|
1
|
Lin L, Zhao C, Lv H, Zhu L, Wang W, Zheng X. Astragaloside IV promotes neuronal axon regeneration by inhibiting the PTEN/AKT pathway. Brain Res 2025; 1850:149451. [PMID: 39793915 DOI: 10.1016/j.brainres.2025.149451] [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: 06/13/2024] [Revised: 11/06/2024] [Accepted: 01/07/2025] [Indexed: 01/13/2025]
Abstract
BACKGROUND Neuronal survival and regeneration are critical aspects of recovery from ischemic brain injuries. Astragaloside IV (AS-IV), a saponin extracted from the traditional Chinese medicine Astragalus membranaceus, has shown promise in promoting neuronal health. This study investigates the effects of AS-IV on neuronal survival and apoptosis post-oxygen-glucose deprivation (OGD), focusing on the modulation of the PTEN/AKT signaling pathway. METHODS Rat primary neuronal cells were isolated and subjected to OGD to simulate ischemic conditions. Afterwards, cells were treated with low and high doses of AS-IV. Neuronal viability and apoptosis were assessed using MTT and flow cytometry (FCM) assays. Immunofluorescence and Western blot analyses were performed to evaluate the expression of neuronal markers and proteins involved in the PTEN/AKT pathway. RESULTS Post-OGD, neuronal cells exhibited decreased viability and increased apoptosis, which were significantly mitigated by AS-IV. Immunofluorescence showed enhanced Tuj1 expression, indicating increased neuronal purity and survival, enhanced NF200 expression, indicating increased axon lengths. FCM results revealed reduced apoptosis rates, particularly with higher doses of AS-IV. Western blot analysis confirmed inhibition of PTEN and activation of AKT, facilitating enhanced neuronal survival and axona regeneration. Additionally, overexpression of PTEN negated the anti-apoptotic effects of AS-IV, underscoring the critical role of the PTEN/AKT pathway in AS-IV mediated neuroprotection. CONCLUSION AS-IV enhances neuronal survival and axona regeneration by modulating the PTEN/AKT pathway, highlighting its potential as a therapeutic agent for ischemic brain injuries. These findings suggest that targeting this pathway could be a strategic focus for developing effective neuroprotective therapies.
Collapse
Affiliation(s)
- Luning Lin
- Department of Traditional Chinese Medicine Pharmacy, Wenling Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Taizhou 317500, China
| | - Chenyang Zhao
- Department of Clinical Lab, Taizhou Hospital of Traditional Chinese and Western Medicine, Taizhou 317200, China
| | - Huijuan Lv
- Department of Acupuncture and Moxibustion, Wenling Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Taizhou 317500, China
| | - Liangrong Zhu
- Department of Pharmacy, Wenling Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Taizhou 317500, China
| | - Wangen Wang
- Department of Traditional Chinese Medicine Pharmacy, Wenling Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Taizhou 317500, China
| | - Xintian Zheng
- Department of Traditional Chinese Medicine Pharmacy, Wenling Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Taizhou 317500, China.
| |
Collapse
|
|
2
|
Zhao J, Zhao G, Lang J, Sun B, Feng S, Li D, Sun G. Astragaloside IV ameliorated neuroinflammation and improved neurological functions in mice exposed to traumatic brain injury by modulating the PERK-eIF2α-ATF4 signaling pathway. J Investig Med 2024; 72:747-762. [PMID: 38869170 DOI: 10.1177/10815589241261293] [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] [Indexed: 06/14/2024]
Abstract
Increasing evidence suggests that endoplasmic reticulum stress (ER stress) and neuroinflammation are involved in the complex pathological process of traumatic brain injury (TBI). However, the pathological mechanisms of their interactions in TBI remain incompletely elucidated. Therefore, investigating and ameliorating neuroinflammation and ER stress post-TBI may represent effective strategies for treating secondary brain injury. Astragaloside IV (AS-IV) has been reported as a potential neuroprotective and anti-inflammatory agent in neurological diseases. This study utilized a mouse TBI model to investigate the pathological mechanisms and crosstalk of ER stress, neuroinflammation, and microglial cell morphology in TBI, as well as the mechanisms and potential of AS-IV in improving TBI. The research revealed that post-TBI, inflammatory factors IL-6, IL-1β, and TNF-α increased, microglial cells were activated, and the specific inhibitor of PERK phosphorylation, GSK2656157, intervened to alleviate neuroinflammation and inhibit microglial cell activation. Post-TBI, levels of ER stress-related proteins (p-PERK, p-eIF2a, ATF4, ATF6, and p-IRE1a) increased. Following AS-IV treatment, neurological dysfunction in TBI mice improved. Levels of p-PERK, p-eIF2a, and ATF4 decreased, along with reductions in inflammatory factors IL-6, IL-1β, and TNF-α. Changes in microglial/macrophage M1/M2 polarization were observed. Additionally, the PERK activator CCT020312 intervention eliminated the impact of AS-IV on post-TBI inflammation and ER stress-related proteins p-PERK, p-eIF2a, and ATF4. These results indicate that AS-IV alleviates neuroinflammation and brain damage post-TBI through the PERK pathway, offering new directions and theoretical insights for TBI treatment.
Collapse
Affiliation(s)
- Jianfei Zhao
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, The People's Republic of China
- Department of Neurosurgery, The People's Hospital of Shijiazhuang City, Shijiazhuang, The People's Republic of China
| | - Gengshui Zhao
- Department of Neurosurgery, The People's Hospital of Hengshui City, Hengshui, The People's Republic of China
| | - Jiadong Lang
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, The People's Republic of China
| | - Boyu Sun
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, The People's Republic of China
| | - Shiyao Feng
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, The People's Republic of China
| | - Dongsheng Li
- Department of Neurosurgery, The People's Hospital of Shijiazhuang City, Shijiazhuang, The People's Republic of China
| | - Guozhu Sun
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, The People's Republic of China
| |
Collapse
|
|
3
|
Lyu S, Zhang CS, Mao Z, Guo X, Li Z, Luo X, Sun J, Su Q. Real-world Chinese herbal medicine for Parkinson's disease: a hospital-based retrospective analysis of electronic medical records. Front Aging Neurosci 2024; 16:1362948. [PMID: 38756536 PMCID: PMC11096516 DOI: 10.3389/fnagi.2024.1362948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 04/22/2024] [Indexed: 05/18/2024] Open
Abstract
Background Parkinson's disease (PD) is a progressive neurodegenerative condition. Chinese medicine therapies have demonstrated effectiveness for PD in controlled settings. However, the utilization of Chinese medicine therapies for PD in real-world clinical practice and the characteristics of patients seeking these therapies have not been thoroughly summarized. Method The study retrospectively analyzed initial patient encounters (PEs) with a first-listed diagnosis of PD, based on electronic medical records from Guangdong Provincial Hospital of Chinese Medicine between July 2018 and July 2023. Results A total of 3,206 PEs, each corresponding to an individual patient, were eligible for analyses. Approximately 60% of patients made initial visits to the Chinese medicine hospital after receiving a PD diagnosis, around 4.59 years after the onset of motor symptoms. Over 75% of the patients visited the Internal Medicine Outpatient Clinic at their initial visits, while a mere 13.85% visited PD Chronic Care Clinic. Rest tremor (61.98%) and bradykinesia (52.34%) are the most commonly reported motor symptoms, followed by rigidity (40.70%). The most commonly recorded non-motor symptoms included constipation (31.88%) and sleep disturbance (25.27%). Integration of Chinese medicine and conventional medicine therapies was the most common treatment method (39.15%), followed by single use of Chinese herbal medicine (27.14%). The most frequently prescribed herbs for PD included Glycyrrhiza uralensis Fisch. (gan cao), Astragalus mongholicus Bunge (huang qi), Atractylodes macrocephala Koidz. (bai zhu), Angelica sinensis (Oliv.) Diels (dang gui), Rehmannia glutinosa (Gaertn.) DC. (di huang), Paeonia lactiflora Pall. (bai shao), Bupleurum chinense DC. (chai hu), Citrus aurantium L. (zhi qiao/zhi shi/chen pi), Panax ginseng C. A. Mey. (ren shen), and Poria cocos (Schw.) Wolf (fu ling). These herbs contribute to formulation of Bu zhong yi qi tang (BZYQT). Conclusion Patients typically initiated Chinese medical care after the establishment of PD diagnosis, ~4.59 years post-onset of motor symptoms. The prevalent utilization of CHM decoctions and patented Chinese herbal medicine products, underscores its potential in addressing both motor and non-motor symptoms. Despite available evidence, rigorous clinical trials are needed to validate and optimize the integration of CHM, particularly BZYQT, into therapeutic strategies for PD.
Collapse
Affiliation(s)
- Shaohua Lyu
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Claire Shuiqing Zhang
- School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, VIC, Australia
| | - Zhenhui Mao
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Xinfeng Guo
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Zhe Li
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Xiaodong Luo
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Jingbo Sun
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| | - Qiaozhen Su
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
| |
Collapse
|
|
4
|
Liu Y, Yu R, Wang X, Chen Y, Yin T, Gao Q, Sun L, Zheng Z. Research progress of the effective active ingredients of Astragalus mongholicus in the treatment of diabetic peripheral neuropathy. Biomed Pharmacother 2024; 173:116350. [PMID: 38430632 DOI: 10.1016/j.biopha.2024.116350] [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: 12/06/2023] [Revised: 02/15/2024] [Accepted: 02/23/2024] [Indexed: 03/05/2024] Open
Abstract
Diabetic peripheral neuropathy (DPN) is one of the most prevalent consequences of diabetes, with a high incidence and disability rate. The DPN's pathogenesis is extremely complex and yet to be fully understood. Persistent high glucose metabolism, nerve growth factor deficiency, microvascular disease, oxidative stress, peripheral nerve cell apoptosis, immune factors, and other factors have been implicated in the pathogenesis of DPN. Astragalus mongholicus is a commonly used plant used to treat DPN in clinical settings. Its rich chemical components mainly include Astragalus polysaccharide, Astragalus saponins, Astragalus flavones, etc., which play a vital role in the treatment of DPN. This review aimed to summarize the pathogenesis of DPN and the studies on the mechanism of the effective components of Astragalus mongholicus in treating DPN. This is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.
Collapse
Affiliation(s)
- Yulian Liu
- Department of Rehabilitation Medicine,The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, China
| | - Runyuan Yu
- Department of Rehabilitation Medicine,The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, China
| | - Xiaoyu Wang
- Department of Rehabilitation Medicine,The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, China
| | - Yuexia Chen
- Department of Skills Training Center,The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, China
| | - Tao Yin
- Department of Rehabilitation Medicine,The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, China
| | - Qiang Gao
- Department of Rehabilitation Medicine,The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, China
| | - Limin Sun
- Department of Rehabilitation Medicine,The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, China
| | - Zuncheng Zheng
- Department of Rehabilitation Medicine,The Affiliated Taian City Central Hospital of Qingdao University, Taian 271000, China.
| |
Collapse
|
|
5
|
Bhusal CK, Uti DE, Mukherjee D, Alqahtani T, Alqahtani S, Bhattacharya A, Akash S. Unveiling Nature's potential: Promising natural compounds in Parkinson's disease management. Parkinsonism Relat Disord 2023; 115:105799. [PMID: 37633805 DOI: 10.1016/j.parkreldis.2023.105799] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 07/25/2023] [Accepted: 08/04/2023] [Indexed: 08/28/2023]
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Although the exact etiology of PD remains elusive, growing evidence suggests a complex interplay of genetic, environmental, and lifestyle factors in its development. Despite advances in pharmacological interventions, current treatments primarily focus on managing symptoms rather than altering the disease's underlying course. In recent years, natural phytocompounds have emerged as a promising avenue for PD management. Phytochemicals derived from plants, such as phenolic acids, flavones, phenols, flavonoids, polyphenols, saponins, terpenes, alkaloids, and amino acids, have been extensively studied for their potential neuroprotective effects. These bioactive compounds possess a wide range of therapeutic properties, including antioxidant, anti-inflammatory, anti-apoptotic, and anti-aggregation activities, which may counteract the neurodegenerative processes in PD. This comprehensive review delves into the pathophysiology of PD, with a specific focus on the roles of oxidative stress, mitochondrial dysfunction, and protein malfunction in disease pathogenesis. The review collates a wealth of evidence from preclinical studies and in vitro experiments, highlighting the potential of various phytochemicals in attenuating dopaminergic neuron degeneration, reducing α-synuclein aggregation, and modulating neuroinflammatory responses. Prominent among the natural compounds studied are curcumin, resveratrol, coenzyme Q10, and omega-3 fatty acids, which have demonstrated neuroprotective effects in experimental models of PD. Additionally, flavonoids like baicalein, luteolin, quercetin, and nobiletin, and alkaloids such as berberine and physostigmine, show promise in mitigating PD-associated pathologies. This review emphasizes the need for further research through controlled clinical trials to establish the safety and efficacy of these natural compounds in PD management. Although preclinical evidence is compelling, the translation of these findings into effective therapies for PD necessitates robust clinical investigation. Rigorous evaluation of pharmacokinetics, bioavailability, and potential drug interactions is imperative to pave the way for evidence-based treatment strategies. With the rising interest in natural alternatives and the potential for synergistic effects with conventional therapies, this review serves as a comprehensive resource for pharmaceutical industries, researchers, and clinicians seeking novel therapeutic approaches to combat PD. Harnessing the therapeutic potential of these natural phytocompounds may hold the key to improving the quality of life for PD patients and moving towards disease-modifying therapies in the future.
Collapse
Affiliation(s)
- Chandra Kanta Bhusal
- Post Graduate Institute of Medical and Research, Madhya Marg, Sector 12, Chandigarh, 160012, India.
| | - Daniel Ejim Uti
- Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, Federal University of Health Sciences, Otukpo, Benue State, Nigeria.
| | - Dattatreya Mukherjee
- Raiganj Government Medical College and Hospital, Uttar Dinajpur, West Bengal, India.
| | - Taha Alqahtani
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia.
| | - Saud Alqahtani
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia.
| | - Arghya Bhattacharya
- Department of Pharmacology, Calcutta Institute of Pharmaceutical Technology and Allied Health Science, Uluberia, Howrah, 711316, India.
| | - Shopnil Akash
- Faculty of Allied Health Science, Department of Pharmacy, Daffodil International University, Daffodil Smart City, Ashulia, Savar, Dhaka, 1207, Bangladesh.
| |
Collapse
|
|
6
|
Stambolov I, Shkondrov A, Kunert O, Bucar F, Kondeva-Burdina M, Krasteva I. Cycloartane Saponins from Astragalus glycyphyllos and Their In Vitro Neuroprotective, Antioxidant, and hMAO-B-Inhibiting Effects. Metabolites 2023; 13:857. [PMID: 37512564 PMCID: PMC10385106 DOI: 10.3390/metabo13070857] [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: 06/22/2023] [Revised: 07/15/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
Astragalus glycyphyllos (Fabaceae) is used in the traditional medicine of many countries against hepatic and cardiac disorders. The plant contains mainly flavonoids and saponins. From a defatted methanol extract from its overground parts, a new triterpenoid saponin, 3-O-[α-L-rhamnopyranosyl-(1→2)]-β-D-xylopyranosyl]-24-O-α-L-arabinopyranosyl-3β,6α,16β,24(R),25-pentahydroxy-20R-cycloartane, together with the rare saponin astrachrysoside A, were isolated using various chromatography methods. The compounds were identified via extensive high resolution electrospray ionisation mass spectrometry (HRESIMS) and NMR analyses. Both saponins were examined for their possible antioxidant and neuroprotective activity in three different in vitro models. Rat brain synaptosomes, mitochondria, and microsomes were isolated via centrifugation using Percoll gradient. They were treated with the compounds in three different concentrations alone, and in combination with 6-hydroxydopamine or tert-butyl hydroperoxide as toxic agents. It was found that the compounds had statistically significant dose-dependent in vitro protective activity on the sub-cellular fractions. The compounds exhibited a weak inhibitory effect on the enzyme activity of human recombinant monoamine oxidase type B (hMAO-B), compared to selegiline.
Collapse
Affiliation(s)
- Ivan Stambolov
- Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., 1000 Sofia, Bulgaria
| | - Aleksandar Shkondrov
- Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., 1000 Sofia, Bulgaria
| | - Olaf Kunert
- Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, A-8010 Graz, Austria
| | - Franz Bucar
- Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Beethovenstrasse 8, A-8010 Graz, Austria
| | - Magdalena Kondeva-Burdina
- Laboratory of Drug Metabolism and Drug Toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., 1000 Sofia, Bulgaria
| | - Ilina Krasteva
- Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., 1000 Sofia, Bulgaria
| |
Collapse
|
|
7
|
Kakoty V, Sarathlal KC, Gulati M, Bey Hing G, Dua K, Kumar Singh S. Senolytics: opening avenues in drug discovery to find novel therapeutics for Parkinson's disease. Drug Discov Today 2023; 28:103582. [PMID: 37023942 DOI: 10.1016/j.drudis.2023.103582] [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: 01/05/2023] [Revised: 03/15/2023] [Accepted: 03/30/2023] [Indexed: 04/08/2023]
Abstract
Aging is one of the major risk factors for most neurodegenerative disorders including Parkinson's disease (PD). More than 10 million people are affected with PD worldwide. One of the predominant factors accountable for progression of PD pathology could be enhanced accumulation of senescent cells in the brain with the progress of age. Recent investigations have highlighted that senescent cells can ignite PD pathology via increased oxidative stress and neuroinflammation. Senolytics are agents that kill senescent cells. This review mainly focuses on understanding the pathological connection between senescence and PD, with emphasis on some of the recent advances made in the area of senolytics and their evolution to potential clinical candidates for future pharmaceuticals against PD.
Collapse
Affiliation(s)
- Violina Kakoty
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara, Punjab, India
| | - K C Sarathlal
- Department of Non-Communicable Disease, Translational Health Science and Technology Institute, Faridabad, India
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara, Punjab, India; Faculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Goh Bey Hing
- Biofunctional Molecule Exploratory Research Group, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara, Punjab, India; Faculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia.
| |
Collapse
|
|
8
|
Chen P, Zhang J, Wang C, Chai YH, Wu AG, Huang NY, Wang L. The pathogenesis and treatment mechanism of Parkinson's disease from the perspective of traditional Chinese medicine. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 100:154044. [PMID: 35338993 DOI: 10.1016/j.phymed.2022.154044] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 02/26/2022] [Accepted: 03/11/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Parkinson's disease (PD) is the second most common neurodegenerative disease with no treatment currently available to modify its progression. Traditional Chinese medicine (TCM) has gained attention for its unique theoretical basis and clinical effects. Many studies have reported on the clinical effects and pharmacological mechanisms of Chinese herbs in PD. However, few studies have focused on the treatment mechanisms of anti-PD TCM drugs from the perspective of TCM itself. PURPOSE To elaborate the treatment mechanisms of anti-PD TCM drugs in the perspective of TCM. METHODS We performed a literature survey using traditional books of Chinese medicine and online scientific databases including PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), and others up to July 2021. RESULTS TCM theory states that PD is caused by a dysfunction of the zang-fu organs (liver, spleen, kidney, and lung) and subsequent pathogenic factors (wind, fire, phlegm, and blood stasis). Based on the pathogenesis, removing pathogenic factors and restoring visceral function are two primary treatment principles for PD in TCM. The former includes dispelling wind, clearing heat, resolving phlegm, and promoting blood circulation, while the latter involves nourishing the liver and kidney and strengthening the spleen. The anti-PD mechanisms of the active ingredients of TCM compounds and herbs at different levels include anti-apoptosis, anti-inflammation, and anti-oxidative stress, as well as the restoration of mitochondrial function and the regulation of autophagy and neurotransmitters. CONCLUSION Chinese herbs and prescriptions can be used to treat PD by targeting multiple pharmacological mechanisms.
Collapse
Affiliation(s)
- Peng Chen
- Basic Medical School, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China; Accreditation Center of Traditional Chinese Medicine Physician, National Administration of Traditional Chinese Medicine, Beijing, China.
| | - Jie Zhang
- Basic Medical School, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Chen Wang
- Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China
| | - Yi-Hui Chai
- Basic Medical School, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - An-Guo Wu
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
| | - Ning-Yu Huang
- Accreditation Center of Traditional Chinese Medicine Physician, National Administration of Traditional Chinese Medicine, Beijing, China.
| | - Long Wang
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
| |
Collapse
|
|
9
|
Miller SJ, Campbell CE, Jimenez-Corea HA, Wu GH, Logan R. Neuroglial Senescence, α-Synucleinopathy, and the Therapeutic Potential of Senolytics in Parkinson’s Disease. Front Neurosci 2022; 16:824191. [PMID: 35516803 PMCID: PMC9063319 DOI: 10.3389/fnins.2022.824191] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 03/22/2022] [Indexed: 12/02/2022] Open
Abstract
Parkinson’s disease (PD) is the most common movement disorder and the second most prevalent neurodegenerative disease after Alzheimer’s disease. Despite decades of research, there is still no cure for PD and the complicated intricacies of the pathology are still being worked out. Much of the research on PD has focused on neurons, since the disease is characterized by neurodegeneration. However, neuroglia has become recognized as key players in the health and disease of the central nervous system. This review provides a current perspective on the interactive roles that α-synuclein and neuroglial senescence have in PD. The self-amplifying and cyclical nature of oxidative stress, neuroinflammation, α-synucleinopathy, neuroglial senescence, neuroglial chronic activation and neurodegeneration will be discussed. Finally, the compelling role that senolytics could play as a therapeutic avenue for PD is explored and encouraged.
Collapse
Affiliation(s)
- Sean J. Miller
- Pluripotent Diagnostics Corp. (PDx), Molecular Medicine Research Institute, Sunnyvale, CA, United States
| | | | | | - Guan-Hui Wu
- Department of Neurology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Robert Logan
- Pluripotent Diagnostics Corp. (PDx), Molecular Medicine Research Institute, Sunnyvale, CA, United States
- Department of Biology, Eastern Nazarene College, Quincy, MA, United States
- *Correspondence: Robert Logan,
| |
Collapse
|
|
10
|
Astragalus membranaceus treatment combined with caloric restriction may enhance genesis factors and decrease apoptosis in the hippocampus of rats. Arch Gerontol Geriatr 2022; 99:104584. [DOI: 10.1016/j.archger.2021.104584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/08/2021] [Accepted: 11/16/2021] [Indexed: 11/21/2022]
|
|
11
|
Liu X, Chu W, Shang S, Ma L, Jiang C, Ding Y, Wang J, Zhang S, Shao B. Preliminary study on the anti-apoptotic mechanism of Astragaloside IV on radiation-induced brain cells. Int J Immunopathol Pharmacol 2021; 34:2058738420954594. [PMID: 32902354 PMCID: PMC7485151 DOI: 10.1177/2058738420954594] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
With multiple targets and low cytotoxicity, natural medicines can be used as potential neuroprotective agents. The increase in oxidative stress levels and inflammatory responses in the brain caused by radiation affects cognitive function and neuronal structure, and ultimately leads to abnormal changes in neurogenesis, differentiation, and apoptosis. Astragaloside Ⅳ (AS-Ⅳ), one of the main active constituents of astragalus, is known for its antioxidant, antihypertensive, antidiabetic, anti-infarction, anti-inflammatory, anti-apoptotic and wound healing, angiogenesis, and other protective effects. In this study, the mechanism of AS-IV against radiation-induced apoptosis of brain cells in vitro and in vivo was explored by radiation modeling, which provided a theoretical basis for the development of anti-radiation Chinese herbal active molecules and brain health products. In order to study the protective mechanism of AS-IV on radiation-induced brain cell apoptosis in mice, the paper constructed a radiation-induced brain cell apoptosis model, using TUNEL staining, flow cytometry, Western blotting to analyze AS-IV resistance mechanism to radiation-induced brain cell apoptosis. The results of TUNEL staining and flow cytometry showed that the apoptosis rate of radiation group was significantly increased. The results of Western blotting indicated that the expression levels of p-JNK, p-p38, p53, Caspase-9 and Caspase-3 protein, and the ratio of Bax to Bcl-2 in radiation group were significantly increased. There was no significant difference in the expression levels of JNK and p38. After AS-IV treatment, the apoptosis was reduced and the expression of apoptosis related proteins was changed. These data suggested that AS-IV can effectively reduce radiation-induced apoptosis of brain cells, and its mechanism may be related to the phosphorylation regulation of JNK-p38.
Collapse
Affiliation(s)
- Xin Liu
- School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, China
| | - Weiwei Chu
- School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, China
| | - Shuying Shang
- School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, China
| | - Liang Ma
- School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, China
| | - Chenxin Jiang
- School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, China
| | - Yanping Ding
- School wof Life Sciences, Northwest Normal University, Lanzhou, Gansu Province, China
| | - Jianlin Wang
- School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, China
| | - Shengxiang Zhang
- School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, China
| | - Baoping Shao
- School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, China
| |
Collapse
|
|
12
|
Durazzo A, Nazhand A, Lucarini M, Silva AM, Souto SB, Guerra F, Severino P, Zaccardelli M, Souto EB, Santini A. Astragalus (Astragalus membranaceus Bunge): botanical, geographical, and historical aspects to pharmaceutical components and beneficial role. RENDICONTI LINCEI. SCIENZE FISICHE E NATURALI 2021. [DOI: 10.1007/s12210-021-01003-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
AbstractMedicinal plants always are part of folk medicine and are nowadays receiving worldwide attention for prophylaxis, management, and treatment of several diseases, as an alternative to chemical drugs. The current work provided a comprehensive overview and analysis of the Astragalus and health relationship in literature. The analysis of their therapeutic potential is thus instrumental to understand their bioactivity. Among these, the flowering medicinal plant Astragalus membranaceus has raised interest due to several beneficial health effects. This perspective review discussed the botanical, geographical, historical, and the therapeutic properties of A. membranaceus, with a special focus on its health improving effects and medicinal applications both in vitro and in vivo.
Graphic abstract
Collapse
|
|
13
|
Salehi B, Carneiro JNP, Rocha JE, Coutinho HDM, Morais Braga MFB, Sharifi-Rad J, Semwal P, Painuli S, Moujir LM, de Zarate Machado V, Janakiram S, Anil Kumar NV, Martorell M, Cruz-Martins N, El Beyrouthy M, Sadaka C. Astragalus species: Insights on its chemical composition toward pharmacological applications. Phytother Res 2021; 35:2445-2476. [PMID: 33325585 DOI: 10.1002/ptr.6974] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 10/02/2020] [Accepted: 11/24/2020] [Indexed: 01/30/2023]
Abstract
Astragalus L. is widely distributed throughout the temperate regions of Europe, Asia, and North America. The genus is widely used in folk medicine and in dietary supplements, as well as in cosmetics, teas, coffee, vegetable gums, and as forage for animals. The major phytoconstituents of Astragalus species with beneficial properties are saponins, flavonoids, and polysaccharides. Astragalus extracts and their isolated components exhibited promising in vitro and in vivo biological activities, including antiaging, antiinfective, cytoprotective, antiinflammatory, antioxidant, antitumor, antidiabesity, and immune-enhancing properties. Considering their proven therapeutic potential, the aim of this work is to give a comprehensive summary of the Astragalus spp. and their active components, in an attempt to provide new insight for further clinical development of these xenobiotics. This is the first review that briefly describes their ethnopharmacology, composition, biological, and toxicological properties.
Collapse
Affiliation(s)
- Bahare Salehi
- Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam, Iran
| | | | | | | | | | - Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador
| | - Prabhakar Semwal
- Department of Biotechnology, Graphic Era University, Dehradun, India
- Uttarakhand State Council for Science and Technology, Dehradun, India
| | - Sakshi Painuli
- Department of Biotechnology, Graphic Era University, Dehradun, India
| | - Laila Moujir Moujir
- Department of Biochemistry, Microbiology, Molecular Biology and Genetics, University of La Laguna, Tenerife, Spain
| | - Victoria de Zarate Machado
- Department of Biochemistry, Microbiology, Molecular Biology and Genetics, University of La Laguna, Tenerife, Spain
| | - Shriyaa Janakiram
- Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, India
| | | | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, Centre for Healthy Living, University of Concepción, Concepción, Chile
- Universidad de Concepción, Unidad de Desarrollo Tecnológico, UDT, Concepción, Chile
| | - Natalia Cruz-Martins
- Faculty of Medicine, University of Porto, Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
- Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | | | - Carmen Sadaka
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| |
Collapse
|
|
14
|
Xu L, Wei K, Jiang J, Zhang L. Extraction Optimization of Astragaloside IV by Response Surface Methodology and Evaluation of Its Stability during Sterilization and Storage. Molecules 2021; 26:2400. [PMID: 33924283 PMCID: PMC8074912 DOI: 10.3390/molecules26082400] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/01/2021] [Accepted: 04/14/2021] [Indexed: 11/26/2022] Open
Abstract
Radix Astragali is referred to as a variety of food-medicine herb, and it is commonly applied as Traditional Chinese Medicine (TCM). However, it is extremely difficult to extract its bio-active compounds (astragaloside IV) and apply it in food processing efficiently, which restricts its practical applications. In this study, the conditions required for the extraction of astragaloside IV were optimized by following the response surface methodology. More specifically, ammonia with a concentration of 24% was used as an extracting solvent, the solid-liquid ratio was 1:10 (w:v); the Radix Astragali was soaked at 25 °C for 120 min in advance and then stirred at 25 °C for 52 min (150 rpm) to extract astragaloside IV. This method promoted the transformation of other astragalosides into astragaloside IV and replaced the traditional approach for extraction, the solvent reflux extraction method. The yield of astragaloside IV reached the range of 2.621 ± 0.019 mg/g. In addition, the stability of astragaloside IV was evaluated by detecting its retention rate during sterilization and 60-day storage. As suggested by the results, the astragaloside IV in acidic, low-acidic, and neutral solutions was maintained above 90% after sterilization (95 °C and 60 min) but below 60% in an alkaline solution. High temperature and short-term sterilization approach is more appropriate for astragaloside IV in an alkaline solution. It was also found out that the astragaloside IV obtained using our method was maintained over 90% when stored at room temperature (25 °C), and there was no significant difference observed to low temperature (4 °C) in solutions regardless of acidity.
Collapse
Affiliation(s)
- Lin Xu
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China;
| | - Kongjiong Wei
- Gansu Longcuitang Nutrition Food Corp., Ltd., Lanzhou 730046, China; (K.W.); (J.J.)
| | - Jiaolong Jiang
- Gansu Longcuitang Nutrition Food Corp., Ltd., Lanzhou 730046, China; (K.W.); (J.J.)
| | - Lianfu Zhang
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China;
| |
Collapse
|
|
15
|
Protective effects of Astragaloside IV against oxidative injury and apoptosis in cultured astrocytes by regulating Nrf2/JNK signaling. Exp Brain Res 2021; 239:1827-1840. [PMID: 33830313 DOI: 10.1007/s00221-021-06096-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/19/2021] [Indexed: 12/24/2022]
Abstract
Ischemic stroke is a worldwide complex brain disease that results in numerous disabilities and deaths. It leads to the deprivation of oxygen and glucose, which causes energy failure and neuronal death. The activation of astrocytes contributes to neuronal damage or repair after brain ischemia/reperfusion, although astrocytes get little attention as potential drug targets. This study investigated the protective effects of Astragaloside IV (AS-IV) on oxygen glucose deprivation/reoxygenation (OGD/R)-induced damage in rat primary cultured astrocytes and the underlying molecular mechanism. The results showed that compared with the control group, astrocytes under OGD/R exposure significantly decreased cell viability and increased the number of apoptotic cells, whereas AS-IV evidently protected the astrocytes against OGD/R-induced cell damage. In addition, low and medium concentrations of AS-IV can promote the increase of intracellular superoxide dismutase (SOD) level, as well as restored the morphological changes caused by OGD/R exposure. Supplementation with AS-IV after OGD/R exposure promoted the expression of oxidation and apoptosis indexes and further study demonstrated that AS-IV inhibited CXCR4 receptor and downregulated the activation of p-JNK/JNK pathway, which suppressed the expression of Bax/Bcl-2, and finally uprising Nrf2/Keap1 signaling. In conclusion, these findings revealed that AS-IV protected against OGD/R-induced astrocytes through inhibiting oxidative stress and apoptotic pathways.
Collapse
|
|
16
|
Xu Z, Yang D, Huang X, Huang H. Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson's Disease via Activating the JAK2/STAT3 Pathway. Front Neurosci 2021; 15:631501. [PMID: 33833662 PMCID: PMC8021720 DOI: 10.3389/fnins.2021.631501] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 02/04/2021] [Indexed: 12/20/2022] Open
Abstract
Objectives Astragaloside IV (AS-IV), the main active component of Astragalus membranaceus, bears anti-inflammatory, antioxidant, and neuroprotective activity. Parkinson’s disease (PD) is a common neurodegenerative disease. This study explored the protective effect of AS-IV on the cell model of PD. Materials and Methods SH-SY5Y cells were incubated with different concentrations (10, 50, 100, 150, and 200 μM) of 6-hydroxydopamine (6-OHDA) for 0, 3, 6, 12, 24, and 48 h to establish the PD cell model. Different concentrations (0, 25, 50, 100, 150, and 200 μM) of AS-IV or 15 mM JAK2/STAT3 pathway inhibitor SC99 was added for intervention 2 h before 6-OHDA treatment. The viability and morphological damage of 6-OHDA-treated SH-SY5Y cells were measured using MTT assay and Hoechst 33258 staining. The expression of microtubule associated protein 2 (MAP2) was detected by immunofluorescence staining. The levels of inflammation and oxidative stress were measured using ELISA. Apoptosis of 6-OHDA-treated SH-SY5Y cells was detected using flow cytometry, and phosphorylation level of JAK2 and STAT3 were detected using Western blot analysis. Results The survival rate of SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h was about 50%. AS-IV (25–100 μM) significantly improved the viability (all p < 0.01), increased MAP2 expression, and repaired the morphological damage induced by 6-OHDA. AS-IV inhibited IL-1β, IL-6, and TNF-α level (all p < 0.05), reduced MDA and ROS content and increased SOD concentration, thereby reducing inflammation and oxidative stress (all p < 0.01) in 6-OHDA-treated SH-SY5Y cells. Moreover, AS-IV decreased apoptosis rate and Bax/Bcl-2 ratio induced by 6-OHDA (all p < 0.05). Mechanically, AS-IV significantly increased the phosphorylation of JAK2 and STAT3 (p < 0.01); the addition of SC99 decreased the cell viability, increased the apoptosis rate, enhanced the levels of inflammatory factors and oxidative stress. Conclusion AS-IV enhanced the cell viability, and inhibited apoptosis, inflammation and oxidative stress of 6-OHDA-treated SH-SY5Y cells via activating the JAK2/STAT3 signaling pathway. This study may confer novel insights for the management of PD.
Collapse
Affiliation(s)
- ZhengHu Xu
- Department of Neurosurgery, Hebei PetroChina Central Hospital, Langfang, China
| | - Dongfeng Yang
- Department of Neurosurgery, Hebei PetroChina Central Hospital, Langfang, China
| | - Xiaojing Huang
- Department of Neurology, Hebei PetroChina Central Hospital, Langfang, China
| | - Huai Huang
- Department of Neurology, Hebei PetroChina Central Hospital, Langfang, China
| |
Collapse
|
|
17
|
Additive Manufacturing of Astragaloside-Containing Polyurethane Nerve Conduits Influenced Schwann Cell Inflammation and Regeneration. Processes (Basel) 2021. [DOI: 10.3390/pr9020353] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The peripheral nervous system is the bridge of communication between the central nervous system and other body systems. Autologous nerve grafting is the mainstream method for repair of nerve lesions greater than 20 mm. However, there are several disadvantages and limitations of autologous nerve grafting, thus prompting the need for fabrication of nerve conduits for clinical use. In this study, we successfully fabricated astragaloside (Ast)-containing polyurethane (PU) nerve guidance conduits via digital light processing, and it was noted that the addition of Ast improved the hydrophilicity of traditional PU conduits by at least 23%. The improved hydrophilicity not only led to enhanced cellular proliferation of rat Schwann cells, we also noted that levels of inflammatory markers tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) significantly decreased with increasing concentrations of Ast. Furthermore, the levels of neural regeneration markers were significantly enhanced with the addition of Ast. This study demonstrated that Ast-containing PU nerve conduits can be potentially used as an alternative solution to regenerate peripheral nerve injuries.
Collapse
|
|
18
|
Ny V, Houška M, Pavela R, Tříska J. Potential benefits of incorporating Astragalus membranaceus into the diet of people undergoing disease treatment: An overview. J Funct Foods 2021. [DOI: 10.1016/j.jff.2020.104339] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
|
|
19
|
Ben Y, Hao J, Zhang Z, Xiong Y, Zhang C, Chang Y, Yang F, Li H, Zhang T, Wang X, Xu Q. Astragaloside IV Inhibits Mitochondrial-Dependent Apoptosis of the Dorsal Root Ganglion in Diabetic Peripheral Neuropathy Rats Through Modulation of the SIRT1/p53 Signaling Pathway. Diabetes Metab Syndr Obes 2021; 14:1647-1661. [PMID: 33883914 PMCID: PMC8055373 DOI: 10.2147/dmso.s301068] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 03/12/2021] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To investigate the effect of astragaloside IV (AS-IV) on mitochondrial-dependent apoptosis in the dorsal root ganglion of diabetic peripheral neuropathy (DPN) rats through the SIRT1/p53 pathway. METHODS Diabetic rat model was induced by high-carbohydrate/high-fat diet and intraperitoneal injection of STZ. Diabetic rats were divided into three groups (n =16 per group): DPN group, AS-IV group (60mg/kg/d) and α-lipoic acid (ALA) group (60mg/kg/d). Weight and blood glucose levels were monitored every 4 weeks for 12 weeks. DPN was evaluated using the Von Frey Filaments Test and nerve conduction velocity. The dorsal root ganglia of rats were isolated and the pathological changes of mitochondria were observed by electron microscopy. The activity of mitochondrial electron transport chain complex, mitochondrial membrane potential, malonaldehyde (MDA) and glutathione (GSH) levels were measured. Neural apoptosis was detected using the Terminal Deoxynucleotidyl Nick-End Labeling (TUNEL) assay kit. The cleaved caspase-3, major proteins in the SIRT1/p53 pathway, including SIRT1, acetyl p53, Drp1, BAX, and BCL-2, were detected using immunohistochemistry and Western blot. Gene expression of major proteins in the SIRT1/p53 pathway was also detected. RESULTS After 12 weeks of treatment, AS-IV and ALA did not significantly affect body weight or fasting glucose levels, but reduced mechanical abnormal pain in DPN and improved nerve conduction velocity. AS-IV and ALA increased the level of GSH and decreased the level of MDA. Both AS-IV and ALA can reduce mitochondrial damage, improve mitochondrial electron transport chain complex activity and mitochondrial membrane potential, and reduce the percentages of positive cells with DNA fragmentation and the expression of cleaved caspase-3 protein. AS-IV and ALA up-regulated the expression of SIRT1 and down-regulated the expression of acetyl-p53, Drp1 and the ratio of BAX to BCL-2. Changes in gene expression were similar. CONCLUSION AS-IV can reduce the occurrence of mitochondrial-dependent apoptosis by regulating the SIRT1/p53 pathway. It has a similar therapeutic effect as ALA and is therefore a promising drug for the potential treatment of DPN.
Collapse
Affiliation(s)
- Ying Ben
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Juan Hao
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Zhihong Zhang
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Yunzhao Xiong
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Cuijuan Zhang
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Yi Chang
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Fan Yang
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Hui Li
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Tianya Zhang
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Xiangting Wang
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
| | - Qingyou Xu
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China
- Correspondence: Qingyou Xu Hebei University of Chinese Medicine, No. 326 Xinshinan Road, Qiaoxi District, Shijiazhuang, Hebei Province, 050090, People’s Republic of ChinaTel +86 13832368865Fax +86 311 89926000 Email
| |
Collapse
|
|
20
|
Tian Y, Jin S, Promes V, Liu X, Zhang Y. Astragaloside IV and echinacoside benefit neuronal properties via direct effects and through upregulation of SOD1 astrocyte function in vitro. Naunyn Schmiedebergs Arch Pharmacol 2020; 394:1019-1029. [PMID: 33219470 DOI: 10.1007/s00210-020-02022-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 11/10/2020] [Indexed: 12/21/2022]
Abstract
Amyotrophic lateral sclerosis (ALS), also known as a major type of motor neuron disease, is a disease characterized by the degeneration of both upper and lower motor neurons. Astragaloside IV (AST) is one of the most effective compounds isolated from Astragalus membranaceus. Echinacoside (ECH) is also an active constituent in Cistanche tubulosa. These two herbs had been used in treating disease described like ALS in ancient China under the guidance of traditional Chinese medicine theory and now they are still being used extensively for ALS in current Chinese medicine practice, but whether AST or ECH has effect on ALS disease condition is still unclear. Survivals of primary cultured neuron and astrocyte were determined by the MTS assay. Proteins including GLT1 and GFAP, from SOD1 G93A Tg (transgenic) astrocyte lysate were determined by Western blot. Synaptic markers, PSD95 and VGLUT1, were stained by immunofluorescence and observed by a confocal microscope. Proper dilution of AST and ECH was confirmed to be not harmful to both astrocytes and neurons. AST and ECH enhanced neuronal synaptic markers density or intensity/area in different aspects. Both AST and ECH could significantly rescue SOD1 astrocyte conditional medium-treated neuronal survival and synapse loss. Ten micromolars ECH could significantly rescue the suppressed GLT1 level expressed by SOD1 Tg astrocyte. This present research proved that AST and ECH could benefit neuronal properties and rescue certain dysfunction, such as GLT1 low expression, loss of neuron-supporting function, of astrocytes under SOD1 condition.
Collapse
Affiliation(s)
- Yang Tian
- Beijing University of Chinese Medicine, Beijing, People's Republic of China.,Tufts University School of Medicine, Boston, MA, USA
| | - Shijie Jin
- Tufts University School of Medicine, Boston, MA, USA
| | | | - Xuemei Liu
- Central Laboratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People's Republic of China
| | - Yunling Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, People's Republic of China.
| |
Collapse
|
|
21
|
Zhang J, Xue X, Qiao Y, Li D, Wei Q, Zhang F, Qin X. Astragaloside IV Extends Lifespan of Caenorhabditis elegans by Improving Age-Related Functional Declines and Triggering Antioxidant Responses. Rejuvenation Res 2020; 24:120-130. [PMID: 32741299 DOI: 10.1089/rej.2020.2312] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Astragaloside IV (AS-IV) is a representative component of astragaloside saponins in dried roots of Astragali Radix. Astragaloside possesses a broad spectrum of pharmacological activities, including antibacterial, anti-fibrosis, antioxidant, anti-inflammatory, and neuroprotective effects. However, the role of AS-IV in antiaging remains unclear. In this article, we studied the function of AS-IV in antiaging by using the Caenorhabditis elegans (C. elegans) model. We showed that AS-IV can prolong the lifespan of C. elegans in a natural aging model, a paraquat injury model, and a heat stress model and improve the movement capacity of nematodes. 1H-NMR data indicate an improvement of glutamate content and a decrease in glucose in the AS-IV treatment group compared with the control. Further investigation revealed that AS-IV can induce the mRNA expression of superoxide dismutase (SOD) and catalase (CAT) genes and increase the activities of SOD and CAT in the nematode. Interestingly, AS-IV could not extend the lifespan of sod-1, sod-2, sod-3, sod-4, sod-5, ctl-1, ctl-2, ctl-3, and daf-16 mutants. These data indicate that AS-IV prevents aging via mainly improving age-related functional declines, the antioxidant capacity of nematodes and partially modulating the insulin/insulin growth factor 1 signaling pathway activity. Our results provide new insights into how AS-IV prevents and treats aging.
Collapse
Affiliation(s)
- Jianqin Zhang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Xiaoli Xue
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Yuqi Qiao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Daqi Li
- Institute of Plant Protection, Shanxi Academy of Agricultural Sciences, Taiyuan, China
| | - Qing Wei
- Center for Reproduction and Health Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China
| | - Fusheng Zhang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Xuemei Qin
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| |
Collapse
|
|
22
|
Korany MA, Moneeb MS, Asaad AM, El-Sebakhy NA, El-Banna AA. Analysis of astragalosides I, II and IV in some Egyptian Astragalus species and Astragalus dietary supplements using high-performance liquid chromatography/evaporative light scattering detector and non-parametric regression. PHYTOCHEMICAL ANALYSIS : PCA 2020; 31:594-605. [PMID: 32023361 DOI: 10.1002/pca.2925] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Revised: 01/02/2020] [Accepted: 01/21/2020] [Indexed: 06/10/2023]
Abstract
INTRODUCTION GenuTs Astragalus L. is characterised by the presence of cycloartane saponins which have wide biological activities such as antioxidant, immunomodulating' hepatoprotective and anti-inflammatory activities. From these cycloartane saponins are astragalosides I, II and IV which have been regarded as the most important active constituents in Astragalus species. OBJECTIVES This work describes the quantitative analysis of astragalosides I, II and IV in some Egyptian Astragalus species and Astragalus dietary supplements in a single run by high-performance liquid chromatography/evaporative light scattering detector (HPLC/ELSD) using gradient elution. METHODOLOGY The method of quantitation adopted in this study is the standard addition method. First and second derivative treatment of the data was performed, and the study presents comparison between two statistical regression methods for handling data; parametric and non-parametric regression methods. RESULTS Derivative treatment of the chromatographic response data gives improved quantitation of the chromatographic signals. Non-parametric regression of the data using Theil's method is advantageous over the usual least squares method as it assumes that errors could occur in both x- and y-directions and they might not be normally distributed. In addition, it could effectively circumvent any outlier data points. CONCLUSION Due to the simplicity and the good accuracy and reproducibility of the suggested methods, they could be used for analysis and quality control of Astragalus species and Astragalus dietary supplements.
Collapse
Affiliation(s)
- Mohamed A Korany
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, 21521, Egypt
| | - Marwa S Moneeb
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, 21521, Egypt
| | - Aya M Asaad
- Department of Pharmacognosy, Faculty of Pharmacy, University of Alexandria, Alexandria, 21521, Egypt
| | - Nadia A El-Sebakhy
- Department of Pharmacognosy, Faculty of Pharmacy, University of Alexandria, Alexandria, 21521, Egypt
| | - Alaa A El-Banna
- Department of Pharmacognosy, Faculty of Pharmacy, University of Alexandria, Alexandria, 21521, Egypt
| |
Collapse
|
|
23
|
Berezutsky MA, Durnova NA, Vlasova IA. Experimental and Clinical Studies of Mechanisms of the Antiaging Effects of Chemical Compounds in Astragalus membranaceus (Review). ADVANCES IN GERONTOLOGY 2020. [DOI: 10.1134/s2079057020020046] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
|
|
24
|
Kardani A, Soltani A, Sewell RDE, Shahrani M, Rafieian-Kopaei M. Neurotransmitter, Antioxidant and Anti-neuroinflammatory Mechanistic Potentials of Herbal Medicines in Ameliorating Autism Spectrum Disorder. Curr Pharm Des 2020; 25:4421-4429. [PMID: 31721693 DOI: 10.2174/1381612825666191112143940] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 11/09/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND Autism spectrum disorder (ASD) is a neurodevelopmental issue that disrupts behavior, nonverbal communication, and social interaction, impacting all aspects of an individual's social development. The underlying origin of autism is unclear, however, oxidative stress, as well as serotonergic, adrenergic and dopaminergic systems are thought to be implicated in ASD. Despite the fact that there is no effective medication for autism, current pharmacological treatments are utilized to ameliorate some of the symptoms such as selfmutilation, aggression, repetitive and stereotyped behaviors, inattention, hyperactivity, and sleep disorders. METHODS In accord with the literature regarding the activity of herbal medicines on neurotransmitter function, we aimed to review the most worthy medicinal herbs possessing neuroprotective effects. RESULTS Based on the outcome, medicinal herbs such as Zingiber officinale, Astragalus membranaceu, Ginkgo biloba, Centella asiatica and Acorus calamus, have antioxidant activity, which can influence neurotransmitter systems and are potentially neuroprotective. CONCLUSION Consequently, these herbs, in theory at least, appear to be suitable candidates within an overall management strategy for those on the autism spectrum.
Collapse
Affiliation(s)
- Arefeh Kardani
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Amin Soltani
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Robert D E Sewell
- Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF10 3NB. Wales, United Kingdom
| | - Mehrdad Shahrani
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mahmoud Rafieian-Kopaei
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| |
Collapse
|
|
25
|
Astragaloside IV inhibits astrocyte senescence: implication in Parkinson's disease. J Neuroinflammation 2020; 17:105. [PMID: 32252767 PMCID: PMC7137443 DOI: 10.1186/s12974-020-01791-8] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Accepted: 03/27/2020] [Indexed: 01/10/2023] Open
Abstract
Background Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson’s disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. Methods Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP+)-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers. Results We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP+-induced premature senescence, evidenced by decreased senescence-associated β-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence. Conclusions Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.
Collapse
|
|
26
|
In Silico Studies on Triterpenoid Saponins Permeation through the Blood-Brain Barrier Combined with Postmortem Research on the Brain Tissues of Mice Affected by Astragaloside IV Administration. Int J Mol Sci 2020; 21:ijms21072534. [PMID: 32260588 PMCID: PMC7177733 DOI: 10.3390/ijms21072534] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 04/01/2020] [Accepted: 04/03/2020] [Indexed: 02/06/2023] Open
Abstract
As the number of central nervous system (CNS) drug candidates is constantly growing, there is a strong need for precise a priori prediction of whether an administered compound is able to cross the blood–brain barrier (BBB). The aim of this study was to evaluate the ability to cross the BBB of triterpenoid saponins occurring in Astragalus mongholicus roots. The research was carried out using in silico methods combined with postmortem studies on the brain tissues of mice treated with isolated astragaloside IV (AIV). Firstly, to estimate the ability to cross the BBB by the tested saponins, new quantitative structure–activity relationship (QSAR) models were established. The reliability and predictability of the model based on the values of the blood–brain barrier penetration descriptor (logBB), the difference between the n-octanol/water and cyclohexane/water logP (ΔlogP), the logarithm of n-octanol/water partition coefficient (logPow), and the excess molar refraction (E) were both confirmed using the applicability domain (AD). The critical leverage value h* was found to be 0.128. The relationships between the standardized residuals and the leverages were investigated here. The application of an in vitro acetylcholinesterase-inhibition test showed that AIV can be recognized as the strongest inhibitor among the tested compounds. Therefore, it was isolated for the postmortem studies on brain tissues and blood using semi-preparative HPLC with the mobile phase composed of water, methanol, and ethyl acetate (1.7:2.1:16.2 v/v/v). The results of the postmortem studies on the brain tissues show a regular dependence of the final concentration of AIV in the analyzed brain samples of animals treated with 12.5 and 25 mg/kg b.w. of AIV (0.00012299 and 0.0002306 mg, respectively, per one brain). Moreover, the AIV logBB value was experimentally determined and found to be equal to 0.49 ± 0.03.
Collapse
|
|
27
|
Chen F, Zhong Z, Tan HY, Guo W, Zhang C, Tan CW, Li S, Wang N, Feng Y. Uncovering the Anticancer Mechanisms of Chinese Herbal Medicine Formulas: Therapeutic Alternatives for Liver Cancer. Front Pharmacol 2020; 11:293. [PMID: 32256363 PMCID: PMC7093640 DOI: 10.3389/fphar.2020.00293] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 02/27/2020] [Indexed: 12/16/2022] Open
Abstract
The potential values of Chinese herbal formulas in treating various diseases are well known. In addition to more than 2,000 years of history, herbal medicine is appreciated for its remarkable efficacy in a lot of cases, which warrants a role in public health care worldwide, especially in East Asian countries. Liver cancer is the second most fatal cancer across the world. Recent studies have extensively investigated the chemical profiles and pharmacological effects of Chinese herbal medicine formulas on liver cancer. Either through observational follow-up or experimental studies, multiple herbal formulas have benefits implicated in the management of liver cancer. However, complex composition of each formula imposes restrictions on promoting clinical practice and global recognition. Therefore, understanding the mode of action of Chinese herbal medicine formulas in depth may offer sufficient evidence for their clinical use. This review highlighted the chemical characteristics and molecular mechanisms of actions of prominent Chinese herbal medicine formulas and summarized the correlated findings on the potential use in liver cancer treatment. At last, the present progresses of Chinese herbal medicine formulas in the perspective of clinical trials are discussed.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| |
Collapse
|
|
28
|
Mei X, Wang Y, Liu Z, Wang S, Dong F, Wang Z, Qiao Y, Zhang J. The chemical transformations for Radix Astragali via different alkaline wash conditions by quantitative and qualitative analyses. J Pharm Biomed Anal 2020; 185:113164. [PMID: 32199325 DOI: 10.1016/j.jpba.2020.113164] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 02/05/2020] [Accepted: 02/09/2020] [Indexed: 02/02/2023]
Abstract
Radix Astragali is a famous Chinese traditional and folk medicine with a wide range of medicinal values in clinic. In this study, an analytical efficient strategy based on UHPLC-QQQ-MS/MS and UHPLC-LTQ-Orbitrap-MS/MS was established to explore and reveal the chemical transformations for Radix Astragali under different alkaline wash conditions for analytical sample preparation. Firstly, a rapid and sensitive UHPLC-QQQ-MS/MS method for the quantification of 14 main constituents in Radix Astragali has been developed and validated. Secondly, according to the standard substance comparison, accurate mass measurements, mass fragmentation behaviors and related literatures, a total of 102 components have been screened and identified using UHPLC-LTQ-Orbitrap method. Among them, 47 compounds are saponins, and the other 55 are flavonoids. Consequently, there were two chemical transformations including hydrolysis and degradation observed when Radix Astragali was treated with alkali. Besides, hydrolysis of glycosides and acetyl played a considerably important role in the process of sample preparation. It has been proved that 10 % ammonia could relatively guarantee the high content of astragaloside IV and avoid the over-degradation of most chemical ingredients in Radix Astragali. In conclusion, this work would provide a scientific and practical method for quality control of Radix Astragali as well as its compound preparations.
Collapse
Affiliation(s)
- Xiaodan Mei
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Yuqi Wang
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Zihan Liu
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Shaoping Wang
- School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Fan Dong
- School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Zijian Wang
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yanjiang Qiao
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China.
| | - Jiayu Zhang
- School of Pharmacy, Binzhou Medical University, Yantai 264003, China.
| |
Collapse
|
|
29
|
Wang CJ, He F, Huang YF, Ma HL, Wang YP, Cheng CS, Cheng JL, Lao CC, Chen DA, Zhang ZF, Sang Z, Luo P, Xiao SY, Xie Y, Zhou H. Discovery of chemical markers for identifying species, growth mode and production area of Astragali Radix by using ultra-high-performance liquid chromatography coupled to triple quadrupole mass spectrometry. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2020; 67:153155. [PMID: 31901890 DOI: 10.1016/j.phymed.2019.153155] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 12/18/2019] [Accepted: 12/20/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND Astragali Radix (AR) is a well-known Chinese herbal medicine. The quality of AR can be affected by many factors such as species, growth mode and production area, but there are still no chemical markers to distinguish it. PURPOSE To explore chemical markers for improving the quality assessment of AR and discover chemical markers for identifying species, growth mode and production area of AR. METHODS A highly sensitive, efficient and accurate method based on ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) for simultaneous quantitative determination of 14 major chemical components (five flavonoids and nine triterpene saponins) in 94 batches of AR from China, Republic of Korea and Germany was developed for the first time. To explore chemical markers and assess changes in the contents of 14 compounds in the 94 batches of AR samples from different regions, hierarchical clustering analysis (HCA) and principal component analysis (PCA) were performed. RESULTS Astragaloside III was not only an important chemical marker for distinguishing two species of AR, i.e.: Astragalus mongholicus and A. membranaceus, but also a potential chemical marker for the classification of cultivated and semi-wild AR. In addition, in the batches of cultivated AR, the content of isoastragaloside II and cyclocephaloside II were greater in batches from the region of Shaanxi Province than that of other Provinces in China, but the content of calycosin-7-O-β-D-glucoside and astragaloside IV, which are the quality control markers of AR required by the Chinese Pharmacopoeia, were higher than that of other Provinces in China. In addition, the content of calycosin-7-O-β-D-glucoside, ononin, calycosin and astragaloside I could be used to identify samples of AR collected from China, Republic of Korea and Germany. CONCLUSION This UHPLC-QQQ-MS/MS method could be applied to the quantitative evaluation of AR and could be an important and meaningful reference to develop chemical markers for quality control of AR.
Collapse
Affiliation(s)
- Can-Jian Wang
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China
| | - Fan He
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China
| | - Yu-Feng Huang
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China; Institute of International Standardization of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China
| | - Hong-Liang Ma
- Zhongshan Zhongzhi Pharmaceutical Group Co., Ltd., Zhongshan 513508, PR China; The Key Laboratory of Technology of Breaking Cell Wall and Application in Chinese Medicine Decoction Pieces, Zhongshan 513508, PR China
| | - Ying-Ping Wang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, PR China
| | - Chun-Song Cheng
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China
| | - Jin-Le Cheng
- Zhongshan Zhongzhi Pharmaceutical Group Co., Ltd., Zhongshan 513508, PR China; The Key Laboratory of Technology of Breaking Cell Wall and Application in Chinese Medicine Decoction Pieces, Zhongshan 513508, PR China
| | - Chi-Chou Lao
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China
| | - Di-An Chen
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China
| | - Zhi-Feng Zhang
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China
| | - Zhen Sang
- Institute of International Standardization of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China
| | - Pei Luo
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Macau University of Science and Technology, Taipa, Macao 999078, PR China
| | - Sheng-Yuan Xiao
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, PR China
| | - Ying Xie
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Macau University of Science and Technology, Taipa, Macao 999078, PR China.
| | - Hua Zhou
- State Key Laboratory of Quality Research in Chinese Medicine, and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, PR China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Macau University of Science and Technology, Taipa, Macao 999078, PR China.
| |
Collapse
|
|
30
|
Costa IM, Lima FOV, Fernandes LCB, Norrara B, Neta FI, Alves RD, Cavalcanti JRLP, Lucena EES, Cavalcante JS, Rego ACM, Filho IA, Queiroz DB, Freire MAM, Guzen FP. Astragaloside IV Supplementation Promotes A Neuroprotective Effect in Experimental Models of Neurological Disorders: A Systematic Review. Curr Neuropharmacol 2020; 17:648-665. [PMID: 30207235 PMCID: PMC6712289 DOI: 10.2174/1570159x16666180911123341] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 08/10/2018] [Accepted: 08/28/2018] [Indexed: 01/22/2023] Open
Abstract
Background: Neurological disorders constitute a growing worldwide concern due to the progressive aging of the population and the risky behavior they represent. Herbal medicines have scientific relevance in the treatment of these pathol-ogies. One of these substances, Astragaloside IV (AS-IV), is the main active compound present in the root of Astragalus membranaceus (Fisch.) Bge, a Chinese medicinal herb with neuroprotective properties. Objective: In the present study we performed a systematic review that sought to comprehend the neuroprotective effect pre-sented by AS-IV in experimental models of neurological disorders. Method: This study is a systematic review, where an electronic search in United States National Library of Medicine (Pub-Med), Science Direct, Cochrane Library, Scientific Electronic Library Online (SciELO), Scopus, Web of Science, Medline via Proquest and Periodicos Capes databases covering the years between 2007 and 2017, using “Astragaloside IV” and “Neurodegenerative diseases”; “Astragaloside IV” and “ Neurological disorders” as reference terms was made. Results: A total of 16 articles were identified, in which the efficacy of AS-IV was described in experimental models of Par-kinson’s disease, Alzheimer’s disease, cerebral ischemia and autoimmune encephalomyelitis, by improving motor deficits and/or neurochemical activity, especially antioxidant systems, reducing inflammation and oxidative stress. Conclusion: The findings of the present study indicate that the administration of AS-IV can improve behavioral and neuro-chemical deficits largely due to its antioxidant, antiapoptotic and anti-inflammatory properties, emerging as an alternative therapeutic approach for the treatment of neurological disorders.
Collapse
Affiliation(s)
- Ianara M Costa
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil
| | - Francisca O V Lima
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil
| | - Luciana C B Fernandes
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil
| | - Bianca Norrara
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil
| | - Francisca I Neta
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil
| | - Rodrigo D Alves
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil
| | - José R L P Cavalcanti
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil
| | - Eudes E S Lucena
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil
| | - Jeferson S Cavalcante
- Laboratory of Neurochemical Studies, Center of Biological Sciences, Federal University of Rio Grande do Norte (UFRN), Natal/RN, Brazil
| | - Amalia C M Rego
- Post Graduation Program in Biotechnology, Health School, Potiguar University (UnP), Natal/RN, Brazil
| | - Irami A Filho
- Post Graduation Program in Biotechnology, Health School, Potiguar University (UnP), Natal/RN, Brazil
| | - Dinalva B Queiroz
- Post Graduation Program in Biotechnology, Health School, Potiguar University (UnP), Natal/RN, Brazil
| | - Marco A M Freire
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil
| | - Fausto P Guzen
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Faculty of Health Sciences, University of the State of Rio Grande do Norte (UERN), Mossoro/RN, Brazil.,Post Graduation Program in Biotechnology, Health School, Potiguar University (UnP), Natal/RN, Brazil
| |
Collapse
|
|
31
|
Rabiei Z, Solati K, Amini-Khoei H. Phytotherapy in treatment of Parkinson's disease: a review. PHARMACEUTICAL BIOLOGY 2019; 57:355-362. [PMID: 31141426 PMCID: PMC6542178 DOI: 10.1080/13880209.2019.1618344] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 05/06/2019] [Accepted: 05/08/2019] [Indexed: 05/30/2023]
Abstract
Context: Parkinson's disease (PD) is a neurodegenerative disorder due to gradual loss of dopaminergic nerves in the substantia nigra (SN) in the midbrain. PD leads to certain motor disorders including resting tremor, muscle stiffness and slow movement. Medicinal plants have shown positive pharmacological effects in treating different models of PD. Objective: Tendency to use natural products, especially plants, for the treatment of PD has been growing. This article reviews the basic aspects of medicinal plants and their bioactive compounds that could be used to treat PD. Methods: Reliable articles indexed in databases ISI, SID, PubMed, PubMed Central, Scopus and Web of Science were used. A total of 12 plant-derived active ingredients and 18 herbal extracts were included. Different compounds have so far been isolated from plants that affect PD especially by targeting pathways associated with the pathogenesis of the disease. Results: Although some herbal extracts such as Hibiscus asper Hook. f. (Malvaceae), Ginkgo biloba L. (Ginkgoaceae), Carthamus tinctorius L (Asteraceae) and certain active ingredients, such as berberine and curcumin, have shown positive effects in animal models of PD, potential active ingredients and mechanisms of action should be investigated in additional studies. Discussion and conclusions: Despite the wide variety of plants in the world, a limited number of them have been studied for anti-Parkinsonian activity, and therefore, there are numerous perspectives in this field for future studies on plants and their bioactive compounds.
Collapse
Affiliation(s)
- Zahra Rabiei
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Kamal Solati
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Hossein Amini-Khoei
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| |
Collapse
|
|
32
|
Neuroprotective effects of phytochemicals on dopaminergic neuron cultures. NEUROLOGÍA (ENGLISH EDITION) 2019. [DOI: 10.1016/j.nrleng.2016.04.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
|
|
33
|
Li Y, Yang Y, Zhao Y, Zhang J, Liu B, Jiao S, Zhang X. Astragaloside IV reduces neuronal apoptosis and parthanatos in ischemic injury by preserving mitochondrial hexokinase-II. Free Radic Biol Med 2019; 131:251-263. [PMID: 30502455 DOI: 10.1016/j.freeradbiomed.2018.11.033] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 11/26/2018] [Accepted: 11/26/2018] [Indexed: 01/02/2023]
Abstract
Cerebral ischemia induces neuronal cell death in different ways and mitochondrial dysfunction is an important cause. Astragaloside IV (AIV) is a natural saponin abandent in Astragalus membranaceus and this study aims to find if AIV protects neuronal survival via preserving mitochondrial hexokinase-II (HK-II). Glutamate stimulation induced HK-II dissociation from mitochondria and impaired mitochondrial function, indicated by the opening of the mitochondrial permeability transition pore, the collapse of mitochondrial membrane potential and reduced mitochondrial oxygen consumption ratio in neurons. Accompanied with apoptosis, oxidative DNA damage, PAR formation and nuclear translocation of apoptosis inducing factor (AIF) indicated the presence of parthanatos. AIV activated Akt and protected mitochondrial HK-II via promoting the binding of Akt to HK-II and protected hexokinase activity with improved glycolysis. As a consequence of preserved mitochondrial HK-II, AIV reduced the release of pro-apoptotic proteins and AIF, resultantly protected neurons from apoptosis and parthanatos. Moreover, the neuroprotective effects of AIV were also reproduced in mice subjected to middle cerebral artery occlusion to support the findings in vitro. Together, these results showed that glutamate excitotoxicity impaired mitochondrial HK-II and simultaneously induced apoptosis and parthanatos owing to mitochondrial dysfunction. AIV activated Akt to promote HK-II binding to mitochondria, and the structural and functional integrity of mitochondria contributed to protecting neurons from apoptosis and DNA damage. These findings address the important role of mitochondrial HK-II in neuronal protection.
Collapse
Affiliation(s)
- Ying Li
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yilin Yang
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Yunpeng Zhao
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Jingmin Zhang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Baolin Liu
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Shujie Jiao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
| | - Xiaojian Zhang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
| |
Collapse
|
|
34
|
Zhao C, Zhang C, Xing Z, Ahmad Z, Li JS, Chang MW. Pharmacological effects of natural Ganoderma and its extracts on neurological diseases: A comprehensive review. Int J Biol Macromol 2019; 121:1160-1178. [DOI: 10.1016/j.ijbiomac.2018.10.076] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Revised: 10/06/2018] [Accepted: 10/14/2018] [Indexed: 01/13/2023]
|
|
35
|
In Vitro Neuroprotection of Rat Hippocampal Neurons by Manninotriose and Astragaloside IV Against Corticosterone-Induced Toxicity. Molecules 2018; 23:molecules23123339. [PMID: 30562980 PMCID: PMC6321307 DOI: 10.3390/molecules23123339] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 12/12/2018] [Accepted: 12/13/2018] [Indexed: 11/16/2022] Open
Abstract
A chronically elevated glucocorticoid level impairs memory and cognition. Manninotriose is the main oligosaccharide of Prepared Radix Rehmanniae, and Astragaloside IV (AS-IV) is the primary ingredient of Astragali Radix; they have been reported to possess neuroprotective effects. The aim of the present study was to investigate the protective effects of Manninotriose and AS-IV on corticosterone (CORT) induced neurotoxicity and the underlying mechanisms. Primary cultured hippocampal neurons from newborn Sprague Dawley rats were treated with CORT in the absence or presence of Manninotriose and AS-IV. Cell Counting Kit-8 experiments and fluorescein diacetate (FDA)/propidium iodide (PI) double staining were conducted to assess the activity and survival rate of neurons. Quantitative Real-time PCR (qRT-PCR) and western blot analysis were performed to detect the expression of glucocorticoid receptor (GR), zinc finger protein (Zif268) and synapsin 1 (SYN1). DNA methylation of the gene promoter was assessed by bisulfite sequencing (BSP) analysis. The results demonstrated that pre-treatment with Manninotriose and AS-IV significantly improved cell viability and survival rate, and ameliorated the downregulation of GR, Zif268 and SYN1 genes in CORT injured neurons. BSP analysis revealed that CORT was able to improve the CpG island methylation rate of SYN1. AS-IV was observed to decrease the hypermethylation of the SYN1 gene induced by CORT. The results of the present study indicated that Manninotriose and AS-IV may have a protective effect against CORT-induced damage and the downregulation of learning and memory associated genes in hippocampal neurons. Regulation of DNA methylation may be important in the pharmaceutical activities of AS-IV. Thus, Manninotriose and AS-IV may be effective agents against learning and memory impairment.
Collapse
|
|
36
|
Shkondrov A, Krasteva I, Bucar F, Kunert O, Kondeva-Burdina M, Ionkova I. A new tetracyclic saponin from Astragalus glycyphyllos L. and its neuroprotective and hMAO-B inhibiting activity. Nat Prod Res 2018; 34:511-517. [DOI: 10.1080/14786419.2018.1491040] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- Aleksandar Shkondrov
- Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria
| | - Ilina Krasteva
- Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria
| | - Franz Bucar
- Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria
| | - Olaf Kunert
- Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria
| | - Magdalena Kondeva-Burdina
- Laboratory of Drug Metabolism and Drug Toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria
| | - Iliana Ionkova
- Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria
| |
Collapse
|
|
37
|
Chen KY, Wu MY, Yang PS, Chiang JH, Hsu CY, Chen CY, Yen HR. Utilization of Chinese herbal medicine and its association with the risk of fracture in patients with Parkinson's disease in Taiwan. JOURNAL OF ETHNOPHARMACOLOGY 2018; 226:168-175. [PMID: 30118835 DOI: 10.1016/j.jep.2018.08.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 08/12/2018] [Accepted: 08/13/2018] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese medicine (TCM) has been used for over two thousand years to treat motor impairments corresponding to the clinical manifestations of Parkinson's disease (PD). AIM OF THE STUDY This study aimed to investigate the prescription of Chinese herbal medicine (CHM) for the management of PD and further determine whether CHM can improve motor function and decrease the risk of incident fracture. MATERIALS AND METHODS Patients older than 40 years newly diagnosed with PD between January 1997 and December 2010 were selected from the National Health Insurance Research Database (NHIRD) and followed up until the end of 2013. We used 1:1 frequency matching by age, sex, index year, and initial diagnostic year to compare the TCM users and non-TCM users. We used a Cox regression model and the Kaplan-Meier method to estimate the risk of developing fracture among the TCM and non-TCM users. RESULTS In total, 7197 patients older than 40 years were newly diagnosed with PD between 1997 and 2010 in Taiwan. Among these patients, 3456 were TCM users, and 3730 were non-TCM users. We compared 2007 PD patients with comparable demographic characteristics and comorbidity profiles between the two cohorts. During the follow-up period, compared with the non-TCM cohort, fewer patients in the TCM cohort had incident fractures (adjusted hazard ratio: 0.5, 95% CI: 0.44-0.56). The cumulative incidence of fracture was lower in the TCM cohort (log-rank test, p < 0.0001). Shi-Chang-Pu (Acorus gramineus Aiton), Yuan-Zhi (Polygala tenuifolia Willd), Bei-Mu (Fritillaria cirrhosa D. Don), Hai-Piao-Xiao (Sepiella maindronide Rochebrune; Sepia esculenta Hoyle), and Tian-Ma (Gastrodia elata Blume) constituted the core Chinese herbal medicine prescriptions used to treat PD patients. CONCLUSIONS The present study identified the core prescription pattern for the management of PD in Taiwan. Complementary CHM therapy was associated with a reduced risk of fracture in PD patients.
Collapse
Affiliation(s)
- Kuan-Yu Chen
- Department of Public Health, China Medical University, Taichung 404, Taiwan; Department of Chinese Medicine, Taipei City Hospital, Yangming Branch, Taipei 111, Taiwan.
| | - Mei-Yao Wu
- Department of Chinese Medicine, China Medical University Hospital, Taichung 404, Taiwan.
| | - Pei-Shan Yang
- Department of Chinese Medicine, China Medical University Hospital, Taichung 404, Taiwan.
| | - Jen-Huai Chiang
- Management Office for Health Data, China Medical University Hospital, Taichung 404, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung 404 Taiwan
| | - Chung-Y Hsu
- Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung 404, Taiwan; Brain Disease Research Center, China Medical University Hospital, Taichung 404, Taiwan.
| | - Chiu-Ying Chen
- Department of Public Health, China Medical University, Taichung 404, Taiwan; Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung 404, Taiwan; Brain Disease Research Center, China Medical University Hospital, Taichung 404, Taiwan.
| | - Hung-Rong Yen
- Department of Chinese Medicine, China Medical University Hospital, Taichung 404, Taiwan; Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan; Research Center for Chinese Herbal Medicine, China Medical University, Taichung 404, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan.
| |
Collapse
|
|
38
|
Jakaria M, Park SY, Haque ME, Karthivashan G, Kim IS, Ganesan P, Choi DK. Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors. Front Mol Neurosci 2018; 11:307. [PMID: 30210294 PMCID: PMC6123546 DOI: 10.3389/fnmol.2018.00307] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 08/13/2018] [Indexed: 12/13/2022] Open
Abstract
Glutamate receptors play a crucial role in the central nervous system and are implicated in different brain disorders. They play a significant role in the pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Although many studies on NDDs have been conducted, their exact pathophysiological characteristics are still not fully understood. In in vivo and in vitro models of neurotoxic-induced NDDs, neurotoxic agents are used to induce several neuronal injuries for the purpose of correlating them with the pathological characteristics of NDDs. Moreover, therapeutic drugs might be discovered based on the studies employing these models. In NDD models, different neurotoxic agents, namely, kainic acid, domoic acid, glutamate, β-N-Methylamino-L-alanine, amyloid beta, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridinium, rotenone, 3-Nitropropionic acid and methamphetamine can potently impair both ionotropic and metabotropic glutamate receptors, leading to the progression of toxicity. Many other neurotoxic agents mainly affect the functions of ionotropic glutamate receptors. We discuss particular neurotoxic agents that can act upon glutamate receptors so as to effectively mimic NDDs. The correlation of neurotoxic agent-induced disease characteristics with glutamate receptors would aid the discovery and development of therapeutic drugs for NDDs.
Collapse
Affiliation(s)
- Md. Jakaria
- Department of Applied Life Sciences, Graduate School, Konkuk University, Chungju, South Korea
| | - Shin-Young Park
- Department of Applied Life Sciences, Graduate School, Konkuk University, Chungju, South Korea
| | - Md. Ezazul Haque
- Department of Applied Life Sciences, Graduate School, Konkuk University, Chungju, South Korea
| | - Govindarajan Karthivashan
- Department of Integrated Bioscience and Biotechnology, College of Biomedical and Health Sciences, Research Institute of Inflammatory Diseases (RID), Konkuk University, Chungju, South Korea
| | - In-Su Kim
- Department of Integrated Bioscience and Biotechnology, College of Biomedical and Health Sciences, Research Institute of Inflammatory Diseases (RID), Konkuk University, Chungju, South Korea
| | - Palanivel Ganesan
- Department of Integrated Bioscience and Biotechnology, College of Biomedical and Health Sciences, Research Institute of Inflammatory Diseases (RID), Konkuk University, Chungju, South Korea
- Nanotechnology Research Center, Konkuk University, Chungju, South Korea
| | - Dong-Kug Choi
- Department of Applied Life Sciences, Graduate School, Konkuk University, Chungju, South Korea
- Department of Integrated Bioscience and Biotechnology, College of Biomedical and Health Sciences, Research Institute of Inflammatory Diseases (RID), Konkuk University, Chungju, South Korea
- Nanotechnology Research Center, Konkuk University, Chungju, South Korea
| |
Collapse
|
|
39
|
Hao M, Liu Y, Chen P, Jiang H, Kuang HY. Astragaloside IV protects RGC-5 cells against oxidative stress. Neural Regen Res 2018; 13:1081-1086. [PMID: 29926836 PMCID: PMC6022471 DOI: 10.4103/1673-5374.233452] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/04/2018] [Indexed: 12/29/2022] Open
Abstract
Astragaloside IV is the main active compound of Astragalus membranaceus. Astragaloside IV has strong anti-oxidative activities and protective effects against progression of peripheral neuropathy. In this study, we determined whether astragaloside IV protects retinal ganglion cells (RGC) from oxidative stress injury using the rat RGC-5 cell line. Hydrogen peroxide (H2O2) was used to induce oxidative stress injury, with the protective effect of astragaloside IV examined. Cell Counting Kit-8 and 4',6-diamidino-2-phenylindole staining showed that astragaloside IV increased cell survival rate and decreased apoptotic cell number. Flow cytometry showed that astragaloside IV decreased H2O2-induced reactive oxygen species levels. While laser confocal microscopy showed that astragaloside IV inhibited the H2O2-induced decrease of mitochondrial membrane potential. Western blot assay showed that astragaloside IV reduced cytochrome c release induced by H2O2, inhibited Bax and caspase-3 expression, and increased Bcl-2 expression. Altogether, these results indicate that astragaloside IV has potential protective effects against H2O2-induced oxidative stress in retinal ganglion cells.
Collapse
Affiliation(s)
- Ming Hao
- Department of Endocrinology, The First Clinical Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Yu Liu
- Department of Endocrinology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang Province, China
| | - Ping Chen
- Department of Endocrinology, The First Hospital of Harbin, Harbin, Heilongjiang Province, China
| | - Hong Jiang
- Department of Endocrinology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang Province, China
| | - Hong-Yu Kuang
- Department of Endocrinology, The First Clinical Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| |
Collapse
|
|
40
|
Ting HC, Chang CY, Lu KY, Chuang HM, Tsai SF, Huang MH, Liu CA, Lin SZ, Harn HJ. Targeting Cellular Stress Mechanisms and Metabolic Homeostasis by Chinese Herbal Drugs for Neuroprotection. Molecules 2018; 23:E259. [PMID: 29382106 PMCID: PMC6017457 DOI: 10.3390/molecules23020259] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Revised: 01/25/2018] [Accepted: 01/26/2018] [Indexed: 12/14/2022] Open
Abstract
Traditional Chinese medicine has been practiced for centuries in East Asia. Herbs are used to maintain health and cure disease. Certain Chinese herbs are known to protect and improve the brain, memory, and nervous system. To apply ancient knowledge to modern science, some major natural therapeutic compounds in herbs were extracted and evaluated in recent decades. Emerging studies have shown that herbal compounds have neuroprotective effects or can ameliorate neurodegenerative diseases. To understand the mechanisms of herbal compounds that protect against neurodegenerative diseases, we summarize studies that discovered neuroprotection by herbal compounds and compound-related mechanisms in neurodegenerative disease models. Those compounds discussed herein show neuroprotection through different mechanisms, such as cytokine regulation, autophagy, endoplasmic reticulum (ER) stress, glucose metabolism, and synaptic function. The interleukin (IL)-1β and tumor necrosis factor (TNF)-α signaling pathways are inhibited by some compounds, thus attenuating the inflammatory response and protecting neurons from cell death. As to autophagy regulation, herbal compounds show opposite regulatory effects in different neurodegenerative models. Herbal compounds that inhibit ER stress prevent neuronal death in neurodegenerative diseases. Moreover, there are compounds that protect against neuronal death by affecting glucose metabolism and synaptic function. Since the progression of neurodegenerative diseases is complicated, and compound-related mechanisms for neuroprotection differ, therapeutic strategies may need to involve multiple compounds and consider the type and stage of neurodegenerative diseases.
Collapse
Affiliation(s)
- Hsiao-Chien Ting
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
| | - Chia-Yu Chang
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan
| | - Kang-Yun Lu
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan
| | - Hong-Meng Chuang
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Agricultural Biotechnology Center, Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan
| | - Sheng-Feng Tsai
- Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan;
| | - Mao-Hsuan Huang
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan;
| | - Ching-Ann Liu
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan
| | - Shinn-Zong Lin
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan
| | - Horng-Jyh Harn
- Bio-innovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; (H.-C.T.); (C.-Y.C.); (K.-Y.L.); (H.-M.C.); (M.-H.H.); (C.-A.L.)
- Department of Pathology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien 970, Taiwan
| |
Collapse
|
|
41
|
Wang ZF, Ma DG, Zhu Z, Mu YP, Yang YY, Feng L, Yang H, Liang JQ, Liu YY, Liu L, Lu HW. Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts. World J Gastroenterol 2017; 23:8512-8525. [PMID: 29358859 PMCID: PMC5752711 DOI: 10.3748/wjg.v23.i48.8512] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 09/29/2017] [Accepted: 11/22/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts, and to explore the underlying mechanism. METHODS Paired gastric normal fibroblast (GNF) and gastric cancer-associated fibroblast (GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside IV. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs, and astragaloside IV-treated GCAFs, and used to culture BGC-823 human gastric cancer cells. Proliferation, migration and invasion capacities of BGC-823 cells were determined by MTT, wound healing, and Transwell invasion assays, respectively. The action mechanism of astragaloside IV was investigated by detecting the expression of microRNAs and the expression and secretion of the oncogenic factor, macrophage colony-stimulating factor (M-CSF), and the tumor suppressive factor, tissue inhibitor of metalloproteinase 2 (TIMP2), in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined. RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation, migration, and invasion than GNFs (P < 0.01). Astragaloside IV treatment strongly inhibited the proliferation-, migration- and invasion-promoting capacities of GCAFs (P < 0.05 for 10 μmol/L, P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs, GCAFs expressed a lower level of microRNA-214 (P < 0.01) and a higher level of microRNA-301a (P < 0.01). Astragaloside IV treatment significantly up-regulated microRNA-214 expression (P < 0.01) and down-regulated microRNA-301a expression (P < 0.01) in GCAFs. Reestablishing the microRNA expression balance subsequently suppressed M-CSF production (P < 0.01) and secretion (P < 0.05), and elevated TIMP2 production (P < 0.01) and secretion (P < 0.05). Consequently, the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside IV. CONCLUSION Astragaloside IV can inhibit the pathological functions of GCAFs by correcting their dysregulation of microRNA expression, and it is promisingly a potent therapeutic agent regulating tumor microenvironment.
Collapse
Affiliation(s)
- Zhen-Fei Wang
- Laboratory for Tumor Molecular Diagnosis, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
| | - Da-Guang Ma
- Laboratory for Tumor Molecular Diagnosis, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
| | - Zhe Zhu
- Department of cytotherapy for tumors, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
| | - Yong-Ping Mu
- Laboratory for Tumor Molecular Diagnosis, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
| | - Yong-Yan Yang
- Laboratory for Tumor Molecular Diagnosis, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
| | - Li Feng
- Department of Abdominal Tumor Surgery, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
| | - Hao Yang
- Department of Radiotherapy, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
| | - Jun-Qing Liang
- Department of cytotherapy for tumors, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
| | - Yong-Yan Liu
- Department of cytotherapy for tumors, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
| | - Li Liu
- Central Laboratory, People’s Hospital of Wuhai City, Wuhai 016000, Inner Mongolia Autonomous Region, China
| | - Hai-Wen Lu
- Laboratory for Tumor Molecular Diagnosis, Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010020, Inner Mongolia Autonomous Region, China
- Affiliated Hospital of Inner Mongolia Medical University, Huhhot 010050, Inner Mongolia Autonomous Region, China
| |
Collapse
|
|
42
|
Liu P, Zhao H, Luo Y. Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic. Aging Dis 2017; 8:868-886. [PMID: 29344421 PMCID: PMC5758356 DOI: 10.14336/ad.2017.0816] [Citation(s) in RCA: 216] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 08/16/2017] [Indexed: 12/20/2022] Open
Abstract
Owing to a dramatic increase in average life expectancy and the Family Planning program of the 1970s - 1990s, China is rapidly becoming an aging society. Therefore, the investigation of healthspan-extending drugs becomes more urgent. Astragalus membranaceus (Huangqi) is a major medicinal herb that has been commonly used in many herbal formulations in the practice of traditional Chinese medicine (TCM) to treat a wide variety of diseases and body disorders, or marketed as life-prolonging extracts for human use in China, for more than 2000 years. The major components of Astragalus membranaceus are polysaccharides, flavonoids, and saponins. Pharmacological research indicates that the extract component of Astragalus membranaceus can increase telomerase activity, and has antioxidant, anti-inflammatory, immunoregulatory, anticancer, hypolipidemic, antihyperglycemic, hepatoprotective, expectorant, and diuretic effects. A proprietary extract of the dried root of Astragalus membranaceus, called TA-65, was associated with a significant age-reversal effect in the immune system. Our review focuses on the function and the underlying mechanisms of Astragalus membranaceus in lifespan extension, anti-vascular aging, anti-brain aging, and anti-cancer effects, based on experimental and clinical studies.
Collapse
Affiliation(s)
- Ping Liu
- 1Cerebrovascular Diseases Research Institute, and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
| | - Haiping Zhao
- 1Cerebrovascular Diseases Research Institute, and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China
| | - Yumin Luo
- 1Cerebrovascular Diseases Research Institute, and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.,2Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,3Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China
| |
Collapse
|
|
43
|
Recent advances in discovery and development of natural products as source for anti-Parkinson's disease lead compounds. Eur J Med Chem 2017; 141:257-272. [PMID: 29031072 DOI: 10.1016/j.ejmech.2017.09.068] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 08/25/2017] [Accepted: 09/29/2017] [Indexed: 02/05/2023]
Abstract
Parkinson's disease (PD) is a common chronic degenerative disease of the central nervous system. Although the cause remains unknown, several pathological processes and central factors such as oxidative stress, mitochondrial injury, inflammatory reactions, abnormal deposition of α-synuclein, and cell apoptosis have been reported. Currently, anti-PD drugs are classified into two major groups: drugs that affect dopaminergic neurons and anti-cholinergic drugs. Unfortunately, the existing conventional strategies against PD are with numerous side effects, and cannot fundamentally improve the degenerative process of dopaminergic neurons. Therefore, novel therapeutic approaches which have a novel structure, high efficiency, and fewer side effects are needed. For many years, natural products have provided an efficient resource for the discovery of potential therapeutic agents. Among them, many natural products possess anti-PD properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding protein misfolding and the regulatory effects of PD related pathways. Indeed, with the steady improvement in the technologies for the isolation and purification of natural products and the in-depth studies on the pathogenic mechanisms of PD, many monomer components of natural products that have anti-PD effects have been gradually discovered. In this article, we reviewed the research status of 37 natural products that have been discovered to have significant anti-PD effects as well as their mode of action. Overall, this review may guide the design of novel therapeutic drugs in PD.
Collapse
|
|
44
|
Liu X, Zhang J, Wang S, Qiu J, Yu C. Astragaloside IV attenuates the H2O2-induced apoptosis of neuronal cells by inhibiting α-synuclein expression via the p38 MAPK pathway. Int J Mol Med 2017; 40:1772-1780. [PMID: 29039448 PMCID: PMC5716437 DOI: 10.3892/ijmm.2017.3157] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 09/19/2017] [Indexed: 01/13/2023] Open
Abstract
An oxidative stress insult is one of the principal causes of Parkinson's disease. Astragaloside IV (AS-IV), a constituent extracted from Astragalus membranaceus, has been demonstrated to exert antioxidant effects. However, the mechanisms responsible for the antioxidant properties and neuro-protective effects of AS-IV remain unclear. In this study, we examined the protective effects of AS-IV against the apoptosis of human neuronal cells (SH-SY5Y cells) induced by hydrogen peroxide (H2O2). The results revealed that AS-IV pre-treatment attenuated the H2O2-induced loss of SH-SY5Y cells in a dose-dependent manner; AS-IV exerted significant protecitve effects by decreasing the apoptotic ratio and attenuating reactive oxygen species overproduction in H2O2-exposed SH-SY5Y cells. By means of immunofluorescence staining, AS-IV was found to decrease the expression of α-synuclein and to increase the expression of tyrosine hydroxylase (TH) in the cells, which had been increased and decreased, respectively by H2O2. As shown by western blot analysis, the protective effects of AS-IV against SH-SY5Y cell injury induced by H2O2 were also mediated via the downregulation of the ratio of Bax/Bcl-2. We found that the neuroprotective effects of AS-IV were associated with the inhibition of the expression of the α-synuclein via the p38 mitogen-activated protein kinase (MAPK) signalling pathway. On the whole, our results suggest that AS-IV exerts protective effects against neurodegenerative diseases by targeting α-synuclein or TH.
Collapse
Affiliation(s)
- Xiang Liu
- Institute of Life Sciences, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Jun Zhang
- Institute of Life Sciences, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Shibo Wang
- Institute of Life Sciences, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Jinfu Qiu
- Institute of Life Sciences, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Chao Yu
- Institute of Life Sciences, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
| |
Collapse
|
|
45
|
da Costa IM, Cavalcanti JRLDP, de Queiroz DB, de Azevedo EP, do Rêgo ACM, Araújo Filho I, Parente P, Botelho MA, Guzen FP. Supplementation with Herbal Extracts to Promote Behavioral and Neuroprotective Effects in Experimental Models of Parkinson's Disease: A Systematic Review. Phytother Res 2017; 31:959-970. [DOI: 10.1002/ptr.5813] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Revised: 03/21/2017] [Accepted: 03/22/2017] [Indexed: 12/21/2022]
Affiliation(s)
- Ianara Mendonça da Costa
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Health Science Center; State University of Rio Grande do Norte; Mossoró RN Brazil
| | - José Rodolfo Lopes de Paiva Cavalcanti
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Health Science Center; State University of Rio Grande do Norte; Mossoró RN Brazil
| | - Dinalva Brito de Queiroz
- Post Graduation Program in Biotechnology; Potiguar University (UnP) School of Health; Natal RN Brazil
| | | | | | - Irami Araújo Filho
- Post Graduation Program in Biotechnology; Potiguar University (UnP) School of Health; Natal RN Brazil
| | - Paulo Parente
- Neural Engineering and Control Lab. Dept. of Biomedical Engineering; Columbia University; New York USA
| | - Marco Antônio Botelho
- Post Graduation Program in Biotechnology; Potiguar University (UnP) School of Health; Natal RN Brazil
| | - Fausto Pierdoná Guzen
- Laboratory of Experimental Neurology, Department of Biomedical Sciences, Health Science Center; State University of Rio Grande do Norte; Mossoró RN Brazil
- Post Graduation Program in Biotechnology; Potiguar University (UnP) School of Health; Natal RN Brazil
| |
Collapse
|
|
46
|
Li L, Hou X, Xu R, Liu C, Tu M. Research review on the pharmacological effects of astragaloside IV. Fundam Clin Pharmacol 2016; 31:17-36. [PMID: 27567103 DOI: 10.1111/fcp.12232] [Citation(s) in RCA: 251] [Impact Index Per Article: 27.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Revised: 07/09/2016] [Accepted: 08/26/2016] [Indexed: 12/11/2022]
Abstract
Astragalus membranaceus Bunge has been used to treat numerous diseases for thousands of years. As the main active substance of Astragalus membranaceus Bunge, astragaloside IV (AS-IV) also demonstrates the potent protective effect on focal cerebral ischemia/reperfusion, cardiovascular disease, pulmonary disease, liver fibrosis, and diabetic nephropathy. Based on studies published during the past several decades, the current state of AS-IV research and the pharmacological effects are detailed, elucidated, and summarized. This review systematically summarizes the pharmacological effects, metabolism mechanism, and the toxicity of AS-IV. AS-IV has multiple pharmacologic effects, including anti-inflammatory, antifibrotic, antioxidative stress, anti-asthma, antidiabetes, immunoregulation, and cardioprotective effect via numerous signaling pathways. According to the existing studies and clinical practices, AS-IV possesses potential for broad application in many diseases.
Collapse
Affiliation(s)
- Lei Li
- College of Animal Science, Anhui Science and Technology University, Chuzhou, China
| | - Xiaojiao Hou
- Engineering Research Center of Chinese Traditional Veterinary Medicine, Beijing, China
| | - Rongfang Xu
- Engineering Research Center of Chinese Traditional Veterinary Medicine, Beijing, China
| | - Chang Liu
- College of Animal Science, Anhui Science and Technology University, Chuzhou, China
| | - Menbayaer Tu
- Engineering Research Center of Chinese Traditional Veterinary Medicine, Beijing, China
| |
Collapse
|
|
47
|
Sun H, Wang W, Han P, Shao M, Song G, Du H, Yi T, Li S. Astragaloside IV ameliorates renal injury in db/db mice. Sci Rep 2016; 6:32545. [PMID: 27585918 PMCID: PMC5009300 DOI: 10.1038/srep32545] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 08/10/2016] [Indexed: 01/22/2023] Open
Abstract
Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model. Results showed that administration of AS-IV reduced albuminuria, ameliorated changes in the glomerular and tubular pathology, and decreased urinary NAG, NGAL, and TGF-β1 in db/db mice. AS-IV also attenuated the diabetes-related activation of Akt/mTOR, NFκB, and Erk1/2 signaling pathways without causing any detectable hepatotoxicity. Collectively, these findings showed AS-IV to be beneficial to type 2 diabetic nephropathy, which might be associated with the inhibition of Akt/mTOR, NFκB and Erk1/2 signaling pathways.
Collapse
Affiliation(s)
- Huili Sun
- Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Wenjing Wang
- Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Pengxun Han
- Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Mumin Shao
- Department of Pathology, Shenzhen Affiliated Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Gaofeng Song
- Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Heng Du
- Department of Biological Sciences, the University of Texas at Dallas, Richardson, Texas, USA
| | - Tiegang Yi
- Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Shunmin Li
- Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| |
Collapse
|
|
48
|
Sandoval-Avila S, Diaz NF, Gómez-Pinedo U, Canales-Aguirre AA, Gutiérrez-Mercado YK, Padilla-Camberos E, Marquez-Aguirre AL, Díaz-Martínez NE. Neuroprotective effects of phytochemicals on dopaminergic neuron cultures. Neurologia 2016; 34:114-124. [PMID: 27342389 DOI: 10.1016/j.nrl.2016.04.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Accepted: 04/25/2016] [Indexed: 01/17/2023] Open
Abstract
INTRODUCTION Parkinson's disease is a progressive neurodegenerative disorder characterised by a loss of dopaminergic neurons in the substantia nigra pars compacta, which results in a significant decrease in dopamine levels and consequent functional motor impairment. DEVELOPMENT Although its aetiology is not fully understood, several pathogenic mechanisms, including oxidative stress, have been proposed. Current therapeutic approaches are based on dopamine replacement drugs; these agents, however, are not able to stop or even slow disease progression. Novel therapeutic approaches aimed at acting on the pathways leading to neuronal dysfunction and death are under investigation. CONCLUSIONS In recent years, such natural molecules as polyphenols, alkaloids, and saponins have been shown to have a neuroprotective effect due to their antioxidant and anti-inflammatory properties. The aim of our review is to analyse the most relevant studies worldwide addressing the benefits of some phytochemicals used in in vitro models of Parkinson's disease.
Collapse
Affiliation(s)
- S Sandoval-Avila
- Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Jalisco, México
| | - N F Diaz
- Departamento de Biología Celular, Instituto Nacional de Perinatología, Ciudad de México, México
| | - U Gómez-Pinedo
- Instituto de Neurociencias, IdISSC, Hospital Clínico San Carlos, Universidad Complutense, Madrid, España
| | - A A Canales-Aguirre
- Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Jalisco, México
| | - Y K Gutiérrez-Mercado
- Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Jalisco, México
| | - E Padilla-Camberos
- Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Jalisco, México
| | - A L Marquez-Aguirre
- Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Jalisco, México
| | - N E Díaz-Martínez
- Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Jalisco, México.
| |
Collapse
|
|
49
|
Xu H, Wang CY, Zhang HN, Lv CY, Wang YZ. Astragaloside IV suppresses inflammatory mediator production in synoviocytes and collagen‑induced arthritic rats. Mol Med Rep 2016; 13:3289-96. [PMID: 26936538 DOI: 10.3892/mmr.2016.4923] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 01/14/2016] [Indexed: 11/06/2022] Open
Abstract
The aim of the current study was to investigate the effects of Astragaloside‑IV (AS‑IV) on inflammatory mediators in synoviocytes and collagen‑induced arthritic rats. Synoviocytes were stimulated with lipopolysaccharides (LPS) and Sprague‑Dawley rats were injected with type II collagen. AS‑IV was administered to the LPS‑stimulated synoviocytes and collagen‑induced arthritis (CIA) rats. The inflammation of LPS‑stimulated synoviocytes and CIA rats was assessed using enzyme‑linked immunosorbent assays and western blotting. Using Cell Counting Kit‑8 analysis, it was demonstrated that AS‑IV (5, 20 and 50 mg/ml) inhibited the LPS‑stimulated synoviocytes proliferation in a dose‑dependent manner. AS‑IV significantly inhibited the LPS‑stimulated inflammatory response, as indicated by the expression levels of TNF‑α, IL‑1β, IL‑6 and IL‑8. In addition, treatment with AS‑IV significantly reduced the LPS‑stimulated cyclooxygenase (COX)‑1, COX‑2, high mobility group box 1 protein (HMGB1) and intercellular adhesion molecule 1 overexpression, and intranuclear nuclear factor (NF)‑κBp65 subunit accumulation and activation of c‑Jun N‑terminal kinase (JNK)1/2 and p38. Similar to the protective effects of AS‑IV on LPS‑stimulated synoviocytes, AS‑IV treatment significantly reduced the expression levels of tumor necrosis factor α, interleukin (IL)‑1β, IL‑6 and IL‑8 expression levels, and attenuated intranuclear NF‑κBp65 subunit accumulation and overexpression of COX‑2 and inducible nitric oxide synthase in CIA rats. In conclusion, the results of the present study demonstrated for the first time, to the best of our knowledge, that AS‑IV protects synoviocytes against LPS‑ and collagen‑induced inflammatory responses through inhibition of the HMGB1‑dependent JNK1/2‑ and p38‑activated NF‑κB/COX‑2 pathway.
Collapse
Affiliation(s)
- Hao Xu
- Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China
| | - Chang-Yao Wang
- Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China
| | - Hai-Ning Zhang
- Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China
| | - Cheng-Yu Lv
- Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China
| | - Ying-Zhen Wang
- Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China
| |
Collapse
|
|
50
|
EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model. PARKINSONS DISEASE 2015; 2015:843906. [PMID: 26770869 PMCID: PMC4684886 DOI: 10.1155/2015/843906] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Accepted: 11/09/2015] [Indexed: 11/17/2022]
Abstract
Background. Parkinson's disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (-)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using (55)Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry. Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly (p < 0.05) increased divalent metal transporter-1 (DMT1) and hepcidin and decreased ferroportin 1 (Fpn1) level, whereas pretreatment with EGCG counteracted the effects. The increased (55)Fe (by 96%, p < 0.01) cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (p < 0.05), supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased (p < 0.0001) TH(+) cell count (~3-fold) and neurite length (~12-fold) compared to 6-OHDA alone in primary mesencephalic neurons. Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels.
Collapse
|