice by activating PPAR-γ and favoring microglial polarization toward anti-inflammatory phenotype.

p-Coumaric-Acid-Containing Adenostemma lavenia Ameliorates Acute Lung Injury by Activating AMPK/Nrf2/HO-1 Signaling and Improving the Anti-oxidant Response.

Adenostemma lavenia is a perennial herb belonging to the Compositae family and is widely distributed in the tropical parts of Asia. It has been widely used as medicine in Taiwan with the whole plant used to treat pulmonary congestion, pneumonia, bacterial infections of the respiratory tract, edema, and inflammation. This study sought to investigate the anti-inflammatory effects of A. lavenia in vitro and in animal models. The anti-inflammatory effects of ethyl acetate fractions of A. lavenia (EAAL) were stimulated with lipopolysaccharide (LPS) murine macrophages (RAW 264.7) and lung injury in mice. EAAL reduced proinflammatory cytokine responses. Preoral EAAL alleviated LPS-induced histological alterations in lung tissue and inhibited the infiltration of inflammatory cells and protein concentrations in bronchoalveolar lavage fluid (BALF). EAAL prevented protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2); phosphorylation of IκB-α, MAPKs, and AMP-activated protein kinase (AMPK); and activated anti-oxidant enzymes (catalase, SOD, and GPx), heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) in LPS-stimulated cells and lung tissues. Fingerprinting of EAAL was performed with HPLC to control its quality, and p-coumaric acid was found to be a major constituent. This study suggests that EAAL is a potential therapeutic agent to treat inflammatory disorders.

Carbon sink calculation model of urban construction land based on building capacity.

The exploitation and utilization of mineral materials during urban construction causes a large amount of carbon emission, but could also contribute to carbon sequestration. In the related literature, carbon sequestration process of building mineral materials has received limited attention and scientific quantification. On the basis of extracting building capacity and identifying building types, we used the technology of remote sensing image shadow height inversion to quantify mineral material consumption and carbon content parameters. Carbonization rate was measured by thermogravimetric analysis (TGA). Finally, a calculation method for carbon sink in urban buildings was constructed. We investigated the uncertainty of this method with Puhe New Town in Shenyang as an example. The results showed that the order of carbon sink density of different types of buildings followed the order of residential buildings > public service buildings > other types of buildings > commercial and financial buildings > industrial buildings; the ratio of carbon sink volumetric in diffe-rent types of construction land followed the order of commercial and financial buildings > residential buildings > public service buildings > other types of buildings > industrial buildings. The carbon sink calculation method based on the urban scale of building capacity in this study could quickly and accurately estimate the magnitude of carbon sinks from the inorganic materials in various types of urban construction lands. Under the background of limited urban natural carbon sequestration, using building carbon sequestration to enhance the urban carbon sequestration could provide new ideas for the low-carbon development of cities in China.

Inotilone from Inonotus linteus suppresses lung cancer metastasis in vitro and in vivo through ROS-mediated PI3K/AKT/MAPK signaling pathways.

Metastasis is one of the main causes of mortality in cancer patients. Inotilone, a major component of Inonotus linteus, is a traditional Chinese medical herb. In this study, MTT results showed that inotilone had no obvious cytotoxicity. Animal model results revealed that inotilone suppressed cancer metastatic efficacy. Serum results showed that inotilone reduced the activity of matrix metalloproteinase (MMP)-2 and -9 and tumor necrosis factor alpha (TNF-α) activity as well as NO content. Additionally, inotilone affected MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-2 protein expression and improved the activity of the antioxidant enzymes in the lung tissues of LLC-bearing mice. In addition, cell experimental results showed that inotilone reduced the activity of MMP-2/-9 and inhibited the ability for cellular migration and invasion. Inotilone decreased interleukin (IL)-8 expression in A549 cells. Western blot results revealed that inotilone affected the protein expression of MMPs, nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, anti-oxidant enzymes, mitogen activated protein kinase (MAPK), focal adhesion kinase (FAK), phosphoinositide-3 kinase (PI3K)-AKT, and nuclear factor (NF)κB. Therefore, we propose that inotilone is a potential therapeutic candidate against metastatic lung cancer cells.

IL-2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells.

AIMS: Demyelination, one of the major pathological changes of white matter injury, is closely related to T-cell-mediated immune responses. Thus, we investigate the role of an IL-2 monoclonal antibody (IL-2mAb, JES6-1) in combatting demyelination during the late phase of stroke. METHODS: IL-2mAb or IgG isotype antibody (0.25 mg/kg) was injected intraperitoneally 2 and 48 hours after middle cerebral artery occlusion (MCAO) surgery. Infarct volume, peripheral immune cell infiltration, microglia activation, and myelin loss were measured by 2,3,5-triphenyte trazoliumchloride staining, immunofluorescence staining, flow cytometry, and Western blot. Intraperitoneal CD8 neutralizing antibody (15 mg/kg) was injected 1 day before MCAO surgery to determine the role of CD8+ T cells on demyelinating lesions. RESULTS: IL-2mAb treatment reduced brain infarct volume, attenuated demyelination, and improved long-term sensorimotor functions up to 28 days after dMCAO. Brain infiltration of CD8+ T cells and peripheral activation of CD8+ T cells were both attenuated in IL-2 mAb-treated mice. The protection of IL-2mAb on demyelination was abolished in mice depleted of CD8+ T cell 1 week after stroke. CONCLUSIONS: IL-2mAb preserved white matter integrity and improved long-term sensorimotor functions following cerebral ischemic injury. The activation and brain infiltration of CD8+ T cells are detrimental for demyelination after stroke and may be the major target of IL-2mAb posttreatment in the protection of white matter integrity after stroke.

The peripheral immune response after stroke-A double edge sword for blood-brain barrier integrity.

The blood-brain barrier (BBB) is a highly regulated interface that separates the peripheral circulation and the brain. It plays a vital role in regulating the trafficking of solutes, fluid, and cells at the blood-brain interface and maintaining the homeostasis of brain microenvironment for normal neuronal activity. Growing evidence has led to the realization that ischemic stroke elicits profound immune responses in the circulation and the activation of multiple subsets of immune cells, which in turn affect both the early disruption and the later repair of the BBB after stroke. Distinct phenotypes or subsets of peripheral immune cells along with diverse intracellular mechanisms contribute to the dynamic changes of BBB integrity after stroke. This review focuses on the interaction between the peripheral immune cells and the BBB after ischemic stroke. Understanding their reciprocal interaction may generate new directions for stroke research and may also drive the innovation of easy accessible immune modulatory treatment strategies targeting BBB in the pursuit of better stroke recovery.

The evolving role of neuro-immune interaction in brain repair after cerebral ischemic stroke.

Stroke is the world's leading cause of disability with limited brain repair treatments which effectively improve long-term neurological deficits. The neuroinflammatory responses persist into the late repair phase of stroke and participate in all brain repair elements, including neurogenesis, angiogenesis, synaptogenesis, remyelination and axonal sprouting, shedding new light on post-stroke brain recovery. Resident brain glial cells, such as astrocytes not only contribute to neuroinflammation after stroke, but also secrete a wide range of trophic factors that can promote post-stroke brain repair. Alternatively, activated microglia, monocytes, and neutrophils in the innate immune system, traditionally considered as major damaging factors after stroke, have been suggested to be extensively involved in brain repair after stroke. The adaptive immune system may also have its bright side during the late regenerative phase, affecting the immune suppressive regulatory T cells and B cells. This review summarizes the recent findings in the evolving role of neuroinflammation in multiple post-stroke brain repair mechanisms and poses unanswered questions that may generate new directions for future research and give rise to novel therapeutic targets to improve stroke recovery.

Alpinumisoflavone attenuates lipopolysaccharide-induced acute lung injury by regulating the effects of anti-oxidation and anti-inflammation both in vitro and in vivo.

Alpinumisoflavone (AIF) is a plant-derived pyranoisoflavone that exhibits a number of pharmacological activities, but the protective effects of AIF against pulmonary inflammation are still unknown. This study aimed to investigate the anti-inflammatory effects and possible molecular mechanisms of AIF in both lipopolysaccharide (LPS)-stimulated macrophages and mice. The results revealed that AIF dramatically suppressed the production of pro-inflammatory mediators [including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, IL-17, intercellular adhesion molecule-1 (ICAM-1), and nitric oxide (NO)] and increased the levels of anti-oxidative enzymes [including catalase (CAT), heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), and superoxide dismutase (SOD)] both in vitro and in vivo. Additionally, pre-treatment with AIF could not only significantly prevent histopathological changes and neutrophil infiltration but also decreased the expression levels of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, as well as IL-17 production in LPS-induced lung tissues. The anti-inflammatory effects of AIF were mediated by up-regulating anti-oxidative enzymes and suppressing the NF-κB, MAPK, NLRP3 inflammasome and IL-17 signaling pathways. This is the first study to reveal that AIF has a protective effect against LPS-induced lung injury in mice.

Torenia concolor Lindley var. formosana Yamazaki extracts improve inflammatory response and lipid accumulation via PPARs activation.

Background/Introduction: At present, human diet is replete with sugar and fat. Abnormal metabolism and hyperglycemia or hyperlipidemia in the body induces the development of an overactive and continuous inflammatory response, resulting in obesity and metabolic syndromes, including hypertension, hyperlipidemia, and insulin resistance. Torenia concolor Lindley var. formosana Yamazaki (TC), a perennial creeping herbaceous plant, is a traditional Chinese medicinal herb widely used for the treatment of heat stroke, aching muscles and bones, cold, dysentery, and ambustion. PURPOSE: This study evaluated the influence of TC on inflammation responses and lipid metabolism. METHODS: In this study, ground TC powder was extracted with 95% ethanol. The ethanol was removed by vacuum concentration, and the resulting extract was further extracted with a number of solvents of different polarity to produce four final extracts: an ethanol extract (TCEE), an ethyl acetate extract (TCEAE), an n-butanol extract (TCBUE), and a water extract (TCWE). The anti-inflammatory efficacy of the extracts and their capability for lipid metabolism regulation was then explored. RESULTS: TCEE, TCEAE, and TCBUE exhibited good anti-inflammatory efficacy; TCEAE also simultaneously regulated lipid metabolism. In RAW264.7 cells, these three extracts suppressed the expression of iNOS and IL-6 via the signaling pathway activation of the transcription factor peroxisome proliferator activated receptor γ (PPARγ) and thereby showed anti-inflammatory efficacy. In 3T3-L1 cells, these three extracts promoted lipid metabolism and reduced lipid accumulation through the activation of PPARα and the increased expression of adiponectin, thus demonstrating regulation of lipid metabolism. CONCLUSION: These results indicate that TC possesses anti-inflammatory efficacy and can regulate lipid metabolism through the activation of transcription factor PPARs. We speculate that these nutraceutical effects are attributable to betulin, an active ingredient in this herbal medicine.

3, 4-dihydroxybenzalacetone attenuates lipopolysaccharide-induced inflammation in acute lung injury via down-regulation of MMP-2 and MMP-9 activities through suppressing ROS-mediated MAPK and PI3K/AKT signaling pathways.

3, 4-Dihydroxybenzalacetone (DBL) is a constituent of Phellinus linteus. This study demonstrated the protective effect of DBL on lipopolysaccharide (LPS)-induced acute lung injuries in mice. Pretreatment with DBL significantly improved LPS-induced histological alterations in lung tissues. In addition, DBL markedly reduced the total cell number, the leukocytes, the protein concentrations, and decreased the release of nitrite, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and the activities of matrix metalloproteinase (MMP)-2 and -9 in the bronchoalveolar lavage fluid. DBL also inhibited the W/D ratio and myeloperoxidase activity in the lung tissues. Western blot analysis indicated DBL efficiently blocked the protein expressions of inducible nitric oxide synthase, cyclooxygenase-2, MMP-2, MMP-9, and the phosphorylation of mitogen-activated protein kinase (MAPK), phosphoinositide-3-kinase (PI3K), AKT, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Moreover, DBL enhanced the expression of anti-oxidant proteins, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Based on our results, DBL might be a potential target for attenuating tissue oxidative injuries and nonspecific pulmonary inflammation.