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Xie DM, Li ZY, Ren BK, Gong R, Yang D, Huang S. Tanshinone II A Facilitates Chemosensitivity of Osteosarcoma Cells to Cisplatin via Activation of p38 MAPK Pathway. Chin J Integr Med 2025; 31:326-335. [PMID: 39499413 DOI: 10.1007/s11655-024-4118-5] [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] [Accepted: 04/19/2024] [Indexed: 11/07/2024]
Abstract
OBJECTIVE To examine the mechanism of action of tanshinone II A (Tan II A) in promoting chemosensitization of osteosarcoma cells to cisplatin (DDP). METHODS The effects of different concentrations of Tan II A (0-80 µ mol/L) and DDP (0-2 µ mol/L) on the proliferation of osteosarcoma cell lines (U2R, U2OS, 143B, and HOS) at different times were examined using the cell counting kit-8 and colony formation assays. Migration and invasion of U2R and U2OS cells were detected after 24 h treatment with 30 µ mol/L Tan II A, 0.5 µ mol/L DDP alone, and a combination of 10 µ mol/L Tan II A and 0.25 µ mol/L DDP using the transwell assay. After 48 h of treatment of U2R and U2OS cells with predetermined concentrations of each group of drugs, the cell cycle was analyzed using a cell cycle detection kit and flow cytometry. After 48 h treatment, apoptosis of U2R and U2OS cells was detected using annexin V-FITC apoptosis detection kit and flow cytometry. U2R cells were inoculated into the unilateral axilla of nude mice and then the mice were randomly divided into 4 groups of 6 nude mice each. The 4 groups were treated with equal volume of Tan II A (15 mg/kg), DDP (3 mg/kg), Tan II A (7.5 mg/kg) + DDP (1.5 mg/kg), and normal saline, respectively. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell-related gene and signaling pathway expression were detected by RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis. p38 MAPK signaling pathway proteins and apoptotic protein expressions were detected by Western blot. RESULTS In vitro studies have shown that Tan II A, DDP and the combination of Tan II A and DDP inhibit the proliferation, migration and invasion of osteosarcoma cells. The inhibitory effect was more pronounced in the Tan II A and DDP combined treatment group (P<0.05 or P<0.01). Osteosarcoma cells underwent significantly cell-cycle arrest and cell apoptosis by Tan II A-DDP combination treatment (P<0.05 or P<0.01). In vivo studies demonstrated that the Tan II A-DD combination treatment group significantly inhibited tumor growth compared to the Tan II A and DDP single drug group (P<0.01). Additionally, we found that the combination of Tan II A and DDP treatment enhanced the p38 MAPK signaling pathway. Western blot assays showed higher p-p38, cleaved caspase-3, and Bax and lower caspase-3, and Bcl-2 expressions with the combination of Tan II A and DDP treatment compared to the single drug treatment (P<0.01). CONCLUSION Tan II A synergizes with DDP by activating the p38/MAPK pathway to upregulate cleaved caspase-3 and Bax pro-apoptotic gene expressions, and downregulate caspase-3 and Bcl-2 inhibitory apoptotic gene expressions, thereby enhancing the chemosensitivity of osteosarcoma cells to DDP.
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Affiliation(s)
- Da-Ming Xie
- Department of Orthopaedics, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, China
| | - Zhi-Yun Li
- Department of Orthopaedics, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
| | - Bing-Kai Ren
- Department of Orthopaedics, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
| | - Rui Gong
- Department of Clinical Medicine, Jiangxi Health Vocational College, Nanchang, 330052, China
| | - Dong Yang
- Department of Orthopaedics, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, China
| | - Sheng Huang
- Department of Orthopaedics, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
- Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang, 330006, China.
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Batool Z, Amjad Kamal M, Shen B. Advanced treatment strategies for high-altitude pulmonary hypertension employing natural medicines: A review. J Pharm Anal 2025; 15:101129. [PMID: 40161446 PMCID: PMC11953983 DOI: 10.1016/j.jpha.2024.101129] [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: 06/16/2024] [Revised: 10/08/2024] [Accepted: 10/22/2024] [Indexed: 04/02/2025] Open
Abstract
High-altitude pulmonary hypertension (HAPH) occurs when blood pressure in the pulmonary arteries rises due to exposure to high altitudes above 2,500 m. At these elevations, reduced atmospheric pressure leads to lower oxygen levels, triggering a series of physiological responses, including pulmonary artery constriction, which elevates blood pressure. This review explored the complex pathophysiological mechanisms of HAPH and reviewed current pharmaceutical interventions for its management. Meanwhile, this review particularly emphasized on the emerging research concerning Chinese medicinal plants as potential treatments for HAPH. Traditional Chinese medicines are rich in diverse natural ingredients that show significant promise in alleviating HAPH symptoms. We reviewed both in vitro and in vivo studies to assess the efficacy, safety, and mechanisms of these natural medicines, along with their potential adverse effects. Additionally, this review highlighted new alternative natural remedies, underscoring the need for ongoing research to expand available treatment options for HAPH.
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Affiliation(s)
- Zahra Batool
- Center of High Altitude Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Mohammad Amjad Kamal
- Center of High Altitude Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
- Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Dhaka, 1216, Bangladesh
- Centre for Global Health Research, Saveetha Medical College and Hospital, Chennai, Tamil Nadu, 600001, India
| | - Bairong Shen
- Center of High Altitude Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
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Zhou R, Zhang J, Zhang W, Zhang X, Zhang H, Shi X, Wang B, Zhang Q, Zhang H. Clinical efficacy and safety of Panax notoginseng saponins in treating chronic obstructive pulmonary disease with blood hypercoagulability: A meta-analysis of randomized controlled trials. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 125:155244. [PMID: 38216446 DOI: 10.1016/j.phymed.2023.155244] [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: 07/16/2023] [Revised: 09/05/2023] [Accepted: 11/24/2023] [Indexed: 01/14/2024]
Abstract
BACKGROUND Panax notoginseng saponins (PNS) are the primary active components of an ancient Chinese herb Panax notoginseng. Hypercoagulable state of blood (HCS) is an independent risk factor and a cause of death in chronic obstructive pulmonary disease (COPD). Several vivo studies have demonstrated the use of PNS preparations for treating COPD with HCS. PURPOSE This study aimed to systematically evaluate the clinical efficacy and safety of PNS preparations in treating COPD with HCS. STUDY DESIGN Meta-analysis of the randomized controlled trials (RCTs) was conducted to review data. METHODS RCTs on the treatment of COPD with HCS and PNS preparations were searched from PubMed, Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure, Vip Information Database, Wanfang data, and Chinese Biomedical Literature Database. Relevant data were extracted from the included studies and methodological quality evaluation was performed. R language (version 4.2.3) was applied for the meta-analysis. RESULTS Twenty RCTs involving 1831 patients were analyzed. The results revealed that PNS preparations considerably increased the total clinical efficiency, improved forced expiratory volume in one second percent of predicted, and forced expiratory volume/forced vital capacity ratio. Further, PNS preparations improved fibrinogen, plasma d-dimer, whole blood viscosity at high cut, whole blood viscosity at low cut, and plasma viscosity levels. The results obtained for activated partial thromboplastin and prothrombin times were not statistically significant. Finally, PNS preparations increased partial pressure of oxygen and decreased carbon dioxide pressure. CONCLUSION This is the first relatively comprehensive systematic review of the clinical efficacy and safety of PNS preparations for treating COPD with HCS. The study revealed that PNS preparations considerably improve lung function, hypoxia, and blood hypercoagulability in patients with COPD and HCS without increasing the risk of hemorrhage and has a good safety profile; therefore, it can be used as a new modulating agent and anticoagulant.
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Affiliation(s)
- Ruiling Zhou
- Beijing University of Chinese medicine, Beijing 100029, China; Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Jie Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Wen Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Xinyu Zhang
- Beijing University of Chinese medicine, Beijing 100029, China; Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Haiyan Zhang
- Beijing University of Chinese medicine, Beijing 100029, China
| | - Xia Shi
- Beijing University of Chinese medicine, Beijing 100029, China
| | - Bing Wang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Qiong Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
| | - He Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
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Li HD, Li MX, Zhang WH, Zhang SW, Gong YB. Effectiveness and safety of traditional Chinese medicine for diabetic retinopathy: A systematic review and network meta-analysis of randomized clinical trials. World J Diabetes 2023; 14:1422-1449. [PMID: 37771328 PMCID: PMC10523233 DOI: 10.4239/wjd.v14.i9.1422] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/14/2023] [Accepted: 07/29/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Diabetic retinopathy (DR) is currently recognized as one of the most serious diabetic microangiopathies and a major cause of adult blindness. Commonly used clinical approaches include etiological control, microvascular improvement, and surgical intervention, but they are ineffective and have many side effects. Oral Chinese medicine (OCM) has been used for thousands of years to treat DR and is still widely used today, but it is unclear which OCM is more effective for DR. AIM To estimate relative effectiveness and safety profiles for different classes of OCMs for DR, and provide rankings of the available OCMs. METHODS The search time frame was from the creation of the database to January 2023. RevMan 5.3 and Stata 14.0 software were used to perform the systematic review and Network meta-analyses (NMA). RESULTS A total of 107 studies and 9710 patients were included, including 4767 cases in the test group and 4973 cases in the control group. Based on previous studies and clinical reports, and combined with the recommendations of Chinese guidelines for the prevention and treatment of DR, 9 OCMs were finally included in this study, namely Compound Xueshuantong Capsules, Qiming Granules, Compound Danshen Dripping Pills, Hexue Mingmu Tablets (HXMM), Qiju Dihuang Pills (QJDH), Shuangdan Mingmu Capsules (SDMM), Danggui Buxue Decoction (DGBX), Xuefu Zhuyu Decoction and Buyang Huanwu Decoction. When these nine OCMs were analyzed in combination with conventional western medicine treatment (CT) compared with CT alone, the NMA results showed that HXMM + CT has better intervention effect on the overall efficacy of DR patients, HXMM + CT has better effect on improving patients' visual acuity, SDMM + CT has better effect on inhibiting vascular endothelial growth factor, DGBX + CT has better effect on reducing fundus hemorrhage area, HXMM + CT has better effect on reducing fasting blood glucose, and QJDH + CT has better effect on reducing glycated hemoglobin. When there are not enough clinical indicators for reference, SDMM + CT or HXMM + CT treatments can be chosen because they are effective for more indicators and demonstrate multidimensional efficacy. CONCLUSION This study provides evidence that combining OCMs with CT leads to better outcomes in all aspects of DR compared to using CT alone. Based on the findings, we highly recommend the use of SDMM or HXMM for the treatment of DR. These two OCMs have demonstrated outstanding efficacy across multiple indicators.
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Affiliation(s)
- Hong-Dian Li
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Ming-Xuan Li
- Capital Medical University, Beijing Hospital of Traditional Chinese Medicine, Beijing 100010, China
| | - Wen-Hua Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Shu-Wen Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Yan-Bing Gong
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
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Bhatia T, Gupta GD, Kurmi BD, Singh D. Role of solid lipid nanoparticle for the delivery of Lipophilic Drugs and Herbal Medicines in the treatment of pulmonary hypertension. Pharm Nanotechnol 2022; 10:PNT-EPUB-126042. [PMID: 36045536 DOI: 10.2174/2211738510666220831113857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 03/02/2022] [Accepted: 03/29/2022] [Indexed: 11/22/2022]
Abstract
Pulmonary arterial hypertension (PAH) is an uncommon condition marked by elevated pulmonary artery pressure that leads to right ventricular failure. The majority of drugs are now been approved by FDA for PAH, however, several biopharmaceutical hindrances lead to failure of the therapy. Various novel drug delivery systems are available in the literature from which lipid-based nanoparticles i.e. solid lipid nanoparticle is widely investigated for improving the solubility and bioavailability of drugs. In this paper, the prototype phytoconstituents used in pulmonary arterial hypertension have limited solubility and bioavailability. We highlighted the novel concepts of SLN for lipophilic phytoconstituents with their potential applications. This paper also reviews the present state of the art regarding production techniques for SLN like High-Pressure Homogenization, Micro-emulsion Technique, and Phase Inversion Temperature Method, etc. Furthermore, toxicity aspects and in vivo fate of SLN are also highlighted in this review. In a nutshell, safer delivery of phytoconstituents by SLN added a novel feather to the cap of successful drug delivery technologies.
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Affiliation(s)
- Tanuja Bhatia
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab (142001), India
| | - G D Gupta
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab (142001), India
| | - Balak Das Kurmi
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab (142001), India
| | - Dilpreet Singh
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab (142001), India
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Xue Z, Li Y, Zhou M, Liu Z, Fan G, Wang X, Zhu Y, Yang J. Traditional Herbal Medicine Discovery for the Treatment and Prevention of Pulmonary Arterial Hypertension. Front Pharmacol 2021; 12:720873. [PMID: 34899290 PMCID: PMC8660120 DOI: 10.3389/fphar.2021.720873] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 10/11/2021] [Indexed: 12/17/2022] Open
Abstract
Pulmonary arterial hypertension (PAH) is characterized by pulmonary artery remodeling that may subsequently culminate in right heart failure and premature death. Although there are currently both non-pharmacological (lung transplantation, etc.) and pharmacological (Sildenafil, Bosentan, and new oral drugs on trial) therapies available, PAH remains a serious and fatal pulmonary disease. As a unique medical treatment, traditional herbal medicine (THM) treatment has gradually exerted its advantages in treating PAH worldwide through a multi-level and multi-target approach. Additionally, the potential mechanisms of THM were deciphered, including suppression of proliferation and apoptosis of pulmonary artery smooth muscle cells, controlling the processes of inflammation and oxidative stress, and regulating vasoconstriction and ion channels. In this review, the effects and mechanisms of the frequently studied compound THM, single herbal preparations, and multiple active components from THM are comprehensively summarized, as well as their related mechanisms on several classical preclinical PAH models. It is worth mentioning that sodium tanshinone IIA sulfonate sodium and tetramethylpyrazine are under clinical trials and are considered the most promoting medicines for PAH treatment. Last, reverse pharmacology, a strategy to discover THM or THM-derived components, has also been proposed here for PAH. This review discusses the current state of THM, their working mechanisms against PAH, and prospects of reverse pharmacology, which are expected to facilitate the natural anti-PAH medicine discovery and development and its bench-to-bedside transformation.
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Affiliation(s)
- Zhifeng Xue
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China
| | - Yixuan Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China
| | - Mengen Zhou
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China
| | - Zhidong Liu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Guanwei Fan
- Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin, China
| | - Xiaoying Wang
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yan Zhu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China
| | - Jian Yang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China
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Wang T, Hou J, Xiao W, Zhang Y, Zhou L, Yuan L, Yin X, Chen X, Hu Y. Chinese medicinal plants for the potential management of high-altitude pulmonary oedema and pulmonary hypertension. PHARMACEUTICAL BIOLOGY 2020; 58:815-827. [PMID: 32883127 PMCID: PMC8641673 DOI: 10.1080/13880209.2020.1804407] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 07/28/2020] [Accepted: 07/28/2020] [Indexed: 05/29/2023]
Abstract
CONTEXT Despite the abundance of knowledge regarding high-altitude pulmonary edoema (HAPE) and high-altitude pulmonary hypertension (HAPH), their prevalence continues to be on the rise. Thus, there is an urgent need for newer safe, effective, and relatively economic drug candidates. China is particularly known for the use of medicinal plants. OBJECTIVE This review summarizes the medicinal plants used for HAPE and HAPH in the past 30 years, as well as some potential plants. METHODS Publications on HAPE and HAPH from 1990 to 2020 were identified using Web of Science, PubMed, SCOPUS, Springer Link, Google Scholar databases, Chinese Clinical Trial Registry and CNKI with the following keywords: 'medicinal plants,' 'hypoxia,' 'high altitude pulmonary edema,' 'high altitude pulmonary hypertension,' 'pathophysiology,' 'mechanisms,' 'prevention,' 'treatment,' 'human,' 'clinical,' 'safety,' and 'pharmacokinetics.' RESULTS We found 26 species (from 20 families) out of 5000 plants which are used for HAPE and HAPH prevention or treatment. Rhodiola rosea Linn. (Crassulaceae) is the most widely utilized. The most involved family is Lamiaceae, which contains 5 species. DISCUSSION AND CONCLUSIONS We mainly reviewed the medicinal plants and mechanisms for the treatment of HAPE and HAPH, and we also assessed related toxicology experiments, pharmacokinetics and bioavailability. Potential medicinal plants were also identified. Further research is needed to determine the pharmacological effects and active ingredients of these potential medicinal plants.
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Affiliation(s)
- Tingting Wang
- Department of Central Laboratory, The General Hospital of Western Theater Command, Chengdu, Sichuan, P. R. China
| | - Jun Hou
- Department of Central Laboratory, The General Hospital of Western Theater Command, Chengdu, Sichuan, P. R. China
| | - Wenjing Xiao
- Department of Central Laboratory, The General Hospital of Western Theater Command, Chengdu, Sichuan, P. R. China
| | - Yaolei Zhang
- Faculty of Medical, Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
| | - Longfu Zhou
- Department of Central Laboratory, The General Hospital of Western Theater Command, Chengdu, Sichuan, P. R. China
| | - Li Yuan
- Faculty of Medical, Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
| | - Xiaoqiang Yin
- Department of Central Laboratory, The General Hospital of Western Theater Command, Chengdu, Sichuan, P. R. China
| | - Xin Chen
- Department of Laboratory Medicine, The Third People’s Hospital of Chengdu/Affiliated Hospital of Southwest, Jiaotong University, Chengdu, Sichuan, P. R. China
| | - Yonghe Hu
- Department of Central Laboratory, The General Hospital of Western Theater Command, Chengdu, Sichuan, P. R. China
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Jasemi SV, Khazaei H, Aneva IY, Farzaei MH, Echeverría J. Medicinal Plants and Phytochemicals for the Treatment of Pulmonary Hypertension. Front Pharmacol 2020; 11:145. [PMID: 32226378 PMCID: PMC7080987 DOI: 10.3389/fphar.2020.00145] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 02/04/2020] [Indexed: 12/18/2022] Open
Abstract
Background Pulmonary hypertension (PH) is a progressive disease that is associated with pulmonary arteries remodeling, right ventricle hypertrophy, right ventricular failure and finally death. The present study aims to review the medicinal plants and phytochemicals used for PH treatment in the period of 1994 – 2019. Methods PubMed, Cochrane and Scopus were searched based on pulmonary hypertension, plant and phytochemical keywords from August 23, 2019. All articles that matched the study based on title and abstract were collected, non-English, repetitive and review studies were excluded. Results Finally 41 studies remained from a total of 1290. The results show that many chemical treatments considered to this disease are ineffective in the long period because they have a controlling role, not a therapeutic one. On the other hand, plants and phytochemicals could be more effective due to their action on many mechanisms that cause the progression of PH. Conclusion Studies have shown that herbs and phytochemicals used to treat PH do their effects from six mechanisms. These mechanisms include antiproliferative, antioxidant, antivascular remodeling, anti-inflammatory, vasodilatory and apoptosis inducing actions. According to the present study, many of these medicinal plants and phytochemicals can have effects that are more therapeutic than chemical drugs if used appropriately.
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Affiliation(s)
- Seyed Vahid Jasemi
- Department of Internal Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Hosna Khazaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ina Yosifova Aneva
- Institute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Javier Echeverría
- Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile
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Ginsenoside Rb1 as an Anti-Diabetic Agent and Its Underlying Mechanism Analysis. Cells 2019; 8:cells8030204. [PMID: 30823412 PMCID: PMC6468558 DOI: 10.3390/cells8030204] [Citation(s) in RCA: 183] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Revised: 02/22/2019] [Accepted: 02/23/2019] [Indexed: 12/19/2022] Open
Abstract
Panax ginseng and Panax notoginseng, two well-known medical plants with economic value, have a long history of use for managing various diseases in Asian countries. Accumulating clinical and experimental evidence suggests that notoginsenosides and ginsenosides, which are the major bioactive components of the plants, have a variety of beneficial effects on several types of disease, including metabolic, vascular, and central nervous system disease. Considerable attention has been focused on ginsenoside Rb1 derived from their common ownership as an anti-diabetic agent that can attenuate insulin resistance and various complications. Particularly, in vitro and in vivo models have suggested that ginsenoside Rb1 exerts various pharmacological effects on metabolic disorders, including attenuation of glycemia, hypertension, and hyperlipidemia, which depend on the modulation of oxidative stress, inflammatory response, autophagy, and anti-apoptosis effects. Regulation of these pathophysiological mechanisms can improve blood glucose and insulin resistance and protect against macrovascular/microvascular related complications. This review summarizes the pharmacological effects and mechanisms of action of ginsenoside Rb1 in the management of diabetes or diabetic complications. Moreover, a multi-target effect and mechanism analysis of its antidiabetic actions were performed to provide a theoretical basis for further pharmacological studies and new drug development for clinical treatment of type 2 diabetes. In conclusion, ginsenoside Rb1 exerts significant anti-obesity, anti-hyperglycemic, and anti-diabetic effects by regulating the effects of glycolipid metabolism and improving insulin and leptin sensitivities. All of these findings suggest ginsenoside Rb1 exerts protective effects on diabetes and diabetic complications by the regulation of mitochondrial energy metabolism, improving insulin resistance and alleviating the occurrence complications, which should be further explored. Hence, ginsenoside Rb1 may be developed as a potential anti-obesity, anti-hyperglycemic, and anti-diabetic agent with multi-target effects.
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Zhang M, Guan Y, Xu J, Qin J, Li C, Ma X, Zhang Z, Zhang B, Tang J. Evaluating the protective mechanism of panax notoginseng saponins against oxidative stress damage by quantifying the biomechanical properties of single cell. Anal Chim Acta 2018; 1048:186-193. [PMID: 30598149 DOI: 10.1016/j.aca.2018.10.030] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 10/09/2018] [Accepted: 10/15/2018] [Indexed: 10/28/2022]
Abstract
Panax notoginseng saponins (PNS) have shown to be the biologically active constituents responsible for the therapeutic action of panax notoginseng. PNS could help to restrain the oxidative stress, however, whether biomechanical properties of the single cell involve in the protective effect exerted by PNS against oxidative stress injury remains unclear. In this work, we investigated the protective mechanism of PNS against oxidative stress based on the PeakForce Tapping technology firstly, focusing on the biomechanical properties of single human umbilical vascular endothelium cell (HUVEC). PNS display distinct inhibition on the reduction of the young's modulus of cells caused by oxidative stress damage. Combining with immunofluorescence assay, it indicates that improving the stability of cytoskeleton is a significant way for PNS to play a protective role in HUVEC cells during oxidative damage. This work provides a new idea for exploring the functional mechanism of traditional Chinese medicine at the single cell level, and reveals great potential of the atomic force microscope in studying the drug mechanism.
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Affiliation(s)
- Miaomiao Zhang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China; University of Science and Technology of China, Hefei, 230026, PR China
| | - Yanxue Guan
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China; University of Science and Technology of China, Hefei, 230026, PR China
| | - Jian Xu
- The Standardized Key Project Technology Laboratory of TCM of Jilin Province, Changchun, 130012, PR China
| | - Juan Qin
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China; University of Science and Technology of China, Hefei, 230026, PR China
| | - Chen Li
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China; University of Science and Technology of China, Hefei, 230026, PR China
| | - Xingxing Ma
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China; University of Science and Technology of China, Hefei, 230026, PR China
| | - Zhe Zhang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China
| | - Bailin Zhang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China; University of Science and Technology of China, Hefei, 230026, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
| | - Jilin Tang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China; University of Science and Technology of China, Hefei, 230026, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
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Xu Y, Tan HY, Li S, Wang N, Feng Y. Panax notoginseng for Inflammation-Related Chronic Diseases: A Review on the Modulations of Multiple Pathways. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2018; 46:971-996. [PMID: 29976083 DOI: 10.1142/s0192415x18500519] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
Panax notoginseng (P. notoginseng) is a well-known and commonly used Chinese herbal medicine in Asian countries. As one of the major species in the Panax genus, it has a distinct chemical composition and medical application compared with other species. P. notoginseng attracts attention and interest due to its potential therapeutic effects not only on blood diseases, but also other kinds of human chronic disorders. This paper critically reviewed the latest advance of knowledge on the pharmacological effects of P. notoginseng on a variety of chronic diseases including inflammatory bowel disease, arthritis, ischemia, atherosclerosis, Alzheimer disease and trauma, as well as hyperlipidemia, diabetes, and so on. As inflammation is considered the fundamental factor involved in the pathogenesis of chronic diseases, our review therefore focuses on understanding the involvement of classical inflammatory pathways underlying the mechanism of action of P. notoginseng. Potential clinical application was also discussed. Furthermore, by combining with network pharmacology, we introduced the major bioactive components of P. notoginseng, analyzed their cellular targets and associated signaling pathways. In conclusion, this review identified inflammatory pathway as the key signaling for determining the efficacy of P. notoginseng on chronic diseases. It is speculated that P. notoginseng is a multi-targeted agent with an anti-inflammatory property in the adjuvant and alternative treatment of human chronic diseases.
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Affiliation(s)
- Yu Xu
- 1 School of Chinese Medicine, The University of Hong Kong, Hong Kong, P. R. China
| | - Hor-Yue Tan
- 1 School of Chinese Medicine, The University of Hong Kong, Hong Kong, P. R. China
| | - Sha Li
- 1 School of Chinese Medicine, The University of Hong Kong, Hong Kong, P. R. China
| | - Ning Wang
- 1 School of Chinese Medicine, The University of Hong Kong, Hong Kong, P. R. China
| | - Yibin Feng
- 1 School of Chinese Medicine, The University of Hong Kong, Hong Kong, P. R. China
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Yi YS. Ameliorative effects of ginseng and ginsenosides on rheumatic diseases. J Ginseng Res 2018; 43:335-341. [PMID: 31308803 PMCID: PMC6606827 DOI: 10.1016/j.jgr.2018.04.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 04/23/2018] [Indexed: 12/23/2022] Open
Abstract
Background Inflammation is a host-defensive innate immune response to protect the body from pathogenic agents and danger signals induced by cellular changes. Although inflammation is a host-defense mechanism, chronic inflammation is considered a major risk factor for the development of a variety of inflammatory autoimmune diseases, such as rheumatic diseases. Rheumatic diseases are systemic inflammatory and degenerative diseases that primarily affect connective tissues and are characterized by severe chronic inflammation and degeneration of connective tissues. Ginseng and its bioactive ingredients, genocides, have been demonstrated to have antiinflammatory activity and pharmacological effects on various rheumatic diseases by inhibiting the expression and production of inflammatory mediators. Methods Literature in this review was searched in a PubMed site of National Center for Biotechnology Information. Results The studies reporting the preventive and therapeutic effects of ginseng and ginsenosides on the pathogenesis of rheumatic diseases were discussed and summarized. Conclusion Ginseng and ginsenosides play an ameliorative role on rheumatic diseases, and this review provides new insights into ginseng and ginsenosides as promising agents to prevent and treat rheumatic diseases.
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Key Words
- ACAN, Aggrecan
- ACLT, Anterior cruciate ligament transection
- BMP, Bone morphogenetic protein
- CIA, Collagen-induced arthritic
- CK, Compound K
- COL, Collagen
- DAMP, Danger-associated molecular pattern
- Ginseng
- Ginsenosides
- Inflammation
- LTMMR, Ligament transection and medial meniscus resection
- Macrophages
- OA, Osteoarthritis
- PAMP, Pathogen-associated molecular pattern
- PPD, Protopanaxadiol
- PPT, Protopanaxatriol
- PRR, Pattern-recognition receptor
- RA, Rheumatoid arthritis
- RNAKL, Receptor activator of NF-κB ligand
- Rheumatic diseases
- SLE, Systemic lupus erythematosus
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Affiliation(s)
- Young-Su Yi
- Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea
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Panax Notoginseng Saponins: A Review of Its Mechanisms of Antidepressant or Anxiolytic Effects and Network Analysis on Phytochemistry and Pharmacology. Molecules 2018; 23:molecules23040940. [PMID: 29673237 PMCID: PMC6017639 DOI: 10.3390/molecules23040940] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 04/04/2018] [Accepted: 04/06/2018] [Indexed: 12/28/2022] Open
Abstract
Panax notoginseng (Burk) F. H. Chen, as traditional Chinese medicine, has a long history of high clinical value, such as anti-inflammatory, anti-oxidation, inhibition of platelet aggregation, regulation of blood glucose and blood pressure, inhibition of neuronal apoptosis, and neuronal protection, and its main ingredients are Panax notoginseng saponins (PNS). Currently, Panax notoginseng (Burk) F. H. Chen may improve mental function, have anti-insomnia and anti-depression effects, alleviate anxiety, and decrease neural network excitation. However, the underlying effects and the mechanisms of Panax notoginseng (Burk) F. H. Chen and its containing chemical constituents (PNS) on these depression-related or anxiety-related diseases has not been completely established. This review summarized the antidepressant or anxiolytic effects and mechanisms of PNS and analyzed network targets of antidepressant or anxiolytic actions with network pharmacology tools to provide directions and references for further pharmacological studies and new ideas for clinical treatment of nervous system diseases and drug studies and development. The review showed PNS and its components may exert these effects through regulating neurotransmitter mechanism (5-HT, DA, NE), modulation of the gamma-amino butyric acid (GABA) neurotransmission, glutamatergic system, hypo-thalamus-pituitary-adrenal (HPA) axis, brain-derived neurotrophic factor (BDNF), and its intracellular signaling pathways in the central nervous system; and produce neuronal protection by anti-inflammatory, anti-oxidation, or inhibition of neuronal apoptosis, or platelet aggregation and its intracellular signaling pathways. Network target analysis indicated PNS and its components also may have anti-inflammatory and anti-apoptotic effects, which leads to the preservation of brain nerves, and regulate the activity and secretion of nerve cells, exerting anti-depression and anxiolytic effects, which may provide new directions for further in-depth researches of related mechanisms.
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Yu J, Liu C, Li Z, Zhang C, Wang Z, Liu X. Inhibitory effects and mechanism of 25-OH-PPD on glomerular mesangial cell proliferation induced by high glucose. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2016; 44:93-98. [PMID: 27135372 DOI: 10.1016/j.etap.2016.04.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Revised: 04/18/2016] [Accepted: 04/23/2016] [Indexed: 06/05/2023]
Abstract
OBJECTIVE To investigate the protective effects and potential mechanism of the compound 25-OH-PPD (PPD) on the glomerular mesangial cells (GMC) under high glucose condition. METHODS The hypertrophic GMC cells were established by DMEM containing glucose and randomly divided into five groups, including the normal control group (Control), the high glucose model group (HG, 25 mmolL(-1)), the PPD low dose group (1μmolL(-1), PPD-L), the PPD middle dose group (5μmolL(-1), PPD -M) and the PPD high dose group (10μmolL(-1), UCN-H). The GMC were incubated for 48h under different treatment factors. Total protein content was determined by Lowry method. The diameter of the single GMC and volume were measured by computer photograph analysis system. The GMC cell viability was analyzed by MTT assay. The level of malondialdehyde (MDA), the content of glutathione (GSH) and superoxide dismutase (SOD) activity were measured by ELISA. [Ca(2+)]і transient was measured by Till image system and by cell-loading Fura-2/AM. The expression of COX-1 and COX-2 were also determined using ELISA method. RESULTS The viability of GMC and the total protein content were decreased in HG group, different dosage PPD group could increase these indexes (P<0.05). The level of MDA was increased, the content of GSH and SOD was decreased in HG group, while PPD could reduce the MDA and enhance GSH and SOD (P<0.05). Following treatment with different dosage (PPD-L, PPD-M or PPD-H), the [Ca(2+)]і transient was reduced (P<0.05 or P<0.01). Moreover, the expression of COX-1 was decreased while COX-2 expression was increased in different dosage PPD groups. CONCLUSION The protective effects of PPD on GMC from HG-induced hypertrophy may be associated with the inhibition of [Ca(2+)]і transient and decreasing expression of COX-1 via the oxidative-stress injure pathway.
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Affiliation(s)
- Junxian Yu
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Chunna Liu
- Department of Pharmacology, Liaoning Medical University, JinZhou 121001, China
| | - Zhe Li
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Chao Zhang
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Zheng Wang
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Xinyu Liu
- The First Affiliated Hospital of Liaoning Medical University, JinZhou 121001, China.
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