The discovery of an anti-inflammatory monoterpenoid, neoroseoside from the Zea mays.

A new monoterpenoid, neoroseoside (1), along with two previously reported compounds, 2″-O-α-l-rhamnosyl-6-C-fucosylluteolin (2) and farobin A (3) were isolated from the Zea mays. The structure of compound 1 was determined through the analysis spectroscopic data, including mass spectrometry (MS), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) data. The absolute configurations of 1 were deduced from the comparing the values of optical rotations and from the interpretation of electronic circular dichroism (ECD) spectra. Compounds 2 and 3 displayed moderate antibacterial activity against Streptococcus mutans ATCC 25175 (inhibition rates 24 % and 28 %, respectively) and Streptococcus sobrinus ATCC 33478 (inhibition rate of 26 %), at a concentration of 100 µg/mL, whereas compound 1 did not have any significant antibacterial activities. The compounds 1-3 also showed anti-inflammatory activity on cytokine IL-6 and TNF-α.

Cold Plasma Treatment Increases Bioactive Metabolites in Oat (Avena sativa L.) Sprouts and Enhances In Vitro Osteogenic Activity of their Extracts.

Cold plasma treatment has been studied to enhance the germination, growth, and bioactive phytochemical production in crops. Here, we aimed to investigate the effects of cold plasma treatment on the growth, bioactive metabolite production, and protein expression related to the physiological and osteogenic activities of oat sprouts. Oat seeds were soaked for 12 h, and then exposed to plasma for 6 min/day for 3 days after sowing. Plasma exposure did not significantly change the growth of oat sprouts; however, increased the content of bioactive metabolites. A single exposure for 6 min on the first day (T-1) increased the content of free amino acids (39.4%), γ-aminobutyric acid (53%), and avenacoside B (23%) compared to the control. Hexacosanol content was the highest in T-3 (6 min exposure on each day for 3 days), 28% higher than that in the control. Oat sprout extracts induced the phosphorylation of adenosine 5'-monophosphate-activated protein kinase and osteoblast differentiation was enhanced by increasing the alkaline phosphatase (ALP) activity; all these effects were induced by plasma treatment. Avenacoside B content was positively correlated with ALP activity (r = 0.911, p < 0.1). These results suggest that plasma treatment has the potential to improve the value of oat sprouts and that it may be used in food fortification to enhance nutritional value for promoting human health.

Lutonarin from Barley Seedlings Inhibits the Lipopolysacchride-Stimulated Inflammatory Response of RAW 264.7 Macrophages by Suppressing Nuclear Factor-κB Signaling.

Extracts from barley seedlings (BS) have known antioxidant and anti-inflammatory activities. The flavonoid lutonarin (LN) is a component of BS extract and has several known bioactivities. Here, we evaluated LN anti-inflammatory efficacy against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Lutonarin was isolated from BS by methanol extraction and characterized by ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Lutonarin did not reduce the viability or enhance the apoptosis rate of RAW 264.7 macrophages at concentrations up to 150 µM. Concentrations within 20-60 µM dose-dependently suppressed the LPS-induced expression, phosphorylation, and nuclear translocation of the inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, LN suppressed the LPS-induced upregulation of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α and of the inflammatory enzyme cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Lutonarin may be a safe and effective therapeutic agent for alleviation of pathological inflammation.

Two new secondary metabolites isolated from Avena sativa L. (Oat) seedlings and their effects on osteoblast differentiation.

Seedlings of natural crops are valuable sources of pharmacologically active phytochemicals. In this study, we aimed to identify new active secondary metabolites in Avena sativa L. (oat) seedlings. Two new compounds, avenafuranol (1) and diosgenoside (2), along with eight known compounds (3-10) were isolated from the A. sativa L. seedlings. Their chemical structures were elucidated via 1D and 2D NMR spectroscopy, high-resolution ESIMS, IR spectroscopy, optical rotation analysis, and comparisons with the reported literature. The effect of each isolated compound on alkaline phosphatase (ALP) activity for osteoblast differentiation induced by bone morphogenetic protein-2 (BMP-2) was investigated using the C2C12 immortal mouse myoblast cell line. Compounds 1, 4, 6, 8, and 9 induced dose-dependent increases in ALP expression relative to ALP expression in cells treated with only BMP-2, and no cytotoxicity was observed. These results suggest that A. sativa L. seedlings are a natural source of compounds that may be useful for preventing bone disorders.

Inhibitory Effect of Oat Bran Ethanol Extract on Survival and Gemcitabine Resistance of Pancreatic Cancer Cells.

Pancreatic cancer (PC) is one of the most aggressive malignancies in the world. Gemcitabine (Gem), a nucleoside pyrimidine analogue, is a first-line chemotherapeutic drug for PC, but the tumor response rate of Gem is very low and resistance to Gem has emerged as a major problem in the treatment of PC. Oat bran, used as animal and human food, has been found to be beneficial to health. In this study, effects of oat bran ethanol extract (OBE) on PC cells and Gem-resistant PC cells were investigated in vitro. OBE decreased cell survival and colony forming ability of PC cells, without any cytotoxicity on the normal pancreatic cells. Flow cytometry analysis and TUNEL assay showed that the OBE reduced G1/S phase transition and induced death in PC cells through AMPK activation and downregulation of JNK. Additionally, OBE could overcome Gem resistance through reduction in RRM1/2 expression and showed synergistic effect by combinatorial treatment with Gem on Gem-resistant PC cells. Additionally, LC-MS data showed that avenacoside A was a component of OBE. Thus, this study elucidated the anti-proliferative effect of OBE and synergistic effect of OBE with Gem on PC cells and Gem-resistant cells.

The Dual Role of Oat Bran Water Extract in Bone Homeostasis Through the Regulation of Osteoclastogenesis and Osteoblast Differentiation.

The number of patients with bone metabolic disorders including osteoporosis is increasing worldwide. These disorders often facilitate bone fractures, which seriously impact the patient's quality of life and could lead to further health complications. Bone homeostasis is tightly regulated to balance bone resorption and formation. However, many anti-osteoporotic agents are broadly categorized as either bone forming or anti-resorptive, and their therapeutic use is often limited due to unwanted side effects. Therefore, safe and effective therapeutic agents are needed for osteoporosis. This study aims to clarify the bone protecting effects of oat bran water extract (OBWE) and its mode of action. OBWE inhibited RANKL (receptor activator of nuclear factor-κB ligand)-induced osteoclast differentiation by blocking c-Fos/NFATc1 through the alteration of I-κB. Furthermore, we found that OBWE enhanced BMP-2-stimulated osteoblast differentiation by the induction of Runx2 via Smad signaling molecules. In addition, the anti-osteoporotic activity of OBWE was also evaluated using an in vivo model. OBWE significantly restored ovariectomy-induced bone loss. These in vitro and in vivo results showed that OBWE has the potential to prevent and treat bone metabolic disorders including osteoporosis.

Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor Growth.

Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production.

Biodegradation of low-density polyethylene by plasma-activated Bacillus strain.

Plastic biodegradation by microorganisms is an eco-friendly and sustainable method without any ramifications. Herein, we used a cultivation method and 16S rRNA sequencing to screen bacteria that can efficiently colonize and degrade low-density polyethylene (LDPE) from various plastic wastes. We identified Bacillus safensis BS-10L through whole-genome sequencing analysis and verified its LDPE-degradation ability. However, the decomposition mechanism of the isolated bacteria was unclear and the decomposition efficiency was insufficient, so low-temperature plasma was used to increase the decomposition efficiency of the bacteria. The population and viability of bacteria treated with cold plasma increased. Plasma-activated bacteria could induce cracks, holes, and roughness on the surface of LDPE films over 90 days, and over 30 days; the LDPE film lost 13.40 ± 0.013% and 27.78 ± 0.014% of its mass by BS-10L and plasma-treated BS-10L, respectively. Fourier-transform infrared spectroscopic analysis identified new peaks of the C=O and C-O groups in the plasma-treated LDPE film, exhibiting high transmittance in the LDPE film that was inoculated with bacteria. X-ray photoelectron spectroscopic analysis showed that C-O bonds were generated by BS-10L strain, and relatively strong C=O bonds were generated in the film inoculated with plasma-treated BS-10L strain. Plasma treatment increased the colonization of the BS-10L strain and changed the chemical bonding of the LDPE film, suggesting that plasma-activated BS-10L could accelerate decomposition by oxidation by increasing the carbonyl group of the PE film. Therefore, plasma technology may be effective for enhancing the plastic-degrading ability of microorganisms.

Exploring nurses' multitasking in clinical settings using a multimethod study.

Nurses often multitask in the process of managing patient care and communicating with healthcare providers simultaneously within a limited time, which can negatively affect patient care and safety. In this multimethod research, we conducted a time and motion study to record nursing activities using eye trackers for 23 participants (9 nurses and 14 patients). The frequency and duration of single and multitasking activities were analyzed. Additionally, we conducted focus group interviews (FGIs) with 12 nurses (2-5 nurses per group) to further investigate their multitasking experience. The total duration of the eye tracker recordings was 3,399 min. Daily nursing activities comprised 23.7%, 21.1%, and 12.5% of scheduled medication, documentation, and monitoring and measurement, respectively. Among these activities, nurses mostly carry out scheduled medication, monitoring, and measurement together. Three themes emerged in the FGIs: "Being involved in every little task regarding patient care," "Getting swamped by the complexity of symptoms and problems of the patients at a given time," and "Getting interrupted at work too often." Nurses performed multiple activities while cooperating with other healthcare providers and providing care to patients. It is important to create an environment where nurses can focus on essential nursing activities to improve patient safety.

"Nulichal" Barley Extract Suppresses Nitric Oxide and Pro-Inflammatory Cytokine Production by Lipopolysaccharides in RAW264.7 Macrophage Cell Line.

The cultivar "Nulichal," a type of naked waxy barley (Hordeum vulgare L.), was developed by the National Institute of Crop Science, Rural Development Administration, Korea, in 2010. In this study, we investigated the anti-inflammatory and antioxidant properties of the "Nulichal" ethanol extract (NRE) using various assays. The NRE exhibited a total phenolic content of 7.55±0.30 mg gallic acid equivalent/g and a flavonoid content of 1.74±0.08 mg rutin equivalent/g. Cell viability assays showed no toxicity of NRE on RAW264.7 macrophage cells up to concentrations of 500 µg/mL. The NRE (300 and 500 µg/mL) significantly reduced nitric oxide (NO) production induced by lipopolysaccharides (LPS). It also down-regulated the mRNA expression and protein levels of inducible NO synthase and cyclooxygenase-2 in a dose-dependent manner. Moreover, the NRE treatment significantly decreased the levels of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, and their mRNA expression compared to LPS treatment alone. The NRE demonstrated strong free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals in a dose-dependent manner. The ferric reducing antioxidant power assay also showed increased antioxidant activity with increasing NRE concentrations. These findings suggest that the NRE can be used as a functional food with anti-inflammatory and antioxidant properties.

Lipids and volatile organic compounds in sesame seeds and their relationships with environmental temperature-induced stress.

Sesame seeds contain several lipids and fragrances that offer health benefits. However, no studies have reported a relationship between the lipids or flavor compounds of sesame seeds and environmental factors. In this study, we aimed to identify this relationship by analyzing the contents of lipidic and flavor compounds in fifteen genotypes of sesame seeds grown in two cultivation regions (Jeonju and Miryang) and years (2018 and 2019). Herein, 17 lipids and 62 flavor compounds were detected. Multivariate statistical analyses revealed that the cultivation year had a larger influence on the contents of lipidic and flavor compounds than the cultivation region and genotype. Furthermore, heat stress due to high cultivation temperature in 2018 caused the accumulation of sugar and secondary metabolites, increased flavor-related substances, and inhibited the degradation of fatty acids. Our study is the first to demonstrate the metabolic changes in lipids and flavor components of sesame in response to environmental temperature changes affected by different cultivation years. Therefore, this study provides guidance for the cultivation of commercially advantageous sesame seeds in improving the quality of sesame seeds and their products.

Korean naked waxy barley (saechalssal) extract reduces blood glucose in diabetic mice by modulating the PI3K-Akt-GSK3ß pathway.

Saechalssal barley is Korea's representative naked waxy barley. This study investigated the anti-diabetic effect of the extract derived from saechalssal and its mechanism. The prethanol extract of saechalssal (SPE) showed greater α-glucosidase inhibitory activity in vitro and a more significant lowering of the postprandial blood glucose levels in normal mice compared to its water extract (SWE). When mice with type 2 diabetes (T2DM) induced by a high-fat diet and streptozotocin were fed SPE (200 mg/kg/day) for six weeks, the fasting blood glucose and serum free fatty acid levels were significantly lower than those of the control group. SPE significantly elevated the hepatic glycogen accumulation with increasing glycogen synthesis-related gene (GYS2 and UGP2) levels compared to the control group. SPE stimulated the expression of the hepatic glycolysis-related genes (GK, PFK1, and PK) and suppressed the gluconeogenesis-related genes (G6Pase, FBP1, and PEPCK). SPE up-regulated the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), whereas it down-regulated the phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) compared to the control. The major flavonoids of SPE were naringin, prunin, and catechin, while its phenolic acids were ferulic acid and vanillic acid. These phytochemical compounds may contribute to the anti-hyperglycemic effects of SPE in diabetes. Overall, these results suggest that SPE has potential anti-diabetic activity through the regulating the PI3K/Akt/GSK3ß pathway.

Comparative Analysis of Policosanols Related to Growth Times from the Seedlings of Various Korean Oat (Avena sativa L.) Cultivars and Screening for Adenosine 5'-Monophosphate-Activated Protein Kinase (AMPK) Activation.

The objectives of this research were to evaluate the policosanol profiles and adenosine-5'-monophosphate-activated protein kinase (AMPK) properties in the seedlings of Korean oat (Avena sativa L.) cultivars at different growth times. Nine policosanols in the silylated hexane extracts were detected using GC-MS and their contents showed considerable differences; specifically, hexacosanol (6) exhibited the highest composition, constituting 88-91% of the total average content. Moreover, the average hexacosanol (6) contents showed remarkable variations of 337.8 (5 days) → 416.8 (7 days) → 458.9 (9 days) → 490.0 (11 days) → 479.2 (13 days) → 427.0 mg/100 g (15 days). The seedlings collected at 11 days showed the highest average policosanol content (541.7 mg/100 g), with the lowest content being 383.4 mg/100 g after 5 days. Interestingly, policosanols from oat seedlings grown for 11 days induced the most prevalent phenotype of AMPK activation in HepG2 cells, indicating that policosanols are an excellent AMPK activator.

Oat Seedlings Extract Inhibits RANKL-Induced c-Fos/NFATc1 Transcription Factors in the Early Stage of Osteoclast Differentiation.

Osteoporosis is a common disease that increases the risk of fractures due to decreased bone density and weakens the bone microstructure. Preventing and diagnosing osteoporosis using the available drugs can be a costly affair with possible side effects. Therefore, natural product-derived therapeutics are promising alternatives. Our study demonstrated that the oat seedlings' extract (OSE) inhibited the receptor activator of the nuclear factor κB ligand (RANKL)-induced osteoclastogenesis from the bone marrow-derived macrophages (BMMs). The OSE treatment significantly attenuated the RANKL-mediated induction of the tartrate-resistant acid phosphatase (TRAP) activity as well as the number of TRAP-positive (TRAP+) multinucleated cells (MNCs) counted through the TRAP staining in a dose-dependent manner. It was also confirmed that the OSE suppressed the formation of the TRAP + MNCs in the early stage of differentiation and not in the middle and late stages. The results of the real-time quantitative polymerase chain reaction (qPCR) and the western blotting showed that the OSE dramatically inhibited the mRNA and protein expressions of the osteoclastogenesis-mediated transcription factors such as the c-Fos and the nuclear factor-activated T cells c1 (NFATc1). In addition, the OSE strongly attenuated the mRNA induction of the c-Fos/NFATc1-dependent molecules such as the TRAP, the osteoclast-associatedimmunoglobulin-like receptor (OSCAR), the dendritic cell-specific transmembrane protein (DC-STAMP), and the cathepsin K. These results suggest that the naturally derived OSE may be useful for preventing bone diseases.

Extracellular acidity­induced expression of Kallikrein­related peptidases 7 and 8 is involved in increased invasiveness of gastric cancer cells.

In several cancers, the acidic microenvironment of cancer cells has been implicated in enhanced malignancy and metastasis. In the present study, it was observed that gastric cancer cell lines, SNU601 and AGS, exposed to an acidic medium had increased invasiveness, as assessed using Matrigel­coated Transwell analysis. The factors regulating such acidity­mediated enhancement of invasiveness were investigated and it was revealed that a low­pH environment markedly increased kallikrein­related peptidase 7 (KLK7) and kallikrein­related peptidase 8 (KLK8) expression. Gene silencing assays confirmed that these peptidases were involved in acidity­promoted invasion. Acidic conditions also increased the expression of cyclooxygenases (COX), key regulatory enzymes in the catalytic pathway of prostaglandin production. Notably, these enzymes appeared to be involved in the acidity­mediated expression of KLK7 and KLK8, as revealed using COX inhibitors. Therefore, it was indicated that tumor invasion enhancement by extracellular acidity is regulated at least in part through the induction of the COX/KLK7 and KLK8 axis in gastric cancer cells.

Policosanol profiles and adenosine 5'-monophosphate-activated protein kinase (AMPK) activation potential of Korean wheat seedling extracts according to cultivar and growth time.

Policosanols is a health promoting aliphatic alcohol known as lipid-lowing agent. To enable maximising the functional properties of wheat, this research investigates the policosanol profiles and adenosine 5'-monophosphate-activated protein kinase (AMPK) activation potential of Korean wheat seedlings according to cultivars and growth times. GC-MS revealed six policosanols that differed markedly in content between 17 cultivars, especially, octacosanol (8) showed the most predominant component (49-83%), varying significantly in average concentrations with growth times as 361.4 (3 days) â†’ 613.0 (6 days) â†’ 203.1 (9 days) â†’ 196.5 (12 days) â†’ 50.9 mg/100 g (19 days). The highest average policosanol (738.7 mg/100 g) exhibited after 6 days, while the lowest was 104.4 mg/100 g on 19 days. Moreover, the wheat cultivars including Shinmichal 1, Anbaek, Namhae, and Joah at 6 days may be recommended as potential sources because of high policosanols (921.7-990.6 mg/100 g). Western blot analysis revealed markedly higher AMPK activation in cells treated with the hexane extracts (150-370% at 100 µg/ml) and octacosanol (8) possessed potent AMPK activator (control; 100 â†’ 280% at 200 µg/ml). It is confirmed that the AMPK activation by wheat seedlings are positively related to the highest policosanol content at the 6 days of growth time, independent of the cultivar. Our results may be contributed to enhance the wheat value regarding development of new cultivars and functional foods.

Development and effects of a self-management efficacy promotion program for adult patients with congenital heart disease.

BACKGROUND: With the recent advances in medicine, patients with congenital heart disease are surviving to adulthood. Adults with congenital heart disease must practice self-management to recognize the symptoms of complications and the appropriate response. AIMS: The purpose of this study was to develop a self-management efficacy promotion program for adults with congenital heart disease and to test the effects of the developed program on disease-related knowledge, self-management implementation and health-related quality of life. METHODS: A non-equivalent, control group, pre-post test design was used. The intervention group received the self-management efficacy promotion program for six weeks. The control group received only the usual care. RESULTS: The study results showed that disease-related knowledge ( F=91.095, p<0.001) was significantly different between the two groups, as was the self-management performance ( F=11.846, p<0.001). However, health-related quality of life (generic core scale: F=0.023, p=0.881, cardiac module scale: F=0.174, p=0.678) was not significantly different between groups. CONCLUSION: The self-management efficacy promotion program for adults with congenital heart disease had a significant effect on disease-related knowledge and self-management implementation, but did not affect health-related quality of life.

A novel protein, MUDENG, induces cell death in cytotoxic T cells.

A screening system comprised of a randomized hybrid-ribozyme library has previously been used to identify pro-death genes in Fas-mediated apoptosis, and short sequence information of candidate genes from this system was previously reported by Kawasaki and Taira [H. Kawasaki, K. Taira, A functional gene discovery in the Fas-mediated pathway to apoptosis by analysis of transiently expressed randomized hybrid-ribozyme libraries, Nucleic Acids Res. 30 (2002) 3609-3614]. In this study, we have cloned the full-length of the candidate's open reading frames and found that one of the candidates, referred to as MUDENG (Mu-2 related death-inducing gene), which is composed of 490 amino acids that contain the adaptin domain found in the mu2 subunit of APs related to clathrin-mediated endocytosis, is able to induce cell death by itself. Ectopic expression of MUDENG induced cell death in Jurkat T cells and HeLa cells. In addition, when MUDENG expression was evaluated by immnuohistochemical staining, it was found in most tissues, including the intestine and testis. Furthermore, MUDENG appears to be evolutionary conserved from mammals to amphibians, suggesting that it may have a common role in cell death. Taken together, these results suggest that MUDENG is likely to play an important role in cell death in various tissues.

Amyloidosis of seminal vesicles and ejaculatory ducts: a histologic analysis of 21 cases among 447 prostatectomy specimens.

To investigate the incidence of amyloidosis of seminal vesicles and ejaculatory system including ejaculatory ducts and vasa deferentia, we reviewed the whole mount sections of 447 radical prostatectomy specimens removed for prostatic cancer, including 273 cases from the United States and 174 cases from Korea. Of these, 21 cases (4.7%) showed amyloidosis in seminal vesicles, vasa deferentia, and in ejaculatory ducts. Ten of these (3.7%) cases were from the United States and 11 cases (6.3%) from Korea. The patients' age ranged from 51 to 79 years (mean, 66.1 years). Amyloid deposition was found in 5 patients in the sixth decade (3.4%), 9 patients in the seventh decade (4.7%), and 7 patients in the eighth decade (9.3%). At the seventh decade of life, the Korean patients showed a higher incidence (8.3%) than American patients (2.5%), but other age groups showed no difference. All cases showed bilateral involvement of the seminal vesicles and ejaculatory systems. The deposits of amyloid tended to be nodular and affected the subepithelial region of seminal vesicles, vasa deferentia, and ejaculatory ducts. There was no amyloid deposit around blood vessels or in the prostatic parenchyma. Localized amyloidosis of the ejaculatory system involves not only the seminal vesicles but also the vasa deferentia and the ejaculatory ducts. The vessels or prostatic stroma are not part of this process. Amyloidosis develops subepithelially spreading to include the wall of these organs and appears to be related to advanced age. The incidence of amyloidosis of the ejaculatory system in Korean patients was higher than in US patients.

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells.

Andrographolide, a natural compound isolated from Andrographis paniculata, has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL). Exposure of GC cells to andrographolide altered the expression level of several growth-inhibiting and apoptosis-regulating proteins, including death receptors. It was demonstrated that activity of the TRAIL-R2 (DR5) pathway was critical in the development of andrographolide-mediated rhTRAIL sensitization, since its inhibition significantly reduced the extent of apoptosis induced by the combination of rhTRAIL and andrographolide. In addition, andrographolide increased reactive oxygen species (ROS) generation in a dose-dependent manner. N-acetyl cysteine prevented andrographolide-mediated DR5 induction and the apoptotic effect induced by the combination of rhTRAIL and andrographolide. Collectively, the present study demonstrated that andrographolide enhances TRAIL-induced apoptosis through induction of DR5 expression. This effect appears to involve ROS generation in GCs.