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Hou YX, Ren W, He QQ, Huang LY, Gao TH, Li H. Tetramethylpyrazine induces reactive oxygen species-based mitochondria-mediated apoptosis in colon cancer cells. World J Gastrointest Oncol 2025; 17:104922. [DOI: 10.4251/wjgo.v17.i4.104922] [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: 01/08/2025] [Revised: 01/26/2025] [Accepted: 02/21/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. Chemotherapy resistance is the main cause of recurrence and progression in colon cancer. Thus, novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors.
AIM To investigate the potential anticancer activity of TMP in colon cancer and the underlying mechanisms.
METHODS Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay, and cell apoptosis was assessed by flow cytometry. Apoptosis-associated protein expression was measured using Western blot analysis. Intracellular reactive oxygen species (ROS) levels were assessed by flow cytometry using DCF fluorescence intensity. Xenografts were established by the subcutaneous injection of colon cancer cells into nude mice; tumor growth was monitored and intracellular ROS was detected in tumors by malondialdehyde assay.
RESULTS TMP induced apoptosis of colon cancer cells via the activation of the mitochondrial pathway. TMP increased the generation of intracellular ROS and triggered mitochondria-mediated apoptosis in a caspase-dependent manner.
CONCLUSION Our study demonstrates that TMP induces the apoptosis of colon cancer cells and increases the generation of intracellular ROS. TMP triggers mitochondria-mediated apoptosis in a caspase-dependent manner. The accumulation of intracellular ROS is involved in TMP-induced apoptosis. Our findings suggest that TMP may be a potential therapeutic drug for the treatment of colon cancer.
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Affiliation(s)
- Yan-Xu Hou
- The Second Department of Gastrointestinal Oncology Surgery, Xingtai People’s Hospital of Hebei Medical University, Xingtai 054001, Hebei Province, China
| | - Wei Ren
- The Second Department of Gastrointestinal Oncology Surgery, Xingtai People’s Hospital of Hebei Medical University, Xingtai 054001, Hebei Province, China
| | - Qing-Qiang He
- The Second Department of Gastrointestinal Oncology Surgery, Xingtai People’s Hospital of Hebei Medical University, Xingtai 054001, Hebei Province, China
| | - Li-Yan Huang
- The Second Department of Gastrointestinal Oncology Surgery, Xingtai People’s Hospital of Hebei Medical University, Xingtai 054001, Hebei Province, China
| | - Tian-Hua Gao
- The Second Department of Gastrointestinal Oncology Surgery, Xingtai People’s Hospital of Hebei Medical University, Xingtai 054001, Hebei Province, China
| | - Hua Li
- The Second Department of Gastrointestinal Oncology Surgery, Xingtai People’s Hospital of Hebei Medical University, Xingtai 054001, Hebei Province, China
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Hassan EA, Abdelnaser A, Ibrahim S, Yousef EH, Mosallam AM, Zayed SE. 5H Pyrolo(3,4-b)Pyrazin-5,7-(6H)-dione 6-(N-Chitosanimide nanoparticle) composite nano silver and encapsulation in γ-cyclodextrin: Synthesis, molecular docking, and biological evaluation for thyroid cancer treatment. Int J Biol Macromol 2025; 304:140859. [PMID: 39947539 DOI: 10.1016/j.ijbiomac.2025.140859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/14/2025] [Accepted: 02/08/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND Thyroid cancer is rapidly increasing worldwide, with some patients facing poor prognosis and recurrence despite current treatments. Chitosan-based nanoparticles have exhibited exciting antitumor efficacy both in vitro and in vivo, which indicates that there is vast scope of clinical application. This study develops a anhydride-modified chitosan and anhydride-modified chitosan‑silver nanoparticles, encapsulated in γ-cyclodextrin to help drug delivery by safe way and enhance thyroid cancer therapy. METHODS 5H pyrolo(3,4-b)pyrazin-5,7-(6H)-dione-6-(N-chitosanimide nanoparticle(composite constructed with nano silver (B1) was prepared and the optimized formula was further investigated regarding FT-IR, X-RD, SEM and TEM. Furthermore, it was encapsulated in γ-CD, and an in vivo study was conducted to investigate its anticancer activity. The binding affinities of 2,3-Pyrazinedicarboxylic anhydride to inhibitor of kappa B kinase beta (IKK-β) was demonstrated by molecular docking. RESULTS SEM and TEM revealed that Ag NPs were mostly uniformly incorporated into the 5H pyrolo(3,4-b)pyrazin-5,7-(6H)-dione 6-(N-chitosanimide nanoparticle, while FT-IR and X-RD findings verified the formation of 5H pyrolo(3,4-b)pyrazin-5,7-(6H)-dione-6-(N-chitosanimide nanoparticle)/composite constructed with nano silver and encapsulated in γ-CD (B2). γ-CD encapsulation induced a significant enhancement in pyrazine thyroid antitumor activity in xenografic model. CONCLUSION B2 could be considered a promising formula for suppression of thyroid cancer by modulating NF-κB signaling pathway, and hence, future studies could be planned to transfer our formula to the clinical field.
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Affiliation(s)
- Entesar A Hassan
- Department of Chemistry, Faculty of Science, South Valley University, Qena, 83523, Egypt
| | - Amira Abdelnaser
- Department of Chemistry, Faculty of Science, South Valley University, Qena, 83523, Egypt
| | - Samar Ibrahim
- Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, Galala University, Ataka, Egypt
| | - Eman H Yousef
- Pharmacology and Biochemistry Department, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt.
| | - Ahmed M Mosallam
- Department of Chemistry, Faculty of Science, South Valley University, Qena, 83523, Egypt
| | - Salem E Zayed
- Department of Chemistry, Faculty of Science, South Valley University, Qena, 83523, Egypt
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Li S, Zhu Z, Chen Z, Guo Z, Wang Y, Li X, Ma K. Network pharmacology-based investigation of the effects of Shenqi Fuzheng injection on glioma proliferation and migration via the SRC/PI3K/AKT signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2024; 328:118128. [PMID: 38561056 DOI: 10.1016/j.jep.2024.118128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/23/2024] [Accepted: 03/28/2024] [Indexed: 04/04/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE In the clinic, Shenqi Fuzheng Injection (SFI) is used as an adjuvant for cancer chemotherapy. However, the molecular mechanism is unclear. AIM OF THE STUDY We screened potential targets of SFI action on gliomas by network pharmacology and performed experiments to validate possible molecular mechanisms against gliomas. MATERIALS AND METHODS We consulted relevant reports on the SFI and glioma incidence from PubMed and Web of Science and focused on the mechanism through which the SFI inhibits glioma. According to the literature, two primary SFI components-Codonopsis pilosula (Franch.) Nannf. and Astragalus membranaceus (Fisch.) Bunge-have been found. All plant names have been sourced from "The Plant List" (www.theplantlist.org). The cell lines U87, T98G and GL261 were used in this study. The inhibitory effects of SFI on glioma cells U87 and T98G were detected by CCK-8 assay, EdU, plate cloning assay, scratch assay, Transwell assay, immunofluorescence, flow cytometry and Western blot. A subcutaneous tumor model of C57BL/6 mice was constructed using GL261 cells, and the SFI was evaluated by HE staining and immunohistochemistry. The targets of glioma and the SFI were screened using network pharmacology. RESULTS A total of 110 targets were enriched, and a total of 26 major active components in the SFI were investigated. There were a total of 3,343 targets for gliomas, of which 79 targets were shared between the SFI and glioma tissues. SFI successfully prevented proliferation and caused cellular S-phase blockage in U87 and T98G cells, thus decreasing their growth. Furthermore, SFI suppressed cell migration by downregulating EMT marker expression. According to the results of the in vivo tests, the SFI dramatically decreased the development of tumors in a transplanted tumour model. Network pharmacological studies revealed that the SRC/PI3K/AKT signaling pathway may be the pathway through which SFI exerts its anti-glioma effects. CONCLUSIONS The findings revealed that the SRC/PI3K/AKT signaling pathway may be involved in the mechanism through which SFI inhibits the proliferation and migration of glioma cells.
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Affiliation(s)
- Shuang Li
- The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University Medical College, Shihezi, 832000, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi, 832002, China; Department of Pathophysiology, School of Medicine, Shihezi University, Shihezi, 832000, China.
| | - Zhenglin Zhu
- The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University Medical College, Shihezi, 832000, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi, 832002, China; Department of Pathophysiology, School of Medicine, Shihezi University, Shihezi, 832000, China.
| | - Zhijian Chen
- The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University Medical College, Shihezi, 832000, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi, 832002, China; Department of Pathophysiology, School of Medicine, Shihezi University, Shihezi, 832000, China.
| | - Zhenli Guo
- The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University Medical College, Shihezi, 832000, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi, 832002, China; Department of Physiology, Shihezi University Medical College, Shihezi, 832000, China.
| | - Yan Wang
- The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University Medical College, Shihezi, 832000, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi, 832002, China.
| | - Xinzhi Li
- The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University Medical College, Shihezi, 832000, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi, 832002, China; Department of Pathophysiology, School of Medicine, Shihezi University, Shihezi, 832000, China.
| | - Ketao Ma
- The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University Medical College, Shihezi, 832000, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi, 832002, China; Department of Physiology, Shihezi University Medical College, Shihezi, 832000, China.
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Ma Y, Cui Q, Zhu W, Wang M, Zhai L, Hu W, Liu D, Liu M, Li Y, Li M, Han W. A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK. Drug Des Devel Ther 2024; 18:1531-1546. [PMID: 38737331 PMCID: PMC11088378 DOI: 10.2147/dddt.s449139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 04/30/2024] [Indexed: 05/14/2024] Open
Abstract
Purpose Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.
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Affiliation(s)
- Yan Ma
- Qingdao Key Laboratory of Common Diseases, Qingdao Municipal Hospital, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 260071, People’s Republic of China
- Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China
| | - Qian Cui
- Department of Respiratory and Critical Care Medicine, Shenzhen Luohu People’s Hospital, Shenzhen, 518000, People’s Republic of China
| | - Wenjing Zhu
- Qingdao Key Laboratory of Common Diseases, Qingdao Municipal Hospital, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 260071, People’s Republic of China
- NMPA Key Laboratory for Quality Research and Evaluation of Traditional Marine Chinese Medicine, Qingdao, 266071, People’s Republic of China
| | - Mei Wang
- Qingdao Key Laboratory of Common Diseases, Qingdao Municipal Hospital, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 260071, People’s Republic of China
- Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China
| | - Li Zhai
- Department of Pharmacy, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China
| | - Wenmin Hu
- Qingdao Key Laboratory of Common Diseases, Qingdao Municipal Hospital, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 260071, People’s Republic of China
- Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China
| | - Dongdong Liu
- Department of Respiratory and Critical Care Medicine, Shanting District People’s Hospital, Zaozhuang, 277200, People’s Republic of China
| | - Min Liu
- Department of Pharmacy, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China
| | - Yongchun Li
- Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China
| | - Meng Li
- Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China
| | - Wei Han
- Qingdao Key Laboratory of Common Diseases, Qingdao Municipal Hospital, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 260071, People’s Republic of China
- Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, People’s Republic of China
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Liu Y, Li M, Hong X, Li H, Huang R, Han S, Hou J, Pan C. Screening and identification of high yield tetramethylpyrazine strains in Nongxiangxing liquor Daqu and study on the mechanism of tetramethylpyrazine production. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:6849-6860. [PMID: 37293782 DOI: 10.1002/jsfa.12773] [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: 03/06/2023] [Revised: 05/30/2023] [Accepted: 06/09/2023] [Indexed: 06/10/2023]
Abstract
BACKGROUND There are few reports on the breeding of high-yielding tetramethylpyrazine (TTMP) strains in strong-flavor Daqu. In addition, studies on the mechanism of TTMP production in strains are mostly based on common physiological and biochemical indicators, and there is no report on RNA level. Therefore, in this study, a strain with high production of TTMP was screened out from strong-flavor liquor, and transcriptome sequencing analysis was performed to analyze its key metabolic pathways and key genes, and to infer the mechanism of TTMP production in the strain. RESULTS In this study, a strain with a high yield of tetramethylpyrazine (TTMP) was screened out, and the yield was 29.83 μg mL-1 . The identified strain was Bacillus velezensis, which could increase the content of TTMP in liquor by about 88%. After transcriptome sequencing, a total of 1851 differentially expressed genes were screened, including 1055 up-regulated genes and 796 down-regulated genes. Three pathways related to the production of TTMP were identified by gene ontology (GO) annotation and COG annotation, including carbohydrate metabolism, cell movement and amino acid metabolism. The key genes of TTMP were analyzed, and the factors that might regulate the production of TTMP, such as the transfer of uracil phosphate ribose and glycosyltransferase, were obtained. CONCLUSIONS A strain of B. velezensis with high TTMP production was screened and identified in strong-flavor Daqu for the first time. The yield of TTMP was 29.83 μg mL-1 , which increased the TTMP content in liquor by 88%. The key metabolic pathways of TTMP production in the strain were obtained: carbohydrate metabolism, cell movement and amino acid metabolism, and the key regulatory genes of each pathway were found, which complemented the gap in gene level in the production regulation of the strain, and provided a theoretical basis for the subsequent study of TTMP in liquor. © 2023 Society of Chemical Industry.
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Affiliation(s)
- Yanbo Liu
- College of Food and Biological Engineering (Liquor College), Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Henan Liquor Style Engineering Technology Research Center, Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Henan Province Brewing Special Grain Development and Application Engineering Research Center, Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Zhengzhou Key Laboratory of Liquor Brewing Microbial Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, China
| | - Mengke Li
- College of Food and Biological Engineering (Liquor College), Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Henan Liquor Style Engineering Technology Research Center, Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Henan Province Brewing Special Grain Development and Application Engineering Research Center, Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Zhengzhou Key Laboratory of Liquor Brewing Microbial Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, China
| | - Xinfeng Hong
- College of Food and Biological Engineering (Liquor College), Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Henan Liquor Style Engineering Technology Research Center, Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Henan Province Brewing Special Grain Development and Application Engineering Research Center, Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Zhengzhou Key Laboratory of Liquor Brewing Microbial Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, China
| | - Haideng Li
- College of Food and Biological Engineering (Liquor College), Henan University of Animal Husbandry and Economy, Zhengzhou, China
- College of Biological Engineering, Henan University of Technology, Zhengzhou, China
| | - Runna Huang
- Henan Yangshao Distillery Co., Ltd., Mianchi, China
| | - Suna Han
- Henan Yangshao Distillery Co., Ltd., Mianchi, China
| | | | - Chunmei Pan
- College of Food and Biological Engineering (Liquor College), Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Henan Liquor Style Engineering Technology Research Center, Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Henan Province Brewing Special Grain Development and Application Engineering Research Center, Henan University of Animal Husbandry and Economy, Zhengzhou, China
- Zhengzhou Key Laboratory of Liquor Brewing Microbial Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, China
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Tetramethylpyrazine: A review on its mechanisms and functions. Biomed Pharmacother 2022; 150:113005. [PMID: 35483189 DOI: 10.1016/j.biopha.2022.113005] [Citation(s) in RCA: 93] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 04/15/2022] [Accepted: 04/19/2022] [Indexed: 11/21/2022] Open
Abstract
Ligusticum chuanxiong Hort (known as Chuanxiong in China, CX) is one of the most widely used and long-standing medicinal herbs in China. Tetramethylpyrazine (TMP) is an alkaloid and one of the active components of CX. Over the past few decades, TMP has been proven to possess several pharmacological properties. It has been used to treat a variety of diseases with excellent therapeutic effects. Here, the pharmacological characteristics and molecular mechanism of TMP in recent years are reviewed, with an emphasis on the signal-regulation mechanism of TMP. This review shows that TMP has many physiological functions, including anti-oxidant, anti-inflammatory, and anti-apoptosis properties; autophagy regulation; vasodilation; angiogenesis regulation; mitochondrial damage suppression; endothelial protection; reduction of proliferation and migration of vascular smooth muscle cells; and neuroprotection. At present, TMP is used in treating cardiovascular, nervous, and digestive system conditions, cancer, and other conditions and has achieved good curative effects. The therapeutic mechanism of TMP involves multiple targets, multiple pathways, and bidirectional regulation. TMP is, thus, a promising drug with great research potential.
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Pei K, Cao L, Cao G, Cai H, Ning Y, Zhao T, Sun L, Liu H, Zhang S. A Reasonable Evaluation of Chuanxiong Rhizoma Processing with Wine through Comparative Pharmacokinetic Study of Bioactive Components: Dominant Effect on Middle Cerebral Artery Occlusion Model Rats. JOURNAL OF ANALYTICAL METHODS IN CHEMISTRY 2022; 2022:8252038. [PMID: 35321518 PMCID: PMC8938140 DOI: 10.1155/2022/8252038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 11/06/2021] [Accepted: 02/15/2022] [Indexed: 06/14/2023]
Abstract
According to the ancient documents and Chinese herbal medicine processing experience, Chuanxiong Rhizoma was usually processed with yellow rice wine to improve efficacy. However, the relevant mechanisms are still unclear so far. In this study, a validated ultrahigh-performance liquid chromatography tandem mass spectrometry method was used to compare the pharmacokinetics of four representative components in middle cerebral artery occlusion rats after oral administration of raw and wine-processed Chuanxiong Rhizoma. The neurobehavioral scores and 2,3,5-triphenyltetrazolium chloride staining were employed to evaluate the model. Biological samples were prepared by protein precipitation with methanol. All analytes were separated on an ACQUITY BEH C18 column through gradient elution using acetonitrile and 0.01% of formic acid as mobile phase, and the flow rate was 0.3 mL/min. The results showed that the maximum plasma concentrations, the area values under the concentration-time curves of senkyunolide A, and ferulic acid in wine-processed Chuanxiong Rhizoma were all higher than in raw Chuanxiong Rhizoma, which were completely opposite to our previous studies in normal rats. Compared with normal rats, the theory that wine processing could enhance the efficacy of Chuanxiong Rhizoma may be better reflected in model rats.
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Affiliation(s)
- Ke Pei
- Shanxi Engineering Laboratory of Modern Chinese Medicine, School of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, China
| | - Lilong Cao
- Shanxi Engineering Laboratory of Modern Chinese Medicine, School of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, China
| | - Gang Cao
- Research Center of TCM Processing Technology, Zhejiang Chinese Medical University, Hangzhou, China
| | - Hao Cai
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yan Ning
- Research Center of TCM Processing Technology, Zhejiang Chinese Medical University, Hangzhou, China
| | - Tingting Zhao
- Shanxi Engineering Laboratory of Modern Chinese Medicine, School of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, China
| | - Lin Sun
- Shanxi Engineering Laboratory of Modern Chinese Medicine, School of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, China
| | - Haixin Liu
- Shanxi Engineering Laboratory of Modern Chinese Medicine, School of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, China
| | - Shuosheng Zhang
- Shanxi Engineering Laboratory of Modern Chinese Medicine, School of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, China
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Ren J, Cai J, Wang C. Tetramethylpyrazine inhibits the proliferation, invasiveness and migration of cervical cancer C33A cells by retarding the Hedgehog signaling pathway. Oncol Lett 2022; 23:66. [PMID: 35069875 PMCID: PMC8756559 DOI: 10.3892/ol.2022.13185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 09/08/2021] [Indexed: 11/05/2022] Open
Affiliation(s)
- Jing Ren
- Department of Biochemistry, Shijiazhuang Medical College, Shijiazhuang, Hebei 050000, P.R. China
| | - Jiping Cai
- Department of Biochemistry, Shijiazhuang Medical College, Shijiazhuang, Hebei 050000, P.R. China
| | - Changfeng Wang
- Department of Biochemistry, Shijiazhuang Medical College, Shijiazhuang, Hebei 050000, P.R. China
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Zhang Y, Yang Y, Liang H, Zeng P, Fu W, Yu J, Chen L, Chai D, Wen Y, Chen A. Synthesis, characterization, and anti-hepatocellular carcinoma effect of glycyrrhizin-coupled bovine serum albumin-loaded luteolin nanoparticles. Pharmacogn Mag 2022. [DOI: 10.4103/pm.pm_34_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Yang S, Wu S, Dai W, Pang L, Xie Y, Ren T, Zhang X, Bi S, Zheng Y, Wang J, Sun Y, Zheng Z, Kong J. Tetramethylpyrazine: A Review of Its Antitumor Potential and Mechanisms. Front Pharmacol 2021; 12:764331. [PMID: 34975475 PMCID: PMC8716857 DOI: 10.3389/fphar.2021.764331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 11/18/2021] [Indexed: 11/13/2022] Open
Abstract
Cancer remains a major public health threat. The mitigation of the associated morbidity and mortality remains a major research focus. From a molecular biological perspective, cancer is defined as uncontrolled cell division and abnormal cell growth caused by various gene mutations. Therefore, there remains an urgent need to develop safe and effective antitumor drugs. The antitumor effect of plant extracts, which are characterized by relatively low toxicity and adverse effect, has attracted significant attention. For example, increasing attention has been paid to the antitumor effects of tetramethylpyrazine (TMP), the active component of the Chinese medicine Chuanqiong, which can affect tumor cell proliferation, apoptosis, invasion, metastasis, and angiogenesis, as well as reverse chemotherapeutic resistance in neoplasms, thereby triggering antitumor effects. Moreover, TMP can be used in combination with chemotherapeutic agents to enhance their effects and reduce the side effect associated with chemotherapy. Herein, we review the antitumor effects of TMP to provide a theoretical basis and foundation for the further exploration of its underlying antitumor mechanisms and promoting its clinical application.
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Affiliation(s)
- Shaojie Yang
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shuodong Wu
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wanlin Dai
- Innovation Institute of China Medical University, Shenyang, China
| | - Liwei Pang
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yaofeng Xie
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tengqi Ren
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaolin Zhang
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shiyuan Bi
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yuting Zheng
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jingnan Wang
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yang Sun
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhuyuan Zheng
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jing Kong
- Biliary Surgery (2nd General) Unit, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Jing Kong,
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11
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Li H, Hou YX, Yang Y, He QQ, Gao TH, Zhao XF, Huo ZB, Chen SB, Liu DX. Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro. World J Clin Cases 2021; 9:4542-4552. [PMID: 34222421 PMCID: PMC8223836 DOI: 10.12998/wjcc.v9.i18.4542] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/27/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. However, chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer, and thus novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors.
AIM To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms.
METHODS Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry.
RESULTS TMP significantly inhibited the proliferation of colon cancer cells in a dose- and time-dependent manner. In addition, flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase. TMP treatment caused early stage apoptosis in SW480 cells, whereas it caused late stage apoptosis in HCT116 cells.
CONCLUSION Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose- and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase. Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.
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Affiliation(s)
- Hua Li
- Institute of Cancer Control, Xingtai People’s Hospital, Xingtai 054001, Hebei Province, China
| | - Yan-Xu Hou
- Institute of Cancer Control, Xingtai People’s Hospital, Xingtai 054001, Hebei Province, China
| | - Yu Yang
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Qing-Qiang He
- Institute of Cancer Control, Xingtai People’s Hospital, Xingtai 054001, Hebei Province, China
| | - Tian-Hua Gao
- Institute of Cancer Control, Xingtai People’s Hospital, Xingtai 054001, Hebei Province, China
| | - Xiao-Feng Zhao
- Institute of Cancer Control, Xingtai People’s Hospital, Xingtai 054001, Hebei Province, China
| | - Zhi-Bin Huo
- Institute of Cancer Control, Xingtai People’s Hospital, Xingtai 054001, Hebei Province, China
| | - Shu-Bo Chen
- Institute of Cancer Control, Xingtai People’s Hospital, Xingtai 054001, Hebei Province, China
| | - Deng-Xiang Liu
- Institute of Cancer Control, Xingtai People’s Hospital, Xingtai 054001, Hebei Province, China
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12
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Wu X, Wang Z, Wu G, Xu X, Zhang J, Li Y, Zhang H, Guo S. Tetramethylpyrazine Induces Apoptosis and Inhibits Proliferation of Hypertrophic Scar-Derived Fibroblasts via Inhibiting the Phosphorylation of AKT. Front Pharmacol 2020; 11:602. [PMID: 32431617 PMCID: PMC7214921 DOI: 10.3389/fphar.2020.00602] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 04/17/2020] [Indexed: 11/13/2022] Open
Abstract
Hypertrophic scar (HS) is a serious fibrotic skin disease and often considered as a kind of benign skin tumor. Tetramethylpyrazine (TMP), the main chemical composition of the traditional Chinese medicine Chuanxiong Rhizoma, has shown significant clinical benefits in the treatment of fibrosis disease and tumor, while the role in HS and the concrete mechanisms remain elusive. Herein, the protective effects of TMP in the treatment of HS was investigated and the results showed that the protein expression levels of type I collagen (Col I), type III collagen (Col III), and α-smooth muscle actin (α-SMA) were all inhibited remarkably after addition of TMP in HS-derived fibroblasts (HFs). Moreover, TMP also suppressed fibroblast proliferative and induced cell apoptosis. The protein expression levels of Caspase-3 and Bcl-2 were all decreased comparing with the control group while proapoptotic proteins Bax and Cleaved Caspase-3 were increased. In addition, TMP treatment markedly reduced the phosphorylation levels of AKT. Taken together, our investigations demonstrated that TMP could down-regulate the expression of fibrosis-related molecules, inhibit scar fibroblast proliferation and activate cell apoptosis, during which AKT pathway was involved. Thus, this study shed more light on the pharmacological mechanisms of TMP, and provided a novel therapeutic alternative for prevention and treatment of HS.
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Affiliation(s)
- Xue Wu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.,Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Zheng Wang
- Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Gaofeng Wu
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Xiaofan Xu
- Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Jian Zhang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Yan Li
- Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China
| | - Hong Zhang
- Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Shuzhen Guo
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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13
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Zhou Y, Zhou Z, Ji Z, Yan W, Li H, Yu X. Tetramethylpyrazine reduces prostate cancer malignancy through inactivation of the DPP10‑AS1/CBP/FOXM1 signaling pathway. Int J Oncol 2020; 57:314-324. [PMID: 32319592 DOI: 10.3892/ijo.2020.5036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Accepted: 02/06/2020] [Indexed: 11/05/2022] Open
Abstract
Tetramethylpyrazine (TMP), a Chinese herbal medicine, has been reported to possess anticancer effects. Emerging evidence suggests that various long noncoding RNAs (lncRNAs) serve important roles in cancer initiation and progression. In the present study, the tumor‑suppressive effects of TMP in human PCa cells was examined and the underlying mechanisms of its actions were determined. The data showed that TMP treatment reduced cell viability and increased apoptosis in a dose‑dependent manner. Reverse transcription‑quantitative PCR showed TMP treatment increased the expression of lncRNA DPP10‑AS1 in PCa cells. Furthermore, DPP10‑AS1 was also upregulated in TMP‑resistant PCa cells. Knockdown of DPP10‑AS1 reversed TMP resistance, whereas increased expression of DPP10‑AS1 abrogated the TMP‑mediated cytotoxicity in PCa cells. In addition, forkhead box M1 (FOXM1) was verified as the functional target of DPP10‑AS1, and knockdown of FOXM1 reversed the TMP/DPP10‑AS1‑induced cell cytotoxicity. Mechanistically, DPP10‑AS1 was associated with CREB binding protein, thereby induced H3K27ac enrichment at the promoter region of the FOXM1 gene. In conclusion, the present study showed that TMP may be a promising treatment agent for PCa and lncRNA DPP10‑AS1 may be a promising therapeutic target for TMP treatment.
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Affiliation(s)
- Yi Zhou
- Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100000, P.R. China
| | - Zhien Zhou
- Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100000, P.R. China
| | - Zhigang Ji
- Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100000, P.R. China
| | - Weigang Yan
- Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100000, P.R. China
| | - Hanzhong Li
- Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100000, P.R. China
| | - Xiao Yu
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100000, P.R. China
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Jiawei Foshou San Induces Apoptosis in Ectopic Endometrium Based on Systems Pharmacology, Molecular Docking, and Experimental Evidence. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:2360367. [PMID: 31781263 PMCID: PMC6855060 DOI: 10.1155/2019/2360367] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 08/09/2019] [Accepted: 09/19/2019] [Indexed: 02/06/2023]
Abstract
Foshou San is a typical gynaecological formula with wild usage in traditional Chinese medicine. Jiawei Foshou San (JFS) is a novel ingredient prescription from Foshou San with antiendometriosis effect in unclear mechanisms. To uncover the potential application and proapoptotic mechanisms of JFS, JFS ingredient-drug target-disease networks, GO enrichment, and pathway analysis were established for potential application prediction. Molecular docking and validation in vivo were investigated by the proapoptotic mechanisms of JFS. In this study, 99 common targets were related to 108 diseases. 484 biological processes, 44 cell components, 59 molecular functions, and 37 pathways were significantly identified in GO enrichment and pathway analysis. In molecular docking, ligustrazine showed binding activity with Bcl-2, Bax, caspase-9, caspase-3, and PARP. In vivo, JFS elevated the shrink rate of ectopic endometrium, by suppressing E2 and PROG. An in-depth study showed that apoptosis was activated through diminishing Bcl-2, rising Bax and Bad, and expressing more caspase-3 and caspase-9 using JFS. JFS promoted the protein level of cleaved-PARP. In brief, JFS might be applied for various diseases through multiple targets and pathways, especially endometriosis by Bcl-2 pathway. These findings reveal the potential application for further evaluation and uncover the proapoptotic mechanism of JFS.
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