Association between History of Pregnancy and Liver Fibrosis Using Fibrosis-4 Index in Korean Postmenopausal Women: A Nationwide Population-Based Study / 가정의학회지

Background@#The association between a history of pregnancy and liver fibrosis remains unclear. Herein, we investigated the association between reproductive factors, including a history of pregnancy and liver fibrosis, in postmenopausal Korean women. @*Methods@#This study used nationally representative, population-based data collected from the Korea National Health and Nutrition Examination Survey 2008–2017. Of 14,624 women with natural menopause, 11,085 with no previous history of any type of cancer, hepatitis, or chronic heavy alcohol consumption were enrolled. We investigated the reproductive factors, including a history of pregnancy, total reproductive years, age at menarche and menopause, and oral contraceptive use. Liver fibrosis was defined as a Fibrosis-4 index score ≥2.67 kg/m2. @*Results@#Of the study participants, 372 (3.3%) had advanced liver fibrosis. Multivariable logistic regression analysis showed that women with a history of more than one pregnancy were associated with a lower risk of liver fibrosis compared to women who had never been pregnant, after adjusting for potential confounders (adjusted odds ratio, 0.30; 95% confidence interval, 0.15–0.59). The risk of liver fibrosis did not increase significantly with an increasing number of pregnancies (P for trend=0.135). Other reproductive factors, including total reproductive years, age at menopause and menarche, and oral contraceptive use, were not significantly associated with liver fibrosis. @*Conclusion@#Postmenopausal women who had experienced one or more pregnancies had a reduced risk of liver fibrosis. Our findings reveal a potential protective role of pregnancy against liver fibrosis.

Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells

Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β ( Ser9 ) and β-catenin (Ser 552 and Ser675 ). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202 /Tyr204 )-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

Vanillic Acid Stimulates Anagen Signaling via the PI3K/Akt/ β-Catenin Pathway in Dermal Papilla Cells

The hair cycle (anagen, catagen, and telogen) is regulated by the interaction between mesenchymal cells and epithelial cells in the hair follicles. The proliferation of dermal papilla cells (DPCs), mesenchymal-derived fibroblasts, has emerged as a target for the regulation of the hair cycle. Here, we show that vanillic acid, a phenolic acid from wheat bran, promotes the proliferation of DPCs via a PI3K/Akt/Wnt/β-catenin dependent mechanism. Vanillic acid promoted the proliferation of DPCs, accompanied by increased levels of cell-cycle proteins cyclin D1, CDK6, and Cdc2 p34. Vanillic acid also increased the levels of phospho(ser473)- Akt, phospho(ser780)-pRB, and phospho(thr37/46)-4EBP1 in a time-dependent manner. Wortmannin, an inhibitor of the PI3K/ Akt pathway, attenuated the vanillic acid-mediated proliferation of DPCs. Vanillic acid-induced progression of the cell-cycle was also suppressed by wortmannin. Moreover, vanillic acid increased the levels of Wnt/β-catenin proteins, such as phospho(ser9)- glycogen synthase kinase-3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin. We found that vanillic acid increased the levels of cyclin D1 and Cox-2, which are target genes of β-catenin, and these changes were inhibited by wortmannin. To investigate whether vanillic acid affects the downregulation of β-catenin by dihydrotestosterone (DHT), implicated in the development of androgenetic alopecia, DPCs were stimulated with DHT in the presence and absence of vanillic acid for 24 h. Western blotting and confocal microscopy analyses showed that the decreased level of β-catenin after the incubation with DHT was reversed by vanillic acid. These results suggest that vanillic acid could stimulate anagen and alleviate hair loss by activating the PI3K/Akt and Wnt/β-catenin pathways in DPCs.

A Novel Antibiotic Agent, Cefiderocol, for Multidrug-Resistant Gram-Negative Bacteria

The threat of antibiotic resistance is an influencing factor in deteriorating public health. Therefore, new antibiotic development is necessary for continued successful treatment of infectious diseases. Cefiderocol is the first licensed injectable siderophore cephalosporin that chemically conjugates a siderophore and cephalosporin.Due to its high stability against various β-lactamases, it is widely used as an effective antibiotic for multidrug-resistant (MDR) gram-negative microorganisms, including Acinetobacter baumannii, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae. Cefiderocol blocks microbial cell membrane synthesis. The binding site of cefiderocol is a penicillin-binding protein. Because of its siderophore-like properties, cefiderocol penetrates gram-negative bacterial periplasmic spaces, increasing its stability against β-lactamases. Unlike earlier cephalosporins, the siderophore of the cefiderocol moiety at position C-3 chelates with iron (ferric form) in the host and is then actively transported into the bacterial periplasmic space. This approach is known as a “Trojan horse” and improves cefiderocol stability against efflux pumps as well as porin channel mutations. Modification at the C-3 and C-7 side-chains produces powerful antibacterial properties against MDR gram-negative bacteria. The U.S. Food and Drug Administration (FDA) approved it as a new treatment option for adult patients with complicated urinary tract infection (cUTI) who have limited and no treatment options. Based on these observations, we conclude that cefiderocol is a potent treatment option for prospective bacterial infections. In this review, we summarize the future prospective use of cefiderocol for bacterial infections.

A Novel Antibiotic Agent, Cefiderocol, for Multidrug-Resistant Gram-Negative Bacteria

The threat of antibiotic resistance is an influencing factor in deteriorating public health. Therefore, new antibiotic development is necessary for continued successful treatment of infectious diseases. Cefiderocol is the first licensed injectable siderophore cephalosporin that chemically conjugates a siderophore and cephalosporin.Due to its high stability against various β-lactamases, it is widely used as an effective antibiotic for multidrug-resistant (MDR) gram-negative microorganisms, including Acinetobacter baumannii, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae. Cefiderocol blocks microbial cell membrane synthesis. The binding site of cefiderocol is a penicillin-binding protein. Because of its siderophore-like properties, cefiderocol penetrates gram-negative bacterial periplasmic spaces, increasing its stability against β-lactamases. Unlike earlier cephalosporins, the siderophore of the cefiderocol moiety at position C-3 chelates with iron (ferric form) in the host and is then actively transported into the bacterial periplasmic space. This approach is known as a “Trojan horse” and improves cefiderocol stability against efflux pumps as well as porin channel mutations. Modification at the C-3 and C-7 side-chains produces powerful antibacterial properties against MDR gram-negative bacteria. The U.S. Food and Drug Administration (FDA) approved it as a new treatment option for adult patients with complicated urinary tract infection (cUTI) who have limited and no treatment options. Based on these observations, we conclude that cefiderocol is a potent treatment option for prospective bacterial infections. In this review, we summarize the future prospective use of cefiderocol for bacterial infections.

Delafloxacin, a New Miracle in Antibiotics Armamentarium for Bacterial Infections

The persistent antibiotics resistant issue has emerged as an influencing factor to deteriorate community health. So, new antibiotics development is urgent for the treatment of bacterial infections. Alternatively, delafloxacin is an eminent new fluoroquinolone, and chemically distinct from older fluoroquinolones. There is lack of proton substituent that indicates the poor acidic property of the drug. It also has a good intracellular penetration capacity that increases the intensity of the bactericidal property in acidic environment. Delafloxacin is a super active drug against the skin and soft tissue infections (SSTIs) and community-acquired respiratory tract infections. Delafloxacin also exhibits better efficacy against pathogens which are resistant to other fluoroquinolones, such as methicillin-resistant Staphylococcus aureus (MRSA). Delafloxacin received approval from the US Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSI). Phase III clinical trial among patients with community-acquired pneumonia (CAP) is ongoing to evaluate the effectiveness of delafloxacin. From the aforementioned arguments, delafloxacin will be a prominent candidate for the upcoming antibacterial agent. Similarly, delafloxacin can be a crucial drug to fight against ABSSI.

Esculetin Prevents the Induction of Matrix Metalloproteinase-1 by Hydrogen Peroxide in Skin Keratinocytes

BACKGROUND: Reactive oxygen species (ROS) are involved in various cellular diseases. Excessive ROS can cause intracellular oxidative stress, resulting in a calcium imbalance and even aging. In this study, we evaluated the protective effect of esculetin on oxidative stress-induced aging in human HaCaT keratinocytes. METHODS: Human keratinocytes were pretreated with esculetin for 30 minutes and treated with H₂O₂. Then, the protective effects on oxidative stress-induced matrix metalloproteinase (MMP)-1 were detected by Flou-4-AM staining, reverse transcription-PCR, Western blotting, and quantitative fluorescence assay. RESULTS: Esculetin prevented H₂O₂-induced aging by inhibiting MMP-1 mRNA, protein, and activity levels. In addition, esculetin decreased abnormal levels of phospho-MEK1, phospho-ERK1/2, phospho-SEK1, phospho-JNK1/2, c-Fos, and phospho-c-Jun and inhibited activator protein 1 binding activity. CONCLUSIONS: Esculetin prevented excessive levels of intracellular calcium and reduced the expression levels of aging-related proteins.

Role of Particulate Matter in Skin Inflammation

Environmental pollution is a major global problem that affects human health. Among different types of environmental pollution, particulate matter (PM) has a key role. As PM spreads in the air so it causes different bronchial and skin inflammatory conditions. PM increases oxidative stress by ROS production and pro-inflammatory cytokines. As a result, matrix metalloproteinase is also produced, such as MMP1, MMP9 and MMP2 that is a known major cause of skin collagen degradation. Recently it has been shown that the PM worsens allergic conditions like dermatitis, psoriasis, and skin cancer. Different extensive efforts have been made across the globe to control this PM.

Niacinamide Protects Skin Cells from Oxidative Stress Induced by Particulate Matter

Niacinamide (NIA) is a water-soluble vitamin that is widely used in the treatment of skin diseases. Moreover, NIA displays antioxidant effects and helps repair damaged DNA. Recent studies showed that particulate matter 2.5 (PM(2.5)) induced reactive oxygen species (ROS), causing disruption of DNA, lipids, and protein, mitochondrial depolarization, and apoptosis of skin keratinocytes. Here, we investigated the protective effects of NIA on PM(2.5)-induced oxidative stress in human HaCaT keratinocytes. We found that NIA could inhibit the ROS generation induced by PM(2.5), as well block the PM(2.5)-induced oxidation of molecules, such as lipids, proteins, and DNA. Furthermore, NIA alleviated PM(2.5)-induced accumulation of cellular Ca²⁺, which caused cell membrane depolarization and apoptosis, and reduced the number of apoptotic cells. Collectively, the findings show that NIA can protect keratinocytes from PM(2.5)-induced oxidative stress and cell damage.

Purpurogallin Protects Keratinocytes from Damage and Apoptosis Induced by Ultraviolet B Radiation and Particulate Matter 2.5

Purpurogallin, a natural phenol obtained from oak nutgalls, has been shown to possess antioxidant, anticancer, and anti-inflammatory effects. Recently, in addition to ultraviolet B (UVB) radiation that induces cell apoptosis via oxidative stress, particulate matter 2.5 (PM(2.5)) was shown to trigger excessive production of reactive oxygen species. In this study, we observed that UVB radiation and PM(2.5) severely damaged human HaCaT keratinocytes, disrupting cellular DNA, lipids, and proteins and causing mitochondrial depolarization. Purpurogallin protected HaCaT cells from apoptosis induced by UVB radiation and/or PM(2.5). Furthermore, purpurogallin effectively modulates the pro-apoptotic and anti-apoptotic proteins under UVB irradiation via caspase signaling pathways. Additionally, purpurogallin reduced apoptosis via MAPK signaling pathways, as demonstrated using MAPK-p38, ERK, and JNK inhibitors. These results indicate that purpurogallin possesses antioxidant effects and protects cells from damage and apoptosis induced by UVB radiation and PM(2.5).

PD-1: A Negative Regulator of Phagocytosis by Tumour-Associated Macrophages in Colon Cancer

Programmed cell death protein 1 (PD-1) is an immuno-inhibitory cell surface receptor protein of the myeloid, and lymphoid cell. PD-L1 is the ligand of PD-1, which is abundant in different malignant tissue e.g. skin, colon and breast cancer. PD-1/PD-L1 interaction helps the tumour cell to escape from the immune response by limiting TCR mediated T lymphocytes proliferation. Recently, PD-1 or PD-L1 blocking immunotherapy proved their efficacy in the treatment of different cancers. However, PD-1/PD-L1 interaction is well studied in T lymphocytes, but little is known about its function in tumour-associated macrophages (TAMs). In the tumour microenvironment, phagocytosis by TAMs plays a vital role in the immune response. In this review, the significance of PD-1 expression by TAMs and how it influences tumour immunity will be discussed. Recently, it has been found that PD-1 can express by TAMs and its expression level is directly related to duration and stages of colon cancer. TAMs expression of PD-1 was shown to be related to significant depletion of cancer cell phagocytosis. Monoclonal antibody against either PD-1 or PD-L1 in mice model of colon cancer promotes tumour cell phagocytosis by TAMs, thereby limiting the growth of the tumour and increase life expectancy. Therefore, PD-1 can be a promising target in macrophage-mediated immune therapy.

Chemicals from Cimicifuga dahurica and Their Inhibitory Effects on Pro-inflammatory Cytokine Production by LPS-stimulated Bone Marrow-derived Dendritic Cells

Inflammation is a biological response caused by overactivation of the immune system and is controlled by immune cells via a variety of cytokines. The overproduction of pro-inflammatory cytokines enhances abnormal host immunity, resulting in diseases such as rheumatoid arthritis, cardiovascular disease, Alzheimer's disease, and cancer. Inhibiting the production of pro-inflammatory cytokines such as interleukin (IL)-12p40, IL-6, and tumor necrosis factor (TNF)-α might be one way to treat these conditions. Here, we investigated the anti-inflammatory activity of compounds isolated from Cimicifuga dahurica (Turcz.) Maxim., which is traditionally used as an antipyretic and analgesic in Korea. In primary cell culture assays, 12 compounds were found to inhibit the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) in vitro in bone marrow-derived dendritic cells stimulated with LPS.

NLRC3 Attenuates Colon Cancer by Down-Regulating PI3K-mTOR Signaling

The nucleotide-binding oligomerization domain-like receptors (NOD-like receptors, NLRs) are intracellular sensors. Most of them positively affect inflammatory responses, particularly the inflammasome forming NLRs. On the other hand, several studies on gene-deficient mice have revealed that several NLRs negatively influence innate immune responses. Some recent studies have identified a novel sub-group of non-inflammasome forming NLRs that negatively influence different pathways related to inflammation and carcinogenesis. Cytosolic pattern recognition receptor NRLC3 is a negative regulator of innate immune response. In this review we will discuss finding related with NLRC3 and its mechanism by which it alter cancer pathogenesis. Recently, it has been found that mice deficient in Nlrc3 are hyper-susceptible to colitis and colitis-associated colon carcinogenesis. Oncogenic inhibitory effect of NLRC3 is more dominant in epithelial compartment than hematopoietic compartment. It down regulates mTOR signaling and reduce cell proliferation. NLRC3 interact with PI3Ks and suppress activation of PI3K dependent kinase AKT. Understanding the role of NLRC3 in cancer may facilitate the recognition of new therapeutic strategies.

Omadacycline, a Magic Antibiotics for Bacterial Infections

Nowadays antibiotic resistance is a worldwide serious problem that mainly affects public health. Omadacycline is a unique antibiotic which has two available dosage forms such as intravenous (IV) and oral that development for community-acquired bacterial infectious disease treatment. It is a modified form of older tetracycline at C-9 aminomethyl substituent of 6-member core ring of tetracycline. Modification form shows its activity against efflux pump and ribosomal protein protection mechanism of tetracycline resistance. Generally, omadacycline is effective against methicillin-resistant S. aureus (MRSA), Streptococcus pneumoniae, vancomycin-resistant Enterococcus (VRE), Legionella and Chlamydia spp. Efficacy, safety and tolerability profile of omadacycline those compares with recent antibiotics shows that omadacycline is less resistant than others. One derivative from tetracycline derivatives is 9-neopentylaminomethylminocycline called omadacycline was discovered and ongoing phase III clinical experiments as a therapy for acute bacterial skin and skin structure infections (ABSSSI) as well as community-acquired bacterial pneumonia (CABP). Omadacycline seems to be a strong drug candidate for future promising new antibacterial agent that is effective against ABSSSI and CABP.

4-O-Methylhonokiol Protects HaCaT Cells from TGF-β1-Induced Cell Cycle Arrest by Regulating Canonical and Non-Canonical Pathways of TGF-β Signaling

4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-β (TGF-β) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-β signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-β-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-β1-induced G1/G0 phase arrest and TGF-β1-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-β1-induced canonical pathway. We observed that ERK phosphorylation by TGF-β1 was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-β1-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-β1-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-β1-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-β1-induced cell cycle arrest.

Texiobactin, a Potent Killer of Antibiotic Resistant Pathogens

Antibiotic resistance is a major global concern that primarily affects public health. Texiobactin is a newly discovered antibiotic produces by soil microbes isolated from natural environment. Drug is active against Gram-positive bacteria as it inhibits biosynthesis of peptidoglycan. Infection of methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae in mice elicits a good response reduce bacterial load. Although extensive efforts have been made to discover new antibiotics but results are still not satisfactory to meet the demands of public health. Recently it has been shown that the discovery of texiobactin by iChip will be a great stone mile to discover more antibiotics.

The Effect of (1S,2S,3E,7E,11E)-3,7,11,15-Cembratetraen-17,2-Olide (LS-1) from Lobophyyum sp. on the Apoptosis Induction of SNU-C5 Human Colorectal Cancer Cells

(1S,2S,3E,7E,11E)-3,7,11,15-cembratetraen-17,2-olide (LS-1), a marine cembrenolide diterpene, has anticancer activity against colon cancer cells such as HT-29, SNU-C5/5-FU (fluorouracil-resistant SNU-C5) and SNU-C5. However, the action mechanism of LS-1 on SNU-C5 human colon cancer cells has not been fully elucidated. In this study, we investigated whether the anticancer effect of LS-1 could result from apoptosis via the modulation of Wnt/β-catenin and the TGF-β pathways. When treated with the LS-1, we could observe the apoptotic characteristics such as apoptotic bodies and the increase of sub-G1 hypodiploid cell population, increase of Bax level, decrease of Bcl-2 expression, cleavage of procaspase-3 and cleavage of poly (ADP-ribose) polymerase in SNU-C5 cells. Furthermore, the apoptosis induction of SNU-C5 cells upon LS-1 treatment was also accompanied by the down-regulation of Wnt/β-catenin signaling pathway via the decrease of GSK-3β phosphorylation followed by the decrease of β-catenin level. In addition, the LS-1 induced the activation of TGF-β signaling pathway with the decrease of carcinoembryonic antigen which leads to decrease of c-Myc, an oncoprotein. These data suggest that the LS-1 could induce the apoptosis via the down-regulation of Wnt/β-catenin pathway and the activation of TGF-β pathway in SNU-C5 human colon cancer cells. The results support that the LS-1 might have potential for the treatment of human colon cancer.

3-Hydroxy-4,7-megastigmadien-9-one, Isolated from Ulva pertusa Kjellman, Inhibits LPS-Induced Inflammatory Response by Down-Regulating Mitogen-Activated Protein Kinase and NF-κB Pathways

In the present study we evaluated the anti-inflammatory potential of 3-hydroxy-4,7-megastigmadien-9-one (Comp) isolated from Ulva pertusa Kjellman, in LPS-stimulated bone marrow-derived dendritic cells (BMDCs). Comp treatment exhibited strong dose dependent inhibition of IL-12 p40 and IL-6 cytokine production with IC₅₀ values of 7.85 ± 0.32 and 7.86 ± 0.18, respectively in LPS-stimulated BMDCs. Treatment of Comp inhibited MAPKs and NF-κB pathways in LPS-stimulated BMDCs by inhibiting the phosphorylation of ERK1/2, JNK1/2, p38 and IκB. Thus, these results suggest that Comp have a significant anti-inflammatory property and affirm further studies concerning the potentials of Comp for medicinal use.

Suppression of Antimicrobial Defense and Stabilization of STAT3 by IRAK-M Expression in Tumor Cells Promotes Colorectal Carcinogenesis

Different environmental and genetic factors have been attributed to the etiology of colorectal cancer. Dysbiotic gut microbiota is associated with initiation and progression of colon carcinogenesis. Hyperactivation of STAT3 promotes carcinogenesis by upregulating cell proliferation, survival, tumor-induced immunosupression and angiogenesis. IRAK-M is a negative regulator of toll-like receptor signaling and inhibits innate immune response. The cancer cell may exploit this property of IRAK-M and evade host immune surveillance. Recently, it has been found that IRAK-M provide controlled feed back to bacteria involved in colorectal cancer by reducing antibacterial response in mice. Furthermore, IRAK-M increased the stability of STAT3 in tumor cells that support tumor promotion by upregulating cell proliferation and survival. Thus, it is suggested that IRAK-M promotes colitis associated colon cancer by enhancing bacterial colonization and stabilization of STAT3.

Acrosorium polyneurum Extract Inhibits the LPS-Induced Inflammatory Response by Impairing the MAPK and NF-κB Pathways

Marine algae exhibit broad spectrum anti-bacterial and anti-inflammatory activities. Acrosorium polyneurum (A. polyneurum) is a marine red alga and belongs to the family Delesseriaceae. The present research evaluates the antiinflammatory effects of A. polyneurum extract (APE) on pro-inflammatory cytokine production. APE demonstrated substantial inhibitory effects on production of pro-inflammatory cytokine in bone marrow-derived macrophages (BMDMs). APE pre-treatment in the lipopolysaccharide (LPS)-stimulated BMDMs exhibited a robust inhibitory effect on production of interleukin (IL)-12, IL-6 and tumor necrosis factor (TNF)-α. It revealed a robust inhibitory effect on phosphorylation of ERK1/2, JNK1/2 and p38. APE also showed remarkable inhibitory effect on phosphorylation and degradation of IκBα. Furthermore, APE pre-treatment demonstrated substantial inhibition of LPS-induced production of nitric oxide and inducible nitric oxide synthase. Collectively, these data suggest that APE has a noteworthy anti-inflammatory property and deserve further studies concerning its potential use as a medicinal agent for inflammation-related disorders.