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Park SH, Lee OY, Lee YC, Park KS, Park JJ, Park MI, Song GA, Lee DH, Jung H, Kim SK, Kim TN, Choi SC, Jee SR, Rew JS, Lee ST, Choi EK, Baik GH, Park SJ. A Phase 2, Multi-Center, Randomized, Double-Blind, Parallel-Group Trial to Evaluate the Efficacy and Safety of CKD-495 in Patients With Acute and Chronic Gastritis. Can J Gastroenterol Hepatol 2025; 2025:2702089. [PMID: 40255536 PMCID: PMC12006708 DOI: 10.1155/cjgh/2702089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 10/18/2024] [Accepted: 02/20/2025] [Indexed: 04/22/2025] Open
Abstract
CKD-495 is a newly developed drug extracted from Cinnamomum cassia Presl. This phase II study assessed the clinical benefits of CKD-495 in the treatment of acute and chronic gastritis. This study randomly assigned 250 patients with endoscopically-proven gastric mucosal erosion to five groups. The groups received either 75 mg or 150 mg of CKD-495, 100 mg of rebamipide, 60 mg of Artemisiae argyi folium 95% ethanol ext. (20 ⟶ 1) (Stillen; Dong-A ST Co., Ltd., Seoul, Korea), or placebo for 2 weeks, respectively. The primary endpoint was the erosion improvement rate, and the secondary endpoints were erosion cure rates, improvement rates of gastrointestinal symptoms, edema, redness, and hemorrhage. Drug-related adverse events were evaluated. The endoscopic erosion improvement rate was significantly higher in the 75 mg CKD-495 group than in the other groups in both the full analysis set (73% vs. 41%, 45%, 52%, 48% for the 75 mg CKD-495, 150 mg CKD-495, placebo, 60 mg Stillen, and 100 mg rebamipide groups, respectively) and the per-protocol set (PPS) (75% vs. 37%, 45%, 51%, 50%). The cure rate of gastric erosion was significantly higher in the 75 mg CKD-495 group than in the other groups. The improvement rates of hemorrhage erosion were significantly higher in the 150-mg CKD-495 group. No significant differences were observed in the safety profiles. No serious adverse events or drug reactions were observed. These results demonstrate that 75 mg of CKD-495 has excellent efficacy for the treatment of endoscopic and symptomatic improvements for acute and chronic gastritis. Trial Registration: ClinicalTrials.gov identifier: NCT03437785.
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Affiliation(s)
- Su Hyun Park
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Oh Young Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University College of Medicine, Daegu, Republic of Korea
| | - Jong Jae Park
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Republic of Korea
| | - Geun Am Song
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea
| | - Hyunsoo Jung
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sung Kook Kim
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Tae Nyeun Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Suck-Chei Choi
- Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, Jeollabuk-do, Republic of Korea
| | - Sam Ryong Jee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
| | - Jong Sun Rew
- Department of Internal Medicine, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Soo Teik Lee
- Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea
| | - Eun Kwang Choi
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University, Chuncheon, Republic of Korea
| | - Shin Jung Park
- Chong Kun Dang Research Institute, Chong Kun Dang Pharmaceutical Corporation, Seoul, Republic of Korea
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Lv M, Huang KY, Wang XK, Wang YX, Qiao XY, Che H, Lv L, Wang FY. Comparative Analysis of Gastroesophageal Reflux Disease Animal Model Methods: A Data Mining of the Past Decade. Dig Dis Sci 2025:10.1007/s10620-025-09022-x. [PMID: 40167947 DOI: 10.1007/s10620-025-09022-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 03/26/2025] [Indexed: 04/02/2025]
Abstract
PURPOSE The differences in the animal model construction of different subtypes of gastroesophageal reflux disease (GERD) have not been clearly demonstrated at present. We aim to reveal the characteristics and differences between them. METHODS The literature related to GERD animal model construction in the past decade was searched and data on animal strains, modeling modes, modeling cycles, and detection indices were extracted, and the results were presented by using descriptive statistical methods of frequency and relative frequency. RESULTS 88 papers finally met the criteria. Sprague-Dawley (68.25%) rats were most often used to induce reflux esophagitis (RE), whereas Swiss mice (50.00%) and C57BL/6 mice (57.89%) for non-erosive reflux disease (NERD) and Barrett's esophagus (BE), respectively. RE and NERD were most frequently constructed using fore-stomach-glandular transition ligation together with pyloric insufficiency (37.68%, 50.00%), yet their median modeling cycles were 14 and 7 days, respectively. BE was most frequently constructed using L2-IL-1β transgenic mice (27.27%), and the median modeling cycle over 270 days. Determining esophageal mucosal permeability was common in NERD, while finding intestinal chemotaxis markers, squamous epithelium, and columnar epithelium was common in BE. In animal models of RE, researchers tended to look for markers associated with the inflammatory response and oxidative stress. CONCLUSIONS The induction methods vary among the animal models of GERD's three subtypes. Inflammatory stimulation is crucial for inducing RE and BE, differing in modeling cycle. In contrast, Visceral hypersensitivity draws more attention in NERD animal models, reflecting researchers' thoughts on distinct pathogenesis.
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Affiliation(s)
- Mi Lv
- Xiyuan Hospital, China Academy of Traditional Chinese Medicine, No. 1 Xiyuan Playground, Haidian District, Beijing, 100091, China
| | - Kai-Yue Huang
- Xiyuan Hospital, China Academy of Traditional Chinese Medicine, No. 1 Xiyuan Playground, Haidian District, Beijing, 100091, China
| | - Xiao-Kang Wang
- Xiyuan Hospital, China Academy of Traditional Chinese Medicine, No. 1 Xiyuan Playground, Haidian District, Beijing, 100091, China
| | - Yu-Xi Wang
- Beijing University of Chinese Medicine, Beisanhuan East Road, Chaoyang District, Beijing, 100029, China
| | - Xi-Yun Qiao
- Xiyuan Hospital, China Academy of Traditional Chinese Medicine, No. 1 Xiyuan Playground, Haidian District, Beijing, 100091, China
| | - Hui Che
- Xiyuan Hospital, China Academy of Traditional Chinese Medicine, No. 1 Xiyuan Playground, Haidian District, Beijing, 100091, China
| | - Lin Lv
- Xiyuan Hospital, China Academy of Traditional Chinese Medicine, No. 1 Xiyuan Playground, Haidian District, Beijing, 100091, China
| | - Feng-Yun Wang
- Xiyuan Hospital, China Academy of Traditional Chinese Medicine, No. 1 Xiyuan Playground, Haidian District, Beijing, 100091, China.
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Komolafe K, Komolafe TR, Crown OO, Ajiboye B, Noubissi F, Ogungbe IV, Graham B. Natural Products in the Management of Gastroesophageal Reflux Disease: Mechanisms, Efficacy, and Future Directions. Nutrients 2025; 17:1069. [PMID: 40292509 PMCID: PMC11944625 DOI: 10.3390/nu17061069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/08/2025] [Accepted: 03/16/2025] [Indexed: 04/30/2025] Open
Abstract
Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder that is defined by the reflux of gastric contents into the esophagus, and it results in symptoms such as esophageal inflammation, regurgitation, and indigestion. Although proton pump inhibitors (PPIs) and histamine-2 receptor antagonists are frequently employed to treat GERD, their prolonged administration is associated with adverse effects, necessitating the development of alternative therapeutic strategies. Natural products are now recognized as promising candidates for the management of GERD due to their bioactive compounds, which possess antioxidant, anti-inflammatory, and mucosal-protective properties. The potential of natural products in the treatment of GERD is comprehensively examined in this review, with a focus on their mechanisms of action, which include acid suppression, esophageal mucosal regeneration, anti-inflammatory activity, and gut microbiota modulation. Also, the efficacy and safety of key natural products, including flavonoids, polyphenols, plant-derived oils, herbal extracts, probiotics, and dietary components, in preclinical and clinical studies, are assessed. Additionally, this review addresses the barriers confronting the translation of natural therapies into clinical practice, such as regulatory obstacles, variability in bioavailability, and the need for dosage standardization. The integration of natural products into the management of GERD has the potential to enhance conventional therapies, providing a more comprehensive and secure approach for patients.
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Affiliation(s)
- Kayode Komolafe
- Environmental Science PhD Program, Jackson State University, Jackson, MS 39217, USA
| | - Titilope Ruth Komolafe
- Environmental Science PhD Program, Jackson State University, Jackson, MS 39217, USA
- Department of Biology, Jackson State University, Jackson, MS 39217, USA
| | - Olamide Olajusi Crown
- Chemistry and Biotechnology Science and Engineering Programs, The University of Alabama in Huntsville, Huntsville, AL 35899, USA
| | - Basiru Ajiboye
- Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye Ekiti, Oye Ekiti 370112, Nigeria
| | - Felicite Noubissi
- Department of Biology, Jackson State University, Jackson, MS 39217, USA
| | - Ifedayo Victor Ogungbe
- Chemistry and Biotechnology Science and Engineering Programs, The University of Alabama in Huntsville, Huntsville, AL 35899, USA
| | - Barbara Graham
- Environmental Science PhD Program, Jackson State University, Jackson, MS 39217, USA
- Department of Biology, Jackson State University, Jackson, MS 39217, USA
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El Shikieri A, Eltahir Z, Aman A, Alhadramy M. Associations of Plant-Based Foods, Animal Products, and Selected Sociodemographic Factors with Gastroesophageal Reflux Disease Risk. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2024; 21:1696. [PMID: 39767535 PMCID: PMC11728439 DOI: 10.3390/ijerph21121696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/04/2024] [Accepted: 12/16/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND Diet influences the symptoms of gastroesophageal reflux disease (GERD). Plant-based diets rich in vegetables, fruits, legumes, seeds, and nuts may reduce inflammation and improve gut health, while high-fat foods may worsen symptoms. OBJECTIVE We examined the association between plant-based and animal-based foods, selected demographic characteristics, and the likelihood of GERD in Al Madinah Al Munawarah, Saudi Arabia. METHOD A cross-sectional study using the GerdQ tool assessed the GERD likelihood among 303 adults. Dietary diversity scores were used to assess the quality of their diet. quality. RESULTS The participants were predominantly women (68.6%) and had low education levels (88.4%). Cereals were the most consumed plant-based foods, while vitamin A-rich fruits and vegetables were the least consumed. There was significant variation in the consumption of legumes, nuts, seeds, and milk and milk products among the GERD groups. The participants with a 50% GERD likelihood had the highest consumption (34.5%), followed by the 89% likelihood group (21.4%) and the 79% likelihood group (14.5%). The lowest consumption of milk and milk products was among those with an 89% GERD likelihood who also consumed more organ meat. In addition, GERD likelihood was inversely associated with age (r = -0.153; p = 0.008). The likelihood of GERD was negatively correlated with the intake of legumes, nuts, and seeds (r = -0.163; p = 0.005). Furthermore, the intake of cereals and tubers (r = 0.114; p = 0.047) and legumes, nuts, and seeds (r = 0.231; p = 0.0001) increased significantly with education. CONCLUSION GERD prevention programs should target women, those with a low education level, and individuals consuming fewer plant-based foods and more organ meats.
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Affiliation(s)
- Ahlam El Shikieri
- Department of Clinical Nutrition, College of Applied Medical Sciences, Taibah University, Al Madinah Al Munawarah 42313, Saudi Arabia
| | - Zakaria Eltahir
- Department of Clinical Laboratories, College of Applied Medical Sciences, Taibah University, Al Madinah Al Munawarah 42313, Saudi Arabia;
| | - Abdulmannan Aman
- University Medical Center, Faculty of Medicine, Taibah University, Al Madinah Al Munawarah 42313, Saudi Arabia;
| | - Mohamad Alhadramy
- Charitable Medical Care Society, Al Madinah Al Munawarah 42313, Saudi Arabia;
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Paulrasu K, Caspa Gokulan R, El-Rifai W, Chen Z, Que J, Wang TC, Boutaud OG, Briegel K, Dikalov SI, Garcia-Buitrago MT, Zaika AI. Chronic Gastroesophageal Reflux Dysregulates Proteostasis in Esophageal Epithelial Cells. Cell Mol Gastroenterol Hepatol 2024; 19:101434. [PMID: 39637942 PMCID: PMC11786911 DOI: 10.1016/j.jcmgh.2024.101434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND & AIMS Gastroesophageal reflux disease (GERD) is a common digestive disorder that is characterized by esophageal tissue damage produced by exposure of the esophageal lining to the gastric refluxate. GERD can raise the risk of multiple serious complications including esophageal tumors. At the molecular levels, GERD-affected tissues are characterized by strong oxidative stress and the formation of reactive isolevuglandins (isoLGs). These products of lipid peroxidation rapidly interact with cellular proteins forming protein adducts. Here, we investigated the interrelationship between isoLG adduction and aggregation of cellular proteins. METHODS Protein misfolding and aggregation were analyzed using multiple protein misfolding and aggregation assays. Pathologic consequences of protein adduction and aggregation were studied using human and murine esophageal tissues. Surgical model of esophageal reflux injury and L2-IL1β transgenic mice were used to investigate the mechanisms of protein misfolding and aggregation. RESULTS Our studies demonstrate that gastroesophageal reflux causes protein misfolding and aggregation that is associated with severity of GERD. Dysregulation of proteostasis induces ferroptotic cell death and is mediated by modification of cellular proteins with reactive isoLGs that can be prevented by isoLG scavengers. CONCLUSIONS GERD causes dysregulation of cellular proteostasis, accumulation of isoLG protein adducts, misfolded, and aggregated proteins that promote ferroptotic cell death. Taken together, this study suggests that GERD has similarities to other known pathologic conditions that are characterized by protein misfolding and aggregation.
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Affiliation(s)
| | - Ravindran Caspa Gokulan
- Department of Surgery, University of Miami, Miami, Florida; Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida
| | - Wael El-Rifai
- Department of Surgery, University of Miami, Miami, Florida
| | - Zhibin Chen
- Department of Microbiology and Immunology, University of Miami, Miami, Florida
| | - Jianwen Que
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Timothy C Wang
- Department of Medicine, Columbia University Medical Center, New York, New York
| | - Olivier G Boutaud
- Department of Pharmacology, Vanderbilt University, Nashville, Tennessee
| | | | - Sergey I Dikalov
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | | | - Alexander I Zaika
- Department of Surgery, University of Miami, Miami, Florida; Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida; Department of Veterans Affairs, Miami VA Healthcare System, Miami, Florida.
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Wu Y, Hussain SA, Luo M. Columbianadin ameliorates experimental acute reflux esophagitis in rats via suppression of NF-κB pathway. Acta Cir Bras 2024; 39:e391824. [PMID: 38716957 PMCID: PMC11068366 DOI: 10.1590/acb391824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 02/05/2024] [Indexed: 05/12/2024] Open
Abstract
PURPOSE Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents into the esophagus. Columbianadin is a coumarin derivative that exhibits anti-inflammatory and antioxidant effects. In this study, we tried to scrutinize the protective effect of Columbianadin against acute reflux esophagitis in rats. METHODS RAW 264.7 cells were utilized to assess cell viability and measure the production of inflammatory parameters. The rats received anesthesia, and reflux esophagitis was induced via ligation of pylorus and fore stomach and corpus junction. Rats received the oral administration of Columbianadin (25, 50 and 100 mg/kg) and omeprazole (20 mg/kg). The gastric secretion volume, acidity, and pH were measured. Additionally, the levels of oxidative stress parameters, cytokines, and inflammatory markers were determined. At the end of the study, mRNA expression was assessed. RESULTS Columbianadin remarkably suppressed the cell viability and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin (PGE2). Columbianadin treatment remarkably suppressed the secretion of gastric volume, total acidity and enhanced the pH level in the stomach. Columbianadin remarkably altered the level of hydrogen peroxidase, free iron, calcium, and plasma scavenging activity, sulfhydryl group; oxidative stress parameters like malonaldehyde, glutathione, superoxide dismutase, catalase, glutathione peroxidase; inflammatory cytokines viz., TNF-α, IL-6, IL-1β, IL-10, IL-17, and monocyte chemoattractant protein-1; inflammatory parameters including PGE2, iNOS, COX-2, and nuclear kappa B factor (NF-κB). Columbianadin remarkably (P < 0.001) suppressed the mRNA expression TNF-α, IL-6, IL-1β and plasminogen activator inhibitor-1. CONCLUSIONS Columbianadin demonstrated a protective effect against acute reflux esophagitis via NF-κB pathway.
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Affiliation(s)
- Ying Wu
- The Second People’s Hospital of Shaanxi Province – Department of Gastroenterology – Xi ‘an, China
| | - Shaik Althaf Hussain
- King Saud University – College of Science – Department of Zoology – Riyadh, Saudi Arabia
| | - Minghai Luo
- Ankang City Central Hospital – Department of Pediatric – AnKang, China
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Hong Y, He S, Zou Q, Li C, Wang J, Chen R. Eupatilin alleviates inflammatory response after subarachnoid hemorrhage by inhibition of TLR4/MyD88/NF-κB axis. J Biochem Mol Toxicol 2023; 37:e23317. [PMID: 36872850 DOI: 10.1002/jbt.23317] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 10/28/2022] [Accepted: 02/02/2023] [Indexed: 03/07/2023]
Abstract
Early brain injury (EBI) is associated with the adverse prognosis of subarachnoid hemorrhage (SAH) patients. The key bioactive component of the Chinese herbal medicine Artemisia asiatica Nakai (Asteraceae) is eupatilin. Recent research reports that eupatilin suppresses inflammatory responses induced by intracranial hemorrhage. This work is performed to validate whether eupatilin can attenuate EBI and deciphers its mechanism. A SAH rat model was established by intravascular perforation in vivo. At 6 h after SAH in rats, 10 mg/kg eupatilin was injected into the rats via the caudal vein. A Sham group was set as the control. In vitro, BV2 microglia was treated with 10 μM Oxyhemoglobin (OxyHb) for 24 h, followed by 50 μM eupatilin treatment for 24 h. The SAH grade, brain water content, neurological score, and blood-brain barrier (BBB) permeability of the rats were measured 24 h later. The content of proinflammatory factors was detected via enzyme-linked immunosorbent assay. Western blot analysis was conducted to analyze the expression levels of TLR4/MyD88/NF-κB pathway-associated proteins. In vivo, eupatilin administration alleviated neurological injury, and decreased brain edema and BBB injury after SAH in rats. Eupatilin markedly reduced the levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), and suppressed the expression levels of MyD88, TLR4, and p-NF-κB p65 in the SAH rats' cerebral tissues. Eupatilin treatment also reduced the levels of IL-1β, IL-6, and TNF-α, and repressed the expression levels of MyD88, TLR4, and p-NF-κB p65 in OxyHb-induced BV2 microglia. Additionally, pyrrolidine dithiocarbamate or resatorvid enhanced the suppressive effects of eupatilin on OxyHb-induced inflammatory responses in BV2 microglia. Eupatilin ameliorates SAH-induced EBI via modulating the TLR4/MyD88/NF-κB pathway in rat model.
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Affiliation(s)
- Yu Hong
- Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Shiqing He
- Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Qin Zou
- Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Chong Li
- Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jianpeng Wang
- Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Rui Chen
- Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
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Beigrezaei S, Sasanfar B, Nafei Z, Behniafard N, Aflatoonian M, Salehi-Abargouei A. Dietary approaches to stop hypertension (DASH)-style diet in association with gastroesophageal reflux disease in adolescents. BMC Public Health 2023; 23:358. [PMID: 36803489 PMCID: PMC9936743 DOI: 10.1186/s12889-023-15225-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 02/06/2023] [Indexed: 02/19/2023] Open
Abstract
BACKGROUND Dietary patterns and food items have been associated with gastroesophageal reflux disease (GERD) risk and they have led to conflicting findings. The aim of this study was to determine the association between a dietary approach to stop hypertension (DASH)-style diet with the risk of GERD and its symptoms in adolescents. STUDY DESIGN Cross-sectional. METHODS This study was performed on 5,141 adolescents aged between 13 and 14 years. Dietary intake was evaluated using a food frequency method. The diagnosis of GERD was done by using a six-item GERD questionnaire that asked about GERD symptoms. A binary logistic regression was used to assess the association between the DASH-style diet score and GERD and its symptoms in crude and multivariable-adjusted models. RESULTS Our findings revealed that after adjustment for all confounding variables, the adolescents with the highest adherence to the DASH-style diet had a lower chance of developing GERD [odds ratio (OR) = 0.50; 95%CI 0.33-0.75, Ptrend< 0.001)], reflux (OR = 0.42; 95%CI 0.25-0.71, Ptrend=0.001), nausea (OR = 0.59; 95% CI:0.32-1.08, Ptrend=0.05) and stomach pain (OR = 0.69; 95%CI 0.49-0.98, P trend=0.03) compared to those with the lowest adherence. Similar results were found for odds of GERD among boys, and the total population (OR = 0.37; 95%CI: 0.18-0.73, Ptrend=0.002, OR = 0.51; 95%CI: 0.34-0.77, P trend<0.0, respectively). CONCLUSION The current study revealed that adherence to a DASH-style diet might protect against GERD and its symptoms including, reflux, nausea, and stomach pain in adolescents. Further prospective research is needed to confirm these findings.
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Affiliation(s)
- Sara Beigrezaei
- grid.412505.70000 0004 0612 5912Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,grid.412505.70000 0004 0612 5912Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Bahareh Sasanfar
- grid.412505.70000 0004 0612 5912Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,grid.412505.70000 0004 0612 5912Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zahra Nafei
- grid.412505.70000 0004 0612 5912Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nasrin Behniafard
- grid.412505.70000 0004 0612 5912Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,grid.412505.70000 0004 0612 5912Mother and Newborn Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Majid Aflatoonian
- Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
| | - Amin Salehi-Abargouei
- grid.412505.70000 0004 0612 5912Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,grid.412505.70000 0004 0612 5912Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran ,grid.412505.70000 0004 0612 5912Yazd Cardiovascular Research Center, Non-communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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N-3 polyunsaturated fatty acids protect esophageal epithelial cells from acid exposure. Food Res Int 2022; 162:111943. [DOI: 10.1016/j.foodres.2022.111943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 06/20/2022] [Accepted: 09/12/2022] [Indexed: 11/18/2022]
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Scutellariae Radix and Citri Reticulatae Pericarpium Mixture Regulate PPAR γ/RXR Signaling in Reflux Esophagitis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:6969241. [PMID: 35027935 PMCID: PMC8752236 DOI: 10.1155/2022/6969241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 12/23/2021] [Indexed: 12/31/2022]
Abstract
Objective Gastroesophageal reflux disease (GERD) is a gastrointestinal disorder in which stomach contents reflux into the esophagus, causing complications such as mucosal damage. GERD is a very common disease and is on the rise worldwide. The aim of this study was to assess the impact of a Scutellariae Radix and Citri Reticulatae Pericarpium mixture (SC) on esophageal mucosal injury in rats with chronic acid reflux esophagitis (CARE). Methods After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks: normal rats (Normal, n = 8), CARE-induced rats were treated with distilled water (Control, n = 8), CARE-induced rats were treated with vitamin E 30 mg/kg body weight (VitE, n = 8), CARE-induced rats were treated with SC 100 mg/kg body weight (SC100, n = 8), and CARE-induced rats were treated with SC 200 mg/kg body weight (SC200, n = 8). Results SC treatment significantly reduced the degree of esophageal mucosal damage, significantly reduced levels of MDA and MPO, and inhibited the activation of the NF-κB inflammatory pathway by activating the PPARγ/RXR pathway. In addition, SC treatment significantly regulated the expression of arachidonic acid-related proteins (COX-1, COX-2, and PGE2) and modulated the MMP/TIMP proteins in reflux esophagitis. Conclusion Consequently, SC improved the damage to the esophageal mucosa. Also, the anti-inflammatory effects of the SC suggested the inhibition of NF-κB pathway through the activation of the PPARγ/RXR pathway, thereby reducing the expression of inflammation-related cytokines.
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Imro'ati TA, Sugihartono T, Widodo B, Nefertiti EP, Rovian I, Nyoman Wibawa IG. The Relationship between Serum Total Oxidant Status, Total Antioxidant Status, and Oxidative Stress Index with Severity Levels of Gastroesophageal Reflux Disease: A Literature Review. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2021.7346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Gastroesophageal reflux disease (GERD) is a global health problem in which the prevalence is increasing over periods. This disease is a significant cause of disorders in the upper gastrointestinal tract with very complex pathogenesis. Oxidative stress (OS) due to gastric acid reflux plays a role in the inflammatory response of the esophageal epithelium. Several OS markers have been widely studied and are thought to affect the severity degree of the esophageal mucosa. However, there has been no research on total oxidant status (TOS), total antioxidant status (TAS), and OS index (OSI) in the adult with GERD; hence the aim of this review was to determine the association between TOS, serum TAS, and OSI with the GERD degree. A literature review was conducted by searching articles related to the TOS, TAS, OSI, and its correlation with GERD degree on an online database, particularly Pubmed and Google scholar. We conclude that TAS and OSI might influence the severity of GERD; however, further clinical study is needed to prove this theory.
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Kim JH, Shin CY, Jang SW, Kim DS, Lee W, Kim HG, Kim HR. Anti-inflammatory effects of DA-9601, an extract of Artemisia asiatica, on aceclofenac-induced acute enteritis. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2021; 25:439-448. [PMID: 34448461 PMCID: PMC8405443 DOI: 10.4196/kjpp.2021.25.5.439] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/16/2021] [Accepted: 05/06/2021] [Indexed: 11/15/2022]
Abstract
DA-9601 is an extract obtained from Artemisia asiatica, which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet. Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4+ T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of IL-6, IL-17, and TNF-α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GM-CSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ+ Th1 cells, IL-4+ Th2 cells, IL-9+ Th9 cells, IL-17+ Th17 cells, and Foxp3+ Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.
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Affiliation(s)
- Ju Hwan Kim
- Department of Pharmacology, College of Medicine, Dankook University, Cheonan 31116, Korea
| | - Chang Yell Shin
- Research Institute of Dong-A ST Co., Ltd., Yongin 17073, Korea
| | - Sun Woo Jang
- Research Institute of Dong-A ST Co., Ltd., Yongin 17073, Korea
| | - Dong-Seok Kim
- Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul 06974, Korea
| | - Wonae Lee
- Department of Pathology, College of Medicine, Dankook University, Cheonan 31116, Korea
| | - Hyung-Gun Kim
- Department of Pharmacology, College of Medicine, Dankook University, Cheonan 31116, Korea.,NeuroVis Inc., Cheonan 31035, Korea
| | - Hak Rim Kim
- Department of Pharmacology, College of Medicine, Dankook University, Cheonan 31116, Korea
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Wenzl EM, Riedl R, Borenich A, Petritsch W, Wenzl HH. Low prevalence of gastroesophageal reflux symptoms in vegetarians. Indian J Gastroenterol 2021; 40:154-161. [PMID: 33846945 DOI: 10.1007/s12664-021-01156-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 02/01/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Dietary modification could reduce the risk of gastroesophageal reflux disease. Circumstantial evidence suggests that gastroesophageal reflux is less prevalent in people adhering to a vegetarian diet. We aimed to study the relationship between vegetarianism and the occurrence of gastroesophageal reflux symptoms (GERS). METHODS This study compares the prevalence of GERS in vegetarians with non-vegetarian controls from the general population. Frequency and severity of GERS (heartburn and/or acid regurgitation) were assessed with a self-administrated questionnaire. RESULTS Within 1 year, any GERS were experienced by 19 of 100 (19%) vegetarians and by 98 of 250 (39.2%) non-vegetarian controls (p < 0.001). Frequent GERS, defined as GERS on at least 1 day per week, were noted in 3% of vegetarians and in 12.8% of controls (p = 0.006). Reflux symptoms were significantly less severe in vegetarians than in non-vegetarians (p < 0.001). According to multivariable analysis, independent predictors of GERS included male sex, current smoking, BMI ≥ 25 (odds ratio [OR] = 1.94; 95% confidence interval [CI], 1.14-3.31), and a non-vegetarian diet (OR = 2.19; 95% CI, 1.20-3.97); non-vegetarian diet independently predicted frequent GERS (OR 4.03; 95% CI, 1.17-13.9). An increased risk of GERS (OR = 2.17; 95% CI, 1.09-4.29) and frequent GERS (OR 4.00; 95% CI, 1.13-14.18) in non-vegetarians were also demonstrated by logistic regression of matched data. In non-vegetarians, the risk of reflux symptoms was not significantly related to meat intake. CONCLUSIONS The prevalence and severity of GERS are lower in vegetarians than in non-vegetarians from the general population. The results are in line with a mitigating effect of vegetarianism on GERS. Data must be interpreted with caution given the retrospective study design and the small sample size.
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Affiliation(s)
| | - Regina Riedl
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Andrea Borenich
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Wolfgang Petritsch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Heimo H Wenzl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
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14
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Cho JH, Yoon H, Shin CM, Park YS, Kim N, Lee DH. Efficacy of DA-5204 (Stillen 2X) for patients with gastroesophageal reflux disease: A randomized, double-blind, placebo-controlled pilot study. Medicine (Baltimore) 2020; 99:e22729. [PMID: 33126310 PMCID: PMC7598846 DOI: 10.1097/md.0000000000022729] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND/AIM Proton pump inhibitor (PPI) alone is not satisfactory for the treatment of gastroesophageal reflux disease (GERD). Therefore, we investigated the efficacy of DA-5204 (Stillen 2X, 90 mg of Artemisia asiatica 95% ethanol extract per tablet) and PPI combination therapy on GERD in comparison to PPI alone. METHODS This randomized, double-blind, placebo-controlled study randomly assigned 70 patients with endoscopically proven esophageal mucosal injury (Los Angeles classification grade A or B) into 2 groups: pantoprazole 40 mg once daily with DA-5204 twice daily (DA-5204 group) or pantoprazole 40 mg once daily with placebo twice daily (placebo group) for 4 weeks. The primary endpoint was endoscopic healing rate. The secondary endpoint was sufficient relief (≥50% reduction) of symptoms using GERD Questionnaire. RESULTS Final analyses included 29 patients with the DA-5204 group and 30 patients with the placebo group. At weeks 4, there was no significant difference in the endoscopic healing rate between the 2 groups (DA-5204 vs placebo; 96.6% vs 93.3%; P = 1.000). However, the rate of residual minimal change was significantly lower in the DA-5204 group (5/28, 17.9%) than in the placebo group (17/28, 60.7%) (P < .001). The rates of symptom relief were not different between the DA-5204 group and the placebo group (all P > .05). CONCLUSION Combined therapy with PPI and DA-5204 has no additional effect on the endoscopic healing rate compared to PPI alone. However, it may be beneficial in resolving minimal change.
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Improvement of Inflammation through Antioxidant Pathway of Gardeniae Fructus 50% EtOH Extract (GE) from Acute Reflux Esophagitis Rats. BIOMED RESEARCH INTERNATIONAL 2020; 2020:4826176. [PMID: 32185206 PMCID: PMC7060875 DOI: 10.1155/2020/4826176] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 01/19/2020] [Accepted: 01/21/2020] [Indexed: 02/06/2023]
Abstract
Gardeniae Fructus 50% EtOH extract (GE) is a traditional herb that has been used to treat a variety of diseases. In this study, we investigate the antioxidant, anti-inflammatory, and antiapoptotic properties of GE on acute reflux-induced esophagitis (RE) model in rats. 2,2′-Azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays were performed to determine the antioxidant activity of GE. GE was given orally at 50 and 100 mg/kg body weight 1h 30 min prior to RE induction. And its effect was assessed in comparison with RE control and normal groups. The administration of the extract of the GE showed remarkable protection of mucosal damage in esophageal tissue, and the histologic observation showed that the gastric lesion was improved. Increased reactive oxygen species (ROS) levels in the serum were diminished by GE treatment. The antioxidative biomarkers including nuclear factor-erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) were significantly increased. GE administration significantly reduced the inflammatory protein expression through MAPK-related signaling pathways and the nuclear factor-kappa B (NF-κB) pathway. These results suggest that GE protects the esophagus mucosal membrane by attenuating oxidative stress and inflammatory response under reflux esophagitis condition through the antioxidant pathway. Therefore, it is suggested that GE may be a potential remedy for the treatment of reflux esophagitis.
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Xue J, Xin H, Ren N, Zhou C, Yang J, Song L, Qin S. Nonalcoholic fatty liver disease increases the risk of gastroesophageal reflux disease: A systematic review and meta-analysis. Eur J Clin Invest 2019; 49:e13158. [PMID: 31338830 DOI: 10.1111/eci.13158] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 04/07/2019] [Accepted: 07/19/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Increasing evidence indicates that nonalcoholic fatty liver disease (NAFLD) is linked to an increased risk of extra-hepatic conditions. However, it is currently uncertain whether NAFLD is associated with the risk of gastroesophageal reflux disease (GERD). We performed a systematic review and meta-analysis of relevant studies to examine the association between NAFLD and the risk of GERD. METHODS We searched PubMed, Scopus, Embase and Web of Science from 1 January 1975 to 15 December 2018, using predefined terms to identify cross-sectional, case-control and cohort studies investigating the association between NAFLD and GERD. RESULTS Nine observational studies involving 185 118 subjects were eligible for inclusion in the meta-analysis. Overall, NAFLD was significantly associated with an increased risk of GERD (random effect OR 1.28; 95% CI: 1.12-1.44, I2 = 82%). Moreover, the significant association between NAFLD and GERD was consistent both for studies with adjusted OR/HR (n = 6, random effect OR = 1.16, 95% CI: 1.03-1.30) and those with unadjusted OR/HR (n = 3, random effect OR = 2.09, 95% CI: 1.62-2.56) as measures of effect. Both funnel plot and Egger's test suggested the existence of publication bias. However, a sensitivity analysis by sequentially omitting each study did not alter the pooled outcome,suggesting the robustness of the association. CONCLUSION NAFLD is associated with an increased risk of GERD. However, future large and cohort studies are still needed to determine the causal relationship between NAFLD and the risk of GERD.
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Affiliation(s)
- Jinru Xue
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Hua Xin
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Na Ren
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Changyu Zhou
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jinghui Yang
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Lina Song
- Department of Laboratory Medicine Center, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Shaoyou Qin
- Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, China
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Balusamy SR, Ramani S, Natarajan S, Kim YJ, Perumalsamy H. Integrated transcriptome and in vitro analysis revealed anti-proliferative effect of citral in human stomach cancer through apoptosis. Sci Rep 2019; 9:4883. [PMID: 30890753 PMCID: PMC6425008 DOI: 10.1038/s41598-019-41406-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 03/05/2019] [Indexed: 12/13/2022] Open
Abstract
Cancer is the second leading cause of death globally, particularly stomach cancer is third most common causes of cancer death worldwide. Citral possesses anti-tumor activity in various cancer cell lines, However its effect toward stomach cancer and its mechanism of action is have yet to be elucidated. The goal of the present study is to elucidate the role of citral in stomach cancer using transcriptome and in vitro approaches. We performed transcriptome analysis using RNA-seq and explored its capability to persuade apoptosis in AGS human stomach cancer cell lines in vitro. Furthermore, the enrichment and KEGG pathway results suggested that there are several genes involved to induce apoptosis pathway. Furthermore, our study also demonstrated that citral arrested colony formation and migration of cancer cells significantly than that of untreated cells. RNA-seq revealed a total of 125 million trimmed reads obtained from both control and citral treated groups respectively. A total number of 612 differentially expressed genes (DEGs) were identified which includes 216 genes up-regulated and 396 genes down-regulated genes after treatment. The enrichment analysis identified DEGs genes from transcriptome libraries including cell death, cell cycle, apoptosis and cell growth. The present study showed the significant inhibition effect upon citral by regulating various genes involved in signaling pathways, inhibits metastasis, colony formation and induced apoptosis both in silico and in vitro.
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Affiliation(s)
- Sri Renukadevi Balusamy
- Department of Food Science and Biotechnology Sejong University, Gwangjin-gu, Seoul, Republic of Korea.
| | - Sivasubramanian Ramani
- Department of Food Science and Biotechnology Sejong University, Gwangjin-gu, Seoul, Republic of Korea
| | | | - Yeon Ju Kim
- Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin, 446- 701, Republic of Korea.
| | - Haribalan Perumalsamy
- Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin, 446- 701, Republic of Korea.
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18
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Park JY, Park DH, Jeon Y, Kim YJ, Lee J, Shin MS, Kang KS, Hwang GS, Kim HY, Yamabe N. Eupatilin inhibits angiogenesis-mediated human hepatocellular metastasis by reducing MMP-2 and VEGF signaling. Bioorg Med Chem Lett 2018; 28:3150-3154. [PMID: 30177376 DOI: 10.1016/j.bmcl.2018.08.034] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 08/23/2018] [Accepted: 08/27/2018] [Indexed: 12/18/2022]
Abstract
Metastasis is responsible for the great majority of deaths in cancer patients. Matrix metalloproteinases (MMPs) have critical functions in cancer metastasis. Especially, MMP-2 and MMP-9 play a major role in tumor-cell migration and invasion. Therefore, to first find out the inhibitory effect of eupatilin on expression of MMPs in SNU182 cells, we used quantitative real-rime PCR to measure MMP-2 and MMP-9 mRNA levels. Eupatilin suppressed transcription of MMP-2 in SNU182 cells more than did the corresponding controls. Also, eupatilin significantly blocked tube formation when treated with a concentration of 3.125 or 6.25 μg/mL on human umbilical vein vascular endothelial cells (HUVECs). Eupatilin induced significant anti-angiogenic potential associated with down-regulation of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated Akt expression. Thus, tube-formation inhibition and MMP-2-mediated migration are likely to be important therapeutic targets of eupatilin in hepatocellular carcinoma metastasis.
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Affiliation(s)
- Jun Yeon Park
- Department of Food Science and Biotechnology, Kyonggi University, Suwon 16227, Republic of Korea
| | - Do Hwi Park
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea
| | - Youngsic Jeon
- Department of Pathology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Young-Joo Kim
- Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, Republic of Korea
| | - Jaemin Lee
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea
| | - Myoung-Sook Shin
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea
| | - Ki Sung Kang
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea
| | - Gwi Seo Hwang
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea
| | - Hyun Young Kim
- Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 660-758, Republic of Korea.
| | - Noriko Yamabe
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea.
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Kim M, Min YS, Sohn UD. Cytoprotective effect of eupatilin against indomethacin-induced damage in feline esophageal epithelial cells: relevance of HSP27 and HSP70. Arch Pharm Res 2018; 41:1019-1031. [PMID: 30109575 DOI: 10.1007/s12272-018-1066-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 08/10/2018] [Indexed: 12/28/2022]
Abstract
Indomethacin is a non-steroidal anti-inflammatory drug with clearly known side effects on the gastrointestinal tract. The purpose of the present study was to investigate whether eupatilin inhibit cell injury induced by indomethacin in cultured feline esophageal epithelial cells (EECs). EECs were used to investigate the ability of eupatilin to induce the expression of heat shock proteins (HSP27 and HSP70) and analyze its cytoprotective effect against indomethacin-induced damage. The treatment of EECs with indomethacin for 8 h decreased cell viability. Western blot analysis showed that the levels of HSPs gradually decreased in cells treated with indomethacin, while eupatilin treatment increased the levels of HSPs. When treated with both indomethacin and eupatilin, the levels of HSPs increased rapidly, and were maintained at 130-140%. In addition, treatment with the specific inhibitors of PTK, PKC, PLC, p38 MAPK, JNKs, and PI3K attenuated the eupatilin-induced expression of HSPs. Pretreatment of EECs with the inhibitors of protein synthesis, actinomycin D or cycloheximide, attenuated the cytoprotective effect of eupatilin on indomethacin-induced cell damage. Reactive oxygen species production was upregulated by indomethacin, but downregulated by eupatilin. Taken together, it was suggested that HSPs were partly responsible for the eupatilin-mediated cytoprotective activity against the indomethacin-induced damage in EECs.
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Affiliation(s)
- Mina Kim
- Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06911, Republic of Korea
| | - Young Sil Min
- Department of Pharmaceutical Engineering, College of Convergence Science and Technology, Jung Won University, Goesan, Chungcheongbuk-do, 28054, Republic of Korea
| | - Uy Dong Sohn
- Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06911, Republic of Korea.
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Ahuja A, Yi YS, Kim MY, Cho JY. Ethnopharmacological properties of Artemisia asiatica: A comprehensive review. JOURNAL OF ETHNOPHARMACOLOGY 2018; 220:117-128. [PMID: 29604379 DOI: 10.1016/j.jep.2018.03.032] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Revised: 03/24/2018] [Accepted: 03/24/2018] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Artemisia asiatica Nakai (Compositae) has a long history as a traditional remedy. Preparation from various parts of the plant (aerial parts and leaves) are used to treat a wide range of diseases including gastric trouble, liver dysfunction, and skin inflammation. AIMS OF THIS REVIEW The aims of this review were: 1) to provide an overview of recent studies and progress on A. asiatica-derived ethnopharmacological compounds and their pharmacological activities; and 2) to summarize existing evidence and provide insight for future studies. MATERIALS AND METHODS This investigation was carried out by analyzing published books and research papers via scientific databases, namely Science Direct, PubMed ACS Publication, Wiley Online Library, CNKI and information obtained online. The keywords "Artemisia asiatica traditional uses," "Compounds isolated and studied in Artemisia asiatica," and "Pharmacological advances in Artemisia asiatica" were used and articles published between 1995 and 2017 were considered. In total, 500 works related to biological activities of A. asiatica were identified, and only materials published in English were included in the review. RESULTS Comparative analysis of literature searched through sources available confirmed that the ethnopharmacological use of A. asiatica was recorded in Korea, China, and Japan. Phytochemical studies revealed the presence of flavonoids, sesquiterpene lactones, monoterpenes, and steroids in A. asiatica. Of these, flavonoids have been shown to exhibit significant pharmacological effects such as gastroprotective, anti-inflammatory, anti-tumor, and anti-microbial actions. CONCLUSIONS Phytochemical and pharmacological studies of Artemisia asiatica have proven that this plant is one of valuable medicinal sources with neuroprotective, gastroprotective, anti-oxidative, anti-inflammatory, and anti-cancer effects. Although ethanol extract of this plant is now being prescribed as gastroprotective and anti-ulcerative medicine, it is now time to expand its application to other human inflammatory diseases such as pancreatitis and hepatitis and further extensive study on toxicity in human. Therefore, the present review will encourage further studies of A. asiatica in the pursuit of wide range of therapeutic remedy.
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Affiliation(s)
- Akash Ahuja
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Young-Su Yi
- Department of Pharmaceutical Engineering, Cheongju University, Cheongju 28503, Republic of Korea
| | - Mi-Yeon Kim
- School of Systems Biomedical Science, Soongsil University, Seoul 06978, Republic of Korea.
| | - Jae Youl Cho
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
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Effects of Platycodin D on Reflux Esophagitis due to Modulation of Antioxidant Defense Systems. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:7918034. [PMID: 29770154 PMCID: PMC5892306 DOI: 10.1155/2018/7918034] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Revised: 02/11/2018] [Accepted: 02/21/2018] [Indexed: 12/11/2022]
Abstract
Aims The effects of platycodin D (PD) pretreatment were examined in reflux esophagitis (RE) induced rats. Methods Sham, control, and omeprazole (OMP) group were pretreated with distilled water or OMP as a reference, respectively, and PD pretreated groups were given 3 different PD doses once a day for 7 days. One hour after last pretreatment, RE was induced by ligation of the forestomach and pylorus. At 8 h after operation, all animals were sacrificed. Results PD showed significant dose-dependent reduction of gastric secretion, myeloperoxidase activity, and RE lesion areas of esophagus and stomach mucosa. There was a reduction of lipid peroxidation in 2 doses of PD groups and elevation of antioxidant enzyme activity in all PD groups. Gastric hexose and sialic acid were significantly increased in PD groups, while collagen was reduced. Plasma histamine levels were significantly reduced in all PD groups, but not in the OMP group. Total invasive lesion sizes of esophagus and gastric fundus were significantly decreased in all PD groups. Thicknesses in esophagus of all PD groups were significantly decreased and thicknesses of funds were significantly increased except lowest PD dose. Conclusions Therapeutic effects of PD on the esophageal and gastric lesions were shown in RE induced rats dose-dependently. The PD pretreatment had significant antioxidant effects with regulation of histamine levels. This study provides useful information regarding the effectiveness of the drug for RE and further novel drug discovery using natural herbal products.
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Kim JI, Park SW, Lim JJ, Sohn SI, Shin JS, Park SC, Jang YP, Chung EK, Lee HW, Lee KT. Gastroprotective effects of the isopropanol extract of Artemisia princeps and its gastroretentive floating tablets on gastric mucosal injury. ACTA PHARMACEUTICA (ZAGREB, CROATIA) 2017; 67:479-494. [PMID: 29337669 DOI: 10.1515/acph-2017-0037] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 09/28/2017] [Indexed: 02/07/2023]
Abstract
In this study, we investigated the gastroprotective effect of an isopropanol extract from the aerial parts of Artemisia princeps (IPAP) and developed a gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on medium surface with more sustained eupatilin release compared to the non-floating control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared to the non-floating control tablet. Based on these data, our data suggest that IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.
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Affiliation(s)
- Joo-Il Kim
- Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro Dongdaemun-gu, Seoul , 02447, Korea Republic of
- Central Research Institute, Daewon Pharmaceutical Company, 520 Cheonho-daero, Gwangjin-gu, Seoul Republic of Korea
| | - Sang-Wook Park
- Central Research Institute, Daewon Pharmaceutical Company, 520 Cheonho-daero, Gwangjin-gu, Seoul Republic of Korea
- Interdisciplinary Program in Agricultural Biotechnology College of Agriculture and Life Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul , 08826 Korea Republic of
| | - Jhong-Jae Lim
- Central Research Institute, Daewon Pharmaceutical Company, 520 Cheonho-daero, Gwangjin-gu, Seoul Republic of Korea
| | - Se-Il Sohn
- Central Research Institute, Daewon Pharmaceutical Company, 520 Cheonho-daero, Gwangjin-gu, Seoul Republic of Korea
| | - Ji-Su Shin
- Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro Dongdaemun-gu, Seoul , 02447, Korea Republic of
| | - Sang Cheol Park
- Department of Life and Nanopharmaceutical Science College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul , 02447, Korea Republic of
- Department of Oriental Pharmaceutical Sciences College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul , 02447, Korea Republic of
| | - Young Pyo Jang
- Department of Life and Nanopharmaceutical Science College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea 5 Department of Oriental Pharmaceutical Sciences College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul , 02447, Korea Republic of
| | - Eun Kyoung Chung
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu Seoul , 02447, Korea Republic of
| | - Hong-Woo Lee
- Central Research Institute, Daewon Pharmaceutical Company, 520 Cheonho-daero, Gwangjin-gu, Seoul Republic of Korea
| | - Kyung-Tae Lee
- Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro Dongdaemun-gu, Seoul , 02447, Korea Republic of
- Department of Life and Nanopharmaceutical Science College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul , 02447, Korea Republic of
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Yang HJ, Chang Y, Park SK, Jung YS, Park JH, Park DI, Cho YK, Ryu S, Sohn CI. Nonalcoholic Fatty Liver Disease Is Associated with Increased Risk of Reflux Esophagitis. Dig Dis Sci 2017; 62:3605-3613. [PMID: 29063416 DOI: 10.1007/s10620-017-4805-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 10/11/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Reflux esophagitis is associated with obesity and metabolic syndrome; however, the relationship between nonalcoholic fatty liver disease (NAFLD) and reflux esophagitis is unclear. AIM We examined the association between NAFLD and the development of reflux esophagitis. METHODS Our cohort consisted of 117,377 Korean adults without reflux esophagitis at baseline who underwent a health checkup program including upper endoscopy between 2002 and 2014 and were followed annually or biennially until December 2014. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or any other identifiable cause. RESULTS Over 520,843.2 person-years of follow-up, 22,500 participants developed reflux esophagitis (incidence density, 43.2 per 1000 person-years). In models adjusted for age and sex, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for incident reflux esophagitis in subjects with NAFLD compared to those without was 1.16 (1.13-1.20). After further adjustment for confounders of center, year of visit, smoking status, alcohol intake, regular exercise, education level, and body mass index, the association between NAFLD and incident reflux esophagitis was attenuated, but remained significant (aHR 1.06; 95% CI 1.02-1.10). CONCLUSIONS In this large cohort of Korean men and women, participants with NAFLD exhibited increased incidence of reflux esophagitis independent of possible confounders, suggesting that NAFLD contributes to the development of reflux esophagitis.
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Affiliation(s)
- Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Samsung Main Building B2, 67 Sejong-daero, Jung-gu, Seoul, 04514, Korea
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Korea
| | - Soo-Kyung Park
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Korea
| | - Yong Kyun Cho
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Samsung Main Building B2, 67 Sejong-daero, Jung-gu, Seoul, 04514, Korea.
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Korea.
| | - Chong Il Sohn
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Korea.
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Wijarnpreecha K, Panjawatanan P, Thongprayoon C, Jaruvongvanich V, Ungprasert P. Association between gastroesophageal reflux disease and nonalcoholic fatty liver disease: A meta-analysis. Saudi J Gastroenterol 2017; 23:311-317. [PMID: 29205182 PMCID: PMC5738791 DOI: 10.4103/sjg.sjg_161_17] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND/AIM The relationship between gastroesophageal reflux disease (GERD) and nonalcoholic fatty liver disease (NAFLD) has been demonstrated in recent epidemiologic studies although the results were inconsistent. This meta-analysis was conducted to summarize all available data and to estimate the risk of NAFLD among patients with GERD. MATERIALS AND METHODS Comprehensive literature review was conducted using MEDLINE and EMBASE database from inception through November 2016, to identify studies that compared the risk of NAFLD among patients with GERD versus those without GERD. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS Eight studies (four cross-sectional studies and four case-control studies) with 31,322 participants met the eligibility criteria and were included in the meta-analysis. The risk of NAFLD among patients with GERD was significantly higher than those without GERD with the pooled odds ratio of 2.07 (95% confidence interval, 1.54-2.79). The statistical heterogeneity was high with an I2 of 87%. CONCLUSIONS A significantly increased risk of NAFLD among patients with GERD was observed in this meta-analysis.
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Affiliation(s)
- Karn Wijarnpreecha
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York, USA
| | | | - Charat Thongprayoon
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York, USA
| | | | - Patompong Ungprasert
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Division of Rheumatology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok
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Protective effects of ethanol extracts of Artemisia asiatica Nakai ex Pamp. on ageing-induced deterioration in mouse oocyte quality. ZYGOTE 2017. [DOI: 10.1017/s0967199417000296] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
SummaryFollowing ovulation, oocytes undergo a time-dependent deterioration in quality referred to as post-ovulatory ageing. Although various factors influence the post-ovulatory ageing of oocytes, oxidative stress is a key factor involved in deterioration of oocyte quality. Artemisia asiatica Nakai ex Pamp. has been widely used in East Asia as a food ingredient and traditional medicine for the treatment of inflammation, cancer, and microbial infections. Recent studies have shown that A. asiatica exhibits antioxidative effects. In this study, we investigated whether A. asiatica has the potential to attenuate deterioration in oocyte quality during post-ovulatory ageing. Freshly ovulated mouse oocytes were cultured with 0, 50, 100 or 200 μg/ml ethanol extracts of A. asiatica Nakai ex Pamp. After culture for up to 24 h, various ageing-induced oocyte abnormalities, including morphological changes, reactive oxygen species (ROS) accumulation, apoptosis, chromosome and spindle defects, and mitochondrial aggregation were determined. Treatment of oocytes with A. asiatica extracts reduced ageing-induced morphological changes. Moreover, A. asiatica extracts decreased ROS generation and the onset of apoptosis by preventing elevation of the Bax/Bcl-2 expression ratio during post-ovulatory ageing. Furthermore, A. asiatica extracts attenuated the ageing-induced abnormalities including spindle defects, chromosome misalignment and mitochondrial aggregation. Our results demonstrate that A. asiatica can relieve deterioration in oocyte quality and delay the onset of apoptosis during post-ovulatory ageing.
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Salehi M, Karegar-Borzi H, Karimi M, Rahimi R. Medicinal Plants for Management of Gastroesophageal Reflux Disease: A Review of Animal and Human Studies. J Altern Complement Med 2016; 23:82-95. [PMID: 27996295 DOI: 10.1089/acm.2016.0233] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disease that causes troublesome symptoms and/or complications. The major therapeutic strategy for GERD focuses mainly on symptom alleviation using proton pump inhibitors (PPIs), which does not produce a perfect response in all patients. An approach with new therapeutic agents for GERD seems to be essential. The aim of this study was to review animal and human studies investigating the effect of medicinal plants in GERD as well as mechanisms underlying their therapeutic effects. METHODS Medline, Scopus, and Cochrane Central Register of Controlled Trials were searched for animal or human studies. The data collected covered January 1966-October 2015. RESULTS A total of 22 studies were included in this review, of which nine were animal studies and 13 were human studies. Ceratonia siliqua as a medicinal plant and rikkunshito as a multicomponent herbal preparation were the most frequently studied herbal medicines in GERD. Antioxidant and anti-inflammatory activities were the main mechanisms demonstrated in animal studies for ameliorating the effects of medicinal plants in GERD. Other mechanisms include downregulation of genes encoding inflammatory proteins, improvement of barrier function and gastric mucus, a decrease in gastric acid, and induction of tonic contractions of the lower esophageal sphincter. All herbal preparations used in human studies have led to the alleviation of symptoms related to GERD. Myrtus communis and Cydonia oblonga showed marked reduction in GERD symptoms comparable to omeprazole. The therapeutic effect of Cydonia oblonga persisted after discontinuation of the drug. Tongjlang and rikkunshito showed therapeutic effects for non-erosive reflux disease (NERD) where PPIs failed to show a promising effect. Studies on Ceratonia siliqua have been solely focused on regurgitation in infants, and a remarkable decrease in the number of regurgitations was demonstrated. CONCLUSION The multiple mechanisms of action of medicinal plants in GERD other than anti-secretory properties appear to provide more efficient treatment and helped to manage the histopathological changes associated with this disorder. Further studies are needed to understand the effects of medicinal plants on GERD better.
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Affiliation(s)
- Mehdi Salehi
- 1 Department of Traditional Medicine, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Karegar-Borzi
- 1 Department of Traditional Medicine, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehrdad Karimi
- 1 Department of Traditional Medicine, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Roja Rahimi
- 2 Department of Traditional Pharmacy, School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Hung WC, Wu JS, Sun ZJ, Lu FH, Yang YC, Chang CJ. Gender differences in the association of non-alcoholic fatty liver disease and metabolic syndrome with erosive oesophagitis: a cross-sectional study in a Taiwanese population. BMJ Open 2016; 6:e013106. [PMID: 27852719 PMCID: PMC5128939 DOI: 10.1136/bmjopen-2016-013106] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES Although metabolic syndrome correlates with erosive oesophagitis, few studies have examined the association between non-alcoholic fatty liver disease (NAFLD), associated with obesity and insulin resistance as metabolic syndrome, and erosive oesophagitis. The possible gender differences in risk factors of erosive oesophagitis should be considered. This study aimed to determine the concomitant effects of NAFLD and metabolic syndrome on erosive oesophagitis with respect to gender. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES This cross-sectional study, conducted between January 2000 and August 2009, included 12 090 participants from the health examination center of a tertiary hospital. NAFLD was diagnosed according to ultrasonographic findings after excluding participants with excessive alcohol consumption or other liver diseases. Metabolic syndrome was determined using the revised National Cholesterol Education Program Adult Treatment Panel III criteria. Erosive oesophagitis was defined according to the Los Angeles classification by oesophagogastroduodenoscopy. RESULTS On the basis of the oesophagogastroduodenoscopic findings, the prevalence of erosive oesophagitis was 20.1% (n=1427/7110) and 9.9% (n=477/4842) in males and females, respectively. After adjusting for other variables, metabolic syndrome (OR 1.26; 95% CI 1.09 to 1.45) but not NAFLD (OR 1.14; 95% CI 0.98 to 1.30) significantly correlated with erosive oesophagitis in males, while NAFLD (OR 1.50; 95% CI 1.21 to 1.86) but not metabolic syndrome (OR 1.24; 95% CI 0.94 to 1.63) positively correlated with erosive oesophagitis in females. CONCLUSIONS The detrimental effect on erosive oesophagitis is greater by metabolic syndrome than by NAFLD in males but greater by NAFLD than by metabolic syndrome in females.
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Affiliation(s)
- Wei-Chieh Hung
- Department of Family Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
- Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Jin-Shang Wu
- Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Zih-Jie Sun
- Department of Family Medicine, National Cheng Kung University College of Medicine and Hospital, Dou-Liou Branch, Yunlin, Taiwan
- Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Feng-Hwa Lu
- Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yi-Ching Yang
- Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chih-Jen Chang
- Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Wei JJ, Tang DP, Xie JJ, Yang LY, Zhuang ZH. Decreased n-6/n-3 polyunsaturated fatty acid ratio reduces chronic reflux esophagitis in rats. Prostaglandins Leukot Essent Fatty Acids 2016; 112:37-43. [PMID: 27637339 DOI: 10.1016/j.plefa.2016.08.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Revised: 06/27/2016] [Accepted: 08/15/2016] [Indexed: 12/12/2022]
Abstract
AIM To investigate the effect of dietary ratio of n-6/n-3 PUFAs on chronic reflux esophagitis (RE) and lipid peroxidation. METHOD Rat RE model were established and then fed on a diet contained different n-6/n-3 PUFA ratios (1:1.5, 5:1, 10:1) or received pure n-6 PUFA diet for 14 days. Esophageal pathological changes were evaluated using macroscopic examination and hematoxyline-eosin staining. IL-1β, IL-8, and TNFα mRNA and protein levels of were determined using RT-PCR and Western blotting, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using ELISA. RESULTS The severity of esophagitis was lowest in the PUFA(1:1.5) group (P<0.05). IL-1β, IL-8, and TNFα mRNA and protein and MDA levels were significantly increased in model groups with the increasing n-6/n-3 PUFA ratios. SOD levels were significantly decreased in all RE PUFA groups (P<0.05). CONCLUSION Esophageal injury and lipid peroxidation appeared to be ameliorated by increased n-3 PUFAs intake.
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Affiliation(s)
- Jing-Jing Wei
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, China.
| | - Du-Peng Tang
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, China.
| | - Jing-Jing Xie
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, China.
| | - Li-Yong Yang
- Department of Endocrinology, the First Affiliated Hospital of Fujian Medical University, China.
| | - Ze-Hao Zhuang
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, China.
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Li F, Tao Y, Qiao Y, Li K, Jiang Y, Cao C, Ren S, Chang X, Wang X, Wang Y, Xie Y, Dong Z, Zhao J, Liu K. Eupatilin inhibits EGF-induced JB6 cell transformation by targeting PI3K. Int J Oncol 2016; 49:1148-54. [DOI: 10.3892/ijo.2016.3600] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 06/17/2016] [Indexed: 11/05/2022] Open
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Chen CH, Lin CL, Kao CH. Gastroesophageal reflux disease with proton pump inhibitor use is associated with an increased risk of osteoporosis: a nationwide population-based analysis. Osteoporos Int 2016; 27:2117-26. [PMID: 26860609 DOI: 10.1007/s00198-016-3510-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 01/29/2016] [Indexed: 12/14/2022]
Abstract
UNLABELLED Gastroesophageal reflux disease (GERD) with proton pump inhibitor (PPI) use is associated with an increased risk of osteoporosis. The risk of hip fracture is not increased in GERD patients with PPI use. INTRODUCTION The relationship between GERD with PPI treatment and the risk of osteoporosis is unclear. We aimed to determine the risk of developing osteoporosis in patients diagnosed with GERD. METHODS Patients diagnosed with GERD and received PPI treatment between 2000 and 2010 were identified from the Longitudinal Health Insurance Database as the study cohort (n = 10,620), which was frequency matched with the comparison cohort (n = 20,738) sampled from the general population according to age, sex, index year, and comorbidities. Both cohorts were followed until the end of 2011. The risk of osteoporosis was evaluated in both groups by using Cox proportional hazards regression models. RESULTS The GERD patients with PPI treatment had a greater incidence (31.4 vs 20.7 per 1000 person-year; crude hazard ratio [cHR] 1.51; 95 % confidence interval [CI] 1.40-1.63) and a higher risk (adjusted HR [aHR] 1.50; 95 % CI 1.39-1.62) of osteoporosis than that of the comparison cohort. However, the overall incidence of hip fracture was not different between the GERD with PPI use and the control cohorts (aHR 0.79; 95 % CI 0.53-1.18). CONCLUSION GERD with PPI use is associated with an increased risk of osteoporosis. The findings of our study do not support an increased risk of hip fracture in GERD patients treated with a PPI.
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Affiliation(s)
- C-H Chen
- Digestive Disease Center, Show-Chwan Memorial Hospital, Changhua, Taiwan
- Department of Food Science and Technology, Hungkuang University, Taichung, Taiwan
- Meiho University of Technology, Pingtung, Taiwan
| | - C-L Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
| | - C-H Kao
- Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung, 40447, Taiwan.
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.
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Li JP, Guo JM, Hua YQ, Zhu KY, Tang YP, Zhao BC, Jia LF, Zhao J, Tang ZS, Duan JA. The mixture of Salvia miltiorrhiza-Carthamus tinctorius (Danhong injection) alleviates low-dose aspirin induced gastric mucosal damage in rats. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2016; 23:662-671. [PMID: 27161407 DOI: 10.1016/j.phymed.2016.03.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Revised: 03/02/2016] [Accepted: 03/09/2016] [Indexed: 06/05/2023]
Abstract
BACKGROUND Danhong injection (DHI) is quite often used in combination with low-dose aspirin (ASA, 75-325mg daily) in clinic, particularly for the treatment of cardiovascular diseases. Exploring their interaction profile is of great clinical importance. PURPOSE The current study aims to explore the interaction between DHI and low-dose ASA in rats. METHODS Sixty four rats were randomly divided into eight groups. Stomach and other four vital organs were collected for histological evaluation. Organs which exhibited histological changes were selected for a further study to evaluate the damage score and mode of action. We tested the protective effect of DHI on gastric mucosal damage in different regimes of administration. COX activity, gastric mucus secretion, pepsin activity, antioxidant activity and ROS level were assayed to reflect the protective effect of DHI on gastric mucosal damage induced by ASA. RESULTS Stomach was the target organ of interaction when DHI and ASA were used in combination. DHI alleviated gastric mucosal damage by 55.8% when DHI was injected before ASA (Group E) and by 53.5% when DHI was injected 2h after ASA administration (Group F). Additionally, if DHI treatment was appended to the long-term administration of ASA, DHI still decreased the gastric mucosal damage score in 52.0% from 2.50 to 1.20. DHI improved gastric mucus secretion, as well as decreased pepsin activity to maintain the integrity of gastric mucosal barrier (P<0.05). Furthermore, DHI recovered antioxidant activity which was impaired by ASA. In details, DHI decreased gastric mucosal ROS level, increased CAT, GSH-Px and SOD activity, and reduced MDA concentration (P<0.05). When ASA (71.9µM) was used in combination with DHI (23-fold dilution, presented in terms of concentrations of DSS, PA, SaD RA, SaB and SaA were 6.45-6.92, 1.10-1.14, 1.09-1.10, 0.86-0.90, 16.76-19.38 and 1.83-1.94µg/ml, respectively) in vitro, the inhibition rate of ASA increased from 38.6% (ASA alone) to 62.8% (ASA-DHI) on COX-1 and from 28.9% (ASA alone) to 38.8% (ASA-DHI) on COX-2 (P<0.05). DHI strengthened the inhibition activity of ASA on both COX-1 and COX-2, which showed that DHI alleviated ASA induced gastric mucosal damage but not antagonized anti-COX effect of ASA. CONCLUSIONS Gastric protective benefits were clearly produced when DHI and ASA were used in combination, which provided rational guidance for clinical combined application of DHI and ASA.
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Affiliation(s)
- Jian-Ping Li
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Jian-Ming Guo
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yong-Qing Hua
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Kevin Yue Zhu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yu-Ping Tang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | | | | | | | - Zhi-Shu Tang
- Shanxi University of Chinese Medicine, Xianyang 712000, China
| | - Jin-Ao Duan
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
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Song JH, Han YM, Kim WH, Park JM, Jeong M, Go EJ, Hong SP, Hahm KB. Oxidative stress from reflux esophagitis to esophageal cancer: the alleviation with antioxidants. Free Radic Res 2016; 50:1071-1079. [DOI: 10.1080/10715762.2016.1181262] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Ji Hyun Song
- Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Korea
| | - Young-Min Han
- CHA Cancer Prevention Research Center, CHA Bio Complex, Seongnam, Korea
| | - Won Hee Kim
- Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Korea
| | - Jong-Min Park
- CHA Cancer Prevention Research Center, CHA Bio Complex, Seongnam, Korea
| | - Migyeong Jeong
- CHA Cancer Prevention Research Center, CHA Bio Complex, Seongnam, Korea
| | - Eun Jin Go
- CHA Cancer Prevention Research Center, CHA Bio Complex, Seongnam, Korea
| | - Sung Pyo Hong
- Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Korea
| | - Ki Baik Hahm
- Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Korea
- CHA Cancer Prevention Research Center, CHA Bio Complex, Seongnam, Korea
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Antioxidant and Anti-Inflammatory Effects of Rhei Rhizoma and Coptidis Rhizoma Mixture on Reflux Esophagitis in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 2016:2052180. [PMID: 27239206 PMCID: PMC4863117 DOI: 10.1155/2016/2052180] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Revised: 01/12/2016] [Accepted: 01/14/2016] [Indexed: 12/13/2022]
Abstract
The purpose of this study was to investigate the antioxidant and anti-inflammatory effects of the combined extract of Rhei rhizoma and Coptidis rhizoma (RC-mix) in experimental model of acute reflux esophagitis. The antioxidant activity was assessed by in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. RC-mix was given at 100, 200, and 400 mg/kg body weight 2 h prior to induction of reflux esophagitis (RE). After 5 h, the effects of RC-mix treated rats were compared with those of normal and control rats. The representative flavonoid contents of RC-mix, such as sennoside A, epiberberine, coptisine, palmatine, and berberine, were detected using HPLC. The elevated esophageal mucosa damage was markedly ameliorated by RC-mix treatment in a dose-dependent manner. Furthermore, the administration of RC-mix reduced the increase of serum reactive oxygen species (ROS) and peroxynitrite (ONOO(-)). The improvement of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) levels were marked in the group given RC-mix. Moreover, the elevation of inflammatory mediators and cytokines by nuclear factor-kappa B (NF-κB) activation in control rats decreased by RC-mix pretreatment. These results indicate that RC-mix treatment reduces the pathological states of esophagitis via regulating NF-κB mediated inflammation related to oxidative stress.
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Honda J, Iijima K, Asanuma K, Ara N, Shiroki T, Kondo Y, Hatta W, Uno K, Asano N, Koike T, Shimosegawa T. Estrogen Enhances Esophageal Barrier Function by Potentiating Occludin Expression. Dig Dis Sci 2016; 61:1028-1038. [PMID: 26660903 DOI: 10.1007/s10620-015-3980-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 11/24/2015] [Indexed: 12/21/2022]
Abstract
BACKGROUND We recently demonstrated that a female sex hormone, estrogen, suppressed esophageal epithelial injury in a reflux esophagitis model of rat, suggesting that estrogen may play an important role in controlling the progress of the gastro-esophageal reflux disease spectrum. However, the precise mechanism of the action is unclear. AIM To investigate the potential role of estrogen in the esophageal barrier function. METHODS Male rabbits were pretreated with either continuous release 17β-estradiol or placebo, and the excised esophageal mucosa was subjected to Ussing chamber experiments after the 2-week pre-treatment. The mucosal side of the chamber was perfused with luminal irritants (HCl or acidified sodium nitrite), while the basal side was perfused by modified Krebs buffer. The epithelial barrier function was evaluated by the transmembrane resistance and the epithelial permeability. The intercellular space of the epithelium was investigated with transmission electron microscopy and the expression of tight junction protein, occludin, claudin-1, and claudin-4, with immunoblotting. RESULTS Estrogen pre-treatment significantly attenuated the decrease in the transmembrane resistance and the increase in the epithelial permeability induced by luminal irritants. Furthermore, the dilation of the intercellular space induced by luminal HCl was significantly alleviated by 17β-estradiol administration. The baseline occludin expression was significantly potentiated by 17β-estradiol administration. CONCLUSIONS This is the first study showing an enhancement of the esophageal barrier function by 17β-estradiol administration. The lack of the protective effect of estrogen could be responsible for the male predominance of erosive reflux esophagitis.
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Affiliation(s)
- Junya Honda
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
| | - Katsunori Iijima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
| | - Kiyotaka Asanuma
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
| | - Nobuyuki Ara
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
| | - Takeharu Shiroki
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
| | - Yutaka Kondo
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
| | - Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
| | - Kaname Uno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
| | - Naoki Asano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
| | - Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan
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Kwon OJ, Choo BK, Lee JY, Kim MY, Shin SH, Seo BI, Seo YB, Rhee MH, Shin MR, Kim GN, Park CH, Roh SS. Protective effect of Rhei Rhizoma on reflux esophagitis in rats via Nrf2-mediated inhibition of NF-κB signaling pathway. Altern Ther Health Med 2016; 16:7. [PMID: 26748627 PMCID: PMC4707002 DOI: 10.1186/s12906-015-0974-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Accepted: 12/16/2015] [Indexed: 02/22/2023]
Abstract
Background Rhei Rhizoma has been widely used as a traditional herbal medicine to treat various inflammatory diseases. The present study was conducted to evaluate its anti-inflammatory activity against experimental reflux-induced esophagitis (RE) in SD rats. Methods Rhei Rhizoma was administered at 125 or 250 mg/kg body weight per day for 7 days prior to the induction of reflux esophagitis, and its effect was compared with RE control and normal rats. Results Rhei Rhizoma administration markedly ameliorated mucosal damage on histological evaluation. The elevated reactive oxygen species in the esophageal tissue of RE control rats decreased with the administration of Rhei Rhizoma. RE control rats exhibited the down-regulation of antioxidant-related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression levels, in the presence of esophagitis; however, the levels with Rhei Rhizoma treatment were significantly higher than those in RE control rats. Moreover, RE control rats exhibited the up-regulation of protein expressions related to oxidative stress in the presence of esophagitis, but Rhei Rhizoma administration significantly reduced the expression of inflammatory proteins through mitogen-activated protein kinase (MAPK)-related signaling pathways. The protein expressions of inflammatory mediators and cytokines by nuclear factor-kappa B (NF-κB) activation were modulated through blocking the phosphorylation of inhibitor of nuclear factor kappa B (IκB)α. Conclusion Our findings support the therapeutic evidence for Rhei Rhizoma ameliorating the development of esophagitis via regulating inflammation through the activation of the antioxidant pathway. Electronic supplementary material The online version of this article (doi:10.1186/s12906-015-0974-z) contains supplementary material, which is available to authorized users.
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Wang Y, Hou H, Li M, Yang Y, Sun L. Anticancer effect of eupatilin on glioma cells through inhibition of the Notch-1 signaling pathway. Mol Med Rep 2015; 13:1141-6. [PMID: 26676446 PMCID: PMC4732834 DOI: 10.3892/mmr.2015.4671] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 11/19/2015] [Indexed: 12/31/2022] Open
Abstract
Eupatilin, one of the major flavonoids in Artemisia asiatica Nakai (Asteraceae), has been reported to possess antitumor properties. However, thus far there have been no reports regarding the effects of eupatilin on glioma. Therefore, in the current study the effects of eupatilin on glioma and the underlying molecular mechanism were explored. The effect of eupatilin on cell viability was detected by the MTT assay. Cell invasion and migration were performed with Transwell assays and cell apoptosis was determined by flow cytometric analysis. Notch-1 knockdown cells were established by transfection with Notch-1 small interfering RNA (siRNA). The expression levels of Notch-1 were detected by quantitative reverse transcription-polymerase chain reaction and western blotting. The results of the present study indicated that eupatilin exhibits an anticancer effect on glioma cells. Eupatilin inhibited proliferation, reduced cell invasion and migration, and promoted the apoptosis of glioma cells. Additionally, it suppressed Notch-1 expression. Knockdown of Notch-1 by siRNA contributed to the inhibitory effect of eupatilin on proliferation and invasion of glioma cells. In conclusion, eupatilin had an inhibitory effect on proliferation, invasion and migration, and promoted apoptosis of glioma cells through suppression of the Notch-1 signaling pathway. Therefore, eupatilin may have potential as an effective agent for the treatment of glioma.
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Affiliation(s)
- Yawei Wang
- Department of Electromyography, Tianjin Hospital, Tianjin 300211, P.R. China
| | - Hongwei Hou
- Department of Infection Control, Hebei Chest Hospital, Shijiazhuang, Hebei 050048, P.R. China
| | - Ming Li
- Basic Medical Institution, Shanghai Jiaotong University, Shanghai 200025, P.R. China
| | - Yang Yang
- Department of Orthopedics, Tianjin Hospital, Tianjin 300211, P.R. China
| | - Lan Sun
- Basic Medical Institution, Shanghai Jiaotong University, Shanghai 200025, P.R. China
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Zhang L, Liu G, Han X, Liu J, Li GX, Zou DW, Li ZS. Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis. Neurogastroenterol Motil 2015; 27:1648-56. [PMID: 26353842 DOI: 10.1111/nmo.12664] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Accepted: 07/31/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Reflux esophagitis (RE) is one of the common gastrointestinal diseases that are increasingly recognized as a significant health problem. This study was designed to investigate the role of p38 mitogen-activated protein kinase (MAPK) in experimental chronic RE model of rats. METHODS Chronic acid RE rats were induced by fundus ligation and partial obstruction of the pylorus and treated with SB203580 (a p38 MAPK inhibitor, i.p., 1 mg/kg/day) for 14 days. KEY RESULTS Immunohistochemical staining and Western blotting results revealed the activation of p38 MAPK signaling in the esophagus mucosa 14 days post injury. Through gross and histological assessment, we found that inhibition of p38 MAPK activation by SB203580 attenuated esophageal mucosal damage in RE rats. Inhibition of p38 MAPK activation in RE rats attenuated esophageal barrier dysfunction, through enhancing the expression of tight junction proteins and reducing the expression of matrix matalloproteinases-3 and -9. Inhibition of p38 MAPK activation in RE rats reduced CD68-positive cells in esophagus mucosa and mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in esophagus and protein levels of TNF-α, IL-6, and IL-1β in serum. In addition, we found that inhibition of p38 MAPK activation in RE rats suppressed protein expression of inducible nitric oxide synthase and reduced formation of nitric oxide (NO), 3-nitrotyrosin, and malondialdehyde in esophagus. CONCLUSIONS & INFERENCES Inhibition of p38 MAPK activation attenuated esophageal mucosal damage in acid RE rats, possibly by modulating esophageal barrier function and regulating inflammatory cell recruitment, and the subsequent formation of cytokines, NO, and reactive oxygen species.
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Affiliation(s)
- L Zhang
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - G Liu
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.,Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou, China
| | - X Han
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - J Liu
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - G-X Li
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - D-W Zou
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Z-S Li
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
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Protective Effect of Artemisia asiatica Extract and Its Active Compound Eupatilin against Cisplatin-Induced Renal Damage. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:483980. [PMID: 26539226 PMCID: PMC4619882 DOI: 10.1155/2015/483980] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 06/14/2015] [Indexed: 12/20/2022]
Abstract
The present study investigated the renoprotective effect of an Artemisia asiatica extract and eupatilin in kidney epithelial (LLC-PK1) cells. Although cisplatin is effective against several cancers, its use is limited due to severe nephrotoxicity. Eupatilin is a flavonoid compound isolated from the Artemisia plant and possesses antioxidant as well as potent anticancer properties. In the LLC-PK1 cellular model, the decline in cell viability induced by oxidative stress, such as that induced by cisplatin, was significantly and dose-dependently inhibited by the A. asiatica extract and eupatilin. The increased protein expressions of phosphorylated JNK and p38 by cisplatin in cells were markedly reduced after A. asiatica extract or eupatilin cotreatment. The elevated expression of cleaved caspase-3 was significantly reduced by A. asiatica extract and eupatilin, and the elevated percentage of apoptotic cells after cisplatin treatment in LLC-PK1 cells was markedly decreased by cotreatment with A. asiatica extract or eupatilin. Taken together, these results suggest that A. asiatica extract and eupatilin could cure or prevent cisplatin-induced renal toxicity without any adverse effect; thus, it can be used in combination with cisplatin to prevent nephrotoxicity.
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Sun D, Wang X, Gai Z, Song X, Jia X, Tian H. Bile acids but not acidic acids induce Barrett's esophagus. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2015; 8:1384-1392. [PMID: 25973022 PMCID: PMC4396229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 01/17/2015] [Indexed: 06/04/2023]
Abstract
Barrett's esophagus (BE) is associated with the development of esophageal adenocarcinoma (EAC). Bile acids (BAs) refluxing into the esophagus contribute to esophageal injury, which results in BE and subsequent EAC. We developed two animal models to test the role of BAs in the pathogenesis of BE. We surgically generated BA reflux, with or without gastric acid, in rats. In a second experiment, we fed animals separately with BAs and gastric acid. Pathologic changes were examined and the expression of Muc2 and Cdx2 in BE tissue was tested by immunostaining. Inflammatory factors in the plasma, as well as differentiation genes in BE were examined through highly sensitive ELISA and semi-quantitative RT-PCR techniques. We found that BAs are sufficient for the induction of esophagitis and Barrett's-like metaplasia in the esophagus. Overexpression of inflammatory cells, IL-6, and TNF-α was observed both in animals fed with BAs and surgically generated BA reflux. Furthermore, elevated levels of Cdx2, Muc2, Bmp4, Kit19, and Tff2 (differentiation genes in BE) were found in BA-treated rats. In conclusion, BAs, but not gastric acid, are a major causative factor for BE. We confirmed that BAs contribute to the development of BE by inducing the inflammatory response in the esophagus. Inhibiting BAs may be a promising therapy for BE.
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Affiliation(s)
- Dongfeng Sun
- Department of Thoracic Surgery, Qianfoshan Hospital, Shandong UniversityJinan, Peoples R China
| | - Xiao Wang
- Department of Pathology, Qi Lu Hospital, Shandong UniversityJinan, Peoples R China
| | - Zhibo Gai
- Department of Clinical Pharmacology and Toxicology, University Hospital ZurichSwitzerland
| | - Xiaoming Song
- Department of Thoracic Surgery, Qianfoshan Hospital, Shandong UniversityJinan, Peoples R China
| | - Xinyong Jia
- Department of Endoscopy, Qianfoshan Hospital, Shandong UniversityJinan, Peoples R China
| | - Hui Tian
- Department of Thoracic Surgery, Qi Lu Hospital, Shandong UniversityJinan, Peoples R China
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Molecular mechanisms of constitutive and inducible NF-kappaB activation in oesophageal adenocarcinoma. Eur J Cancer 2015; 51:464-472. [PMID: 25596807 DOI: 10.1016/j.ejca.2014.11.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 11/13/2014] [Accepted: 11/16/2014] [Indexed: 01/27/2023]
Abstract
BACKGROUND Nuclear factor-kappaB (NF-κB) regulates the expression of a large number of genes involved in the immune and inflammatory response. NF-κB is constitutively activated in oesophageal tumour tissues and induced in oesophageal cells by bile and acid. The aim of the present study was to define the mechanisms underlying NF-κB activation in oesophageal adenocarcinoma. PATIENTS AND METHODS Fresh biopsy specimens were obtained from 20 patients with oesophageal adenocarcinoma. The activation of NF-κB in oesophageal tumour specimens and oesophageal SKGT-4 cells was assessed by gel mobility shift and Western blotting. Phosphorylation of protein kinase B (AKT/PKB), Ikappa kinase-alpha/beta (IKK-α/β) and extracellular signal-regulated kinase 1/2 (ERK1/2) was examined by Western blotting. High content analysis was used to quantify NF-κB translocation in oesophageal cells. RESULTS Oesophageal tumour tissues had higher levels of NF-κB. Increased levels of phosphorylated AKT and IKK-α/β and ERK1/2 were detected in tumour tissues compared with normal oesophageal mucosa. Exposure of SKGT-4 cells to deoxycholic acid (DCA) or acid resulted in NF-κB activation and phosphorylation of AKT, IKK-α/β and ERK1/2. Specific inhibitors for phosphoinositide 3-kinase; PI3K (LY294002 and worhmannin) and ERK1/2 inhibitors (PD98059 and U0126) suppressed DCA- and acid-induced NF-κB activation. The proteasome inhibitor MG-132 and the antioxidants vitamin C and pyrrolidine dithiocarbamate (PDTC) also inhibited NF-κB activation. CONCLUSIONS Our data demonstrate a major role for PI3K/AKT-IKK-α/β-ERK1/2 signalling pathway in NF-κB activation in oesophageal adenocarcinoma. These results suggest that NF-κB may be a prognostic marker for oesophageal adenocarcinoma, and modulating of NF-κB may uncover new therapeutic strategies.
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Hung WC, Wu JS, Yang YC, Sun ZJ, Lu FH, Chang CJ. Nonalcoholic fatty liver disease vs. obesity on the risk of erosive oesophagitis. Eur J Clin Invest 2014; 44:1143-9. [PMID: 25293867 DOI: 10.1111/eci.12348] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 10/03/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Erosive oesophagitis (EE) may be complicated by oesophageal ulcers, peptic stricture, Barrett's oesophagus and oesophageal adenocarcinoma. There have been few studies examining the influence of nonalcoholic fatty liver disease (NAFLD) on EE, and even fewer exploring the simultaneous effects of NAFLD, general and central obesity on EE. We thus aim to clarify the relationship between NAFLD and EE when general and/or central obesity are considered simultaneously. MATERIALS AND METHODS In this cross-sectional study, we enrolled 12 090 subjects who underwent a health check-up at the Health Examination Center of a university hospital between January 2000 and August 2009 for analysis. NAFLD was diagnosed using liver ultrasound and EE was defined according to the Los Angeles classification by oesophagogastroduodenoscopy. RESULTS Subjects with EE (1922; 15·9%) had a higher proportion of NAFLD, general and central obesity. With adjustment for age, gender, hypertension, diabetes mellitus, hiatal hernia, hypertriglyceridemia, high-density lipoprotein cholesterol, alcohol consumption, tea drinking, smoking and habitual exercise, the results of the multivariate analyses showed that general obesity, central obesity and NAFLD were all significantly associated with EE in their separate models. When considering general obesity, central obesity and NAFLD simultaneously, NAFLD, but neither general nor central obesity, remained positively correlated to EE. In addition, male gender, hiatal hernia and hypertriglyceridemia were all significantly associated with EE. CONCLUSION In addition to general and central obesity, NAFLD is independently associated with increased risk of EE, and the detrimental effect of NAFLD on EE might be greater than those of general and central obesity.
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Affiliation(s)
- Wei-Chieh Hung
- Department of Family Medicine, E-Da Hospital/I-Shou University, Kaohsiung; Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
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Park JM, Han YM, Lee JS, Ko KH, Hong SP, Kim EH, Hahm KB. Nrf2-mediated mucoprotective and anti-inflammatory actions of Artemisia extracts led to attenuate stress related mucosal damages. J Clin Biochem Nutr 2014; 56:132-42. [PMID: 25759519 PMCID: PMC4345182 DOI: 10.3164/jcbn.14-76] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 08/10/2014] [Indexed: 12/16/2022] Open
Abstract
The aim of this study was to compare biological actions between isopropanol and ethanol extracts of Artemisia including antioxidant, anti-inflammatory, and cytoprotective actions. Antioxidant activities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and confocal microscopy on lipopolysaccharide-induced RGM1 cells, cytoprotection effects evaluated by detecting heme oxygenase-1 (HO-1), Nf-E2 related factor2 (Nrf2) and heat shock protein 70 (HSP70), and anti-inflammatory effects investigated by measuring inflammatory mediators. Water immersion restraint stress was imposed to provoke stress related mucosal damages (SRMD) in rats. Isopropanol extracts of Artemisia showed the higher DPPH radical scavenging activity and lesser LPS-induced reactive oxygen species productions and increased HO-1 expression through increased nuclear translocation of Nrf2 transcription factor compared to ethanol extracts. The increased expression of HSP70 and decreased expression of endothelin-1 were only increased with isopropanol extracts. A concentration-dependent inhibition of LPS-induced COX-2 and iNOS even at a rather lower concentration than ethanol extract was achieved with isopropanol extracts. Cytokine protein array revealed Artemisia extracts significantly attenuated the levels of CXCL-1, CXCL-16, and MCP-1. These orchestrated actions led to significant rescue from SRMD. Conclusively, Artemisia extracts imposed significant antioxidant and anti-inflammatory activity against SRMD and isopropanol extracts were superior to ethanol extracts in these beneficiary actions of Artemisia.
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Affiliation(s)
- Jong-Min Park
- CHA Cancer Prevention Research Center, CHA University, 605 Yeoksam 1-dong, Gangnam-gu, Seoul 135-081, Korea
| | - Young-Min Han
- CHA Cancer Prevention Research Center, CHA University, 605 Yeoksam 1-dong, Gangnam-gu, Seoul 135-081, Korea
| | - Jin-Seok Lee
- Jeil pharmaceutical Co., Ltd., Seoul 137-041, Korea
| | - Kwang Hyun Ko
- Digestive Disease Center, CHA University Bundang Medical Center, Seongnam 463-838, Korea
| | - Sung-Pyo Hong
- Digestive Disease Center, CHA University Bundang Medical Center, Seongnam 463-838, Korea
| | - Eun-Hee Kim
- CHA Cancer Prevention Research Center, CHA University, 605 Yeoksam 1-dong, Gangnam-gu, Seoul 135-081, Korea
| | - Ki-Baik Hahm
- CHA Cancer Prevention Research Center, CHA University, 605 Yeoksam 1-dong, Gangnam-gu, Seoul 135-081, Korea ; Digestive Disease Center, CHA University Bundang Medical Center, Seongnam 463-838, Korea
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Park JM, Hahm KB, Kwon SO, Kim EH. The Anti-inflammatory Effects of Acidic Polysaccharide from Artemisia capillaris on Helicobacter pylori Infection. J Cancer Prev 2014; 18:161-8. [PMID: 25337542 PMCID: PMC4189452 DOI: 10.15430/jcp.2013.18.2.161] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2013] [Revised: 06/19/2013] [Accepted: 06/19/2013] [Indexed: 01/06/2023] Open
Abstract
Background: Helicobacter pylori infection is associated with diverse upper gastrointestinal diseases, such as peptic and duodenal ulcers as well as gastric cancer. Longstanding period of infection impose great risk of H. pylori-related gastric disease, based on the evidence that early childhood infection is responsible for ensuing atrophic gastritis and gastric cancer related to H. pylori infection. Artemisiahas been known to be beneficial for heath for a long time. In spite of well-acknowledged cytoprotective and anti-inflammatory actions of Artemisia, the effects of the acidic polysaccharide fractions on the gastroprotection remain to be investigated. Methods: In the current study, we compared anti-inflammatory actions of the acidic polysaccharide fraction between Artemisia and Panax ginseng against H. pylori infection in vitro. The polysaccharide fractions were pretreated 1 h before H. pylori infection on normal gastric mucosal RGM-1 cells and gastric cancer MKN-28 cells. RT-PCR and Western blot was performed to check anti-inflammatory actions. Results: The expressions of inflammatory markers including COX-2, iNOS and IL-8 increased after H. pylori infection, of which levels were significantly decreased when treating with the polysaccharide fractions from Artemisia and ginseng in RGM1 and gastric cancer MKN-28 cells. In addition, the polysaccharide fractions significantly ameliorated H. pylori-induced angiogenic and invasive markers such as HIF-1α and ICAM1. Moreover, H. pylori-induced apoptosis were prevented by pretreatment with the polysaccharide fractions. The polysaccharide fraction from Artemisia showed the most protective effects among the several polysaccharide fractions used in this study. Conclusions: The polysaccharide fraction of Artemisia capillariscan is a candidate substance which can attenuate either H. pylori-induced gastritis or tumorigenesis based on potent anti-inflammatory action.
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Affiliation(s)
- Jong-Min Park
- CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul
| | - Ki-Baik Hahm
- CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul ; Department of Gastroenterology, CHA Bundang Medical Center, Seongnam
| | | | - Eun-Hee Kim
- CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul ; College of Pharmacy, CHA University, Pocheon, Korea
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Ryoo SB, Oh HK, Yu SA, Moon SH, Choe EK, Oh TY, Park KJ. The effects of eupatilin (stillen®) on motility of human lower gastrointestinal tracts. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2014; 18:383-90. [PMID: 25352757 PMCID: PMC4211121 DOI: 10.4196/kjpp.2014.18.5.383] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Revised: 06/18/2014] [Accepted: 06/19/2014] [Indexed: 12/15/2022]
Abstract
Gastrointestinal motility consists of phasic slow-wave contractions and the migrating motor complex (MMC). Eupatilin (Stillen®) has been widely used to treat gastritis and peptic ulcers, and various cytokines and neuropeptides are thought to be involved, which can affect gastrointestinal motility. We performed a study to identify the effects of eupatilin on lower gastrointestinal motility with electromechanical recordings of smooth muscles in the human ileum and colon. Ileum and colon samples were obtained from patients undergoing bowel resection. The tissues were immediately stored in oxygenated Krebs-Ringer's bicarbonate solution, and conventional microelectrode recordings from muscle cells and tension recordings from muscle strips and ileal or colonic segments were performed. Eupatilin was perfused into the tissue chamber, and changes in membrane potentials and contractions were measured. Hyperpolarization of resting membrane potential (RMP) was observed after administration of eupatilin. The amplitude, AUC, and frequency of tension recordings from circular and longitudinal smooth muscle strips and bowel segments of the ileum and colon were significantly decreased after admission of eupatilin. Eupatilin elicited dose-dependent decreases during segmental tension recordings. In conclusion, eupatilin (Stillen®) showed inhibitory effects on the human ileum and colon. We propose that this drug may be useful for treating diseases that increase bowel motility, but further studies are necessary.
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Affiliation(s)
- Seung-Bum Ryoo
- Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea
| | - Heung-Kwon Oh
- Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea
| | - Sung A Yu
- Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Department of Physiology, Seoul National University College of Medicine, Seoul 110-744, Korea
| | - Sang Hui Moon
- Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea
| | - Eun Kyung Choe
- Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 135-984, Korea
| | | | - Kyu Joo Park
- Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea
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45
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Kang JW, Lee SM. Protective Effects of Chlorogenic Acid against Experimental Reflux Esophagitis in Rats. Biomol Ther (Seoul) 2014; 22:420-5. [PMID: 25414772 PMCID: PMC4201226 DOI: 10.4062/biomolther.2014.066] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2014] [Revised: 06/25/2014] [Accepted: 07/08/2014] [Indexed: 01/11/2023] Open
Abstract
Esophageal reflux of gastric contents causes esophageal mucosal damage and inflammation. Recent studies show that oxygen-derived free radicals mediate mucosal damage in reflux esophagitis (RE). Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and possesses anti-inflammatory, antibacterial and anti-oxidant activities. In this context, we investigated the effects of CGA against experimental RE in rats. RE was produced by ligating the transitional region between the forestomach and the glandular portion and covering the duodenum near the pylorus ring with a small piece of catheter. CGA (10, 30 and 100 mg/kg) and omeprazole (positive control, 10 mg/kg) were administered orally 48 h after the RE operation for 12 days. CGA reduced the severity of esophageal lesions, and this beneficial effect was confirmed by histopathological observations. CGA reduced esophageal lipid peroxidation and increased the reduced glutathione/oxidized glutathione ratio. CGA attenuated increases in the serum level of tumor necrosis factor-α, and expressions of inducible nitric oxide synthase and cyclooxygenase-2 protein. CGA alleviates RE-induced mucosal injury, and this protection is associated with reduced oxidative stress and the anti-inflammatory properties of CGA.
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Affiliation(s)
- Jung-Woo Kang
- School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
| | - Sun-Mee Lee
- School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
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46
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O'Sullivan KE, Phelan JJ, O'Hanlon C, Lysaght J, O'Sullivan JN, Reynolds JV. The role of inflammation in cancer of the esophagus. Expert Rev Gastroenterol Hepatol 2014; 8:749-60. [PMID: 24857183 DOI: 10.1586/17474124.2014.913478] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Esophageal adenocarcinoma is the eighth most common malignancy worldwide. The overall prognosis is poor, with 5-year survival ranges of approximately 15-25%, and 30-50% for patients who can be treated with curative intent. There has been a marked increase in incidence of esophageal adenocarcinoma over the last 30 years, with chronic and severe reflux, diet and obesity identified as principal factors fuelling this rise in the West. Esophageal adenocarcinoma is an exemplar model of an inflammation-associated cancer. The key molecular pathways driving tumor development and influencing tumor biology are the subject of considerable research efforts, and is the principal focus of this review. In addition, the diverse range of changes occurring in the local immune response, tissue microenvironment, metabolic profile, intracellular signaling mechanisms and microRNA signatures are discussed, as well as novel targeted therapies.
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Affiliation(s)
- Katie E O'Sullivan
- Department of Surgery, Institute of Molecular Medicine, St. James Hospital, Dublin 8, Ireland
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47
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Lee OY, Kang DH, Lee DH, Chung IK, Jang JY, Kim JI, Cho JW, Rew JS, Lee KM, Kim KO, Choi MG, Lee SW, Lee ST, Kim TO, Shin YW, Seol SY. A comparative study of DA-9601 and misoprostol for prevention of NSAID-associated gastroduodenal injury in patients undergoing chronic NSAID treatment. Arch Pharm Res 2014; 37:1308-16. [PMID: 24871787 PMCID: PMC4176566 DOI: 10.1007/s12272-014-0408-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 05/02/2014] [Indexed: 12/22/2022]
Abstract
Misoprostol is reported to prevent non-steroidal anti-inflammatory drug (NSAID)-associated gastroduodenal complications. There is, however, limited information regarding the efficacy of DA-9601 in this context. We performed a comparative study on the relative efficacy of DA-9601 and misoprostol for prevention of NSAID-associated complications. In this multicenter, double-blinded, active-controlled, stratified randomized, parallel group, non-inferiority trial, 520 patients who were to be treated with an NSAID (aceclofenac, 100 mg, twice daily) over a 4-week period were randomly assigned to groups for coincidental treatment with DA-9601 (60 mg, thrice daily) (236 patients for full analysis) or misoprostol (200 μg, thrice daily) (242 patients for full analysis). A total of 236 patients received DA-9601 and 242 received misoprostol. The primary endpoint was the gastric protection rate, and secondary endpoints were the duodenal protection rate and ulcer incidence rate. Endpoints were assessed by endoscopy after the 4-week treatment period. Drug-related adverse effects, including gastrointestinal (GI) symptoms, were also compared. At week 4, the gastric protection rates with DA-9601 and misoprostol were 81.4 % (192/236) and 89.3 % (216/242), respectively. The difference between the groups was −14.2 %, indicating non-inferiority of DA-9601 to misoprostol. Adverse event rates were not different between the two groups; however, the total scores for GI symptoms before and after administration were significantly lower in the DA-9601 group than in the misoprostol group (−0.2 ± 2.8 vs 1.2 ± 3.2; p < 0.0001). DA-9601 is as effective as misoprostol in preventing NSAID-associated gastroduodenal complications, and has a superior adverse GI effect profile.
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Affiliation(s)
- Oh Young Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea
| | - Dae-Hwan Kang
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Busan, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Hospital of Bundang, Seongnam, South Korea
| | - Il-Kwun Chung
- Department of Internal Medicine, Soonchonhyang University Hospital Cheonan, Cheonan, South Korea
| | - Jae-Young Jang
- Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Jin-Il Kim
- Department of Internal Medicine, The Catholic University of Korea Yeouido St.Mary’s Hospital, Seoul, South Korea
| | - Jin-Woong Cho
- Department of Internal Medicine, Presbyterian Medical Center, Jeonju, South Korea
| | - Jong-Sun Rew
- Department of Internal Medicine, Chonnam National University College of Medicine, Gwangju, South Korea
| | - Kang-Moon Lee
- Department of Internal Medicine, The Catholic University of Korea St.Vincent’s Hospital, Suwon, South Korea
| | - Kyoung Oh Kim
- Department of Internal Medicine, Gacheon University Gil Medical Center, Incheon, South Korea
| | - Myung-Gyu Choi
- Department of Internal Medicine, The Catholic University of Korea Seoul St.Mary’s Hospital, Seoul, South Korea
| | - Sang-Woo Lee
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, South Korea
| | - Soo-Teik Lee
- Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, South Korea
| | - Tae-Oh Kim
- Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, South Korea
| | - Yong-Woon Shin
- Department of Internal Medicine, Inha University Hospital, Incheon, South Korea
| | - Sang-Yong Seol
- Department of Internal Medicine, Inje University Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan, 614-735 Korea
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48
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Iijima K, Shimosegawa T. Involvement of luminal nitric oxide in the pathogenesis of the gastroesophageal reflux disease spectrum. J Gastroenterol Hepatol 2014; 29:898-905. [PMID: 24863184 DOI: 10.1111/jgh.12548] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/29/2014] [Indexed: 12/16/2022]
Abstract
Over the last 3 decades, the incidence of esophageal adenocarcinoma has dramatically increased in Western countries; a similar increase may be observed in Asian countries in the near future. Esophageal adenocarcinoma arises from a sequential gastroesophageal reflux disease (GERD) spectrum from reflux erosive esophagitis, to Barrett's esophagus, and finally to esophageal adenocarcinoma. At present, gastric acid and bile are assumed to be primarily involved in the etiology of the GERD spectrum. We reported in 2002 that, at the gastroesophageal junction in humans, abundant amounts of nitric oxide (NO) are generated luminally through the entero-salivary re-circulation of dietary nitrate. Since then, we have carried out a series of experiments to demonstrate that NO diffuses into the adjacent epithelium at cytotoxic levels. This diffusion results in disruption of the epithelial barrier function, exacerbation of inflammation, acceleration of columnar transformation in the esophagus (Barrett's esophagus) via the induction of caudal-type homeobox 2, and the shifting of carcinogenic N-nitroso compound formation from the luminal to epithelial compartment. These results suggest that, in addition to conventionally recognized causative factors, luminal NO could also be involved in the pathogenesis of the GERD spectrum. In addition, we recently showed that there is a prominent gender-related difference in NO-related cytotoxicity in the esophagus and that estrogen attenuated the esophageal tissue damage via the estrogen receptor in female rats. The role of estrogen in attenuating the esophageal tissue damage in NO-related esophageal damage could explain the well-recognized male predominance in the GERD spectrum in humans.
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Affiliation(s)
- Katsunori Iijima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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49
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The esophagitis to adenocarcinoma sequence; the role of inflammation. Cancer Lett 2013; 345:182-9. [PMID: 23994342 DOI: 10.1016/j.canlet.2013.08.017] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2013] [Revised: 08/08/2013] [Accepted: 08/13/2013] [Indexed: 12/19/2022]
Abstract
Esophageal adenocarcinoma (EAC) is the eighth most common cancer worldwide, and approximately 15% of patients survive 5years. Reflux disease (GERD) and Barrett's esophagus (BE) are major risk factors for the development of EAC, and epidemiologic studies highlight a strong association with obesity. The immune, inflammatory and intracellular signaling changes resulting from chronic inflammation of the esophageal squamous epithelium are increasingly well characterized. In GERD and Barrett's, an essential role for T-cells in the initiation of inflammation in the esophagus has been identified, and a balance between T-cell responses and phenotype may play an important role in disease progression. Obesity is a chronic low-grade inflammatory state, fueled by adipose tissue derived- inflammatory mediators such as IL-6, TNF-α and leptin, representing a novel area for targeted research. Additionally, reactive oxygen species (ROS) and receptor tyrosine kinase (RTK) activation may drive progression from esophagitis to EAC, and downstream signaling pathways employed by these molecules may be important. This review will explain the diverse range of mechanisms potentially driving and maintaining inflammation within the esophagus and explore both existing and future therapeutic strategies targeting the process.
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50
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Arya E, Saha S, Saraf SA, Kaithwas G. Effect of Perilla frutescens fixed oil on experimental esophagitis in albino Wistar rats. BIOMED RESEARCH INTERNATIONAL 2013; 2013:981372. [PMID: 24027769 PMCID: PMC3762191 DOI: 10.1155/2013/981372] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 06/22/2013] [Accepted: 06/29/2013] [Indexed: 01/10/2023]
Abstract
The present study was undertaken to elucidate the effect of Perilla frutescens fixed oil on experimental esophagitis in albino rats. A group of rats (n = 6), treated with control vehicle (0.9% NaCl in double distilled water, 3 mL/kg, i.p.) and Perilla frutescens fixed oil (100%) (1, 2, and 3 mL/kg, i.p.), or pantoprazole (30 mg/kg, i.p.), were subjected to pylorus and forestomach ligation. Animals were sacrificed after 6 h and evaluated for the gastric pH, volume of gastric juices, total acidity, esophagitis index and free acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH, catalase, and SOD. Treatment with fixed oil significantly inhibited the gastric secretion, total acidity, and esophagitis index. The oil also helped to restore the altered levels of oxidative stress parameters to normal. The present study also makes evident the in vitro antihistaminic and anticholinergic activity of alpha linolenic acid (ALA) (18 : 3, n - 3) on isolated rat ileum preparation. The lipoxygenase inhibitory, histamine antagonistic, antisecretory (anticholinergic), and antioxidant activity of the oil was attributed for its efficacy in reflux esophagitis.
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Affiliation(s)
- Ekta Arya
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (Central University), Vidya Vihar, Rai Bareli Road, Lucknow 226025, India
| | - Sudipta Saha
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (Central University), Vidya Vihar, Rai Bareli Road, Lucknow 226025, India
| | - Shubhini A. Saraf
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (Central University), Vidya Vihar, Rai Bareli Road, Lucknow 226025, India
| | - Gaurav Kaithwas
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (Central University), Vidya Vihar, Rai Bareli Road, Lucknow 226025, India
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