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Wang L, Lian YJ, Dong JS, Liu MK, Liu HL, Cao ZM, Wang QN, Lyu WL, Bai YN. Traditional Chinese medicine for chronic atrophic gastritis: Efficacy, mechanisms and targets. World J Gastroenterol 2025; 31:102053. [DOI: 10.3748/wjg.v31.i9.102053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/06/2024] [Accepted: 01/21/2025] [Indexed: 02/18/2025] Open
Abstract
Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.
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Affiliation(s)
- Li Wang
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yan-Jie Lian
- Division of Cardiovascular, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
| | - Jin-Sheng Dong
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ming-Kun Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Hong-Liang Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Zheng-Min Cao
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qing-Nan Wang
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Wen-Liang Lyu
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yu-Ning Bai
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Wang B, Xiao L, Chen P, Zhang T, Zhang P, Cao L, Zhou Z, Cheng H, Zhang T, Li S. Uncovering the role of traditional Chinese medicine in immune-metabolic balance of gastritis from the perspective of Cold and Hot: Jin Hong Tablets as a case study. Chin Med 2024; 19:134. [PMID: 39367502 PMCID: PMC11451182 DOI: 10.1186/s13020-024-00998-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 09/05/2024] [Indexed: 10/06/2024] Open
Abstract
Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs.
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Affiliation(s)
- Boyang Wang
- Institute for TCM-X, MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Lihao Xiao
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co.,Ltd., Lianyungang, 222047, Jiangshu, China
| | - Pan Chen
- Institute for TCM-X, MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, Beijing, 100084, China
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangshu, China
| | - Tingyu Zhang
- Institute for TCM-X, MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Peng Zhang
- Institute for TCM-X, MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Liang Cao
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co.,Ltd., Lianyungang, 222047, Jiangshu, China
| | - Ziyi Zhou
- Institute for TCM-X, MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Haibo Cheng
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangshu, China
| | - Tong Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Shao Li
- Institute for TCM-X, MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, Beijing, 100084, China.
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Zhou P, Zheng ZH, Wan T, Liao CW, Wu J. Yiqi Jiedu Huayu decoction inhibits precancerous lesions of chronic atrophic gastritis by inhibiting NLRP3 inflammasome-mediated pyroptosis. World J Gastrointest Oncol 2024; 16:3158-3168. [PMID: 39072181 PMCID: PMC11271778 DOI: 10.4251/wjgo.v16.i7.3158] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 04/25/2024] [Accepted: 05/17/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND Chronic atrophic gastritis (CAG) is a prevalent chronic gastritis usually accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The increasing application of traditional Chinese medicine in CAG treatment has shown promising results with low side effects and significant efficacy. AIM To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG. METHODS A CAG rat model was established by Helicobacter pylori bacteria solution combined with N-methyl-N'-nitro-N-nitrosoguanidine. Histopathological measurements were conducted by hematoxylin-eosin and alcian blue and periodic acid-Schiff staining. Serum levels of inflammatory factors and gastric mucosal-related factors were examined using enzyme-linked immunosorbent assay. Protein and mRNA levels were quantified via western blot and quantitative real-time polymerase chain reaction analysis, respectively. Molecular interaction was verified by chromatin immunoprecipitation (ChIP) assay. RESULTS YJHD greatly attenuated pathological changes in the gastric mucosa and precancerous lesions in CAG rats. Meanwhile, YJHD treatment reduced serum levels of inflammatory factors [interleukin (IL)-6, tumor necrosis factor-α and C-reactive protein] and increased serum levels of gastric mucosal-related factors (gastrin, pepsin, somatostatin and prostaglandin E2) in CAG rats. In addition, YJHD administration suppressed NLRP3 inflammasome-mediated cell pyroptosis, as well as the activation of TLR4/NF-κB and IL-6/STAT3 signaling pathways. Mechanically, ChIP experiments confirmed that NLRP3 transcription was regulated by TLR4/NF-κB and IL-6/STAT3 signaling. CONCLUSION Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.
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Affiliation(s)
- Peng Zhou
- Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
| | - Zi-Han Zheng
- Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
| | - Tao Wan
- Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
| | - Chuan-Wen Liao
- Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
| | - Jie Wu
- Department of Gastrointestinal Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
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Lian X, Fan K, Qin X, Liu Y. Amalgamated Pharmacoinformatics Study to Investigate the Mechanism of Xiao Jianzhong Tang against Chronic Atrophic Gastritis. Curr Comput Aided Drug Des 2024; 20:598-615. [PMID: 37475552 DOI: 10.2174/1573409919666230720141115] [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: 11/23/2022] [Revised: 05/24/2023] [Accepted: 06/14/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND Traditional Chinese medicine (TCM) Xiao Jianzhong Tang (XJZ) has a favorable efficacy in the treatment of chronic atrophic gastritis (CAG). However, its pharmacological mechanism has not been fully explained. OBJECTIVE The purpose of this study was to find the potential mechanism of XJZ in the treatment of CAG using pharmacocoinformatics approaches. METHODS Network pharmacology was used to screen out the key compounds and key targets, MODELLER and GNNRefine were used to repair and refine proteins, Autodock vina was employed to perform molecular docking, Δ Lin_F9XGB was used to score the docking results, and Gromacs was used to perform molecular dynamics simulations (MD). RESULTS Kaempferol, licochalcone A, and naringenin, were obtained as key compounds, while AKT1, MAPK1, MAPK14, RELA, STAT1, and STAT3 were acquired as key targets. Among docking results, 12 complexes scored greater than five. They were run for 50ns MD. The free binding energy of AKT1-licochalcone A and MAPK1-licochalcone A was less than -15 kcal/mol and AKT1-naringenin and STAT3-licochalcone A was less than -9 kcal/mol. These complexes were crucial in XJZ treating CAG. CONCLUSION Our findings suggest that licochalcone A could act on AKT1, MAPK1, and STAT3, and naringenin could act on AKT1 to play the potential therapeutic effect on CAG. The work also provides a powerful approach to interpreting the complex mechanism of TCM through the amalgamation of network pharmacology, deep learning-based protein refinement, molecular docking, machine learning-based binding affinity estimation, MD simulations, and MM-PBSA-based estimation of binding free energy.
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Affiliation(s)
- Xu Lian
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road, Taiyuan, 030006, Shanxi, P.R. China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, No. 92, Wucheng Road, Taiyuan, 030006, Shanxi, P.R. China
| | - Kaidi Fan
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road, Taiyuan, 030006, Shanxi, P.R. China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, No. 92, Wucheng Road, Taiyuan, 030006, Shanxi, P.R. China
| | - Xuemei Qin
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road, Taiyuan, 030006, Shanxi, P.R. China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, No. 92, Wucheng Road, Taiyuan, 030006, Shanxi, P.R. China
| | - Yuetao Liu
- Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Road, Taiyuan, 030006, Shanxi, P.R. China
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, No. 92, Wucheng Road, Taiyuan, 030006, Shanxi, P.R. China
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Cao Y, Wang D, Mo G, Peng Y, Li Z. Gastric precancerous lesions:occurrence, development factors, and treatment. Front Oncol 2023; 13:1226652. [PMID: 37719006 PMCID: PMC10499614 DOI: 10.3389/fonc.2023.1226652] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 08/10/2023] [Indexed: 09/19/2023] Open
Abstract
Patients with gastric precancerous lesions (GPL) have a higher risk of gastric cancer (GC). However, the transformation of GPL into GC is an ongoing process that takes several years. At present, several factors including H.Pylori (Hp), flora imbalance, inflammatory factors, genetic variations, Claudin-4, gastric stem cells, solute carrier family member 26 (SLC26A9), bile reflux, exosomes, and miR-30a plays a considerable role in the transformation of GPL into GC. Moreover, timely intervention in the event of GPL can reduce the risk of GC. In clinical practice, GPL is mainly treated with endoscopy, acid suppression therapy, Hp eradication, a cyclooxygenase-2 inhibitor, aspirin, and diet. Currently, the use of traditional Chinese medicine (TCM) or combination with western medication to remove Hp and the use of TCM to treat GPL are common in Asia, particularly China, and have also demonstrated excellent clinical efficacy. This review thoroughly discussed the combining of TCM and Western therapy for the treatment of precancerous lesions as conditions allow. Consequently, this review also focuses on the causes of the development and progression of GPL, as well as its current treatment. This may help us understand GPL and related treatment.
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Affiliation(s)
- Yue Cao
- Emergency of Department, Yunnan Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Dongcai Wang
- Emergency of Department, Yunnan Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Guiyun Mo
- Emergency Teaching and Research Department of the First Clinical School of Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Yinghui Peng
- Emergency of Department, Yunnan Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Zengzheng Li
- Department of Hematology, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
- Yunnan Province Clinical Center for Hematologic Disease, The First People’s Hospital of Yunnan Province, Kunming, China
- Yunnan Blood Disease Hospital, The First People’s Hospital of Yunnan Province, Kunming, China
- National Key Clinical Specialty of Hematology, The First People’s Hospital of Yunnan Province, Kunming, China
- Yunnan Province Clinical Research Center for Hematologic Disease, The First People’s Hospital of Yunnan Province, Kunming, China
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Lu L, Chen B, Zhang X, Xu Y, Jin L, Qian H, Liang ZF. The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer. Front Pharmacol 2023; 14:1203265. [PMID: 37456745 PMCID: PMC10339287 DOI: 10.3389/fphar.2023.1203265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 06/20/2023] [Indexed: 07/18/2023] Open
Abstract
Gastric cancer is a common malignant tumor of the digestive tract, with a low early diagnosis rate. N-methyl-N-nitro-N-nitroguanidine (MNNG) is one of the main risk factors for gastric cancer. Phytochemicals are healthy active substances derived from vegetables, fruits, nuts, tea, herbal medicines and other plants. Taking phytochemicals is a very promising strategy for the prevention and treatment of gastric cancer. Many studies have proved that phytochemicals have protective effects on MNNG induced gastric cancer via inhibiting cell proliferation, enhancing immunity, suppressing cell invasion and migration, inducing apoptosis and autophagy, blocking angiogenesis, inhibiting Helicobacter pylori infection as well as regulating metabolism and microbiota. The intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer have attracted more and more attention. In order to better study and explore the role, advantages and challenges of phytochemicals in MNNG induced gastric cancer, we summarized the intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer. This review may help to further promote the research and clinical application of phytochemicals in MNNG induced gastric cancer, and provide some new insights.
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Affiliation(s)
- Ling Lu
- Child Healthcare Department, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Bei Chen
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - XinYi Zhang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yumeng Xu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Longtao Jin
- Child Healthcare Department, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Hui Qian
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Zhao feng Liang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
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Fu SJ, Xu MT, Wang B, Li BW, Ling H, Li Y, Wang Q, Liu XT, Zhang XY, Li AL, Liu MM. Global trend and future landscape of intestinal microcirculation research from 2000 to 2021: A scientometric study. World J Gastroenterol 2023; 29:1523-1535. [PMID: 36998427 PMCID: PMC10044859 DOI: 10.3748/wjg.v29.i9.1523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 02/01/2023] [Accepted: 02/24/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND The intestinal microcirculation functions in food absorption and metabolic substance exchanges. Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases. To date, there has not been a scientometric analysis of intestinal microcirculatory research.
AIM To investigate the current status, development trends, and frontiers of intestinal microcirculatory research based on bibliometric analysis.
METHODS VOSviewer and CiteSpace 6.1.R2 were used to identify the overall characteristics and knowledge map of intestinal microcirculatory research based on the core literature published from 2000 to 2021 in the Web of Science database. The characteristics of each article, country of origin, institution, journal, cocitations, and other information were analyzed and visualized.
RESULTS There were 1364 publications enrolled in the bibliometric analysis, exhibiting an upward trend from 2000 to 2021 with increased participation worldwide. The United States and Dalhousie University took the lead among countries and institutions, respectively. Shock was the most prolific journal, and Nature Reviews Microbiology Clinical had the most citations. The topical hotspots and frontiers in intestinal microcirculatory research were centered on the pathological processes of functional impairment of intestinal microvessels, diverse intestinal illnesses, and clinical treatment.
CONCLUSION Our study highlights insights into trends of the published research on the intestinal microcirculation and offers serviceable guidance to researchers by summarizing the prolific areas in intestinal disease research to date.
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Affiliation(s)
- Sun-Jing Fu
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Meng-Ting Xu
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Bing Wang
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Bing-Wei Li
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Hao Ling
- Department of Radiology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, Hunan Province, China
| | - Yuan Li
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Qin Wang
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Xue-Ting Liu
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Xiao-Yan Zhang
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Ai-Ling Li
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Ming-Ming Liu
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
- Diabetes Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
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Zhong YL, Wang PQ, Hao DL, Sui F, Zhang FB, Li B. Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review. World J Gastrointest Oncol 2023; 15:36-54. [PMID: 36684050 PMCID: PMC9850768 DOI: 10.4251/wjgo.v15.i1.36] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 12/06/2022] [Accepted: 12/28/2022] [Indexed: 01/10/2023] Open
Abstract
Gastric cancer (GC) is a common gastrointestinal tumor. Gastric precancerous lesions (GPL) are the last pathological stage before normal gastric mucosa transforms into GC. However, preventing the transformation from GPL to GC remains a challenge. Traditional Chinese medicine (TCM) has been used to treat gastric disease for millennia. A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL. This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC, especially focusing on anti-inflammatory, anti-angiogenesis, proliferation, and apoptosis. This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.
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Affiliation(s)
- Yi-Lin Zhong
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Peng-Qian Wang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Dan-Li Hao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Feng Sui
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Feng-Bin Zhang
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Bing Li
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
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Pei B, Wen Z, Yang Q, Wang J, Cao Q, Dai L, Li X. Risk Factors Analysis and Prediction Model Establishment of Intestinal Metaplasia or Dysplasia in Patients With Chronic Atrophic Gastritis: A Multi-Center Retrospective Study. Front Med (Lausanne) 2022; 9:912331. [PMID: 35665336 PMCID: PMC9157492 DOI: 10.3389/fmed.2022.912331] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 04/19/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To investigate the risk factors and construct a prediction model of chronic atrophic gastritis (CAG) patients with intestinal metaplasia or dysplasia. Method The clinical data of 450 patients with CAG who were diagnosed and treated in the Department of Gastroenterology of the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine from June 2016 to February 2022 were collected. Single and multiple factors logistic regression analysis were used to explore the risk factors of intestinal metaplasia or dysplasia in patients of training cohort. Then, we constructed a model to predict the onset of intestinal metaplasia or dysplasia based on the data of training cohort, following which we tested the model in an external validation cohort of 193 patients from a local university teaching hospital. The ROC curve, calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. Result Helicobacter pylori (H. pylori, HP) infection, pepsinogen I, gastrin-17, and the number of lesions were found to be independent rick factors of the model. The liner prediction model showed excellent predictive value in both training cohort and validation cohort. Conclusion HP infection, pepsinogen I, gastrin-17, and the number of lesions are independent risk factors for intestinal metaplasia or dysplasia in patients with CAG. The prediction model constructed based on these factors has a high accuracy and excellent calibration, which can provide a great basis for condition assessment and individualized treatment of the patients.
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Affiliation(s)
- Bei Pei
- The Graduated School, Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Ziang Wen
- The Graduated School, Anhui Medical University, Hefei, China
| | - Qi Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Jieyu Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Qinglin Cao
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Longfei Dai
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xuejun Li
- Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
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10
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Xu W, Li B, Xu M, Yang T, Hao X. Traditional Chinese medicine for precancerous lesions of gastric cancer: A review. Biomed Pharmacother 2021; 146:112542. [PMID: 34929576 DOI: 10.1016/j.biopha.2021.112542] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 12/12/2021] [Accepted: 12/13/2021] [Indexed: 01/30/2023] Open
Abstract
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years of precancerous lesions of gastric cancer (PLGC) stages before progressing to gastric malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven effective in treating PLGC. Classical TCM formulas and chemical components isolated from some Chinese herbal medicines have been administered to treat PLGC, and the main advantage is their comprehensive intervention with multiple approaches and multiple targets. In this review, we focus on recent studies using TCM treatment for PLGC, including clinical observations and experimental research, with a focus on targets and mechanisms of drugs. This review provides some ideas and a theoretical basis for applying TCM to treat PLGC and prevent GC.
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Affiliation(s)
- Weichao Xu
- Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China; Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine Gastroenterology, Shijiazhuang 050011, China
| | - Bolin Li
- Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China; Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine Gastroenterology, Shijiazhuang 050011, China
| | - Miaochan Xu
- Hebei University of Chinese Medicine, Shijiazhuang 050200, China
| | - Tianxiao Yang
- Hebei University of Chinese Medicine, Shijiazhuang 050200, China
| | - Xinyu Hao
- Peking University Third Hospital, Beijing 100191, China.
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11
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Huang MP, Gu SZ, Huang B, Li GW, Xiong ZP, Tang T, Zeng SN. Apatinib Inhibits Angiogenesis in Intrahepatic Cholangiocarcinoma by Regulating the Vascular Endothelial Growth Factor Receptor-2/Signal Transducer and Activator of Transcription Factor 3/Hypoxia Inducible Factor 1 Subunit Alpha Signaling Axis. Pharmacology 2021; 106:509-519. [PMID: 34412054 DOI: 10.1159/000514410] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 11/24/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of effective treatment, has risen over the past decades but without much improvement in prognosis. OBJECTIVE The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. METHODS MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. RESULTS We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. CONCLUSIONS Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy.
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Affiliation(s)
- Man-Ping Huang
- Department of Intervention Hunan, Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University, Changsha, China
| | - Shan-Zhi Gu
- Department of Intervention Hunan, Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University, Changsha, China
| | - Bin Huang
- Department of Intervention Hunan, Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University, Changsha, China
| | - Guo-Wen Li
- Department of Intervention Hunan, Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University, Changsha, China
| | - Zheng-Ping Xiong
- Department of Intervention Hunan, Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University, Changsha, China
| | - Tian Tang
- Department of Intervention Hunan, Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University, Changsha, China
| | - Sai-Nan Zeng
- Infection Controlling Center, The Third Xiangya Hospital of Central South University, Changsha, China
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12
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Yan Z, Xu T, Xu Y, Chen W, An Z, Zhu F. Jianpiyiqi formula ameliorates chronic atrophic gastritis in rats by modulating the Wnt/β-catenin signaling pathway. Exp Ther Med 2021; 22:878. [PMID: 34194556 PMCID: PMC8237394 DOI: 10.3892/etm.2021.10310] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 04/23/2021] [Indexed: 12/14/2022] Open
Abstract
Jianpiyiqi formula is a Traditional Chinese Medicine (TCM) prescription and is used for the clinical treatment of patients with chronic atrophic gastritis (CAG). The aim of the present study was to examine the underlying mechanisms of Jianpiyiqi formula treatment for CAG via the Wnt/β-catenin signaling pathway. The high-performance liquid chromatography (HPLC) chromatogram of Jianpiyiqi formula was constructed. A CAG rat model induced by N-methyl-N'-nitro-N-nitrosoguanidine and ranitidine was established. The body weight and food intake of the rats was recorded and rat gastric morphology was visually examined. Pathological analysis of rat gastric tissue was also performed. The levels of gastrin (GAS), pepsin (PP), somatostatin (SS) and prostaglandin E2 (PGE2) in rat serum were detected using ELISAs. The expression levels of proteins and genes associated with the Wnt/β-catenin signaling pathway were measured via immunohistochemistry and reverse transcription-quantitative PCR. The HPLC chromatogram of Jianpiyiqi formula was determined and as active components, liquiritin and hesperidin were identified from the chromatogram. Compared with the blank group, the body weight and feed intake of the rats were decreased, and gastric mucosal atrophy and inflammation appeared in the model group. Treatment with Jianpiyiqi formula increased the body weight and feed intake of the rats, as well as relieved the gastric atrophy and inflammation. The contents of GAS, PP, SS and PGE2 were significantly reduced in the model group compared with the blank group. Jianpiyiqi formula significantly increased GAS, PP, SS and PGE2 levels in serum of rats with CAG. In the model group, Wnt1, β-catenin and cyclin D1 protein expression levels were increased, and glycogen synthase kinase-3β (GSK-3β) protein expression levels were decreased. Jianpiyiqi formula decreased the protein expression levels of Wnt1, β-catenin and cyclin D1 and increased the protein expression levels of GSK-3β. Compared with the blank group, the mRNA expression levels of Wnt1, Wnt5a, β-catenin, cyclin D1 and MMP7 were upregulated, and the mRNA expression levels of GSK-3β were downregulated in the model group. Treatment with Jianpiyiqi formula downregulated the mRNA expression levels of Wnt1, Wnt5a, β-catenin, cyclin D1 and MMP7 and upregulated the mRNA expression levels of GSK-3β. All of the experimental results indicated that Jianpiyiqi formula exerted a therapeutic effect on rats with CAG and inhibited the activation of the Wnt/β-catenin signaling pathway. Thus, Jianpiyiqi formula, as an effective TCM prescription for treating patients with CAG, may be more widely used in the clinic.
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Affiliation(s)
- Zhanpeng Yan
- Clinical Research Department of Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.,Clinical Research Department of Chinese and Western Medicine, Jiangsu Province Institute of Traditional Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China
| | - Tingting Xu
- Clinical Research Department of Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.,Clinical Research Department of Chinese and Western Medicine, Jiangsu Province Institute of Traditional Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China
| | - Yuxuan Xu
- Clinical Research Department of Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China
| | - Wanzhen Chen
- Clinical Research Department of Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China
| | - Zhentao An
- Clinical Research Department of Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.,Clinical Research Department of Chinese and Western Medicine, Jiangsu Province Institute of Traditional Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China
| | - Fangshi Zhu
- Clinical Research Department of Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.,Clinical Research Department of Chinese and Western Medicine, Jiangsu Province Institute of Traditional Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China
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Integrating Network Pharmacology and Experimental Validation to Investigate the Mechanisms of Huazhuojiedu Decoction to Treat Chronic Atrophic Gastritis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:2638362. [PMID: 33354218 PMCID: PMC7735863 DOI: 10.1155/2020/2638362] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 10/05/2020] [Accepted: 10/21/2020] [Indexed: 12/14/2022]
Abstract
Background Chronic atrophic gastritis (CAG) is an important stage in the normal gastric mucosa's transformation into gastric cancer. Huazhuojiedu decoction (HZJD), a Chinese herbal preparation, has proven clinically effective to treat CAG. However, few studies have explored the mechanism of HZJD in CAG treatment. Purpose This study aimed to shed light on the mechanisms underlying HZJD decoction CAG treatment using a network pharmacology approach and experimental validation. Methods The active components of HZJD decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Their targets were predicted through the SwissTargetPrediction database. Disease targets were screened using the GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets, which then were input into the Search Tool for the Retrieval of Interacting Genes to build a protein-protein interaction network. The “herb-compound-target-disease” and the “herb-target-pathway” network diagrams were constructed in Cytoscape 3.3.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of effective targets were performed using the Database for Annotation, Visualization, and Integrated Discovery. Finally, the core targets were preliminarily verified by CAG rat model. The gastric mucosa's histopathological changes were observed via hematoxylin-eosin staining. The expressions of MAPK1, AKT1, TNF, VEGFA, and EGFR were detected by western blot and quantitative real-time reverse transcription-polymerase chain reaction. Results A total of 155 nodes, including 20 putative targets of HZJD decoction, were selected as core hubs based on topological importance and were closely associated with the regulation of cell proliferation, apoptotic process, and cancer-related pathways (AKT1, TNF, VEGFA, and EGFR) in CAG. Further animal experiments showed that the expression of AKT1 in CAG rats was significantly increased, which was suppressed by HZJD decoction. TNF and VEGFA expression increased in the model group, but did not change in the HZJD group. MAPK1 and EGFR expression showed no significant differences among control, model, and HZJD groups. Conclusion Taken together, the results suggest that the components of HZJD decoction can alleviate and prevent the severity of gastric precancerous lesions via AKT1 inhibition in CAG.
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Li RL, He LY, Zhang Q, Liu J, Lu F, Duan HXY, Fan LH, Peng W, Huang YL, Wu CJ. HIF-1α is a Potential Molecular Target for Herbal Medicine to Treat Diseases. DRUG DESIGN DEVELOPMENT AND THERAPY 2020; 14:4915-4949. [PMID: 33235435 PMCID: PMC7680173 DOI: 10.2147/dddt.s274980] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 10/22/2020] [Indexed: 12/12/2022]
Abstract
HIF-1α is an important factor regulating oxygen balance in mammals, and its expression is closely related to various physiological and pathological conditions of the body. Because HIF-1α plays an important role in the occurrence and development of cancer and other diseases, it has become an enduring research hotspot. At the same time, natural medicines and traditional Chinese medicine compounds have amazing curative effects in various diseases related to HIF-1 subtype due to their unique pharmacological effects and more effective ingredients. Therefore, in this article, we first outline the structure of HIF-1α and the regulation related to its expression, then introduce various diseases closely related to HIF-1α, and finally focus on the regulation of natural medicines and compound Chinese medicines through various pathways. This will help us understand HIF-1α systematically, and use HIF-1α as a target to discover more natural medicines and traditional Chinese medicines that can treat related diseases.
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Affiliation(s)
- Ruo-Lan Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People's Republic of China
| | - Li-Ying He
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People's Republic of China
| | - Qing Zhang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People's Republic of China
| | - Jia Liu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People's Republic of China
| | - Feng Lu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People's Republic of China
| | - Hu-Xin-Yue Duan
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People's Republic of China
| | - Lin-Hong Fan
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People's Republic of China
| | - Wei Peng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People's Republic of China
| | - Yong-Liang Huang
- Pharmacy Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, People's Republic of China
| | - Chun-Jie Wu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, People's Republic of China
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A Systematic Review of the Mechanisms Underlying Treatment of Gastric Precancerous Lesions by Traditional Chinese Medicine. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:9154738. [PMID: 32454874 PMCID: PMC7212333 DOI: 10.1155/2020/9154738] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 03/08/2020] [Accepted: 03/16/2020] [Indexed: 01/19/2023]
Abstract
Gastric precancerous lesions (GPLs) are an essential precursor in the occurrence and development of gastric cancer, known to be one of the most common and lethal cancers worldwide. Traditional Chinese medicine (TCM) has a positive prospect for the prevention and therapy of GPL owing to several advantages including a definite curative effect, fewer side effects compared to other treatments, multiple components, and holistic regulation. Despite these characteristic advantages, the mechanisms of TCM in treating GPL have not been fully elucidated. In this review, we summarize the current knowledge with respect to herbal formulations and the therapeutic mechanisms of TCM active ingredients for GPL. This paper elaborates on the mechanisms of TCM underlying the prevention and treatment of GPL, specifically those that are linked to anti-H. pylori, anti-inflammation, antiproliferation, proapoptotic, antioxidation, antiglycolytic, and antiangiogenesis effects.
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