Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (H2O2)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated β-galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against H2O2-induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress.

Accumulating evidence suggests that developmentally regulated GTP-binding protein 2 (DRG2), an evolutionarily conserved GTP-binding protein, plays an important role in regulating cell growth, inflammation, and mitochondria dynamics. However, the effect of DRG2 in aging remains unclear. In this study, we found that endogenous DRG2 protein expression is upregulated in oxidative stress-induced premature senescence models and tissues of aged mice. Ectopic expression of DRG2 significantly promoted senescence-associated β-galactosidase (SA-β-gal) activity and inhibited cell growth, concomitant with increase in levels of acetyl (ac)-p53 (Lys382), ac-nuclear factor-kB (NF-κB) p65 (Lys310), p21Waf1/Cip1, and p16Ink4a and a decrease in cyclin D1. In this process, reactive oxygen species (ROS) and phosphorylation of H2A histone family member X (H2A.X), forming γ-H2A.X, were enhanced. Mechanistically, ectopic expression of DRG2 downregulated Sirtuin-1 (SIRT1), resulting in augmented acetylation of p53 and NF-κB p65. Additionally, DRG2 knockdown significantly abolished oxidative stress-induced premature senescence. Our results provide a possible molecular mechanism for investigation of cellular senescence and aging regulated by DRG2.

Objective: To investigate the potential anti-aging mechanism of 9-hydroxy-6,7-dimethoxydalbergiquinol (HDDQ) on hydrogen peroxide (H2O2)-induced oxidative stress in human dermal fibroblasts (HDFs). Methods: The effect of HDDQ on cell viability was assessed by MTT assay, and the effects of HDDQ on senescence-like phenotypes were determined by senescence-associated β-galactosidase (SA-β-gal) staining, Western blotting analysis, and a cell proliferation assay. The expression level and activity of sirtuin-1 (SIRT1) induced by HDDQ were also measured. Results: HDDQ reversed senescence-like phenotypes in the oxidant-challenged model, through reducing SA-β-gal activity and promoting cell growth. Meanwhile, decreases in ac-p53, p21Cip1/WAF1, and p16Ink4a and an increase in pRb were observed. HDDQ induced the expression of SIRT1 in a concentration- and time-dependent manner. Moreover, HDDQ inhibited H2O2-induced phosphorylation of Akt by SIRT1 up-regulation and reduced SA-β-gal staining. Conclusions: HDDQ inhibits H2O2-induced premature senescence and upregulation of SIRT1 expression plays a vital role in the inhibition of the senescence phenotype in HDFs.

Oxidative stress-induced cellular senescence is now regarded as an important driving mechanism in chronic lung diseases-particularly chronic obstructive pulmonary disease (COPD). 4[Formula: see text],5,7-trihydroxyflavone (Apigenin) is a natural flavonoid product abundantly present in fruits, vegetables, and Chinese medicinal herbs. It has been known that apigenin has anti-oxidant, anti-inflammatory and liver-protecting effects. The efficacy of apigenin for lung aging, however, has not been reported. In this study, we selected the hydrogen peroxide (H2O[Formula: see text]- or doxorubicin (DOXO)-induced senescence model in WI-38 human embryonic lung fibroblast cells to determine the potential anti-aging effects of apigenin in vitro and associated molecular mechanisms. We found that apigenin reduced senescence-associated [Formula: see text]-galactosidase (SA-[Formula: see text]-gal) activity and promoted cell growth, concomitant with a decrease in levels of Acetyl (ac)-p53, p21[Formula: see text], and p16[Formula: see text] and an increase in phospho (p)-Rb. Apigenin also increased the activation ratio of silent information regulator 1 (SIRT1), nicotinamide adenine dinucleotide (NAD[Formula: see text], and NAD[Formula: see text]/NADH and inhibited cluster of differentiation 38 (CD38) activity in a concentration-dependent manner. SIRT1 inhibition by SIRT1 siRNA abolished the anti-aging effect of apigenin. In addition, CD38 inhibition by CD38 siRNA or apigenin increased the SIRT1 level and reduced H2O2-induced senescence. Our findings suggest that apigenin is a promising phytochemical for reducing the impact of senescent cells in age-related lung diseases such as COPD.

Pancreatic cancer (PC) is one of the most severe cancers, and its incidence and mortality rates have steadily increased in the past decade. In this study, we demonstrate the effect of Angelica gigas Nakai extract on pancreatic ductal adenocarcinoma cells. We prepared A. gigas Nakai ethanol extract (AGE) using roots of A. gigas Nakai and detected its active compound decursin from AGE by ultra-performance liquid chromatography analysis. AGE and decursin significantly decreased viability and colony formation of PANC-1 and MIA PaCa-2 cells. AGE and decursin induced G0/G1 phase arrest through downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). Caspase-3-dependent apoptosis of PANC-1 cells was promoted by AGE and decursin. Additionally, nontoxic concentrations of AGE and decursin treatment could suppress matrix metalloproteinase (MMP)-2 and MMP-9 expression and activity by inhibiting p38 phosphorylation. Taken together, this study demonstrates that AGE and decursin have potential properties to be considered in PC treatment.

Isoparvifuran is a benzofuran compound isolated from the heartwood of Dalbergia odorifera. Related research reported that isoparvifuran has antioxidant property. However, it is unclear whether isoparvifuran has anti-aging effects. In this research, we established an aging model, hydrogen peroxide (H2O2)-induced BJ cell senescence, to explore the protective effect of isoparvifuran on cell senescence and its related mechanisms. Our results revealed that isoparvifuran obviously attenuated H2O2-induced cell senescence, increased the cell proliferation rate,and reversed senescence-associated molecular markers expression such as cyclin D1, pRb, caveolin-1, ace-p53, p21 and p16. Moreover, isoparvifuran dose and time dependently increased the expression level of Sirtuin 1 (SIRT1) in BJ cells. The inhibition of SIRT1 obviously reversed the reduction of SA-β-gal activity and the alteration of senescence-associated molecular markers induced by isoparvifuran. Additionally, isoparvifuran also inhibited H2O2-induced AKT and S6 phosphorylation and increase of SA-β-gal activity. In summary, isoparvifuran protects BJ cells from H2O2-induced premature senescence, the anti-senescence effect of isoparvifuran is associated with the activation of SIRT1 and the suppression of AKT/mTOR signaling pathway.

BACKGROUND:Cachexia induced by cancer is a systemic wasting syndrome and it accompanies continuous body weight loss with the exhaustion of skeletal muscle and adipose tissue. Cancer cachexia is not only a problem in itself, but it also reduces the effectiveness of treatments and deteriorates quality of life. However, effective treatments have not been found yet. Although Arctii Fructus (AF) has been studied about several pharmacological effects, there were no reports on its use in cancer cachexia.METHODS:To induce cancer cachexia in mice, we inoculated CT-26 cells to BALB/c mice through subcutaneous injection and intraperitoneal injection. To mimic cancer cachexia in vitro, we used conditioned media (CM), which was CT-26 colon cancer cells cultured medium.RESULTS:In in vivo experiments, AF suppressed expression of interleukin (IL)-6 and atrophy of skeletal muscle and adipose tissue. As a result, the administration of AF decreased mortality by preventing weight loss. In adipose tissue, AF decreased expression of uncoupling protein 1 (UCP1) by restoring AMP-activated protein kinase (AMPK) activation. In in vitro model, CM increased muscle degradation factors and decreased adipocytes differentiation factors. However, these tendencies were ameliorated by AF treatment in C2C12 myoblasts and 3T3-L1 cells.CONCLUSION:Taken together, our study demonstrated that AF could be a therapeutic supplement for patients suffering from cancer cachexia.

Latifolin, a natural flavonoid found in Dalbergia odorifera T. Chen, has been reported to exhibit anti-inflammatory and anticarcinogenic activities in vitro. However, the anti-aging effects of latifolin are unknown. In this study, we selected a model in vitro system, hydrogen peroxide (H2O2)-induced senescence in human dermal fibroblasts (HDFs), to examine the protective effects of latifolin against senescence and the detailed molecular mechanisms involved. Latifolin reversed the senescence-like phenotypes of the oxidant-challenged model, including senescence-associated β-galactosidase (SA-β-gal) staining, cell proliferation, and the expression of senescence-related proteins, such as caveolin-1, ac-p53, p21Cip1/WAF1, p16Ink4α, pRb, and cyclinD1. We also found that latifolin induced the expression of silent information regulator 1 (SIRT1) in a concentration- and time-dependent manner, and the anti-senescence effect of latifolin was abrogated by SIRT1 inhibition. Latifolin also suppressed the activation of Akt and S6K1 and attenuated the increase in SA-β-gal activity after H2O2 exposure. Our results indicate that latifolin exerts protective effects against senescence in HDFs and that induction of SIRT1 and inhibition of the mammalian target of rapamycin (mTOR) pathway are key mediators of its anti-aging effects.

6, 4′-Dihydroxy-7-methoxyflavanone (DMF) has been shown to possess anti-inflammatory, anti-oxidative, and neuroprotective activities. However, its effect on oxidative stress-induced aging remains undemonstrated. This study aimed at investigating the anti-senescence effect of DMF on hydrogen peroxide (H 2 O 2 )-induced premature senescence, and associated molecular mechanisms in human dermal fibroblasts (HDFs). The cells were DMF pretreated with small interfering RNA (siRNAs) of control or sirtuin 1 (SIRT1) before H 2 O 2 exposure, and western blot analysis, senescence-associated β-galactosidase (SA-β-gal) activity, cell counting, gene silencing, and SIRT1 activity assay were performed. Pretreatment with DMF inhibited H 2 O 2 -induced senescence phenotypes, which showed decreased SA-β-gal activity and increased cell growth in comparison with H 2 O 2 -treated HDFs. Meanwhile, the decreases in ac-p53, p21 Cip1/WAF1 , and p16 Ink4a and the increases in pRb and cyclin D1 were observed. DMF was also found to induce SIRT1 expression and activity level concentration- and time-dependently. Moreover, SIRT1 inhibition abrogated DMF senescence prevention. Additionally, Akt and ERK were activated with different kinetics after H 2 O 2 exposure, and Akt activity inhibition attenuated SA-β-gal activity augmentation. We also found that DMF inhibited H 2 O 2 -induced Akt phosphorylation. This study indicates that DMF effectively protects against oxidative stress-induced premature senescence through SIRT1 expression up-regulation and Akt pathway inhibition in HDFs. These results suggest that DMF can be a potential therapeutic molecule for age-related diseases, or a protective agent against the aging process.

Acute pancreatitis (AP) refers to inflammation in the pancreas, which may lead to death in severe cases. Coenzyme Q10 (Q10), generally known to generate energy, plays an important role as an anti-oxidant and anti-inflammatory effector. Here, we showed the effect of Q10 on inflammatory response in murine AP model. For this study, we induced AP by injection of cerulein intraperitoneally or pancreatic duct ligation (PDL) in mice. The level of cytokines and digestive enzymes were measured in pancreas, and blood. All pancreatic tissues were excised for investigation such as histological changes, infiltration of immune cells. Administration of Q10 attenuated the severity of AP and its associated pulmonary complication as shown by reduction of acinar cell death, parenchymal edema, inflammatory cell infiltration and alveolar thickening in both cerulein-induced AP and PDL-induced AP. Moreover, reduction of the cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were observed in pancreas and pancreatic acinar cells by Q10. Furthermore, Q10 reduced the infiltration of immune cells such as monocytes and neutrophils and augmentation of chemokines such as CC chemokine-2 (CCL2) and C-X-C chemokine-2 (CXCL2) in pancreas of AP mice. In addition, Q10 deactivates the phosphorylation of extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) in pancreas. In conclusion, these observations suggest that Q10 could attenuate the pancreatic damage and its associated pulmonary complications via inhibition of inflammatory cytokines and inflammatory cell infiltration and that the deactivation of ERK and JNK by Q10 might contribute to the attenuation of AP.

Our previous report revealed that Gardenia jasminoides (GJ) has protective effects against acute pancreatitis. So, we examined whether aqueous extract of GJ has anti-inflammation and antifibrotic effects even against cerulein-induced chronic pancreatitis (CP). CP was induced in mice by an intraperitoneal injection of a stable cholecystokinin (CCK) analogue, cerulein, six times a day, four days per week for three weeks. GJ extract (0.1 or 1[Formula: see text]g/kg) or saline (control group) were intraperitoneally injected 1[Formula: see text]h before first cerulein injection. After three weeks of stimulation, the pancreas was harvested for the examination of several fibrotic parameters. In addition, pancreatic stellate cells (PSCs) were isolated using gradient methods to examine the antifibrogenic effects of GJ. In the cerulein-induced CP mice, the histological features of the pancreas showed severe tissue damage such as enlarged interstitial spaces, inflammatory cell infiltrate and glandular atrophy, and tissue fibrosis. However, treatment of GJ reduced the severity of CP such as pancreatic edema and inflammatory cell infiltration. Furthermore, treatment of GJ increased pancreatic acinar cell survival, and reduced pancreatic fibrosis and activation of PSC in vivo and in vitro. In addition, GJ treatment inhibited the activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) in the PSCs. These results suggest that GJ attenuated the severity of CP and the pancreatic fibrosis by inhibiting JNK and ERK activation during CP.

BACKGROUND:This study evaluated echocardiographic changes in full-term healthy neonates during early transitional period from postnatal 0-72 hours at 12-hour intervals by echocardiography. METHODS:This was a prospective, observational, and longitudinal single-center cohort study. Morphometric, functional, systolic, diastolic, and tissue Doppler imaging (TDI) parameters (patent ductus arteriosus [PDA], aorta, superior vena cava [SVC], stroke volume [SV], cardiac output [CO], cardiac index [CI], early diastolic flow velocity [E], late diastolic flow velocity [A], early filling in TDI [E'], peak systolic annular velocity in TDI [S'], late velocity peak in TDI [A'], and myocardial performance index [MPI]) were evaluated in left ventricle (LV) and right ventricle (RV) with 56 newborns. RESULTS:Sizes and peak velocities of PDA before postnatal 24 hours were significantly changed than those after postnatal 24 hours. Aortic velocity time integral (VTI), systolic blood pressure (BP), LV SV/kg, LV CO/kg, LV CI, and SVC flow/LV CO before 24 hours showed significantly changes than those after 24 hours. Also, LV and RV MPI before 24 hours were significantly higher than those after 24 hours. LV E/E' was significantly higher than RV E/E'. CONCLUSION:Postnatal 24 hours is critical time for hemodynamic closure of PDA because aortic VTI, systolic BP, LV SV, LV CO, LV CI, and SVC flow/LV CO showed simultaneously significant changes after 24 hours at the same time as 24 hours of physiological closure of PDA. Chronological and dramatic changes of systolic, diastolic, and TDI parameters during early postnatal period can be used to compile normal baseline data of healthy full-term neonates.

BackgroundChimeras are composed of two or more different populations that originated from different zygotes. Blood chimerism arising from twins have been reported in the literature. Herein, we report the first blood group chimerism in triplets.MethodsABO blood grouping was carried out by manual tile methods (Merck Millipore, UK) and micro‐column agglutination method (Bio‐Rad, Cressier sur Morat, Switzerland). Flow cytometric analysis was performed with Anti‐A‐PE conjugated monoclonal antibodies (BD Biosciences, San Jose, CA, USA) and FACS Canto II (BD Biosciences). Molecular analysis was performed with allele‐specific polymerase chain reaction (AS‐PCR) and direct sequencing of the exons 6 and 7.ResultsMixed‐field agglutination and weak agglutination against anti‐A were revealed by ABO blood grouping. Flow cytometric analysis revealed the presence of both A cells and O cells. AS‐PCR and sequencing showed two neonates with chimerism, with each neonate`s genotype being A102/O01/O02.ConclusionThis is the first recorded case of blood chimera from a triplet in Korea. We recommend full investigation of blood group chimerism in neonates with ABO discrepancy, as blood chimerism is subject to certain caution in the clinical environment.

PurposeSmall for gestational age (SGA) is confusingly defined as birth weight (BW) either below 3rd percentile or 10th percentile for infants. This study aimed to compare postnatal catch-up growth between SGA groups according to different definitions.MethodsData of 129 infants born with BW below the 10th percentile and admitted to Korea University Anam Hospital and Ansan Hospital were retrospectively reviewed. Height and weight were measured at 6, 12, and 24 months. Results were compared between group A (BW: <3rd percentile) and group B (BW: 3rd–10th percentile).ResultsGroup A included 66 infants and group B included 63. At age 6 months (n=122), 62.9% of group A and 71.7% (P=0.303) of group B showed catch-up growth in weight. At 6 months (n=69), 55.9% of group A and 80.0% of group B (P<0.05) showed catch-up growth in height. At 12 months (n=106), 58.5% of group A, and 75.5% (P=0.062) of group B showed catch-up growth in weight. At 12 months (n=75), 52.8% of group A and 64.1% of group B (P=0.320) showed catch-up growth in height. Up to age 24 months, 66.7%/80.0% in group A and 63.6%/80.0% in group B showed catch-up growth in weight/height.ConclusionDespite different definitions, there were no significant differences between the two SGA groups in postnatal catch-up growth up to age 24 months, except for height at 6 months. Compared to infants with appropriate catch-up growth, low gestational age and BW were risk factors for failed catch-up growth at 6 months.

AimSufficient sleep is an important factor in physical and mental health. Sleep duration can be affected by socio‐economic status (SES). This study aimed to examine the association between sleep duration and SES in Korean adolescents.MethodsThis study was conducted with 1608 adolescents aged 12–18 years, based on data from the 2010 to 2012 Korean National Health and Nutrition Examination Survey (KNHANES). Sleep duration was self‐reported in hours and three SES indicators were used: household income, basic livelihood security programmes and type of health insurance. Confounding factors in this study were age, mental health and physical activity.ResultsParticipants’ average age was 15.6 ± 0.05 years and average sleep duration was 7.04 ± 0.05 h. There was a strong association between sleep duration and household income (P < 0.05) rather than other socio‐economic indicators. In addition, it showed that sleep duration was significantly associated with age, body mass index (P < 0.05) and low mood is associated with short sleep and long sleep (>9 h/night). We found similar results in both genders, that is, that the highest income group had shorter sleep duration than the lowest income group.ConclusionsThis study shows that the SES, particularly household income, is an important factor in short sleep duration in Korean adolescents. Our findings suggest that, in future investigations of the adolescent's sleep problem, attention should be paid to household income.

BACKGROUND AND OBJECTIVE:TThe environment of a pregnant woman can affect not only fetal growth and development, but also diseases in childhood. Neonatal cord blood cytokines are commonly used to evaluate the immune development of neonates. The purpose of this study was to evaluate the effects of the environment and diet during pregnancy on IL-4 and IFN-γ in neonatal cord blood.METHOD:A total of 111 pregnant women participated in this study from April to November 2010. Allergy history, sensitization assessed by the skin prick test, dietary intake and indoor environment were evaluated. IL-4 and IFN-γ levels were measured in the complete cord blood of neonates using real-time PCR.RESULTS:There were 54 pregnant women with allergic disease. Both IL-4 and IFN-γ levels in neonatal cord blood were higher in samples from allergic mothers than in non-allergic mothers (p<0.05). The indoor environment and nutrient intake were not different between allergic and non-allergic mothers, except regarding carpet use. When the cytokine levels were divided into quartiles, lower folate and vitamin B6 intake was associated with the highest levels of IL-4 in neonatal cord blood (p<0.05), and higher folate and vitamin B6 intake was associated with highest levels of IFN-γ in neonatal cord blood.CONCLUSIONS:In this study, a strong association between IL-4 and IFN-γ levels in cord blood and the intake of folate and vitamin B6 was found, which indicates that food intake during pregnancy might have a strong influence on IL-4 and IFN-γ levels in cord blood, to a greater extent than environmental factors.

Purpose This study aimed to evaluate the correlation, according to postnatal age, between plasma B-type natriuretic peptide (BNP) levels and echocardiographic parameters for the assessment of patent ductus arteriosus (PDA) in preterm infants with respiratory distress. Methods We enrolled 42 preterm infants with respiratory distress who underwent serial echocardiographic evaluation with simultaneous plasma BNP measurements until ductal closure. The correlations between BNP levels and the following 4 representative echocardiographic parameters were studied: diameter of the ductus arteriosus (DA), ratio of the left atrial diameter to the aortic diameter (LA/Ao), ratio of the PDA diameter to the infant's left pulmonary artery diameter (PDA/LPA), and the antegrade diastolic flow of LPA (DFLPA). Results BNP levels were significantly correlated to the magnitude of the ductal shunt, comprising the DA diameter, PDA/LPA ratio, LA/Ao ratio, and antegrade DFLPA for the overall study period. The earliest significant correlation, starting from postnatal day 2, was observed between the LA/Ao ratio and BNP levels. The PDA/LPA ratio and the antegrade DFLPA showed significant correlations with BNP levels postnatal day 3 onward, and with the DA diameter, postnatal day 5 onward. Conclusion BNP levels and echocardiographic parameters showed a positive correlation, but the significance of the correlations differed according to the postnatal age, especially during the first few days of life.

Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

In this study, we found that alpha-pinene (α-pinene) exhibits anti-inflammatory activity through the suppression of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappa B (NF-κB) pathway in mouse peritoneal macrophages. α-Pinene is found in the oils of many coniferous trees and rosemary. We investigated the inhibitory effects of α-Pinene on inflammatory responses induced by lipopolysaccharide (LPS) using mouse peritoneal macrophages. α-Pinene significantly decreased the LPS-induced production of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO). α-Pinene also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-stimulated macrophages. Additionally, the activations of MAPKs and NF-κB were attenuated by means of α-pinene treatment. These results indicate that α-pinene has an anti-inflammatory effect and that it is a potential candidate as a new drug to treat various inflammatory diseases.

Objectives We aimed to evaluate the anti-inflammatory and inhibitory effects of Lithospermum erythrorhizon (LE) on cerulein-induced acute pancreatitis (AP) in a mouse model.Methods Acute pancreatitis was induced via intraperitoneal injection of cerulein (50 g/kg) every hour for 6 times. In the LE, water extract (100, 250, or 500 mg/kg) was administered intraperitoneally 1 hour before the first injection of cerulein. Six hours after AP, blood, the pancreas, and the lung were harvested for further examination. In addition, pancreatic acinar cells were isolated using a collagenase method, and then, we investigated the acinar cell viability and cytokine productions.Results Treatment with LE reduced pancreatic damage and AP-associated lung injury and attenuated the severity of AP, as evidenced by the reduction in neutrophil infiltration, serum amylase and lipase levels, trypsin activity, and proinflammatory cytokine expression. In addition, treatment with LE inhibited high mobility group box 1 expression in the pancreas during AP. In accordance with in vivo data, LE inhibited the cerulein-induced acinar cell death, cytokine productions, and high-mobility group box 1 expression. Furthermore, LE also inhibited the activation of p38 mitogen-activated protein kinases.Conclusions These results suggest that LE plays a protective role during the development of AP by inhibiting the activation of p38.