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Ali MA, Kaleem N, Ali A, Khan N, Khaliq M, Arif N, Almarhoon ZM, Habtemariam S, Setzer WN, Calina D, Sharifi-Rad J. Pterostilbene as a Multifaceted Anticancer Agent: Molecular Mechanisms, Therapeutic Potential and Future Directions. Med Oncol 2025; 42:220. [PMID: 40411697 DOI: 10.1007/s12032-025-02721-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 04/14/2025] [Indexed: 05/26/2025]
Abstract
Pterostilbene (PT), a natural dimethoxy analogue of resveratrol, exhibits enhanced bioavailability and lipophilicity, making it a more effective therapeutic candidate than resveratrol. These pharmacokinetic advantages improve its cellular uptake and metabolic stability, positioning PT as a promising compound in cancer treatment. PT has shown significant anticancer activity in several malignancies, including melanoma, breast, colorectal, and ovarian cancers. Its mechanisms of action include induction of apoptosis through caspase activation, cell cycle arrest, and inhibition of angiogenesis and metastasis via downregulation of matrix metalloproteinase-9 and vascular endothelial growth factor. PT also modulates epigenetic processes such as DNA methylation and histone modifications, and targets cancer stem cells by reducing the expression of stemness markers like CD44 and c-Myc. Additionally, PT enhances the efficacy of standard chemotherapeutic agents such as cisplatin, doxorubicin, and 5-fluorouracil, with preclinical studies showing synergistic effects and reversal of drug resistance. A Phase II clinical trial (NCT03671811) in endometrial cancer patients has confirmed the safety of PT and revealed its ability to modulate immune-related gene expression and suppress mechanistic target of rapamycin (mTOR) signaling. Despite promising results, several challenges remain particularly low water solubility, limited systemic bioavailability, lack of large-scale human studies, and undefined therapeutic protocols. Future research should focus on advanced formulation strategies, rigorous clinical trials across cancer types, and identification of patient-specific therapeutic responses to support PT's integration into oncology practice.
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Affiliation(s)
- Muhammad Asif Ali
- Department of Food Science and Human Nutrition, UVAS, Lahore, Pakistan
| | - Nabeeha Kaleem
- Department of Food Science and Human Nutrition, UVAS, Lahore, Pakistan
| | - Ahmad Ali
- Department of Food Science and Human Nutrition, UVAS, Lahore, Pakistan
| | - Noohela Khan
- Department of Nutrition Sciences, Riphah International University, Lahore, Pakistan
| | - Muniba Khaliq
- Department of Food Science and Human Nutrition, UVAS, Lahore, Pakistan
| | - Nafeesa Arif
- Department of Food Science and Human Nutrition, UVAS, Lahore, Pakistan
| | - Zainab M Almarhoon
- Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, 11451, Riyadh, Saudi Arabia
| | - Solomon Habtemariam
- Pharmacognosy Research &, Herbal Analysis Services UK, Central Avenue, Chatham-Maritime, Kent, ME4 4TB, UK
| | - William N Setzer
- Aromatic Plant Research Center, 230 N 1200 E, Suite 100, Lehi, UT, 84043, USA
- Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL, 35899, USA
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania.
| | - Javad Sharifi-Rad
- Universidad Espíritu Santo, 092301, Samborondón, Ecuador.
- Department of Medicine, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.
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Tian R, Miao L, Cheang WS. Effects of Pterostilbene on Cardiovascular Health and Disease. Curr Issues Mol Biol 2024; 46:9576-9587. [PMID: 39329921 PMCID: PMC11430207 DOI: 10.3390/cimb46090569] [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: 08/02/2024] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 09/28/2024] Open
Abstract
Pterostilbene is a phenolic compound commonly found in blueberries, peanuts, grapes, and other plants. It is a dimethoxy derivative of resveratrol. In recent years, it has gained significant attention due to its remarkable anti-inflammatory and antioxidant effects. In addition, its high bioavailability and low toxicity in many species has contributed to its promising research prospects. Cardiovascular disease is closely related to pathological processes such as inflammation and oxidative stress, which aligns well with the treatment applications of pterostilbene. As a result, numerous studies have investigated the effects of pterostilbene on cardiovascular health and disease. This paper summarizes the current research on pterostilbene, with a specific focus on its potential therapeutic role in treating cardiovascular disease.
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Affiliation(s)
- Rui Tian
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China
| | - Lingchao Miao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China
| | - Wai-San Cheang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China
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Liu P, Tang W, Xiang K, Li G. Pterostilbene in the treatment of inflammatory and oncological diseases. Front Pharmacol 2024; 14:1323377. [PMID: 38259272 PMCID: PMC10800393 DOI: 10.3389/fphar.2023.1323377] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 12/20/2023] [Indexed: 01/24/2024] Open
Abstract
Pterostilbene (PTS), a naturally occurring analog of resveratrol (RSV), has garnered significant attention due to its potential therapeutic effects in treating inflammatory and oncological diseases. This comprehensive review elucidates the pharmacological properties, mechanisms of action, and therapeutic potential of PTS. Various studies indicate that PTS exhibits anti-inflammatory, antioxidant, and antitumour properties, potentially making it a promising candidate for clinical applications. Its influence on regulatory pathways like NF-κB and PI3K/Akt underscores its diverse strategies in addressing diseases. Additionally, PTS showcases a favorable pharmacokinetic profile with better oral bioavailability compared to other stilbenoids, thus enhancing its therapeutic potential. Given these findings, there is an increased interest in incorporating PTS into treatment regimens for inflammatory and cancer-related conditions. However, more extensive clinical trials are imperative to establish its safety and efficacy in diverse patient populations.
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Affiliation(s)
- Peijun Liu
- Department of Respiratory and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Weihua Tang
- Department of Radiology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Kali Xiang
- Department of Respiratory and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Guangcai Li
- Department of Respiratory and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
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Wu W, Huang J, Han P, Zhang J, Wang Y, Jin F, Zhou Y. Research Progress on Natural Plant Molecules in Regulating the Blood-Brain Barrier in Alzheimer's Disease. Molecules 2023; 28:7631. [PMID: 38005352 PMCID: PMC10674591 DOI: 10.3390/molecules28227631] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 11/07/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder. With the aging population and the continuous development of risk factors associated with AD, it will impose a significant burden on individuals, families, and society. Currently, commonly used therapeutic drugs such as Cholinesterase inhibitors, N-methyl-D-aspartate antagonists, and multiple AD pathology removal drugs have been shown to have beneficial effects on certain pathological conditions of AD. However, their clinical efficacy is minimal and they are associated with certain adverse reactions. Furthermore, the underlying pathological mechanism of AD remains unclear, posing a challenge for drug development. In contrast, natural plant molecules, widely available, offer multiple targeting pathways and demonstrate inherent advantages in modifying the typical pathologic features of AD by influencing the blood-brain barrier (BBB). We provide a comprehensive review of recent in vivo and in vitro studies on natural plant molecules that impact the BBB in the treatment of AD. Additionally, we analyze their specific mechanisms to offer novel insights for the development of safe and effective targeted drugs as well as guidance for experimental research and the clinical application of drugs for the prevention and treatment of AD.
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Affiliation(s)
- Weidong Wu
- Basic Theory of Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China; (W.W.); (J.Z.); (Y.W.)
| | - Jiahao Huang
- Department of Chinese Pharmacology, Heilongjiang University of Chinese Medicine, Harbin 150040, China;
| | - Pengfei Han
- Science and Education Section, Zhangjiakou First Hospital, Zhangjiakou 075041, China;
| | - Jian Zhang
- Basic Theory of Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China; (W.W.); (J.Z.); (Y.W.)
| | - Yuxin Wang
- Basic Theory of Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China; (W.W.); (J.Z.); (Y.W.)
| | - Fangfang Jin
- Department of Internal Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China
| | - Yanyan Zhou
- Basic Theory of Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China; (W.W.); (J.Z.); (Y.W.)
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New Insights into Dietary Pterostilbene: Sources, Metabolism, and Health Promotion Effects. Molecules 2022; 27:molecules27196316. [PMID: 36234852 PMCID: PMC9571692 DOI: 10.3390/molecules27196316] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 09/17/2022] [Accepted: 09/21/2022] [Indexed: 11/17/2022] Open
Abstract
Pterostilbene (PTS), a compound most abundantly found in blueberries, is a natural analog of resveratrol. Several plant species, such as peanuts and grapes, produce PTS. While resveratrol has been extensively studied for its antioxidant properties, recent evidence also points out the diverse therapeutic potential of PTS. Several studies have identified the robust pharmacodynamic features of PTS, including better intestinal absorption and elevated hepatic stability than resveratrol. Indeed, due to its higher bioavailability paired with reduced toxicity compared to other stilbenes, PTS has become an attractive drug candidate for the treatment of several disease conditions, including diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging. This review article provides an extensive summary of the nutraceutical potential of PTS in various disease conditions while discussing the crucial mechanistic pathways implicated. In particular, we share insights from our studies about the Nrf2-mediated effect of PTS in diabetes and associated complications. Moreover, we elucidate the important sources of PTS and discuss in detail its pharmacokinetics and the range of formulations and routes of administration used across experimental studies and human clinical trials. Furthermore, this review also summarizes the strategies successfully used to improve dietary availability and the bio-accessibility of PTS.
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Islam F, Nafady MH, Islam MR, Saha S, Rashid S, Akter A, Or-Rashid MH, Akhtar MF, Perveen A, Md Ashraf G, Rahman MH, Hussein Sweilam S. Resveratrol and neuroprotection: an insight into prospective therapeutic approaches against Alzheimer's disease from bench to bedside. Mol Neurobiol 2022; 59:4384-4404. [PMID: 35545730 DOI: 10.1007/s12035-022-02859-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 04/28/2022] [Indexed: 02/07/2023]
Abstract
Alzheimer's disease (AD) is the most common cause of dementia and cognitive impairment; yet, there is currently no treatment. A buildup of Aβ, tau protein phosphorylation, oxidative stress, and inflammation in AD is pathogenic. The accumulation of amyloid-beta (Aβ) peptides in these neurocognitive areas is a significant characteristic of the disease. Therefore, inhibiting Aβ peptide aggregation has been proposed as the critical therapeutic approach for AD treatment. Resveratrol has been demonstrated in multiple studies to have a neuroprotective, anti-inflammatory, and antioxidant characteristic and the ability to minimize Aβ peptides aggregation and toxicity in the hippocampus of Alzheimer's patients, stimulating neurogenesis and inhibiting hippocampal degeneration. Furthermore, resveratrol's antioxidant effect promotes neuronal development by activating the silent information regulator-1 (SIRT1), which can protect against the detrimental effects of oxidative stress. Resveratrol-induced SIRT1 activation is becoming more crucial in developing novel therapeutic options for AD and other diseases that have neurodegenerative characteristics. This review highlighted a better knowledge of resveratrol's mechanism of action and its promising therapeutic efficacy in treating AD. We also highlighted the therapeutic potential of resveratrol as an AD therapeutic agent, which is effective against neurodegenerative disorders.
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Grants
- This publication was supported by the Deanship of Scientific Research at Prince Sattam Bin Abdulaziz University This publication was supported by the Deanship of Scientific Research at Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia, as well as Egyptian Russian University, Badr City, Egypt.
- Al-Kharj This publication was supported by the Deanship of Scientific Research at Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia, as well as Egyptian Russian University, Badr City, Egypt.
- Saudi Arabia This publication was supported by the Deanship of Scientific Research at Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia, as well as Egyptian Russian University, Badr City, Egypt.
- as well as Egyptian Russian University This publication was supported by the Deanship of Scientific Research at Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia, as well as Egyptian Russian University, Badr City, Egypt.
- Badr City This publication was supported by the Deanship of Scientific Research at Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia, as well as Egyptian Russian University, Badr City, Egypt.
- Egypt. This publication was supported by the Deanship of Scientific Research at Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia, as well as Egyptian Russian University, Badr City, Egypt.
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Affiliation(s)
- Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Mohamed H Nafady
- Faculty of Applied Health Science Technology, Misr University for Science and Technology, Giza, Egypt
| | - Md Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Susmita Saha
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Salma Rashid
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Aklima Akter
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Md Harun- Or-Rashid
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Muhammad Furqan Akhtar
- Riphah Institute of Pharmaceutical Sciences, Riphah International University Lahore Campus, Lahore, Pakistan
| | - Asma Perveen
- Glocal School of Life Sciences, Glocal University, Uttar Pradesh, Mirzapur Pole, Saharanpur, India
| | - Ghulam Md Ashraf
- Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Md Habibur Rahman
- Department of Pharmacy, Southeast University, Banani, Dhaka, 1213, Bangladesh
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Gangwon-do, Wonju, 26426, South Korea
| | - Sherouk Hussein Sweilam
- Department of Pharmacognosy, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
- Department of Pharmacognosy, Faculty of Pharmacy, Egyptian Russian University, Cairo-Suez Road, Badr City 11829, Egypt.
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Chemotherapy-Induced Myopathy: The Dark Side of the Cachexia Sphere. Cancers (Basel) 2021; 13:cancers13143615. [PMID: 34298829 PMCID: PMC8304349 DOI: 10.3390/cancers13143615] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/11/2021] [Accepted: 07/14/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary In addition to cancer-related factors, anti-cancer chemotherapy treatment can drive life-threatening body wasting in a syndrome known as cachexia. Emerging evidence has described the impact of several key chemotherapeutic agents on skeletal muscle in particular, and the mechanisms are gradually being unravelled. Despite this evidence, there remains very little research regarding therapeutic strategies to protect muscle during anti-cancer treatment and current global grand challenges focused on deciphering the cachexia conundrum fail to consider this aspect—chemotherapy-induced myopathy remains very much on the dark side of the cachexia sphere. This review explores the impact and mechanisms of, and current investigative strategies to protect against, chemotherapy-induced myopathy to illuminate this serious issue. Abstract Cancer cachexia is a debilitating multi-factorial wasting syndrome characterised by severe skeletal muscle wasting and dysfunction (i.e., myopathy). In the oncology setting, cachexia arises from synergistic insults from both cancer–host interactions and chemotherapy-related toxicity. The majority of studies have surrounded the cancer–host interaction side of cancer cachexia, often overlooking the capability of chemotherapy to induce cachectic myopathy. Accumulating evidence in experimental models of cachexia suggests that some chemotherapeutic agents rapidly induce cachectic myopathy, although the underlying mechanisms responsible vary between agents. Importantly, we highlight the capacity of specific chemotherapeutic agents to induce cachectic myopathy, as not all chemotherapies have been evaluated for cachexia-inducing properties—alone or in clinically compatible regimens. Furthermore, we discuss the experimental evidence surrounding therapeutic strategies that have been evaluated in chemotherapy-induced cachexia models, with particular focus on exercise interventions and adjuvant therapeutic candidates targeted at the mitochondria.
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Hseu YC, Vudhya Gowrisankar Y, Wang LW, Zhang YZ, Chen XZ, Huang PJ, Yen HR, Yang HL. The in vitro and in vivo depigmenting activity of pterostilbene through induction of autophagy in melanocytes and inhibition of UVA-irradiated α-MSH in keratinocytes via Nrf2-mediated antioxidant pathways. Redox Biol 2021; 44:102007. [PMID: 34049220 PMCID: PMC8167190 DOI: 10.1016/j.redox.2021.102007] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/26/2021] [Accepted: 05/10/2021] [Indexed: 12/13/2022] Open
Abstract
Pterostilbene (Pt) is a natural polyphenol found in blueberries and several grape varieties. Pt's pharmacological importance was well documented. Nevertheless, the depigmenting effects are not demonstrated. We evaluated the Pt's depigmenting effects through autophagy induction in B16F10 cells and inhibition of UVA (3 J/cm2)-irradiated α-MSH in keratinocyte HaCaT cells via Nrf2-mediated antioxidant pathways. Pt (2.5–5μM) attenuated ROS production and downregulated the POMC/α-MSH pathway in HaCaT cells. The conditioned medium-derived from UVA-irradiated HaCaT pretreated with Pt suppressed melanogenesis in B16F10 through MITF-CREB-tyrosinase pathway downregulation. Interestingly, Pt-induced HaCaT autophagy was revealed by enhanced LC3-II accumulation, p62/SQSTM1 activation, and AVO formation. Pt significantly decreased melanosome gp100 but increased LC3-II levels in HaCaT cells exposed to B16F10-derived melanin. Pt activated and facilitated the Nrf2 antioxidant pathway in HaCaT cells leading to increased HO-1, γ-GCLC, and NQO-1 antioxidant protein expression. ERK, AMPK, and ROS pathways mediate the Nrf2 activation. However, Nrf2 knockdown suppressed Pt's antioxidant ability leading to uncontrolled ROS and α-MSH levels after UVA-irradiation suggested the essentiality of the Nrf2 pathway. Moreover, in α-MSH-stimulated B16F10 cells, Pt (10–30 μM) downregulated the MC1R, MITF, tyrosinase, TRP-1/-2, and melanin expression. Further, Pt showed potent anti-melanogenic effects through autophagy induction mechanism in B16F10 cells, verified by increased LC3-II/p62 levels, AVO formation, and Beclin-1/Bcl-2 ratio, decreased ATG4B levels and PI3K/AKT/mTOR pathway. Transmission electron microscopy provided direct evidence by showing autophagosomes engulfing melanosomes following Pt treatment in α-MSH-stimulated B16F10 cells. Moreover, Pt-induced anti-melanogenic activity through the downregulation of CREB-MITF pathway-mediated TRP-1/-2, tyrosinase expressions, melanosome formation, and melanin synthesis was substantially reversed due to 3-MA (autophagy inhibitor) pretreatment or LC3 silencing in B16F10 cells. In vivo results also confirmed that Pt-inhibited tyrosinase expression/activity and endogenous pigmentation in the zebrafish model. Therefore, pterostilbene is a potent skin-whitening and antioxidant agent and could be used in skin-whitening formulations as a topical applicant.
Pt inhibits ROS-mediated POMC/α-MSH pathway in UVA-irradiated HaCaT cells. Pt activates Nrf2-mediated HO-1, γ-GCLC, and NQO-1 expression in HaCaT cells. Pt-induces autophagy in B16F10 cells leading to melanogenesis inhibition. Pt-mediates anti-melanogenic mechanisms in α-MSH-stimulated B16F10 cells. Pt-inhibits tyrosinase expression and endogenous pigmentation in zebrafish model.
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Affiliation(s)
- You-Cheng Hseu
- Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan; Research Center of Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan.
| | | | - Li-Wei Wang
- Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
| | - Yan-Zhen Zhang
- Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
| | - Xuan-Zao Chen
- Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
| | - Pei-Jane Huang
- Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
| | - Hung-Rong Yen
- Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan; Research Center of Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan; School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
| | - Hsin-Ling Yang
- Institute of Nutrition, College of Health Care, China Medical University, Taichung 40402, Taiwan.
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Moustafa EM, Rashed ER, Rashed RR. Pterostilbene Inhibits Dyslipidemia-Induced Activation of Progenitor Adipose Gene Under High-Fat Diet and Radiation Stressor. Nat Prod Commun 2021. [DOI: 10.1177/1934578x211001267] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Repeated exposure to ionizing radiation has been reported to increase the risk of chronic metabolic disorders such as systemic hyperlipidemia and intracellular lipid accumulation that might lead to diabetes-induced heart disease. The purpose of this study was to investigate the effect of pterostilbene on high-fat diet rats suffering from ionizing radiation-induced hyperlipidemia. High-fat diet rats showed an increase in body weight and body fat compared with rats fed with normal chow. Pterostilbene and Orlistat treatments resulted in lower body weight and body fat gain, insulin resistance, reduced lipid peroxidation with attenuated liver enzyme levels, and regulated lipogenesis-related genes in the HFD + IR rat group. Regulation of Peroxisome proliferator-activated receptor-γ (PPAR-γ) mRNA enhanced paraoxonase-1 (PON-1) and arylesterase (AE) activities and inhibited that of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA). It also increased the activities of plasma lecithin-cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). Pterostilbene and Orlistat also corrected the alterations of serum leptin and adiponectin levels in lipidemic rats. Such findings provide evidence that Pterostilbene and Orlistat can act as normolipidemic agents that possess lipid-lowering effects and potential as a radioprotector.
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Affiliation(s)
- Enas M. Moustafa
- Department of Radiation Biology, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Nasr City, Egypt
| | - Engy R. Rashed
- Department of Drug Radiation Research, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Nasr City, Egypt
| | - Rasha R. Rashed
- Department of Drug Radiation Research, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Nasr City, Egypt
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Oduro PK, Fang J, Niu L, Li Y, Li L, Zhao X, Wang Q. Pharmacological management of vascular endothelial dysfunction in diabetes: TCM and western medicine compared based on biomarkers and biochemical parameters. Pharmacol Res 2020; 158:104893. [PMID: 32434053 DOI: 10.1016/j.phrs.2020.104893] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 04/18/2020] [Accepted: 05/03/2020] [Indexed: 12/20/2022]
Abstract
Diabetes, a worldwide health concern while burdening significant populace of countries with time due to a hefty increase in both incidence and prevalence rates. Hyperglycemia has been buttressed both in clinical and experimental studies to modulate widespread molecular actions that effect macro and microvascular dysfunctions. Endothelial dysfunction, activation, inflammation, and endothelial barrier leakage are key factors contributing to vascular complications in diabetes, plus the development of diabetes-induced cardiovascular diseases. The recent increase in molecular, transcriptional, and clinical studies has brought a new scope to the understanding of molecular mechanisms and the therapeutic targets for endothelial dysfunction in diabetes. In this review, an attempt made to discuss up to date critical and emerging molecular signaling pathways involved in the pathophysiology of endothelial dysfunction and viable pharmacological management targets. Importantly, we exploit some Traditional Chinese Medicines (TCM)/TCM isolated bioactive compounds modulating effects on endothelial dysfunction in diabetes. Finally, clinical studies data on biomarkers and biochemical parameters involved in the assessment of the efficacy of treatment in vascular endothelial dysfunction in diabetes was compared between clinically used western hypoglycemic drugs and TCM formulas.
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Affiliation(s)
- Patrick Kwabena Oduro
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin 301617, PR China
| | - Jingmei Fang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin 301617, PR China
| | - Lu Niu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin 301617, PR China
| | - Yuhong Li
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin 301617, PR China; Tianjin Key Laboratory of Chinese medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Lin Li
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin 301617, PR China; Tianjin Key Laboratory of Chinese medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Xin Zhao
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin 301617, PR China; Tianjin Key Laboratory of Chinese medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Qilong Wang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin 301617, PR China; Tianjin Key Laboratory of Chinese medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
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Chen Y, Chen Y, Zhang H, Wang T. Pterostilbene as a protective antioxidant attenuates diquat-induced liver injury and oxidative stress in 21-day-old broiler chickens. Poult Sci 2020; 99:3158-3167. [PMID: 32475452 PMCID: PMC7597657 DOI: 10.1016/j.psj.2020.01.021] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 12/29/2019] [Accepted: 01/11/2020] [Indexed: 12/27/2022] Open
Abstract
This study investigated the effects of pterostilbene (PT) supplementation on growth performance, hepatic injury, and antioxidant variables in a broiler chicken model with diquat (DQ)-induced oxidative stress. There were 192 one-day-old male Ross 308 broiler chicks randomly allocated to one of two treatment groups: 1) broilers fed a basal diet and 2) broilers fed a diet supplemented with 400 mg/kg PT. At 20 D of age, half of the broilers in each group were intraperitoneally injected with DQ (20 mg per kg BW), whereas the other half were injected with an equivalent amount of sterile saline. Diquat induced a rapid loss of BW (P < 0.001) 24 h post-injection, but dietary PT supplementation improved the BW change of broilers (P = 0.014). Compared with unchallenged controls, the livers of DQ-treated broilers were in severe cellular damage and oxidative stress, with the presence of higher plasma transaminase activities (P < 0.05), a greater number of apoptotic hepatocytes (P < 0.001), and an increased malondialdehyde content (P = 0.007). Pterostilbene supplementation prevented the increases in plasma aspartate aminotransferase activity (P = 0.001), the percentage of hepatocyte apoptosis (P < 0.001), and the hepatic malondialdehyde accumulation (P = 0.011) of the DQ-treated broilers. Regarding the hepatic antioxidant function, PT significantly increased total antioxidant capacity (P = 0.007), superoxide dismutase activity (P = 0.016), reduced glutathione content (P = 0.011), and the ratio of reduced glutathione to oxidized glutathione (P = 0.003), whereas it reduced the concentration of oxidized glutathione (P = 0.017). Pterostilbene also boosted the expression levels of nuclear factor erythroid 2–related factor 2 (P = 0.010), heme oxygenase 1 (P = 0.037), superoxide dismutase 1 (P = 0.014), and the glutamate–cysteine ligase catalytic subunit (P = 0.001), irrespective of DQ challenge. In addition, PT alleviated DQ-induced adenosine triphosphate depletion (P = 0.010). In conclusion, PT attenuates DQ-induced hepatic injury and oxidative stress of broilers presumably by restoring hepatic antioxidant function.
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Affiliation(s)
- Yanan Chen
- College of Animal Science & Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China
| | - Yueping Chen
- College of Animal Science & Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China; Postdoctoral Research Station of Food Science and Engineering, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China
| | - Hao Zhang
- College of Animal Science & Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China; Postdoctoral Research Station of Clinical Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China; Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai 200240, China
| | - Tian Wang
- College of Animal Science & Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
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12
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The Function and Mechanisms of Autophagy in Traumatic Brain Injury. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1207:635-648. [PMID: 32671781 DOI: 10.1007/978-981-15-4272-5_46] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Traumatic brain injury (TBI) is one of the most common causes of long-term disability and death worldwide. Autophagy is activated and autophagic flux is impaired following TBI. But the controversial roles and underlying mechanisms of autophagy after TBI are not clear. This chapter will update the current state of knowledge in the process of autophagy, the roles of autophagy in TBI as well as some upstream moleculars and pharmacological regulators of autophagy involved in TBI. We also discuss autophagy mechanism-based preclinical pharmacological intervention. These observations make autophagy an attractive therapeutic target for developing new therapeutic strategies to achieve better outcomes for patients suffering from TBI.
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13
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Chen YB. Autophagy and its role in pulmonary hypertension. Aging Clin Exp Res 2019; 31:1027-1033. [PMID: 30406918 DOI: 10.1007/s40520-018-1063-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 10/19/2018] [Indexed: 01/16/2023]
Abstract
Pulmonary hypertension (PH) is a very common kind of pulmonary vascular disease, which can cause a heavier burden on patient's quality of life, even lead to death. Yet, the mechanism of PH is incomprehensive and not so clear nowadays. In recent years, more and more studies show that autophagy plays a pivotal role in the development of PH. Some modalities target on the formation or maturation of autophagosome that has emerged from our increasing knowledge of autophagy machinery, which may prevent or eliminate the process of PH. The deciphering of molecular selectivity of autophagy has also been a source of novel modulators that act specifically on selective forms of autophagy. Tremendous recent progress has opened a new possibility for modulating autophagy in complex diseases. Thus, autophagy may become a prospective choice for treatment of PH. Herein, we reviewed the literatures and discussed the role of autophagy in the development and treatment of PH.
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Wu S, Hu Y, Bai W, Zhao J, Huang C, Wen C, Deng L, Lu D. Cyanidin-3-o-glucoside inhibits UVA-induced human dermal fibroblast injury by upregulating autophagy. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2019; 35:360-368. [PMID: 31166622 DOI: 10.1111/phpp.12493] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 04/13/2019] [Accepted: 06/02/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND/PURPOSE Ultraviolet (UV) A (315-400 nm) is the UV light that most frequently reaches the Earth's surface and can penetrate the epidermis through to the dermis, causing various issues, including skin aging and skin cancer. The results of our previous studies have shown that the flavonoid monomer cyanidin-3-o-glucoside (C3G) can effectively inhibit primary human dermal fibroblast (HDF) oxidative damage and apoptosis caused by UVA radiation. Many flavonoids can regulate the level of autophagy. However, whether C3G inhibits UVA-induced oxidative damage to primary HDFs by regulating autophagy levels remains unclear. METHODS AND RESULTS In this study, we used different doses (0-12 J/cm2 ) of UVA to irradiate cells and showed that the expression levels of autophagy-related gene 5 (Atg5) and microtubule-associated protein 1 light chain 3 (LC3)-II in primary HDFs first increased and then decreased. The expression of Atg5 and LC3-II was significantly decreased under 12 J/cm2 (light-damage model). C3G increased the levels of Atg5 and LC3-II. Primary HDFs were pretreated with C3G, followed by treatment with the autophagy inhibitor 3-methyladenine (3-MA) after 12 J/cm2 UVA irradiation. The inhibitory effects of C3G on morphological changes, oxidative damage, and apoptosis in primary HDFs induced by UVA were significantly decreased. CONCLUSION C3G can inhibit UVA-induced damage to primary HDFs by inducing autophagy. These results provide a theoretical basis for the application of natural compounds to resist light damage to the skin in the future.
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Affiliation(s)
- Shi Wu
- Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yunfeng Hu
- Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Weibin Bai
- Department of Food Science and Engineering, Jinan University, Guangzhou, China
| | - Jiayi Zhao
- Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, China
| | - Cuiqin Huang
- Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, China
| | - Caiyan Wen
- Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, China
| | - Liehua Deng
- Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Daxiang Lu
- Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, China
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15
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Kang KY, Shin JK, Lee SM. Pterostilbene protects against acetaminophen-induced liver injury by restoring impaired autophagic flux. Food Chem Toxicol 2019; 123:536-545. [PMID: 30543896 DOI: 10.1016/j.fct.2018.12.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 12/07/2018] [Accepted: 12/08/2018] [Indexed: 12/27/2022]
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16
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Mei H, Xiang Y, Mei H, Fang B, Wang Q, Cao D, Hu Y, Guo T. Pterostilbene inhibits nutrient metabolism and induces apoptosis through AMPK activation in multiple myeloma cells. Int J Mol Med 2018; 42:2676-2688. [PMID: 30226553 PMCID: PMC6192759 DOI: 10.3892/ijmm.2018.3857] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 08/13/2018] [Indexed: 12/25/2022] Open
Abstract
Multiple myeloma (MM) cells are characterized by an abnormal nutrient metabolism that is distinct from normal plasma cells. Pterostilbene (PTE), a bioactive component of blueberries, has been demonstrated to induce apoptosis in multiple types of cancer cell. The present study evaluated whether PTE treatment affected the survival of MM cells from a metabolic perspective, and the potential mechanisms of this. It was observed that the administration of PTE induced apoptosis, which was mediated by the increased activation of AMP‑activated protein kinase (AMPK). Once activated, AMPK decreased the expression and/or activity of key lipogenic enzymes, including fatty acid synthase and acetyl‑CoA carboxylase. In addition, the activation of AMPK suppressed the downstream substrate, mechanistic target of rapamycin, which dephosphorylated eukaryotic initiation factor 4E‑binding protein 1, leading to a general decrease in mRNA translation. Pre‑treatment with the AMPK inhibitor compound C prior to PTE treatment compromised the anti‑myeloma apoptosis effect, suggesting the critical role of AMPK in mediating PTE‑induced cell toxicity. Consistent results were obtained in vivo. Finally, autophagy was adaptively upregulated subsequent to PTE treatment; the pro‑apoptotic efficacy of PTE was potentiated once autophagic flux was inhibited by 3‑methyladenine. Taken together, these data demonstrated that PTE exerts anti‑tumor effects on MM cells via AMPK‑induced nutrient suppression.
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Affiliation(s)
- Huiling Mei
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei 430022
| | - Yu Xiang
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Heng Mei
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei 430022
| | - Bin Fang
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Qiuguo Wang
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Dedong Cao
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Yu Hu
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei 430022
- Correspondence to: Dr Yu Hu or Dr Tao Guo, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1,277 Jiefang Avenue, Wuhan, Hubei 430022, P.R. China, E-mail: , E-mail:
| | - Tao Guo
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei 430022
- Correspondence to: Dr Yu Hu or Dr Tao Guo, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1,277 Jiefang Avenue, Wuhan, Hubei 430022, P.R. China, E-mail: , E-mail:
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17
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The Signaling Pathways Involved in the Antiatherosclerotic Effects Produced by Chinese Herbal Medicines. BIOMED RESEARCH INTERNATIONAL 2018; 2018:5392375. [PMID: 30009170 PMCID: PMC6020658 DOI: 10.1155/2018/5392375] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 05/15/2018] [Accepted: 05/21/2018] [Indexed: 12/19/2022]
Abstract
Cardiovascular diseases (CVDs) are considered to be the predominant cause of death in the world. Chinese herb medicines (CHMs) have been widely used for the treatment of CVDs in Asian countries for thousands of years. One reason of high efficacy of CHMs in treating CVDs is attributed to their inhibition in atherosclerosis (AS) development, a critical contributor to CVDs occurrence. Cumulative studies have demonstrated that CHMs alleviate atherogenesis via mediating pathophysiologic events involved in AS. However, there is deficiency in the summaries regarding antiatherogenic signal pathways regulated by CHMs. In this review, we focus on the signal cascades by which herb medicines and relevant extractives, derivatives, and patents improve proatherogenic processes including endothelium dysfunction, lipid accumulation, and inflammation. We mainly elaborate the CHMs-mediated signaling pathways in endothelial cells, macrophages, and vascular smooth muscle cells of each pathogenic event. Moreover, we briefly describe the other AS-related factors such as thrombosis, autophagy, immune response, and noncoding RNAs and effects of CHMs on them in the way of cascade regulation, which is helpful to further illustrate the molecular mechanisms of AS initiation and progression and discover newly effective agents for AS management.
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18
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Chu BX, Fan RF, Lin SQ, Yang DB, Wang ZY, Wang L. Interplay between autophagy and apoptosis in lead(II)-induced cytotoxicity of primary rat proximal tubular cells. J Inorg Biochem 2018; 182:184-193. [DOI: 10.1016/j.jinorgbio.2018.02.015] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 02/18/2018] [Accepted: 02/19/2018] [Indexed: 12/13/2022]
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19
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Ou H, Liu C, Feng W, Xiao X, Tang S, Mo Z. Role of AMPK in atherosclerosis via autophagy regulation. SCIENCE CHINA-LIFE SCIENCES 2018; 61:1212-1221. [PMID: 29656339 DOI: 10.1007/s11427-017-9240-2] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 12/05/2017] [Indexed: 01/12/2023]
Abstract
Atherosclerosis is characterized by the accumulation of lipids and deposition of fibrous elements in the vascular wall, which is the primary cause of cardiovascular diseases. Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism that regulates multiple physiological processes, including lipid and glucose metabolism and the normalization of energy imbalances. Overwhelming evidence indicates that AMPK activation markedly attenuates atherosclerosis development. Autophagy inhibits cell apoptosis and inflammation and promotes cholesterol efflux and efferocytosis. Physiological autophagy is essential for maintaining normal cardiovascular function. Increasing evidence demonstrates that autophagy occurs in developing atherosclerotic plaques. Emerging evidence indicates that AMPK regulates autophagy via a downstream signaling pathway. The complex relationship between AMPK and autophagy has attracted the attention of many researchers because of this close relationship to atherosclerosis development. This review demonstrates the role of AMPK and autophagy in atherosclerosis. An improved understanding of this interrelationship will create novel preventive and therapeutic strategies for atherosclerosis.
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Affiliation(s)
- Hanxiao Ou
- Clinical Anatomy & Reproductive Medicine Application Institute, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, 421001, China
| | - Chuhao Liu
- Clinical Anatomy & Reproductive Medicine Application Institute, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, 421001, China.,2016 Grade Excellent Doctor Class of Medical School, University of South China, Hengyang, 421001, China
| | - Wenjie Feng
- Clinical Anatomy & Reproductive Medicine Application Institute, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, 421001, China.,2015 Grade Medical Imaging Class of Medical School, University of South China, Hengyang, 421001, China
| | - Xinwen Xiao
- Clinical Anatomy & Reproductive Medicine Application Institute, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, 421001, China.,2015 Grade Medical Imaging Class of Medical School, University of South China, Hengyang, 421001, China
| | - Shengsong Tang
- Clinical Anatomy & Reproductive Medicine Application Institute, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, 421001, China. .,Center for Life Science, Hunan University of Medicine, Huaihua, 418000, China.
| | - Zhongcheng Mo
- Clinical Anatomy & Reproductive Medicine Application Institute, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, 421001, China.
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20
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Abstract
Stilbenoids are a group of naturally occurring phenolic compounds found in various plant species. They share a common backbone structure known as stilbene, but differ in the nature and position of substituents. Stilbenoids are classified as phytoalexins, which are antimicrobial compounds produced de novo in plants to protect against fungal infection and toxins. In this review, the biological effects of stilbenoids such as resveratrol, pterostilbene, gnetol and piceatannol are discussed. Stilbenoids exert various biological activities ranging from cardioprotection, neuroprotection, anti-diabetic properties, depigmentation, anti-inflammation, cancer prevention and treatment. The results presented cover a myriad of models, from cell culture to animal studies as well as clinical human trials. Although positive results were obtained in most cell culture and animal studies, further human studies are needed to substantiate beneficial effects of stilbenoids. Resveratrol remains the most widely studied stilbenoid. However, there is limited information regarding the potential of less common stilbenoids. Therefore, further research is warranted to evaluate the salutary effects of various stilbenoids.
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Affiliation(s)
- Bolanle C Akinwumi
- College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada.
- Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada.
| | - Kimberly-Ann M Bordun
- Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada.
| | - Hope D Anderson
- College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada.
- Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada.
- Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada.
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21
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Wang P, Zhu L, Sun D, Gan F, Gao S, Yin Y, Chen L. Natural products as modulator of autophagy with potential clinical prospects. Apoptosis 2018; 22:325-356. [PMID: 27988811 DOI: 10.1007/s10495-016-1335-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Natural compounds derived from living organisms are well defined for their remarkable biological and pharmacological properties likely to be translated into clinical use. Therefore, delving into the mechanisms by which natural compounds protect against diverse diseases may be of great therapeutic benefits for medical practice. Autophagy, an intricate lysosome-dependent digestion process, with implications in a wide variety of pathophysiological settings, has attracted extensive attention over the past few decades. Hitherto, accumulating evidence has revealed that a large number of natural products are involved in autophagy modulation, either inducing or inhibiting autophagy, through multiple signaling pathways and transcriptional regulators. In this review, we summarize natural compounds regulating autophagy in multifarious diseases including cancer, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and immune diseases, hoping to inspire further investigation of the underlying mechanisms of natural compounds and to facilitate their clinical use for multiple human diseases.
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Affiliation(s)
- Peiqi Wang
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Lingjuan Zhu
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Dejuan Sun
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Feihong Gan
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Suyu Gao
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China
| | - Yuanyuan Yin
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.,State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Lixia Chen
- Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
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22
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He JL, Dong XH, Li ZH, Wang XY, Fu ZA, Shen N. Pterostilbene inhibits reactive oxygen species production and apoptosis in primary spinal cord neurons by activating autophagy via the mechanistic target of rapamycin signaling pathway. Mol Med Rep 2018; 17:4406-4414. [PMID: 29328494 PMCID: PMC5802216 DOI: 10.3892/mmr.2018.8412] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 11/13/2017] [Indexed: 01/14/2023] Open
Abstract
Autophagy is an important self-adaptive mechanism that is involved in inhibiting reactive oxygen species (ROS) in spinal cord neurons. Pterostilbene, a natural plant extract, has been demonstrated to possess antioxidant effects; however, it has not yet been investigated whether pterostilbene could activate autophagy and protect spinal cord neurons from oxidative stress. In the present study, primary spinal cord neurons of Sprague Dawley rats were cultured. Cell counting kit‑8 analysis was used to detect cytotoxicity of pterostilbene. Cells were treated with various doses of pterostilbene for 24 and 48 h, respectively, and H2O2 was used to induce ROS production. Western blot analysis was performed to assess the protein expression of microtubule‑associated protein 1 light chain 3 (LC3)‑II, Beclin‑1, p62, p‑p70S6K and p‑mechanistic target of rapamycin (mTOR). Furthermore, the green fluorescent protein (GFP)‑LC3 assay was used to detect the level of autophagy level and activation mechanism. 2',7'‑Dichlorofluorescin diacetate and MitoSOX Red staining were used to detect ROS production, and Terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling assay was used to analyze apoptosis percentage. ATG5 small interfering (si)RNA transfection was used to analyze the involvement of autophagy. A dose‑dependent increase in the expression of LC3‑II and Beclin‑1, as well as the p62 decline, were observed in the pterostilbene‑treated neurons; however, p‑p70S6K and p‑mTOR expression was inhibited by pterostilbene. Pterostilbene increased the expression of LC3‑II in H2O2‑treated cells, and GFP‑LC3 analysis demonstrated an increased number of autophagosomes. Furthermore, pterostilbene significantly inhibited the ROS production and apoptosis induced by H2O2; however, ATG5 siRNA transfection significantly reversed the protection of pterostilbene. These results indicate that pterostilbene may inhibit the ROS production and apoptosis in spinal cord neurons by activating autophagy via the mTOR signaling pathway.
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Affiliation(s)
- Jing-Lan He
- Department of Orthopedic Surgery, The Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
| | - Xiao-Hui Dong
- Department of Orthopedic Surgery, The Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
| | - Zong-Hu Li
- Department of Orthopedic Surgery, The Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
| | - Xiao-Ying Wang
- Department of Orthopedic Surgery, The Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
| | - Zhi-An Fu
- Department of Orthopedic Surgery, The Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
| | - Na Shen
- Department of Orthopedic Surgery, The Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
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23
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Li YR, Li S, Lin CC. Effect of resveratrol and pterostilbene on aging and longevity. Biofactors 2018; 44:69-82. [PMID: 29210129 DOI: 10.1002/biof.1400] [Citation(s) in RCA: 231] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 10/26/2017] [Indexed: 12/17/2022]
Abstract
Over the past years, several studies have found that foods rich in polyphenols protect against age-related disease, such as atherosclerosis, cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes (T2D), hypertension and Alzheimer's disease. Resveratrol and pterostilbene, the polyphenol found in grape and blueberries, have beneficial effects as anti-aging compounds through modulating the hallmarks of aging, including oxidative damage, inflammation, telomere attrition and cell senescence. In this review, we discuss the relationship between resveratrol and pterostilbene and possible aging biomarker, including oxidative stress, inflammation, and high-calorie diets. Moreover, we also discuss the positive effect of resveratrol and pterostilbene on lifespan, aged-related disease, and health maintenance. Furthermore, we summarize a variety of important mechanisms modulated by resveratrol and pterostilbene possibly involved in attenuating age-associated disorders. Overall, we describe resveratrol and pterostilbene potential for prevention or treatment of several age-related diseases by modulating age-related mechanisms. © 2017 BioFactors, 44(1):69-82, 2018.
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Affiliation(s)
- Yi-Rong Li
- Changhua Christian Hospital, Thoracic Medicine Research center, Changhua 50006, Taiwan, Republic of China
- Institute of Biomedical Science, National Chung-Hsing University, Taichung 40227, Taiwan, Republic of China
| | - Shiming Li
- Hubei Key Laboratory of Processing and Application of Catalytic Materials, College of Chemical Engineering, Huanggang Normal University, Huanggang, Hubei, China
| | - Chi-Chien Lin
- Institute of Biomedical Science, National Chung-Hsing University, Taichung 40227, Taiwan, Republic of China
- Department of Health and Nutrition, Asia University, Taichung 41354, Taiwan, Republic of China
- Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan, Republic of China
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24
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Boteon YL, Laing R, Mergental H, Reynolds GM, Mirza DF, Afford SC, Bhogal RH. Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion. World J Gastroenterol 2017; 23:8443-8451. [PMID: 29358854 PMCID: PMC5752706 DOI: 10.3748/wjg.v23.i48.8443] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 06/19/2017] [Accepted: 07/12/2017] [Indexed: 02/06/2023] Open
Abstract
Ischaemia-reperfusion injury (IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells (LSEC). Recent evidence suggests that LSEC co-ordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion (NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.
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Affiliation(s)
- Yuri L Boteon
- The Liver Unit, University Hospitals of Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TT, United Kingdom
- The Centre for Liver Research, Centre for Liver Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Richard Laing
- The Liver Unit, University Hospitals of Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TT, United Kingdom
- The Centre for Liver Research, Centre for Liver Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Hynek Mergental
- The Liver Unit, University Hospitals of Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TT, United Kingdom
- The Centre for Liver Research, Centre for Liver Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Gary M Reynolds
- The Centre for Liver Research, Centre for Liver Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Darius F Mirza
- The Liver Unit, University Hospitals of Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TT, United Kingdom
- The Centre for Liver Research, Centre for Liver Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Simon C Afford
- The Centre for Liver Research, Centre for Liver Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - Ricky H Bhogal
- The Liver Unit, University Hospitals of Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TT, United Kingdom
- The Centre for Liver Research, Centre for Liver Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom
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25
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Jiang F. Autophagy in vascular endothelial cells. Clin Exp Pharmacol Physiol 2017; 43:1021-1028. [PMID: 27558982 DOI: 10.1111/1440-1681.12649] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 07/30/2016] [Accepted: 08/08/2016] [Indexed: 12/18/2022]
Abstract
The importance of autophagy in cardiovascular physiology and cardiovascular disease is increasingly recognized; however, the precise biological effects and underlying mechanisms of autophagy in the cardiovascular system are still poorly understood. In the last few years, the effects of autophagy in endothelial cells have attracted great interests. This article provides a summary of our current knowledge on the regulatory factors, signalling mechanisms, and functional outcomes of autophagy in endothelial cells. It is suggested that in most situations, induction of an autophagic response has cytoprotective effects. The beneficial effects of autophagy in endothelial cells are likely to be context-dependent, since autophagy may also contribute to cell death under certain circumstances. In addition to regulating endothelial cell survival or death, autophagy is also involved in modulating other important functions, such as nitric oxide production, angiogenesis and haemostasis/thrombosis. The mounting data will help us draw a clear picture of the roles of autophagy in endothelial cell biology and dysfunction. Given the pivotal role of endothelial dysfunction in the pathogenesis of vascular disease, disruptions of autophagy in endothelial cells are likely to have significant contributions. This is supported by some preliminary ex vivo data indicating that compromised autophagic functions may be important in the development of endothelial dysfunctions associated with diabetes and ageing.
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Affiliation(s)
- Fan Jiang
- Department of Pathology and Pathophysiology, School of Basic Medicine, Shandong University, Jinan, Shandong Province, China.
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26
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Luo Y, Meng X, Zhou P, Lu S, Qin M, Xu X, Sun G, Sun X. Elatoside C protects against ox-LDL-induced HUVECs injury by FoxO1-mediated autophagy induction. Biochim Biophys Acta Mol Basis Dis 2017; 1863:1654-1665. [DOI: 10.1016/j.bbadis.2017.01.017] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 12/31/2016] [Accepted: 01/23/2017] [Indexed: 12/27/2022]
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Up-regulation of the active form of small GTPase Rab13 promotes macroautophagy in vascular endothelial cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2017; 1864:613-624. [DOI: 10.1016/j.bbamcr.2017.01.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 12/21/2016] [Accepted: 01/06/2017] [Indexed: 12/25/2022]
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Jacob JA, Salmani JMM, Jiang Z, Feng L, Song J, Jia X, Chen B. Autophagy: An overview and its roles in cancer and obesity. Clin Chim Acta 2017; 468:85-89. [PMID: 28153737 DOI: 10.1016/j.cca.2017.01.028] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 01/26/2017] [Accepted: 01/26/2017] [Indexed: 12/20/2022]
Abstract
Autophagy is a normal physiological process necessary for cellular homeostasis to maintain adequate levels of cellular components. It is essential to stabilize the source of energy during development and nutritional stress and plays the dual role of survival or cell killing in various diseases including cancer. The selectivity of the response to removal of selected organelles may vary according to the each type. Macroautophagy forms a double-membraned autophagosome around the organelle destined for processing. Microautophagy involves direct engulfment of the cellular components by lysosomal invagination. Chaperone mediated autophagy (CMA) is highly selective and is dependent on the chaperone hsc70 for its activity. The effects of all these types are implemented by autophagy related genes. In this review, the markers, activators, inhibitors biological effects and roles of the three classes of autophagy in cancer and obesity are discussed.
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Affiliation(s)
- Joe Antony Jacob
- Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China
| | - Jumah Masoud Mohammad Salmani
- Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China
| | - Ziyu Jiang
- Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China; Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China
| | - Liang Feng
- Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, People's Republic of China
| | - Jie Song
- Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, People's Republic of China
| | - Xiaobin Jia
- Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, People's Republic of China
| | - Baoan Chen
- Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China.
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Zenkov NK, Chechushkov AV, Kozhin PM, Kandalintseva NV, Martinovich GG, Menshchikova EB. Plant Phenols and Autophagy. BIOCHEMISTRY (MOSCOW) 2017; 81:297-314. [PMID: 27293088 DOI: 10.1134/s0006297916040015] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Many plant phenols (stilbenes, curcumins, catechins, flavonoids, etc.) are effective antioxidants and protect cells during oxidative stress. Extensive clinical studies on the potential of phenolic compounds for treatment of cardiovascular, neurodegenerative, oncological, and inflammatory diseases are now being conducted. In addition to direct antioxidant effect, plant phenols may provide a protective effect via activation of the Keap1/Nrf2/ARE redox-sensitive signaling system and regulation of autophagy. In this review, mechanisms of effects of the most common plant phenols on autophagy are presented.
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Affiliation(s)
- N K Zenkov
- Research Institute of Experimental and Clinical Medicine, Novosibirsk, 630117, Russia.
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30
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Chen RJ, Lee YH, Yeh YL, Wu WS, Ho CT, Li CY, Wang BJ, Wang YJ. Autophagy-inducing effect of pterostilbene: A prospective therapeutic/preventive option for skin diseases. J Food Drug Anal 2016; 25:125-133. [PMID: 28911530 PMCID: PMC9333432 DOI: 10.1016/j.jfda.2016.10.022] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 10/03/2016] [Accepted: 10/03/2016] [Indexed: 12/24/2022] Open
Abstract
Pterostilbene is a naturally occurring analog of resveratrol with many health benefits. These health benefits are associated with its antioxidant activity, anti-inflammatory effects, and chemopreventive effects attributed to its unique structure. The skin cancer chemopreventive potential of pterostilbene is supported by a variety of mechanistic studies confirming the anti-inflammatory effects in skin cancer models. Molecular biological studies have identified that pterostilbene targets pleotropic signaling pathways, including those involved in mitogenesis, cell cycle regulation, and apoptosis. Recently, pterostilbene has been reported to induce autophagy in cancer and normal cells. Through autophagy induction, the inflammatory-related skin diseases can be attenuated. This finding suggests the potential use of pterostilbene in the treatment and prevention of skin disorders via alleviating inflammatory responses by autophagy induction. This review summarizes the protective and therapeutic benefits of pterostilbene in skin diseases from the viewpoint of its antioxidant, anti-inflammatory, and autophagy-inducing effects. Novel underlying mechanisms regarding these effects are discussed. We proposed that pterostilbene, a promising natural product, can be used as a preventive and therapeutic agent for inflammation-related skin disorders through induction of autophagy.
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Affiliation(s)
- Rong-Jane Chen
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Hsuan Lee
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ya-Ling Yeh
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wun-Syuan Wu
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, NJ, USA
| | - Chia-Yi Li
- Robert Thirsk High School, Calgary, AB, Canada
| | - Bour-Jr Wang
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
| | - Ying-Jan Wang
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biomedical Informatics, Asia University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 110, Taiwan.
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31
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Kosuru R, Rai U, Prakash S, Singh A, Singh S. Promising therapeutic potential of pterostilbene and its mechanistic insight based on preclinical evidence. Eur J Pharmacol 2016; 789:229-243. [PMID: 27475678 DOI: 10.1016/j.ejphar.2016.07.046] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 07/26/2016] [Accepted: 07/26/2016] [Indexed: 11/30/2022]
Abstract
Pterostilbene (PS) is a well-recognized antioxidant that primarily exists in blueberries, grapevines and heartwood of red sandalwood. Interest in this compound has been renewed in recent years, and studies have found that PS possesses an array of pharmacological properties, including chemopreventive, antiinflammatory, antidiabetic, antidyslipidemic, antiatherosclerotic and neuroprotective effects. However, the greater in vivo bioavailability of PS, as compared to resveratrol, is an added advantage for its efficacy. This review provides a summary regarding the sources, pharmacokinetic aspects and pharmacodynamics of PS, with a focus on the molecular mechanisms underlying its protective effects against cancer, brain injuries and heart disease. Studies regarding the safety profile of PS have also been included. Based on the presently available evidence, we conclude that PS represents an active phytonutrient and a potential drug with pleiotropic health applications.
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Affiliation(s)
- Ramoji Kosuru
- Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India
| | - Uddipak Rai
- Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India
| | - Swati Prakash
- Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India
| | - Abhishank Singh
- Faculty of Pharmacy, Pharmaceutical Medicine, Jamia Hamdard, New Delhi, India
| | - Sanjay Singh
- Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India.
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Ahmed T, Javed S, Javed S, Tariq A, Šamec D, Tejada S, Nabavi SF, Braidy N, Nabavi SM. Resveratrol and Alzheimer’s Disease: Mechanistic Insights. Mol Neurobiol 2016; 54:2622-2635. [DOI: 10.1007/s12035-016-9839-9] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 03/04/2016] [Indexed: 12/28/2022]
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Restoration of sirt1 function by pterostilbene attenuates hypoxia-reoxygenation injury in cardiomyocytes. Eur J Pharmacol 2016; 776:26-33. [PMID: 26921129 DOI: 10.1016/j.ejphar.2016.02.052] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 02/19/2016] [Accepted: 02/23/2016] [Indexed: 11/21/2022]
Abstract
Restoration of blood supply to ischemic myocardium causes cardiomyocyte damage, a process known as ischemia-reperfusion injury. Excess reactive oxygen species and intracellular calcium contribute to cell damage but the involvement of sirt1, a versatile protein deacetylase in reperfusion-induced cell damage remains unknown. Here, we found that hypoxia-reoxygenation, an in vitro model of ischemia-reperfusion injury, induced H9c2 cardiomyocyte apoptosis as revealed by caspase-3 assay, Hoechst 33258 staining, flow cytometric analysis and JC-1 staining. Molecular docking analysis showed that, pterostilbene, a natural dimethyl ether derivative of resveratrol, binds to the enzymatic active pocket of sirt1. Importantly, application of pterostilbene at low concentrations of 0.1-3.0 μM rescued H9c2 cells from apoptosis, an effect comparable with resveratrol at 20 μM. Mechanistically, pterostilbene exerted its cardioprotective effects via 1) stimulation of sirt1 activity, since pretreatment of H9c2 cells with splitomicin, an antagonist of sirt1, removed the effects of pterostilbene, and 2) enhancement of sirt1 expression. Therefore, the present study demonstrates that activation of sitr1 during ischemia-reperfusion is cardioprotective and that the natural compound-pterostilbene-could be used therapeutically to alleviate ischemia-reperfusion injury.
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35
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Lin HC, Hsieh MJ, Peng CH, Yang SF, Huang CN. Pterostilbene Inhibits Vascular Smooth Muscle Cells Migration and Matrix Metalloproteinase-2 through Modulation of MAPK Pathway. J Food Sci 2015; 80:H2331-5. [DOI: 10.1111/1750-3841.13002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2015] [Accepted: 07/23/2015] [Indexed: 12/14/2022]
Affiliation(s)
- Hsing-Chun Lin
- Inst. of Medicine; Chung Shan Medical Univ; Taichung Taiwan
- School of Nutrition; Chung Shan Medical Univ; Taichung Taiwan
- and with Dept. of Nutrition; Chung Shan Medical Univ. Hospital; Taichung Taiwan
| | - Ming-Ju Hsieh
- Inst. of Medicine; Chung Shan Medical Univ; Taichung Taiwan
- Cancer Research Center; Changhua Christian Hospital; Changhua Taiwan
| | | | - Shun-Fa Yang
- Inst. of Medicine; Chung Shan Medical Univ; Taichung Taiwan
- Dept. of Medical Research; Chung Shan Medical Univ. Hospital; Taichung Taiwan
| | - Chien-Ning Huang
- Inst. of Medicine; Chung Shan Medical Univ; Taichung Taiwan
- Dept. of Internal Medicine; Chung Shan Medical Univ. Hospital; Taichung Taiwan
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Soural I, Vrchotová N, Tříska J, Balík J, Horník Š, Cuřínová P, Sýkora J. Various extraction methods for obtaining stilbenes from grape cane of Vitis vinifera L. Molecules 2015; 20:6093-112. [PMID: 25856060 PMCID: PMC6272250 DOI: 10.3390/molecules20046093] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Revised: 03/30/2015] [Accepted: 04/02/2015] [Indexed: 01/30/2023] Open
Abstract
Grape cane, leaves and grape marc are waste products from viticulture, which can be used to obtain secondary stilbene derivatives with high antioxidant value. The presented work compares several extraction methods: maceration at laboratory temperature, extraction at elevated temperature, fluidized-bed extraction, Soxhlet extraction, microwave-assisted extraction, and accelerated solvent extraction. To obtain trans-resveratrol, trans-ε-viniferin and r2-viniferin from grape cane of the V. vinifera variety Cabernet Moravia, various conditions were studied: different solvents, using powdered versus cut cane material, different extraction times, and one-step or multiple extractions. The largest concentrations found were 6030 ± 680 µg/g dry weight (d.w.) for trans-resveratrol, 2260 ± 90 µg/g d.w. for trans-ε-viniferin, and 510 ± 40 µg/g d.w. for r2-viniferin. The highest amounts of stilbenes (8500 ± 1100 µg/g d.w.) were obtained using accelerated solvent extraction in methanol.
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Affiliation(s)
- Ivo Soural
- Department of Post-Harvest Technology of Horticultural Products, Faculty of Horticulture, Mendel University in Brno, Valtická 337, Lednice 69144, Czech Republic.
| | - Naděžda Vrchotová
- Global Change Research Centre, Academy of Sciences of the Czech Republic, v. v. i., Branišovská 31, České Budějovice 37005, Czech Republic.
| | - Jan Tříska
- Global Change Research Centre, Academy of Sciences of the Czech Republic, v. v. i., Branišovská 31, České Budějovice 37005, Czech Republic.
| | - Josef Balík
- Department of Post-Harvest Technology of Horticultural Products, Faculty of Horticulture, Mendel University in Brno, Valtická 337, Lednice 69144, Czech Republic.
| | - Štěpán Horník
- Institute of Chemical Process Fundamentals, Academy of Sciences of the Czech Republic, v.v.i., Rozvojová 2/135, 16502 Prague 6, Czech Republic.
| | - Petra Cuřínová
- Institute of Chemical Process Fundamentals, Academy of Sciences of the Czech Republic, v.v.i., Rozvojová 2/135, 16502 Prague 6, Czech Republic.
| | - Jan Sýkora
- Institute of Chemical Process Fundamentals, Academy of Sciences of the Czech Republic, v.v.i., Rozvojová 2/135, 16502 Prague 6, Czech Republic.
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Zhang L, Dai F, Cui L, Jing H, Fan P, Tan X, Guo Y, Zhou G. Novel role for TRPC4 in regulation of macroautophagy by a small molecule in vascular endothelial cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2015; 1853:377-87. [DOI: 10.1016/j.bbamcr.2014.10.030] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Revised: 10/24/2014] [Accepted: 10/27/2014] [Indexed: 12/21/2022]
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Abstract
Autophagy is a reparative, life-sustaining process by which cytoplasmic components are sequestered in double-membrane vesicles and degraded on fusion with lysosomal compartments. Growing evidence reveals that basal autophagy is an essential in vivo process mediating proper vascular function. Moreover, autophagy is stimulated by many stress-related stimuli in the arterial wall to protect endothelial cells and smooth muscle cells against cell death and the initiation of vascular disease, in particular atherosclerosis. Basal autophagy is atheroprotective during early atherosclerosis but becomes dysfunctional in advanced atherosclerotic plaques. Little is known about autophagy in other vascular disorders, such as aneurysm formation, arterial aging, vascular stiffness, and chronic venous disease, even though autophagy is often impaired. This finding highlights the need for pharmacological interventions with compounds that stimulate the prosurvival effects of autophagy in the vasculature. A large number of animal studies and clinical trials have indicated that oral or stent-based delivery of the autophagy inducer rapamycin or derivatives thereof, collectively known as rapalogs, effectively inhibit the basic mechanisms that control growth and destabilization of atherosclerotic plaques. Other autophagy-inducing drugs, such as spermidine or add-on therapy with widely used antiatherogenic compounds, including statins and metformin, are potentially useful to prevent vascular disease with minimal adverse effects.
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Affiliation(s)
- Guido R.Y. De Meyer
- From the Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
| | - Mandy O.J. Grootaert
- From the Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
| | - Cédéric F. Michiels
- From the Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
| | - Ammar Kurdi
- From the Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
| | - Dorien M. Schrijvers
- From the Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
| | - Wim Martinet
- From the Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
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Hsieh MT, Chen HP, Lu CC, Chiang JH, Wu TS, Kuo DH, Huang LJ, Kuo SC, Yang JS. The novel pterostilbene derivative ANK-199 induces autophagic cell death through regulating PI3 kinase class III/beclin 1/Atg‑related proteins in cisplatin‑resistant CAR human oral cancer cells. Int J Oncol 2014; 45:782-94. [PMID: 24889814 DOI: 10.3892/ijo.2014.2478] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Accepted: 05/02/2014] [Indexed: 11/05/2022] Open
Abstract
Pterostilbene is an effective chemopreventive agent against multiple types of cancer cells. A novel pterostilbene derivative, ANK-199, was designed and synthesized by our group. Its antitumor activity and mechanism in cisplatin-resistant CAR human oral cancer cells were investigated in this study. Our results show that ANK-199 has an extremely low toxicity in normal oral cell lines. The formation of autophagic vacuoles and acidic vesicular organelles (AVOs) was observed in the ANK-199-treated CAR cells by monodansylcadaverine (MDC) and acridine orange (AO) staining, suggesting that ANK-199 is able to induce autophagic cell death in CAR cells. Neither DNA fragmentation nor DNA condensation was observed, which means that ANK-199-induced cell death is not triggered by apoptosis. In accordance with morphological observation, 3-MA, a specific inhibitor of PI3K kinase class III, can inhibit the autophagic vesicle formation induced by ANK-199. In addition, ANK-199 is also able to enhance the protein levels of autophagic proteins, Atg complex, beclin 1, PI3K class III and LC3-II, and mRNA expression of autophagic genes Atg7, Atg12, beclin 1 and LC3-II in the ANK-199-treated CAR cells. A molecular signaling pathway induced by ANK-199 was therefore summarized. Results presented in this study show that ANK-199 may become a novel therapeutic reagent for the treatment of oral cancer in the near future (patent pending).
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Affiliation(s)
- Min-Tsang Hsieh
- School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C
| | - Hao-Ping Chen
- Department of Biochemistry, Tzu Chi University, Hualien 970, Taiwan, R.O.C
| | - Chi-Cheng Lu
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan, R.O.C
| | - Jo-Hua Chiang
- Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, R.O.C
| | - Tian-Shung Wu
- Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, R.O.C
| | - Daih-Huang Kuo
- Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung 907, Taiwan, R.O.C
| | - Li-Jiau Huang
- Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 404, Taiwan, R.O.C
| | - Sheng-Chu Kuo
- Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 404, Taiwan, R.O.C
| | - Jai-Sing Yang
- Department of Pharmacology, China Medical University, Taichung 404, Taiwan, R.O.C
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Engedal N, Torgersen ML, Guldvik IJ, Barfeld SJ, Bakula D, Sætre F, Hagen LK, Patterson JB, Proikas-Cezanne T, Seglen PO, Simonsen A, Mills IG. Modulation of intracellular calcium homeostasis blocks autophagosome formation. Autophagy 2013; 9:1475-90. [PMID: 23970164 DOI: 10.4161/auto.25900] [Citation(s) in RCA: 88] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Cellular stress responses often involve elevation of cytosolic calcium levels, and this has been suggested to stimulate autophagy. Here, however, we demonstrated that agents that alter intracellular calcium ion homeostasis and induce ER stress-the calcium ionophore A23187 and the sarco/endoplasmic reticulum Ca (2+)-ATPase inhibitor thapsigargin (TG)-potently inhibit autophagy. This anti-autophagic effect occurred under both nutrient-rich and amino acid starvation conditions, and was reflected by a strong reduction in autophagic degradation of long-lived proteins. Furthermore, we found that the calcium-modulating agents inhibited autophagosome biogenesis at a step after the acquisition of WIPI1, but prior to the closure of the autophagosome. The latter was evident from the virtually complete inability of A23187- or TG-treated cells to sequester cytosolic lactate dehydrogenase. Moreover, we observed a decrease in both the number and size of starvation-induced EGFP-LC3 puncta as well as reduced numbers of mRFP-LC3 puncta in a tandem fluorescent mRFP-EGFP-LC3 cell line. The anti-autophagic effect of A23187 and TG was independent of ER stress, as chemical or siRNA-mediated inhibition of the unfolded protein response did not alter the ability of the calcium modulators to block autophagy. Finally, and remarkably, we found that the anti-autophagic activity of the calcium modulators did not require sustained or bulk changes in cytosolic calcium levels. In conclusion, we propose that local perturbations in intracellular calcium levels can exert inhibitory effects on autophagy at the stage of autophagosome expansion and closure.
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Affiliation(s)
- Nikolai Engedal
- Centre for Molecular Medicine Norway (NCMM); Nordic EMBL Partnership; University of Oslo, Norway
| | - Maria L Torgersen
- Department of Biochemistry; Institute of Basic Medical Sciences; Faculty of Medicine; University of Oslo, Norway
| | - Ingrid J Guldvik
- Centre for Molecular Medicine Norway (NCMM); Nordic EMBL Partnership; University of Oslo, Norway
| | - Stefan J Barfeld
- Centre for Molecular Medicine Norway (NCMM); Nordic EMBL Partnership; University of Oslo, Norway
| | - Daniela Bakula
- Autophagy Laboratory; Department of Molecular Biology; Interfaculty Institute for Cell Biology; Faculty of Science; Eberhard Karls University; Tuebingen, Germany
| | - Frank Sætre
- Department of Cell Biology; Institute for Cancer Research; Norwegian Radium Hospital; Oslo University Hospital; Nydalen, Oslo Norway
| | - Linda K Hagen
- Department of Cell Biology; Institute for Cancer Research; Norwegian Radium Hospital; Oslo University Hospital; Nydalen, Oslo Norway
| | | | - Tassula Proikas-Cezanne
- Autophagy Laboratory; Department of Molecular Biology; Interfaculty Institute for Cell Biology; Faculty of Science; Eberhard Karls University; Tuebingen, Germany
| | - Per O Seglen
- Department of Cell Biology; Institute for Cancer Research; Norwegian Radium Hospital; Oslo University Hospital; Nydalen, Oslo Norway
| | - Anne Simonsen
- Department of Biochemistry; Institute of Basic Medical Sciences; Faculty of Medicine; University of Oslo, Norway
| | - Ian G Mills
- Centre for Molecular Medicine Norway (NCMM); Nordic EMBL Partnership; University of Oslo, Norway; Department of Cancer Prevention and Department of Urology; Oslo University Hospitals; Oslo, Norway
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Estrela JM, Ortega A, Mena S, Rodriguez ML, Asensi M. Pterostilbene: Biomedical applications. Crit Rev Clin Lab Sci 2013; 50:65-78. [DOI: 10.3109/10408363.2013.805182] [Citation(s) in RCA: 128] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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McCormack D, McFadden D. A review of pterostilbene antioxidant activity and disease modification. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2013; 2013:575482. [PMID: 23691264 PMCID: PMC3649683 DOI: 10.1155/2013/575482] [Citation(s) in RCA: 210] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/13/2013] [Accepted: 03/18/2013] [Indexed: 12/02/2022]
Abstract
Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a natural dietary compound and the primary antioxidant component of blueberries. It has increased bioavailability in comparison to other stilbene compounds, which may enhance its dietary benefit and possibly contribute to a valuable clinical effect. Multiple studies have demonstrated the antioxidant activity of pterostilbene in both in vitro and in vivo models illustrating both preventative and therapeutic benefits. The antioxidant activity of pterostilbene has been implicated in anticarcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes. In this review, we explore the antioxidant properties of pterostilbene and its relationship to common disease pathways and give a summary of the clinical potential of pterostilbene in the prevention and treatment of various medical conditions.
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Affiliation(s)
- Denise McCormack
- Mailman School of Public Health, Columbia University, Allan Rosenfield Building, 722 West 168th Street, New York, NY 10032, USA
| | - David McFadden
- Department of Surgery, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
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Yeo SCM, Ho PC, Lin HS. Pharmacokinetics of pterostilbene in Sprague-Dawley rats: The impacts of aqueous solubility, fasting, dose escalation, and dosing route on bioavailability. Mol Nutr Food Res 2013; 57:1015-25. [DOI: 10.1002/mnfr.201200651] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Revised: 12/21/2012] [Accepted: 12/21/2012] [Indexed: 12/30/2022]
Affiliation(s)
| | - Paul C. Ho
- Department of Pharmacy; National University of Singapore; Singapore
| | - Hai-Shu Lin
- Department of Pharmacy; National University of Singapore; Singapore
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Zou Y, Huang Q, Huang TK, Ni QC, Zhang ES, Xu TL, Yuan M, Li J. CuI/1,10-phen/PEG promoted decarboxylation of 2,3-diarylacrylic acids: synthesis of stilbenes under neutral and microwave conditions with an in situ generated recyclable catalyst. Org Biomol Chem 2013; 11:6967-74. [DOI: 10.1039/c3ob41588k] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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