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Gumede NAC, Khathi A. The Role of Pro-Opiomelanocortin Derivatives in the Development of Type 2 Diabetes-Associated Myocardial Infarction: Possible Links with Prediabetes. Biomedicines 2024; 12:314. [PMID: 38397916 PMCID: PMC10887103 DOI: 10.3390/biomedicines12020314] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/14/2024] [Accepted: 01/23/2024] [Indexed: 02/25/2024] Open
Abstract
Myocardial infarction is a major contributor to CVD-related mortality. T2DM is a risk factor for MI. Stress activates the HPA axis, SNS, and endogenous OPS. These POMC derivatives increase the blood glucose and cardiovascular response by inhibiting the PI3K/AkT insulin signaling pathway and increasing cardiac contraction. Opioids regulate the effect of the HPA axis and SNS and they are cardioprotective. The chronic activation of the stress response may lead to insulin resistance, cardiac dysfunction, and MI. Stress and T2DM, therefore, increase the risk of MI. T2DM is preceded by prediabetes. Studies have shown that prediabetes is associated with an increased risk of MI because of inflammation, hyperlipidemia, endothelial dysfunction, and hypertension. The HPA axis is reported to be dysregulated in prediabetes. However, the SNS and the OPS have not been explored during prediabetes. The effect of prediabetes on POMC derivatives has yet to be fully explored and understood. The impact of stress and prediabetes on the cardiovascular response needs to be investigated. This study sought to review the potential impact of prediabetes on the POMC derivatives and pathways that could lead to MI.
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Affiliation(s)
- Nompumelelo Anna-Cletta Gumede
- Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban X54001, South Africa;
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Hendijani F, Hosseini FS. Interindividual variability in diabetic patients’ response to opium poppy: an overview of impressive factors. Per Med 2022; 19:155-163. [PMID: 35220727 DOI: 10.2217/pme-2021-0107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Diabetic patients always seek alternative treatments to lower their blood glucose level efficiently, because antidiabetic drugs produce adverse effects and many patients experience reduced response after a treatment period. Opium poppy ( Papaver somniferum) is frequently consumed by diabetic patients for reduction of blood glucose level. Scientific studies found controversial results in the investigation of the blood glucose-lowering effects of opium poppy. In this regard, we explored the antidiabetic effect of opium poppy more closely. The antidiabetic or antihyperglycemic effect of P. somniferum alkaloids were reviewed. Next, opioid receptors and their role in diabetes were explored. In the final part origins of interindividual variabilities in opioid receptors and metabolizing enzymes’ functions including genetic and epigenetic factors were reviewed.
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Affiliation(s)
- Fatemeh Hendijani
- Department of Pharmacognosy & Pharmaceutical Biotechnology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Fatemeh Sadat Hosseini
- Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
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Li YX, Cheng KC, Liu IM, Niu HS. Myricetin Increases Circulating Adropin Level after Activation of Glucagon-like Peptide 1 (GLP-1) Receptor in Type-1 Diabetic Rats. Pharmaceuticals (Basel) 2022; 15:ph15020173. [PMID: 35215286 PMCID: PMC8877079 DOI: 10.3390/ph15020173] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/16/2022] [Accepted: 01/22/2022] [Indexed: 02/05/2023] Open
Abstract
Myricetin is a common plant-derived flavonoid, considered an agonist of glucagon-like peptide 1 (GLP-1) receptor. It improves glycemic control and helps reduce body weight in diabetic subjects. The potential mechanisms of action of myricetin in this context might be enhancing the secretion of β-endorphin (BER) to activate peripheral μ-opioid receptors. Moreover, adropin is a nutritionally regulated peptide hormone, which regulates energy metabolism, and plays a role in ameliorating diabetes. Because their mechanisms of insulin sensitivity are closely related, we hypothesized that myricetin may interact with adropin and plasma BER. The present study investigated the glucose-lowering effect of acute and chronic treatments of myricetin in type-1 diabetic rats. Plasma BER and adropin levels were determined by enzyme-linked immunosorbent assay (ELISA). The secretion of BER was measured in rats who received adrenalectomy. The changes in adropin gene (Enho) or mRNA level of GLP-1 receptor were measured using qPCR analysis. The results showed that myricetin dose-dependently increased plasma BER and adropin levels like the reduction of hyperglycemia after bolus injection as acute treatment. In addition, these effects of myricetin were inhibited by the antagonist of GLP-1 receptor. Moreover, in HepG2 cell line, myricetin induced GLP-1 receptor activation, which modulated the expression of adropin. In diabetic rats, the plasma adropin increased by myricetin is mainly through endogenous β-endorphin after activation of GLP-1 receptor via bolus injection as acute treatment. Additionally, chronic treatment with myricetin increased adropin secretion in diabetic rats. In conclusion, our results provide a new finding that activation of opioid μ-receptor in the liver may enhance circulating adropin in animals.
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Affiliation(s)
- Ying-Xiao Li
- Department of Nursing, Tzu Chi University of Science and Technology, Hualien 970302, Taiwan;
| | - Kai-Chun Cheng
- Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan; (K.-C.C.); (I.-M.L.)
| | - I-Min Liu
- Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan; (K.-C.C.); (I.-M.L.)
| | - Ho-Shan Niu
- Department of Nursing, Tzu Chi University of Science and Technology, Hualien 970302, Taiwan;
- Correspondence:
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Zhang Y, Yuan S, Che T, He J. Agmatine and glycolipid metabolism. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2021; 46:889-893. [PMID: 34565735 PMCID: PMC10929974 DOI: 10.11817/j.issn.1672-7347.2021.200351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Indexed: 11/03/2022]
Abstract
The prevalence of abnormal glucose and lipid metabolism and its relevant diseases has increased year by year, and it has become a problem that threatens human health. Therefore, finding a more effective way to prevent and treat diseases related to abnormal glucose and lipid metabolism has become an urgent public problem. Agmatine is a polyamine substance which widely presents in mammals.It is a metabolite produced by decarboxylation of L-arginine under the action of arginine decarboxylase, hence also known as decarboxylated arginine. Its biological effects have been confirmed. Previous studies have shown that agmatine possesses anti-diabetic effects in diabetic animals. Agmatine not only increases the insulin secretion form β-pancreatic cells to inhibit the hyperglycemia, but also attenuates insulin resistance in rats. Agmatine also plays a positive role in lipid metabolism disorders and related diseases by modulating lipid metabolism and fatty acid oxidation.
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Affiliation(s)
- Yanpei Zhang
- First School of Clinical Medicine, Lanzhou University, Lanzhou 730000.
| | - Shuqiao Yuan
- Clinical Laboratory, First Hospital of Lanzhou University, Lanzhou 730000
| | - Tuanjie Che
- Gansu Key Laboratory of Functional Genomics and Molecular Diagnostics, Lanzhou 730000, China
| | - Jinchun He
- First School of Clinical Medicine, Lanzhou University, Lanzhou 730000.
- Clinical Laboratory, First Hospital of Lanzhou University, Lanzhou 730000.
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Hedayati-Moghadam M, Moezi SA, Kazemi T, Sami A, Akram M, Zainab R, Khazdair MR. The effects of Papaver somniferum (Opium poppy) on health, its controversies and consensus evidence. TOXIN REV 2021. [DOI: 10.1080/15569543.2021.1958232] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
| | - Seyyed Ali Moezi
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Toba Kazemi
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Abdul Sami
- University College of Conventional Medicine, Faculty of Medicine and Allied Health Sciences, The Islamia University of Bahawalpur, Pakistan
| | - Muhammad Akram
- Department of Eastern Medicine, Government College University Faisalabad, Pakistan
| | - Rida Zainab
- Department of Eastern Medicine, Government College University Faisalabad, Pakistan
| | - Mohammad Reza Khazdair
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
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Moustafa SR. The immune-opioid axis in prediabetes: predicting prediabetes with insulin resistance by plasma interleukin-10 and endomorphin-2 to kappa-opioid receptors ratio. Diabetol Metab Syndr 2021; 13:61. [PMID: 34099024 PMCID: PMC8185911 DOI: 10.1186/s13098-021-00677-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 05/20/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Prediabetes is characterized by a hemoglobin A1c of 5.7-6.4% and fasting blood glucose of 100-125 mg/dl. A high percentage of prediabetes subjects develop type 2 diabetes mellitus in the next years. The effects of opioid peptides and their receptors, in addition to immunological cytokines, on prediabetes are not well understood. Therefore, molecular, physiological, and clinical studies are required to link the opioid system, immune system, and insulin resistance (IR) in prediabetes. We hypothesize that opioid peptides (endomorphin-2 (EM2), and β-endorphin (βEP)), and their receptors (µ-opioid receptors (MOR) and κ-opioid receptors (KOR)), in addition to the inflammatory cytokines (IL-6) and anti-inflammatory cytokine (IL-10), affect IR parameters in patients with prediabetes. METHODS Sixty prediabetes patients with IR (prediabetes+IR) and sixty prediabetes patients without IR (prediabetes-IR), in addition to 58 controls, have participated in the study. IL-6, IL-10, EM2, βEP, MOR, and KOR were measured by the ELISA technique. RESULTS In general, most prediabetes subjects have dyslipidemia. The IL-6, IL-10, β-endorphin, MOR, and endomorphin-2 were higher in the prediabetes subgroups than the control group. The immune system was activated in the prediabetes in an IR-dependent manner. Prediabetes+IR can be predicted by the increased levels of IL-10, βEP, and EM2 and by the combination of IL-10 and EM2/KOR with good sensitivity and specificity. CONCLUSION Opioid peptides and their receptors were upregulated in patients with prediabetes, depending on the significance of IR and the immune cytokines. The intercorrelation between the immune system, EOS, and insulin in prediabetes was confirmed.
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Affiliation(s)
- Shatha Rouf Moustafa
- Clinical Analysis Department, College of Pharmacy, Hawler Medical University, Roya Towers C21, Erbil, Iraq.
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Abo El Gheit RE, Soliman NA, Badawi GA, Madi NM, El-Saka MH, Badr SM, Emam MN. Retinoprotective effect of agmatine in streptozotocin-induced diabetic rat model: avenues for vascular and neuronal protection : Agmatine in diabetic retinopathy. J Physiol Biochem 2021; 77:305-320. [PMID: 33635523 DOI: 10.1007/s13105-021-00799-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 02/08/2021] [Indexed: 12/20/2022]
Abstract
Diabetic retinopathy (DR) is the most common diabetic neurovascular complication, and the leading cause of preventable blindness among working-age individuals. Recently, agmatine, the endogenous decarboxylated L-arginine, has gained attention as a pleiotropic agent that modulates the diabetes-associated decline in quality of life, and exhibited varied protective biological effects. Diabetes was induced by a single streptozotocin (STZ, 50 mg/kg, i.p.) injection. When diabetes was verified, the animals were randomly allocated into three groups (16 rat each); diabetic, agmatine-treated diabetic (1 mg/kg, daily, for 12 weeks), and control group. Blood glucose homeostasis, retinal redox status, apoptotic parameters, nitric oxide synthase (NOS), nitric oxide (NO), vascular endothelial growth factor (VEGF), glutamate, glutamine, glutamine synthase (GS) activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and mitogen-activated protein kinase (MAPKs) pathways were assayed biochemically. Retinal vascular permeability was measured. Retinal morphology was evaluated by hematoxylin and eosin staining. Retinal N-methyl-D-aspartic acid receptor1 (NMDAR1) and glutamate aspartate transporter (GLAST) mRNA were quantified. Glucose transporter 1, pro-caspase3, and glial fibrillary acidic protein (GFAP) expression were quantified by immunohistochemistry. Chronic agmatine treatment abrogated STZ-induced retinal neurodegeneration features including gliosis, and neuronal apoptosis, restored retinal vascular permeability, mostly through antioxidant, anti-apoptotic capacity, abolishing glutamate excitotoxicity, modulating the activity of NMDARs, MAPKs/NFκB, and NOS/NO pathways. By restoring the molecular and functional background of retinal neurovascular homeostatic balance, agmatine would be appropriate therapeutic option acting upstream of the DR, impeding its progression.
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Affiliation(s)
| | - Nema A Soliman
- Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Ghada A Badawi
- Pharmacology and Toxicology Department, Faculty of Pharmacy and Pharmaceutical Industries, Sinai University, El-Arish, Egypt
| | - Nermin M Madi
- Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Mervat H El-Saka
- Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Shimaa M Badr
- Histology Departments, Tanta University, Tanta, Egypt
| | - Marwa N Emam
- Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
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Cheng KC, Li YX, Shieh PC, Cheng JT, Hsu CC. Liraglutide Activates Glucagon-Like Peptide 1 Receptor to Attenuate Hyperglycemia through Endogenous Beta-Endorphin in Diabetic Rats. Pharmaceuticals (Basel) 2020; 13:407. [PMID: 33233692 PMCID: PMC7699724 DOI: 10.3390/ph13110407] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/19/2020] [Accepted: 11/19/2020] [Indexed: 02/01/2023] Open
Abstract
Liraglutide, an acylated analog of glucagon-like peptide 1 (GLP-1), could improve glycemic control in diabetes. Moreover, endogenous opioid peptides play a role in blood sugar regulation. Since GLP-1 receptors are also expressed in extra-pancreatic tissues, this study investigates the effect of liraglutide on endogenous opioid secretion in type 1-like diabetes. The endogenous opioid level was determined by enzyme-linked immunosorbent assay. The direct effect of liraglutide on endogenous opioid secretion was determined in the isolated adrenal medulla. Acute treatment with liraglutide dose-dependently attenuated hyperglycemia, and increased the plasma opioid neuropeptide, beta-endorphin (BER) levels in diabetic rats. These effects have been blocked by GLP-1 receptor antagonist, naloxone. Additionally, the effects of liraglutide were markedly reduced in adrenalectomized diabetic rats. In the isolated adrenal medulla, liraglutide induced BER secretion and increased the BER mRNA levels. Subcellular effects of liraglutide on the adrenal gland were further identified to mediate through the exchange proteins directly activated by cAMP, mainly using the pharmacological blockade. After repeatedly administering liraglutide, metabolic changes in diabetic rats were investigated, and genes associated with gluconeogenesis in the liver were downregulated. Naloxone pretreatment inhibited these effects of liraglutide, indicating the involvement of endogenous opioids. The present study indicated that liraglutide had an acute effect of reducing hyperglycemia by regulating endogenous opioid BER and modifying the glucose homeostasis.
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Affiliation(s)
- Kai-Chun Cheng
- Department of Pharmacy, College of Pharmacy, Tajen University, Pingtung 907, Taiwan; (K.-C.C.); (P.-C.S.)
- Pharmacological Department of Herbal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
- Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
| | - Ying-Xiao Li
- Department of Nursing, Tzu Chi University of Science and Technology, Hualien City 970, Taiwan;
| | - Po-Chuen Shieh
- Department of Pharmacy, College of Pharmacy, Tajen University, Pingtung 907, Taiwan; (K.-C.C.); (P.-C.S.)
| | - Juei-Tang Cheng
- Department of Medical Research, Chi-Mei Medical Center, Tainan City 710, Taiwan
| | - Chia-Chen Hsu
- Graduate Institute of Gerontology and Health Care Management, Chang Gung University of Science and Technology, Taoyuan City 613, Taiwan
- Department of Otorhinolaryngology, Taipei City Hospital, Taipei City 110, Taiwan
- Department of Exercise and Health Sciences, University of Taipei, Taipei City 110, Taiwan
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Nakhaee S, Brent J, Hoyte C, Farrokhfall K, Shirazi FM, Askari M, Mehrpour O. The effect of tramadol on blood glucose concentrations: a systematic review. Expert Rev Clin Pharmacol 2020; 13:531-543. [PMID: 32295441 DOI: 10.1080/17512433.2020.1756773] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
INTRODUCTION Studies comprehensively summarizing the impact of tramadol use on glucose homeostasis are very sparse. Thus, the present study was performed to collect and summarize the latest information about this issue in a systematic way. AREAS COVERED An exhaustive literature search was carried out using relevant keywords. Web of Sciences, PubMed, Scopus, and Google scholar were interrogated until 30 June 2019. Case-control, cohort, cross-sectional, clinical trial, case report, and animal studies that focused on the objective of the study were retrieved. This review summarizes the results of 761 papers on glycemic changes due to tramadol exposure. Thirty-six publications reported hypoglycemia and 17 hyperglycemia during tramadol use. Twenty-two studies either reported normal blood glucose concentrations, or did not observe any difference in the blood glucose levels following tramadol use. Finally, hypoglycemia was reported in diabetic individuals exposed to tramadol in 12 studies. EXPERT OPINION The data suggest that primarily hypoglycemia but some degree of hyperglycemia has been reported with tramadol use. Importantly, all studies on tramadol use in diabetes reported hypoglycemia. Tramadol-induced hypoglycemia may be severe in some cases. The risk of alterations in glucose homeostasis accompanying tramadol exposure indicates time importance of careful blood glucose monitoring during tramadol use.
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Affiliation(s)
- Samaneh Nakhaee
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS) , Birjand, Iran
| | - Jeffrey Brent
- School of Medicine, University of Colorado , Aurora, CO, USA
| | | | - Khadijeh Farrokhfall
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS) , Birjand, Iran
| | - Farshad M Shirazi
- Arizona Poison & Drug Information Center, the University of Arizona, college of pharmacy and university of Arizona, college of medicine , Tucson, Arizona, USA.,Department of Medical toxicology, Rocky Mountain Poison and Drug Safety , Denver, CO, USA
| | - Masoumeh Askari
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS) , Birjand, Iran
| | - Omid Mehrpour
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS) , Birjand, Iran.,Department of Medical toxicology, Rocky Mountain Poison and Drug Safety , Denver, CO, USA
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The therapeutic and nutraceutical potential of agmatine, and its enhanced production using Aspergillus oryzae. Amino Acids 2019; 52:181-197. [DOI: 10.1007/s00726-019-02720-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Accepted: 03/05/2019] [Indexed: 12/30/2022]
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Hsu CC, Lin MH, Cheng JT, Wu MC. Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β-endorphin in type I-like diabetic rats. Clin Exp Pharmacol Physiol 2017; 44:549-555. [PMID: 28218955 DOI: 10.1111/1440-1681.12739] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 02/01/2017] [Accepted: 02/14/2017] [Indexed: 12/13/2022]
Abstract
Diosmin is one of the flavonoids contained in citrus and has been demonstrated to improve glucose metabolism in diabetic disorders. However, the mechanism(s) of diosmin in glucose regulation remain obscure. Therefore, we investigated the potential mechanism(s) for the antihyperglycaemic action of diosmin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Diosmin lowered hyperglycaemia in a dose-dependent manner in STZ-diabetic rats. This action was inhibited by naloxone at a dose sufficient to block opioid receptors. Additionally, we determined the changes in plasma β-endorphin-like immunoreactivity (BER) using enzyme-linked immunosorbent assay (ELISA). Diosmin also increased BER dose-dependently in the same manner. Repeated treatment of STZ-diabetic rats with diosmin for 1 week resulted in an increase in the expression of the glucose transporter subtype 4 (GLUT 4) in the soleus muscle and a reduction in the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. These effects were also inhibited by naloxone at a dose sufficient to block opioid receptors. Bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of diosmin, including both the reduction in hyperglycemia and the elevation of plasma BER. In conclusion, our results suggest that diosmin may act on the adrenal glands to enhance the secretion of β-endorphin, which can stimulate the opioid receptors to attenuate hepatic gluconeogenesis and increase glucose uptake in soleus muscle, resulting in reduced hyperglycemia in STZ-diabetic rats.
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Affiliation(s)
- Chia-Chen Hsu
- Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan
| | - Mang Hung Lin
- Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan.,Chief Secretary 's Office, Chiayi Hospital, Ministry of Health and Welfare, Chiayi, Taiwan
| | - Juei Tang Cheng
- Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan, Taiwan.,Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan, Taiwan
| | - Ming Chang Wu
- Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan
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Hsu CC, Lin MH, Cheng JT, Wu MC. Diosmin, a Citrus Nutrient, Activates Imidazoline Receptors to Alleviate Blood Glucose and Lipids in Type 1-Like Diabetic Rats. Nutrients 2017; 9:684. [PMID: 28665324 PMCID: PMC5537799 DOI: 10.3390/nu9070684] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 06/26/2017] [Accepted: 06/29/2017] [Indexed: 11/20/2022] Open
Abstract
Diosmin is a nutrient that is widely contained in citrus and that has been indicated to improve glucose metabolism in diabetic disorders. Recently, we demonstrated that diosmin induces β-endorphin to lower hyperglycemia in diabetic rats. However, the mechanisms of diosmin in opioid secretion were unclear. Therefore, we focused on the secretion of opioids from isolated adrenal glands induced by diosmin. The changes in the released β-endorphin-like immunoreactivity (BER) were determined using ELISA. Diosmin increased the BER level in a dose-dependent manner, and this effect was markedly reduced in the absence of calcium ions. Activation of the imidazoline I-2 receptor (I-2R) has been introduced to induce opioid secretion. Interestingly, we observed that diosmin activates CHO cells expressing I-R. Additionally, diosmin-increased BER was inhibited by the blockade of I-2R in isolated adrenal glands. Additionally, an antagonist of I-2R blocked diosmin-induced effects, including the reduction in hyperglycemia and the increase in plasma BER in streptozotocin-induced diabetic rats (STZ-diabetic rats). Repeated treatment of STZ-diabetic rats with diosmin for one week induced changes in hepatic glycogen, lipid levels, and the expression of phosphoenolpyruvate carboxykinase (PEPCK). Furthermore, an antagonist of I-2R blocked the diosmin-induced changes. Additionally, plasma lipids modified by diosmin were also reversed by the blockade of I-2R in STZ-diabetic rats. Taken together, we suggest that diosmin may activate I-2R to enhance the secretion of β-endorphin from adrenal glands and to influence metabolic homeostasis, resulting in alleviation of blood glucose and lipids in STZ-diabetic rats.
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Affiliation(s)
- Chia-Chen Hsu
- Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung City 90801, Taiwan.
| | - Mang Hung Lin
- Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung City 90801, Taiwan.
- Chief Secretary's Office, Chiayi Hospital, Ministry of Health and Welfare, Chiayi City 60001, Taiwan.
| | - Juei-Tang Cheng
- Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City 73101, Taiwan.
- Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City 71101, Taiwan.
| | - Ming Chang Wu
- Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung City 90801, Taiwan.
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Najafipour H, Beik A. The Impact of Opium Consumption on Blood Glucose, Serum Lipids and Blood Pressure, and Related Mechanisms. Front Physiol 2016; 7:436. [PMID: 27790151 PMCID: PMC5061814 DOI: 10.3389/fphys.2016.00436] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 09/13/2016] [Indexed: 11/23/2022] Open
Abstract
Aim: Substance abuse has become a universal crisis in our modern age. Among illegal substances, opium and its derivatives have been ranked second in terms of usage after cannabis in the world. In many Asian regions, the use of opium enjoys a high social acceptance; hence, some common people and even medical practitioners believe that opium lowers blood glucose and pressure and treat dyslipidemia. How much this belief is scientifically justified? Method: The results of available studies on both humans and animals searched in different search engines up to mid-2016 were integrated (78 articles). Upon the findings we try to offer a more transparent picture of the effects of opium on the mentioned factors along with the probable underlying mechanisms of its action. Results: Taken together, a variety of evidences suggest that the consumption of opium has no scientific justification for amendment of these biochemical variables. The mechanisms proposed so far for the action of opium in the three above disorders are summarized at the end of the article. Short term effects seems to be mostly mediated through central nervous system (neural and hormonal mechanisms), but long term effects are often due to the structural and functional alterations in some body organs. Conclusion: Although opium may temporarily reduce blood pressure, but it increases blood glucose and most of blood lipids. Moreover its long term use has negative impacts and thus it aggravates diabetes, dyslipidemia and hypertension. Accordingly, it is necessary to inform societies about the potential disadvantages of unauthorized opium consumption.
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Affiliation(s)
- Hamid Najafipour
- Cardiovascular Research Center and Department of Physiology, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences Kerman, Iran
| | - Ahmad Beik
- Physiology Research Center, Kerman University of Medical Sciences Kerman, Iran
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Barzehkar S, Gozashti MH, Divsalar K, Mashrouteh M, Darvishi-Lardi AH. Investigating Changes in Serum Biochemical Parameters in Opium Addicts Before and During Addiction Treatment. ADDICTION & HEALTH 2016; 8:211-217. [PMID: 28819551 PMCID: PMC5554800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Iran is one of the major consumers of opium and opiate substances in the world. Addiction has become a very important issue in the 21st century and an urgent one in Iran. The consumption of this substance leaves a variety of impacts on the human body. The goal of this study is to investigate the changes of the biochemical parameters derived from opiate substances in addicts during their treatment. METHODS This is a cross-sectional research that focused on 40 individuals dependent on the consumption of opium. Their blood samples were taken before and during treatment, and their fasting blood sugar (FBS), sodium, calcium, phosphorus, creatinine, urea, uric acid, total protein, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol were measured. Data were analyzed by SPSS using paired t-test. FINDINGS The results showed that serum uric acid, LDL, cholesterol, and the total protein levels significantly decreased during the treatment in comparison with the time before the treatment (P < 0.050). Yet, the serum fasting glucose, urea, creatinine, HDL, triglycerides, calcium, phosphorous, sodium, and potassium showed no significant change the time prior and during the treatment. CONCLUSION Given the findings of the analysis, opium addiction has a number of destructive impacts on the lipid profile and uric acid. In addition, the level of total protein decreased during the treatment.
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Affiliation(s)
- Sedigheh Barzehkar
- Resident, Neurosciences Research Center AND Department of Internal Medicine, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Hossein Gozashti
- Associate Professor, Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran,Correspondence to: Mohammad Hossein Gozashti MD,
| | - Kouros Divsalar
- Researcher, Neurosciences Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahdieh Mashrouteh
- General Practitioner, Modeling in Health Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
| | - Amir Hossein Darvishi-Lardi
- Student of Medicine, Infectious Disease and Tropical Research Center, Kerman University of Medical Sciences, Kerman, Iran
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Signals for increase of μ-opioid receptor expression in muscle by hyperglycemia. Neurosci Lett 2014; 582:109-14. [PMID: 25220705 DOI: 10.1016/j.neulet.2014.09.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2014] [Revised: 08/28/2014] [Accepted: 09/02/2014] [Indexed: 12/19/2022]
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El-Abhar HS, Schaalan MF. Phytotherapy in diabetes: Review on potential mechanistic perspectives. World J Diabetes 2014; 5:176-197. [PMID: 24748931 PMCID: PMC3990312 DOI: 10.4239/wjd.v5.i2.176] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Revised: 01/07/2014] [Accepted: 03/14/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a widely spread epidemic disease that results from the absence of insulin, decreased secretion and/or impaired function. Since DM is a multi-factorial disease, the available pharmaceuticals, despite their sensible treatment, target mostly one pathway to control hyperglycemia and encounter several side effects. Therefore, new therapeutic paradigms aim to hit several pathways using only one agent. Traditionally, antidiabetic plants and/or their active constituents may fulfill this need. More than 200 species of plants possess antidiabetic properties which were evaluated mostly by screening tests without digging far for the exact mode of action. Searching among the different literature resources and various database and in view of the above aspects, the present article provides a comprehensive review on the available antidiabetic plants that have been approved by pharmacological and clinical evaluations, and which their mechanism(s) of action is assured. These plants are categorized according to their proved mode of action and are classified into those that act by inhibiting glucose absorption from intestine, increasing insulin secretion from the pancreas, inhibiting glucose production from hepatocytes, or enhancing glucose uptake by adipose and muscle tissues. The current review also highlights those that mimic in their action the new peptide analogs, such as exenatide, liraglutide and dipeptidylpeptidase-4 inhibitors that increase glucagon-like peptide-1 serum concentration and slow down the gastric emptying.
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Niu CS, Chen LJ, Niu HS. Antihyperglycemic action of rhodiola-aqeous extract in type1-like diabetic rats. Altern Ther Health Med 2014; 14:20. [PMID: 24417880 PMCID: PMC3897963 DOI: 10.1186/1472-6882-14-20] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2013] [Accepted: 01/09/2014] [Indexed: 12/21/2022]
Abstract
Background Rhodiola rosea (Rhodiola) is a plant in the Crassulaceae family that grows in cold regions of the world. It is mainly used in clinics as an adaptogen. Recently, it has been mentioned that Rhodiola increases plasma β-endorphin to lower blood pressure. Thus, the present study aims to investigate the antidiabetic action of Rhodiola in relation to opioids in streptozotocin-induced diabetic rats (STZ-diabetic rats). Methods In the present study, the plasma glucose was analyzed with glucose oxidase method, and the determination of plasma β-endorphin was carried out using a commercially available enzyme-linked immunosorbent assay. The adrenalectomy of STZ-diabetic rats was used to evaluate the role of β-endorphin. In addition, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to investigate mRNA and protein expressions. Results Rhodiola-water extract dose-dependently lowered the plasma glucose in STZ-diabetic rats and this action was reversed by blockade of opioid μ-receptors using cyprodime. An increase of plasma β-endorphin by rhodiola-water extract was also observed in same manner. The plasma glucose lowering action of rhodiola-water extract was attenuated in bilateral adrenalectomized rats. In addition, continuous administration of rhodiola-water extract for 3 days in STZ-diabetic rats resulted in an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle and a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. These effects were also reversed by blockade of opioid μ-receptors. Conclusions Taken together, rhodiola-water extract improves hyperglycemia via an increase of β-endorphin secretion from adrenal gland to activate opioid μ-receptors in STZ-diabetic rats.
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Cheng KC, Asakawa A, Li YX, Liu IM, Amitani H, Cheng JT, Inui A. Opioid μ-receptors as new target for insulin resistance. Pharmacol Ther 2013; 139:334-40. [PMID: 23688574 DOI: 10.1016/j.pharmthera.2013.05.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Accepted: 04/12/2013] [Indexed: 10/26/2022]
Abstract
Type-2 diabetes is one of the fastest growing public health problems worldwide resulting from both environmental and genetic factors. Activation of μ-opioid receptor (MOR) could result in reversal of the impairment of insulin-stimulated glucose disposal in genetically obese Zucker rats via exercise training. This improvement of insulin resistance was associated with an elevation of circulating β-endorphin to ameliorate the post-receptor insulin signaling cascade, including downstream effectors of the phosphatidylinositol 3-kinase (PI3-kinase) signaling pathway. In insulin resistant rats, Loperamide treatment effected on the insulin receptor substrate (IRS)-1/PI3-kinase/Akt signaling cascade and subsequent insulin-stimulated glucose transport trafficking on skeletal muscle, which were all suppressed by MOR antagonism. In addition, induction of insulin resistance by the intake of high fructose is more rapid in MOR knockout mice than in wild-type mice. Improvements in insulin sensitivity through the peripheral MOR activation overcoming defects related to the post-receptor in IRS-1-associated PI3-kinase step have been defined. Opioid receptor activation, especially of the μ-subtype, may provide merits in the amelioration of defective insulin action. Atypical zeta (ζ) isoform of protein kinase C serves as a factor that integrates with peripheral MOR pathway and insulin signals for glucose utilization. The developments call new insights into the chemical compounds and/or herbal products that might enhance opioid peptide secretion and/or stimulate MOR in peripheral insulin-sensitive tissues to serve as potential agents or adjuvants for helping the glucose metabolism. In the present review, we update these topics and discuss the concept of targeting peripheral MOR pathway for the treatment of insulin resistance.
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Affiliation(s)
- Kai-Chun Cheng
- Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan
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Lee WJ, Chung HH, Cheng YZ, Lin HJ, Cheng JT. Rhodiola-water extract induces β-endorphin secretion to lower blood pressure in spontaneously hypertensive rats. Phytother Res 2012. [PMID: 23192943 DOI: 10.1002/ptr.4900] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Rhodiola rosea (Rhodiola) is grown at high altitudes and northern latitudes. It is mainly used clinically as an adaptogen, but antihypertensive effects have been reported for the extract. These have not been well investigated, so in the present study, we evaluated the effect of Rhodiola-water extract on blood pressure in spontaneously hypertensive rats (SHRs) and investigated the potential mechanism(s) for this action. In conscious male SHRs, systolic blood pressure (SBP) and heart rate were recorded using the tail-cuff method. Plasma β-endorphin was measured by enzyme-linked immunosorbent assay. Rhodiola-water extract decreased SBP in SHRs in a dose-dependent manner, and this action was more significant than that in normal group named Wistar-Kyoto (WKY) rats. This reduction of SBP in SHRs was inhibited by pretreatment with the selective opioid μ-receptor antagonist, cyprodime, but not by naloxonazine, an antagonist specific to opioid μ1-receptor. Also, the SBP-lowering action of Rhodiola-water extract was attenuated in adrenalectomized SHRs. Moreover, Rhodiola-water extract dose-dependently increased β-endorphin release in SHRs, and the elevation of β-endorphin in SHRs was higher than that in WKY. Thus, we suggest that Rhodiola-water extract can induce release of β-endorphin to lower SBP in SHRs.
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Affiliation(s)
- Wei-Jing Lee
- Department of Emergency Medicine, Chi-Mei Medical Center, Yong Kang, Tainan City, 73101, Taiwan
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Tzeng TF, Liou SS, Liu IM. Myricetin Ameliorates Defective Post-Receptor Insulin Signaling via β-Endorphin Signaling in the Skeletal Muscles of Fructose-Fed Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2011; 2011:150752. [PMID: 21785619 PMCID: PMC3136182 DOI: 10.1093/ecam/neq017] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2009] [Accepted: 01/25/2010] [Indexed: 01/05/2023]
Abstract
β-Endorphin plays a major role in the amelioration of insulin resistance. The present study documents that myricetin (3,5,7,3′, 4′, 5′-hexahydroxyflavone) ameliorates insulin resistance by enhancing β-endorphin production in insulin-resistant rats. The rats were induced for insulin resistance by feeding them a diet containing 60% fructose for 6 weeks. The degree of insulin resistance was measured by the homeostasis model assessment of basal insulin resistance (HOMA-IR). The plasma levels of insulin and β-endorphin were measured by an enzyme-linked immunosorbent assay. The insulin receptor-related signaling mediators in the soleus muscles of rats were evaluated by immunoprecipitation or immunoblotting. Myricetin was injected daily (1 mg kg−1 per injection, thrice daily) for 14 days. Consequently, the high-glucose plasma levels in fructose-fed rats decreased significantly concomitant with an increase in plasma β-endorphin. The reduction of the elevated HOMA-IR index following treatment with myricetin was subsequently inhibited by the administration of β-funaltrexamine hydrochloride (β-FNA) at doses sufficient to block μ-opioid receptors (MOR). The myricetin treatment was also observed to affect the phosphorylation of the insulin receptor, insulin receptor substrate-1, Akt and Akt substrate of 160 kDa, with subsequent effects on glucose-transporter subtype 4 translocation, all of which were blocked by β-FNA pretreatment. These results indicated that enhancement of β-endorphin secretion, which in turn leads to peripheral MOR activation, is involved in the action of myricetin on the amelioration of impaired signaling intermediates downstream of insulin receptors.
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Affiliation(s)
- Thing-Fong Tzeng
- Department of Internal Medicine, Pao Chien Hospital, Ping Tung City, China
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Varma A, Padh H, Shrivastava N. Andrographolide: a new plant-derived antineoplastic entity on horizon. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2011; 2011:815390. [PMID: 19752167 PMCID: PMC3139959 DOI: 10.1093/ecam/nep135] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2009] [Accepted: 08/05/2009] [Indexed: 12/25/2022]
Abstract
Plant-derived natural products occupy an important position in the area of cancer chemotherapy. Molecules such as vincristine, vinblastine, paclitaxel, camptothecin derivatives, epipodophyllotoxin, and so forth, are invaluable contributions of nature to modern medicine. However, the quest to find out novel therapeutic compounds for cancer treatment and management is a never-ending venture; and diverse plant species are persistently being studied for identification of prospective anticancer agents. In this regard, Andrographis paniculata Nees, a well-known plant of Indian and Chinese traditional system of medicines, has drawn attention of researchers in recent times. Andrographolide, the principal bioactive chemical constituent of the plant has shown credible anticancer potential in various investigations around the globe. In vitro studies demonstrate the capability of the compound of inducing cell-cycle arrest and apoptosis in a variety of cancer cells at different concentrations. Andrographolide also shows potent immunomodulatory and anti-angiogenic activities in tumorous tissues. Synthetic analogues of the compound have also been created and analyzed, which have also shown similar activities. Although it is too early to predict its future in cancer chemotherapy, the prologue strongly recommends further research on this molecule to assess its potential as a prospective anticancer agent.
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Affiliation(s)
- Astha Varma
- B. V. Patel Pharmaceutical Education & Research Development (PERD) Centre, Sarkhej-Gandhinagar Highway, Thaltej, Ahmedabad 380054, Gujarat, India
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