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Fan Z, Liu J, Wang X, Yang S, Wang Q, Yan L, Zhang Y, Wu X. Paeoniae Radix Rubra: A Review of Ethnopharmacology, Phytochemistry, Pharmacological Activities, Therapeutic Mechanism for Blood Stasis Syndrome, and Quality Control. Chem Biodivers 2024; 21:e202401119. [PMID: 38850115 DOI: 10.1002/cbdv.202401119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 06/06/2024] [Accepted: 06/07/2024] [Indexed: 06/09/2024]
Abstract
Paeoniae Radix Rubra (PRR) known as Chishao, in China, is the dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, with a history of over 2000 years in traditional Chinese medicine, is employed to clear heat, cool the blood, dispel blood stasis, and alleviate pain. Phytochemical investigations identified 264 compounds that contained monoterpenes and their glycosides, sesquiterpenes, triterpenes, steroids, flavonoids, lignans, tannins, volatile oils, and other compounds. It has been reported to have different pharmacological activities, including cardiovascular-protective, antidepressive, neuroprotective, antitumor, hepatoprotective, and anti-inflammatory effects. This study offers a comprehensive review covering ethnopharmacology, phytochemistry, pharmacological activities, therapeutic mechanism for blood stasis syndrome, and quality control of PRR. The comprehensive analysis aims to achieve a thorough understanding of its effects and serves as a foundation for future research and development.
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Affiliation(s)
- Zuowang Fan
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
- Sanming Medical and Polytechnic Vocational College, Sanming, 365000, China
| | - Jing Liu
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Xu Wang
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Saisai Yang
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Qi Wang
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Li Yan
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Yao Zhang
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Xiuhong Wu
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
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Demirel S. Vasorelaxant effects of biochemical constituents of various medicinal plants and their benefits in diabetes. World J Diabetes 2024; 15:1122-1141. [PMID: 38983824 PMCID: PMC11229960 DOI: 10.4239/wjd.v15.i6.1122] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 03/07/2024] [Accepted: 05/06/2024] [Indexed: 06/11/2024] Open
Abstract
Endothelial function plays a pivotal role in cardiovascular health, and dysfunction in this context diminishes vasorelaxation concomitant with endothelial activity. The nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin-cyclic adenosine monophosphate pathway, inhibition of phosphodiesterase, and the opening of potassium channels, coupled with the reduction of calcium levels in the cell, constitute critical mechanisms governing vasorelaxation. Cardiovascular disease stands as a significant contributor to morbidity and mortality among individuals with diabetes, with adults afflicted by diabetes exhibiting a heightened cardiovascular risk compared to their non-diabetic counterparts. A plethora of medicinal plants, characterized by potent pharmacological effects and minimal side effects, holds promise in addressing these concerns. In this review, we delineate various medicinal plants and their respective biochemical constituents, showcasing concurrent vasorelaxant and anti-diabetic activities.
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Affiliation(s)
- Sadettin Demirel
- Medicine School, Physiology Department, Bursa Uludag University, Bursa 16059, Türkiye
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Wei B, Sun C, Wan H, Shou Q, Han B, Sheng M, Li L, Kai G. Bioactive components and molecular mechanisms of Salvia miltiorrhiza Bunge in promoting blood circulation to remove blood stasis. JOURNAL OF ETHNOPHARMACOLOGY 2023; 317:116697. [PMID: 37295577 DOI: 10.1016/j.jep.2023.116697] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 05/09/2023] [Accepted: 05/28/2023] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Salvia miltiorrhiza Bunge (SM) is an outstanding herbal medicine with various traditional effects, especially promoting blood circulation to remove blood stasis. It has been widely used for centuries to treat blood stasis syndrome (BSS)-related diseases. BSS is one of the basic pathological syndromes of diseases such as cardiovascular and cerebrovascular diseases in traditional East Asian medicine, which is characterized by disturbance of blood circulation. However, the bioactive components and mechanisms of SM in the treatment of BSS have not been systematically reviewed. Therefore, this article outlines the anti-BSS effects of bioactive components of SM, concentrating on the molecular mechanisms. AIM OF THE REVIEW To summarize the bioactive components of SM against BSS and highlight its potential targets and signaling pathways, hoping to provide a modern biomedical perspective to understand the efficacy of SM on enhancing blood circulation to remove blood stasis. MATERIALS AND METHODS A comprehensive literature search was performed to retrieve articles published in the last two decades on bioactive components of SM used for BSS treatment from the online electronic medical literature database (PubMed). RESULTS Phenolic acids and tanshinones in SM are the main bioactive components in the treatment of BSS, including but not limited to salvianolic acid B, tanshinone IIA, salvianolic acid A, cryptotanshinone, Danshensu, dihydrotanshinone, rosmarinic acid, protocatechuic aldehyde, and caffeic acid. They protect vascular endothelial cells by alleviating oxidative stress and inflammatory damage and regulating of NO/ET-1 levels. They also enhance anticoagulant and fibrinolytic capacity, inhibit platelet activation and aggregation, and dilate blood vessels. Moreover, lowering blood lipids and improving blood rheological properties may be the underlying mechanisms of their anti-BSS. More notably, these compounds play an anti-BSS role by mediating multiple signaling pathways such as Nrf2/HO-1, TLR4/MyD88/NF-κB, PI3K/Akt/eNOS, MAPKs (p38, ERK, and JNK), and Ca2+/K+ channels. CONCLUSIONS Both phenolic acids and tanshinones in SM may act synergistically to target different signaling pathways to achieve the effect of promoting blood circulation.
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Affiliation(s)
- Baoyu Wei
- Zhejiang Key TCM Laboratory for Chinese Resource Innovation and Transformation, School of Pharmaceutical Sciences, School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, PR China.
| | - Chengtao Sun
- Zhejiang Key TCM Laboratory for Chinese Resource Innovation and Transformation, School of Pharmaceutical Sciences, School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, PR China.
| | - Haitong Wan
- Zhejiang Key TCM Laboratory for Chinese Resource Innovation and Transformation, School of Pharmaceutical Sciences, School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, PR China.
| | - Qiyang Shou
- Zhejiang Key TCM Laboratory for Chinese Resource Innovation and Transformation, School of Pharmaceutical Sciences, School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, PR China.
| | - Bing Han
- Zhejiang Key TCM Laboratory for Chinese Resource Innovation and Transformation, School of Pharmaceutical Sciences, School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, PR China.
| | - Miaomiao Sheng
- Zhejiang Key TCM Laboratory for Chinese Resource Innovation and Transformation, School of Pharmaceutical Sciences, School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, PR China.
| | - Liqing Li
- Huzhou Central Hospital, Huzhou, Zhejiang, 31300, PR China.
| | - Guoyin Kai
- Zhejiang Key TCM Laboratory for Chinese Resource Innovation and Transformation, School of Pharmaceutical Sciences, School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311402, PR China.
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Arena K, Trovato E, Mangraviti D, Occhiuto C, Rigano F, Occhiuto F, Cacciola F, Mondello L. Metabolomic profiling and antianginal activity of the bark of Sterculia setigera from Mali. J Pharm Biomed Anal 2023; 230:115399. [PMID: 37084664 DOI: 10.1016/j.jpba.2023.115399] [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: 01/27/2023] [Revised: 04/11/2023] [Accepted: 04/14/2023] [Indexed: 04/23/2023]
Abstract
The present work focuses on the phytochemical characterization and evaluation of antianginal activity of the bark of Sterculia setigera. It was collected and authenticated in the African region of Mali, where the local population largely employs this plant for the treatment of several diseases. In the context of traditional or folk medicine and recent progresses in alternative medicine practices, it is essential to expand the knowledge about the chemical composition of such medicinal plants. In this research, a direct-Mass Spectrometry (MS) technique, known as Rapid Evaporative Ionization Mass Spectrometry (REIMS) was used for the identification of the main constituents of the Sterculia setigera bark. The REIMS source is here coupled with an electroknife as sampling device, so that the dried and pulverized bark was directly cut through the electroknife to generate a vapor, which was online transferred to the source via a Venture tube. In this way, an ambient MS approach was realized, which avoids any sample preparation procedure or pretreatment; the sample was analyzed in its native state according to a time-saving analytical process. A quadrupole-time of flight MS/MS analyzer was exploited for the identification process, based on mass accuracy data and MS/MS experiments for structure elucidation purposes. Lipids, including triterpenes, fatty acids, γ-sitosterol and α-tocopherol, and phenolic compounds were identified, some of them reported for the first time in a plant of the Sterculia genus and further confirmed through a gas chromatography-mass spectrometry analysis. The obtained metabolomic profile was successfully correlated to the antianginal activity of this plant.
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Affiliation(s)
- Katia Arena
- Foundation A. Imbesi c/o University of Messina, I-98168 Messina, Italy; Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98168 Messina, Italy
| | - Emanuela Trovato
- Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98168 Messina, Italy
| | - Domenica Mangraviti
- Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98168 Messina, Italy
| | - Cristina Occhiuto
- Foundation A. Imbesi c/o University of Messina, I-98168 Messina, Italy; Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98168 Messina, Italy
| | - Francesca Rigano
- Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98168 Messina, Italy.
| | - Francesco Occhiuto
- Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98168 Messina, Italy
| | - Francesco Cacciola
- Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, 98125 Messina, Italy
| | - Luigi Mondello
- Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98168 Messina, Italy; Chromaleont s.r.l., c/o Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98168 Messina, Italy; Department of Sciences and Technologies for Human and Environment, University Campus Bio-Medico of Rome, 00128, Rome, Italy
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Liubertas T, Poderys JL, Zigmantaite V, Viskelis P, Kucinskas A, Grigaleviciute R, Jurevicius J, Urbonaviciene D. The Effect of Potassium Nitrate Supplementation on the Force and Properties of Extensor digitorum longus (EDL) Muscles in Mice. Nutrients 2023; 15:nu15061489. [PMID: 36986219 PMCID: PMC10057731 DOI: 10.3390/nu15061489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/16/2023] [Accepted: 03/17/2023] [Indexed: 03/22/2023] Open
Abstract
Adding potassium nitrate (KNO3) to the diet improves the physiological properties of mammalian muscles (rebuilds weakened muscle, improves structure and functionality). The aim of this study was to investigate the effect of KNO3 supplementation in a mouse model. BALB/c mice were fed a KNO3 diet for three weeks, followed by a normal diet without nitrates. After the feeding period, the Extensor digitorum longus (EDL) muscle was evaluated ex vivo for contraction force and fatigue. To evaluate the possible pathological changes, the histology of EDL tissues was performed in control and KNO3-fed groups after 21 days. The histological analysis showed an absence of negative effects in EDL muscles. We also analyzed 15 biochemical blood parameters. After 21 days of KNO3 supplementation, the EDL mass was, on average, 13% larger in the experimental group compared to the controls (p < 0.05). The muscle-specific force increased by 38% in comparison with the control group (p < 0.05). The results indicate that KNO3 has effects in an experimental mouse model, showing nitrate-diet-induced muscle strength. This study contributes to a better understanding of the molecular changes in muscles following nutritional intervention and may help develop strategies and products designated to treat muscle-related issues.
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Affiliation(s)
- Tomas Liubertas
- Department of Coaching Science, Lithuanian Sports University, 44221 Kaunas, Lithuania
- Correspondence: ; Tel.: +370-6126-6664
| | - Jonas Liudas Poderys
- Department of Coaching Science, Lithuanian Sports University, 44221 Kaunas, Lithuania
| | - Vilma Zigmantaite
- Biological Research Centre, Lithuanian University of Health Science, 47181 Kaunas, Lithuania
| | - Pranas Viskelis
- Institute of Horticulture, Lithuanian Research Centre for Agriculture and Forestry, 54333 Babtai, Lithuania
| | - Audrius Kucinskas
- Biological Research Centre, Lithuanian University of Health Science, 47181 Kaunas, Lithuania
| | - Ramune Grigaleviciute
- Biological Research Centre, Lithuanian University of Health Science, 47181 Kaunas, Lithuania
| | - Jonas Jurevicius
- Institute of Cardiology, Membrane Biophysics Laboratory, Lithuanian University of Health Sciences, 50162 Kaunas, Lithuania
| | - Dalia Urbonaviciene
- Institute of Horticulture, Lithuanian Research Centre for Agriculture and Forestry, 54333 Babtai, Lithuania
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Niloofar H, Raheleh B, Roshanak S, Jamshid J. Evaluation of the safety and efficacy of wormwood vaginal gel in improving sexual function and sexual satisfaction in women of reproductive age: A randomized, triple-blinds, placebo-controlled clinical trial. Eur J Obstet Gynecol Reprod Biol 2023; 280:1-6. [PMID: 36368248 DOI: 10.1016/j.ejogrb.2022.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 10/23/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022]
Abstract
INTRODUCTION All aspects of sexual function are related to sexual satisfaction, and not paying attention to sexual problems leads to sexual dissatisfaction. According to studies, sexual satisfaction is a key factor in a couple's quality of life. The aim of this study was to evaluate the safety and efficacy of wormwood vaginal gel in improving sexual function and sexual satisfaction in women of reproductive age. METHODS This study was a randomized, triple-blinds, parallel-groups clinical trial performed on 76 women of reproductive age (18-45 years) referred to the gynecological clinic of Ghaem Hospital in Mashhad who had sexual dysfunction and low sexual satisfaction. 76 women were assigned to the wormwood gel (n = 38) and placebo (n = 38) groups using random permuted blocks of sizes 4 or 6 and an allocation ratio of 1:1. Wormwood gel or placebo was used for 4 weeks and 3 times a week for 4 weeks from22 May to 23 October 2021. The main data collection tools were the Female Sexual Function Index (FSFI) and Larson Sexual Satisfaction Questionnaire (LSSQ) to access changes in sexual function and sexual satisfaction at baseline and after 4 weeks. RESULTS The Mean and Standard Deviation of the age of the studied women was 36.8 ± 5.9 years in the intervention group and 37.1 ± 7.3 years in the placebo group. Before the intervention, the Mean and Standard Deviation of the total score of sexual function and sexual satisfaction in the studied women were 17.70 ± 3.66 and 72.20 ± 6.56 in the intervention group and in the placebo group were 18.23 ± 3.84 and 73.26 ± 5.86, respectively. At the end of the intervention, the Mean and Standard Deviation of the total score of female sexual function and sexual satisfaction in the intervention group were 32.11 ± 2.03 and 96.91 ± 7.93 and in the placebo group were 21.07 ± 3.22 and 75.91 ± 8.87, respectively. sexual function and satisfaction improved significantly in the wormwood gel compared to the control group(p < 0.0001). CONCLUSIONS Based on the findings of this trial, it seems that the wormwood vaginal gel can be used as a topical supplement to improve sexual function and sexual satisfaction in women of reproductive age who have sexual dysfunction and low sexual satisfaction.
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Affiliation(s)
- Hajatpour Niloofar
- Faculty of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Babazadeh Raheleh
- Nursing and Midwifery Care Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Salari Roshanak
- Department of Pharmaceutical Sciences in Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Jamali Jamshid
- Department of Biostatistics, School of Health, Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Yorsin S, Sriwiriyajan S, Chongsa W. Vasorelaxing effect of Garcinia cowa leaf extract in rat thoracic aorta and its underlying mechanisms. J Tradit Complement Med 2022; 13:219-225. [PMID: 37128198 PMCID: PMC10148127 DOI: 10.1016/j.jtcme.2022.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 11/28/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Background and aim The leaves of Garcinia cowa (G. cowa) are used in Thai traditional medicine to improve blood circulation. However, there is no scientific evidence to confirm this therapeutic claim. Here, we investigated the vasorelaxing effect and its underlying mechanisms of an aqueous extract of G. cowa leaves in rat thoracic aortic rings. Materials and methods Dried leaves of G. cowa were extracted with water, followed by phytochemical analysis. Vascular reactivity experiments were performed in isolated rat thoracic aortic rings using an organ bath system. The results were recorded using the data acquisition system Power Lab. Results Phytochemical analysis showed that the leaves of G. cowa are rich in polyphenols and flavonoids, especially kaempferol, vitexin, and isovitexin. The G. cowa leaf extract caused a concentration-dependent relaxation of aortic rings. This effect was attenuated by denudation of the endothelium, or by pre-treatment of the aortic rings with l-NAME, ODQ, indomethacin, or glibenclamide, but not with TEA. Conclusion This study indicates that G. cowa leaf extract induces vasorelaxation through both endothelium-dependent and endothelium-independent manners. Its mechanism of action mainly involves the production of nitric oxide and prostanoids, as well as opening ATP-sensitive K+ channels. The vasorelaxing effect of G. cowa leaf extract is probable promoted by the action of flavonoids.
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Kaneda T, Ifadotunnikmah F, Nugroho AE, Koshikawa S, Tadahiro S, Hirasawa Y, Morita H. Calofolic Acid-A from Calophyllum scriblitifolium Bark Has Vasorelaxant Activity via Indirect PKA Activation Caused by PI-3 Kinase Inhibition in Rat Vascular Smooth Muscle Cells. JOURNAL OF NATURAL PRODUCTS 2022; 85:2192-2198. [PMID: 35983865 DOI: 10.1021/acs.jnatprod.2c00502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Previously, we isolated 2R,3S,15R-calofolic acids (CAs) from Calophyllum scriblitifolium bark, which showed vasorelaxant activity on phenylephrine (PE)-precontracted rat aortic rings. Although the effect was suggested to be induced via an extracellular Ca2+-independent manner and mainly acts on vascular smooth muscle, the exact mechanism of action of CAs remained unclear. Thus, this study investigated the detailed mechanism of calofolic acid-A (CA-A) induced vasorelaxation in an aortic ring specimen using rat vascular smooth muscle cells (VSMCs). The levels of PE-induced phosphorylation on MLC Ser19 decreased in VSMCs pretreated with CA-A. CA-A also decreased the phosphorylation of MYPT1 Thr696 and MYPT1 Thr853. On the other hand, CA-A increased the PE-induced phosphorylation of MYPT1 Ser695 and MYPT1 Ser668, which are reported to be phosphorylated by a cAMP-dependent protein kinase (PKA). CA-A slightly increased PKA substrate phosphorylation in a concentration-dependent manner. Furthermore, CA-A enhanced isoproterenol (ISO)-induced cAMP accumulation and PKA substrate phosphorylation. Treatment with PI-3 kinase (PI3K) inhibitor, LY294002, enhanced ISO-induced cAMP accumulation and PKA substrate phosphorylation in the same manner as CA-A treatment. Furthermore, CA-A was found to directly inhibit PI3K enzyme activity in a dose-dependent manner. Taken together, the present study indicated that CA-A induces vasorelaxation through an indirectly activated PKA-MYPT1 pathway caused by inhibition of PI3K activity.
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Affiliation(s)
- Toshio Kaneda
- Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
| | - Farida Ifadotunnikmah
- Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
| | - Alfarius Eko Nugroho
- Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
| | - Sae Koshikawa
- Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
| | - Sasaki Tadahiro
- Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
| | - Yusuke Hirasawa
- Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
| | - Hiroshi Morita
- Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
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Yang S, Zhang J, Chen D, Ding J, Zhang Y, Song L. Quercetin Supplement to Aspirin Attenuates Lipopolysaccharide-Induced Pre-eclampsia-Like Impairments in Rats Through the NLRP3 Inflammasome. Drugs R D 2022; 22:271-279. [PMID: 36136273 DOI: 10.1007/s40268-022-00402-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/16/2022] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Aspirin is a common drug for the treatment of pre-eclampsia. We aimed to explore whether quercetin as a supplement to aspirin could enhance the therapeutic outcome in pre-eclampsia rat models. We further aimed to evaluate the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome as a potential pre-eclampsia-related molecular mechanism, which can be affected by quercetin treatment. METHODS Rat pre-eclampsia models were established using an intravenous lipopolysaccharide injection after gestation. Rats were treated with aspirin and quercetin at 6-18 days after pregnancy. On day 20, blood, fetus, and placenta were harvested. Blood pressure and the level of proteinuria were measured every 4 days. Fetal outcomes were analyzed by pup body weight. Serum soluble Fms-like tyrosine kinase-1, PIGF, interleukin-6, and interleukin-10 levels were measured using the enzyme-linked immunosorbent assay. Caspase-1, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and p-caspase-1 levels in the placenta were assessed using western blot or quantitative real-time polymerase chain reaction analyses. RESULTS Pre-eclampsia rat models showed a pronounced increase in systolic blood pressure and proteinuria after 4 days of pregnancy, while aspirin, quercetin, and aspirin/quercetin combinatory treatment significantly attenuated the blood pressure and proteinuria abnormalities. Notably, the aspirin/quercetin combinatory treatment showed the highest efficacy in attenuating pre-eclampsia-like symptoms. Placental caspase-1 and NLRP3 levels also showed the greatest attenuation in pre-eclampsia rats after aspirin/quercetin treatment. CONCLUSIONS Our data suggested that quercetin supplementation to aspirin is more effective in attenuating symptoms of pre-eclampsia and improving pregnancy outcomes compared with quercetin or aspirin alone. Quercetin can ameliorate placental NLRP3 inflammasome activation, which might serve as an underlying mechanism for its therapeutic efficacies in pre-eclampsia.
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Affiliation(s)
- Shuangyan Yang
- Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China.
| | - Junfeng Zhang
- Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China.
| | - Dan Chen
- Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China
| | - Jie Ding
- Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China
| | - Yanhong Zhang
- Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China
| | - Lili Song
- Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China
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Vasorelaxant Effect of Trachelospermi caulis Extract on Rat Mesenteric Resistance Arteries. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27165300. [PMID: 36014534 PMCID: PMC9413539 DOI: 10.3390/molecules27165300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 06/13/2022] [Accepted: 08/17/2022] [Indexed: 12/04/2022]
Abstract
Background: Trachelospermi caulis (T. caulis) has been used as a traditional herbal medicine in Asian countries. Although it is well known that T. caulis has beneficial effects, no sufficient research data are available on the cardiovascular effect of T. caulis. We investigated whether T. caulis extract has vascular effects in rat resistance arteries in this study. Methods: To examine whether T. caulis extract affects vascular reactivity, we measured isometric tension of rat mesenteric resistance arteries using a multi-wire myograph system. T. caulis extract was administered after arteries were pre-contracted with high K+ (70 mM) or phenylephrine (5 µM). Vanillin, a single active component of T. caulis, was used to treat mesenteric arteries. Results: T. caulis extract caused vascular relaxation in a concentration-dependent manner, which was endothelium-independent. To further identify the mechanism, we incubated the arteries in Ca2+-free solution containing high K+, followed by a cumulative administration of CaCl2 (0.01–2.0 mM) with or without T. caulis extract (250 µg/mL). The treatment of T. caulis extract decreased contractile responses induced by the addition of Ca2+, which suggested that the extracellular Ca2+ influx was inhibited by the T. caulis extract. Moreover, an active compound of T. caulis extract, vanillin, also induced vasodilation in mesenteric resistance arteries. Conclusion: T. caulis extract and its active compound, vanillin, concentration-dependently induced vascular relaxation in mesenteric resistance arteries. These results suggest that the administration of T. caulis extract could help decrease blood pressure.
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Vasodilatory Effect of Alpinia officinarum Extract in Rat Mesenteric Arteries. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27092711. [PMID: 35566064 PMCID: PMC9104054 DOI: 10.3390/molecules27092711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 04/18/2022] [Accepted: 04/20/2022] [Indexed: 11/24/2022]
Abstract
Background: Alpinia officinarum (A. officinarum) is known to exhibit a beneficial effect for anti-inflammatory, anti-oxidant, and anti-hyperlipidemic effects. However, no sufficient research data are available on the cardiovascular effect of A. officinarum. Thus, in this study, we investigate whether A. officinarum extract has direct effects on vascular reactivity. Methods: To examine whether A. officinarum extract affects vascular functionality, we measured isometric tension in rat mesenteric resistance arteries using a wire myograph. After arteries were pre-contracted with high-K+ (70 mM), phenylephrine (5 µM), or U46619 (1 µM), A. officinarum extract was treated. Results: A. officinarum extract induced vasodilation in a concentration-dependent manner, and this effect was endothelium independent. To further investigate the mechanism, we incubated arteries in a Ca2+-free and high-K+ solution, followed by the cumulative addition of CaCl2 (0.01–2.5 mM) with or without A. officinarum extract (30 µg/mL). Pre-treatment of A. officinarum extract reduced the contractile responses induced by cumulative administration of Ca2+, which suggests that extracellular Ca2+ influx was inhibited by the treatment of A. officinarum extract. These results were associated with a reduction in phosphorylated MLC20 in VSMCs treated with A. officinarum extract. Furthermore, eucalyptol, an active compound of A. officinarum extract, had a similar effect as A. officinarum extract, which causes vasodilation in mesenteric resistance arteries. Conclusion: A. officinarum extract and its active compound eucalyptol induce concentration-dependent vasodilation in mesenteric resistance arteries. These results suggest that administration of A. officinarum extract could exert beneficial effects to treat high blood pressure.
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Cabral B, Gonçalves TAF, Abreu LS, Andrade AWL, de Azevedo FDLAA, de Castro FD, Tavares JF, Guerra GCB, de Rezende AA, de Medeiros IA, Zucolotto SM. Cardiovascular Effects Induced by Fruit Peels from Passiflora edulis in Hypertensive Rats and Fingerprint Analysis by HPLC-ESI-MSn spectrometry. PLANTA MEDICA 2022; 88:356-366. [PMID: 34344056 DOI: 10.1055/a-1385-8863] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Hypertension is a chronic disease and a global health problem. Due to its high prevalence, it constitutes the most important risk factor for cardiovascular disease. Fruit peels from Passiflora edulis fo. flavicarpa are rich in bioactive natural compounds that may have action in hypertension. This study aimed to perform a fingerprinting analysis of Passiflora edulis fruit peel extract and evaluate its actions on the cardiovascular system in an in vivo model. The extract was obtained from the dried and powdered fruit peels of Passiflora edulis. Glycoside flavonoids were identified in the extract by HPLC-ESI-MSn. The extract showed a significant hypotensive effect after 28 days of treatment and improved vascular function in the mesenteric artery. This effect was verified by decreased vascular hypercontractility and increased vasorelaxant in response to sodium nitroprusside and acetylcholine. There was also a decrease in endothelial dysfunction, which can be attributed to nitric oxide's increased bioavailability. Thus, we hypothesize that all these effects contributed to a reduction in peripheral vascular resistance, leading to a significant hypotensive effect. These results are novel for fruit peels from P. edulis. Also, there was a decrease in plasma and cardiac malondialdehyde levels and an increase in glutathione, suggesting a reduction in oxidative stress, as well as an increase of anti-inflammatory cytokines such as IL-10 in the plasma. This study demonstrated that the extract can be a new source of raw material to be applied as food or medicine adjuvant for treating hypertension.
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Affiliation(s)
- Bárbara Cabral
- Research Group on Bioactive Natural Products (PNBio), Laboratory of Pharmacognosy, Postgraduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Norte (UFRN), Natal, RN, Brazil
| | | | - Lucas Silva Abreu
- Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, PB, Brazil
| | - Anderson Wilbur Lopes Andrade
- Department of Biophysics and Pharmacology, Center for Biosciences, Federal University of Rio Grande do Norte, Natal, Brazil
| | | | - Francker Duarte de Castro
- Research Group on Bioactive Natural Products (PNBio), Laboratory of Pharmacognosy, Postgraduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Norte (UFRN), Natal, RN, Brazil
| | - Josean Fechine Tavares
- Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, PB, Brazil
| | - Gerlane Coelho Bernardo Guerra
- Department of Biophysics and Pharmacology, Center for Biosciences, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Adriana Augusto de Rezende
- Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil
| | | | - Silvana Maria Zucolotto
- Research Group on Bioactive Natural Products (PNBio), Laboratory of Pharmacognosy, Postgraduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Norte (UFRN), Natal, RN, Brazil
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Loh YC, Chan SY, Oo CW, Yam MF. Discovery of trans-3,4,4'-trihydroxystilbene as new lead vasorelaxant agent for antihypertensive drug development. Life Sci 2021; 278:119560. [PMID: 33915131 DOI: 10.1016/j.lfs.2021.119560] [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: 01/05/2021] [Revised: 04/08/2021] [Accepted: 04/22/2021] [Indexed: 11/23/2022]
Abstract
AIMS The structure-vasorelaxant activity relationships (SARs) assessment in previous study has found that trans-3,4,4'-trihydroxystilbene (344OH) could potentially act as a vasorelaxing agent with demonstration of over 2-fold maximal relaxation (Rmax) compared to its analogue, resveratrol. The present study focuses on the mechanism of actions and pathways employed by 344OH and compared to its analogue to further speculate the SAR of stilbenoids towards vasorelaxation. MATERIALS AND METHODS The 344OH employed in present study was synthesized based on the protocol in previous study. The vascular responses towards the cumulative addition of 344OH were evaluated using in vitro rat aortic rings assays. KEY FINDINGS The pEC50 and Rmax values were found to be 4.33 ± 0.05 and 106 ± 3.99%, respectively. Results showed that the vasorelaxation of 344OH were predominated by G-protein-coupled muscarinic- (M3) and β2-adrenergic receptors, followed by PGI2/AC/cAMP- and NO/sGC/cGMP-dependent pathways. It was also identified that 344OH employed voltage-activated- (Kv), calcium-activated- (Kca) and inwardly-rectifying (Kir) potassium channels and act as an antagonist for both VOCC and IP3R while regulating the action potential in the vasculature. SIGNIFICANCE The different position of hydroxyl substituent located in A-ring of the stilbenoid backbone in 344OH compared to resveratrol resulted in a significant difference in mechanistic actions that lead to 344OH's fast-acting and less time-dependent vasorelaxation behaviour. This has substantially increased the potential of 344OH to be developed as an effective antihypertensive drug in future. Present findings further strengthen our inferences where the SARs study approach should be carried out as the mainstream methodology in future drug development research.
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Affiliation(s)
- Yean Chun Loh
- Department of Organic Chemistry, School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
| | - Sock Ying Chan
- Department of Organic Chemistry, School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
| | - Chuan Wei Oo
- Department of Organic Chemistry, School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
| | - Mun Fei Yam
- Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia; College of Pharmacy, Fujian University of Traditional Chinese Medicine, 1 Qiuyanng Road, Shangjie, Minhou, Fuzhou 350122, Fujian, China.
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Ferreira LLDM, Leão VDF, de Melo CM, Machado TDB, Amaral ACF, da Silva LL, Simas NK, Muzitano MF, Leal ICR, Raimundo JM. Ethyl Acetate Fraction and Isolated Phenolics Derivatives from Mandevilla moricandiana Identified by UHPLC-DAD-ESI-MS n with Pharmacological Potential for the Improvement of Obesity-Induced Endothelial Dysfunction. Pharmaceutics 2021; 13:pharmaceutics13081173. [PMID: 34452134 PMCID: PMC8401510 DOI: 10.3390/pharmaceutics13081173] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/21/2021] [Accepted: 07/26/2021] [Indexed: 01/11/2023] Open
Abstract
Endothelial dysfunction in obesity plays a key role in the development of cardiovascular diseases, and it is characterized by increased vascular tonus and oxidative stress. Thus, this study aimed to investigate the vasodilatory and antioxidant activities of Mandevilla moricandiana ethyl acetate fraction and subfractions. Vascular effects were investigated on aorta isolated from control and monosodium glutamate (MSG) induced-obese Wistar rats, and antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) methods. The ethyl acetate fraction (MMEAF) induced a concentration-dependent vasodilation on aortic rings through the NO pathway, with the involvement of histamine H1 and estrogen ERα receptors and showed potent antioxidant activity. In aorta of MSG obese rats, maximal relaxation to acetylcholine was increased in the presence of MMEAF (3 µg/mL), indicating that MMEAF ameliorated obesity-induced endothelial dysfunction. Quercetin and kaempferol aglycones and their correspondent glycosides, as well as caffeoylquinic acid derivatives, A-type procyanidin trimer, ursolic and oleanolic triterpenoid acids were identified in subfractions from MMEAF and seem to be the metabolites responsible for the vascular and antioxidant activities of this fraction.
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Affiliation(s)
- Leticia L. D. M. Ferreira
- Pharmacology of Bioactive Products Research Group, Federal University of Rio de Janeiro—Macaé Campus, Macaé 27930-560, RJ, Brazil; (L.L.D.M.F.); (V.d.F.L.); (C.M.d.M.); (L.L.d.S.)
- Laboratory of Natural Products and Biological Assays, Pharmacy Faculty, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil;
| | - Valéria de F. Leão
- Pharmacology of Bioactive Products Research Group, Federal University of Rio de Janeiro—Macaé Campus, Macaé 27930-560, RJ, Brazil; (L.L.D.M.F.); (V.d.F.L.); (C.M.d.M.); (L.L.d.S.)
| | - Cinthya M. de Melo
- Pharmacology of Bioactive Products Research Group, Federal University of Rio de Janeiro—Macaé Campus, Macaé 27930-560, RJ, Brazil; (L.L.D.M.F.); (V.d.F.L.); (C.M.d.M.); (L.L.d.S.)
| | - Thelma de B. Machado
- LAQV-REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal;
- Faculty of Pharmacy, Federal Fluminense University, Niterói 24241-000, RJ, Brazil
| | - Ana Claudia F. Amaral
- Laboratory of Medicinal Plants and Derivatives, Farmanguinhos, Oswaldo Cruz Foundation, Rio de Janeiro 21041-250, RJ, Brazil;
| | - Leandro L. da Silva
- Pharmacology of Bioactive Products Research Group, Federal University of Rio de Janeiro—Macaé Campus, Macaé 27930-560, RJ, Brazil; (L.L.D.M.F.); (V.d.F.L.); (C.M.d.M.); (L.L.d.S.)
| | - Naomi K. Simas
- Laboratory of Natural Products and Biological Assays, Pharmacy Faculty, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil;
| | - Michelle F. Muzitano
- Laboratory of Bioactive Products, Federal University of Rio de Janeiro—Macaé Campus, Macaé 27933-378, RJ, Brazil;
| | - Ivana C. R. Leal
- Laboratory of Natural Products and Biological Assays, Pharmacy Faculty, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil;
- Correspondence: (I.C.R.L.); (J.M.R.); Tel.: +55-21965620428 (I.C.R.L.); +55-2221414019 (J.M.R.)
| | - Juliana M. Raimundo
- Pharmacology of Bioactive Products Research Group, Federal University of Rio de Janeiro—Macaé Campus, Macaé 27930-560, RJ, Brazil; (L.L.D.M.F.); (V.d.F.L.); (C.M.d.M.); (L.L.d.S.)
- Correspondence: (I.C.R.L.); (J.M.R.); Tel.: +55-21965620428 (I.C.R.L.); +55-2221414019 (J.M.R.)
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Sailaja GR, Sriramavaratharajan V, Murugan R, Mallavarapu GR, Chellappan DR. Vasorelaxant property of Plectranthus vettiveroides root essential oil and its possible mechanism. JOURNAL OF ETHNOPHARMACOLOGY 2021; 274:114048. [PMID: 33781875 DOI: 10.1016/j.jep.2021.114048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 02/20/2021] [Accepted: 03/15/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Plectranthus vettiveroides (Jacob) N.P. Singh & B.D. Sharma is a traditional medicinal plant used in Siddha System of Medicine and its aromatic root is used to reduce the elevated blood pressure. AIM The aim of the present study was to study vasorelaxant property of the root essential oil nanoemulsion (EON) of P. vettiveroides. METHODS The EON was formulated to enhance the solubility and bioavailability and characterized. The preliminary screening was performed by treating the EON with aortic rings pre-contracted with phenylephrine (1 μM) and potassium chloride (80 mM). The role of K⁺ channels in EON induced vasorelaxation was investigated by pre-incubating the aortic rings with different K⁺ channel inhibitors namely, glibenclamide (a non-specific ATP sensitive K⁺ channel blocker, 10 μM), TEA (a Ca2⁺ activated non-selective K⁺ channel blocker, 10-2 M), 4-AP (a voltage-activated K⁺ channel blocker, 10-3 M) and barium chloride (inward rectifier K⁺ channel blocker, 1 mM). The involvement of extracellular Ca2+ was performed by adding cumulative dose of extracellular calcium in the presence and absence of EON and the concentration-response curve (CRC) obtained is compared. Similarly, the role of nitric oxide synthase, muscarinic and prostacyclin receptors on EON induced vasorelaxation were evaluated by pre-incubating the aortic rings with their inhibitors and the CRC obtained in the presence and absence of inhibitor were compared. RESULTS The GC-MS and GC-FID analyses of the root essential oil revealed the presence of 62 volatile compounds. The EON exhibited significant vasorelaxant effect through nitric oxide-mediated pathway, G-protein coupled muscarinic (M3) receptor pathway, involvement of K+ channels (KATP, KIR, KCa), and blocking of the calcium influx by receptor-operated calcium channel. CONCLUSION It is concluded that the root essential oil of P. vettiveroides is possessing marked vasorelaxant property. The multiple mechanisms of action of the essential oil of P. vettiveroides make it a potential source of antihypertensive drug.
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Affiliation(s)
- Govinda Rajan Sailaja
- School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, 613 401, Tamil Nadu, India
| | | | - Ramar Murugan
- Centre for Research and Postgraduate Studies in Botany, Ayya Nadar Janaki Ammal College (Autonomous), Sivakasi, 626 124, Tamil Nadu, India
| | - Gopal Rao Mallavarapu
- Flat No. 602, A-Block, Renaissance Temple Bells, Opp. ISKCON Temple, Yeshwantpur, Bengaluru, 560 022, Karnataka, India
| | - David Raj Chellappan
- Central Animal Facility, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, 613 401, Tamil Nadu, India.
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Sherikar A, Dhavale R, Bhatia M. Vasorelaxant Effect of Novel Nitric Oxide-Hydrogen Sulfide Donor Chalcone in Isolated Rat Aorta: Involvement of cGMP Mediated sGC and Potassium Channel Activation. Curr Mol Pharmacol 2021; 13:126-136. [PMID: 31654520 DOI: 10.2174/1874467212666191025092346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 10/03/2019] [Accepted: 10/15/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND AND OBJECTIVE Recently, nitric oxide (NO) and hydrogen sulfide (H2S) donating moieties were extensively studied for their role in the vasculature as they are responsible for many cellular and pathophysiological functioning. The objective of the present study is to evaluate novel NO and H2S donating chalcone moieties on isolated rat aorta for vasorelaxation, and to investigate the probable mechanism of action. METHODS To extend our knowledge of vasorelaxation by NO and H2S donor drugs, here we investigated the vasorelaxing activity of novel NO and H2S donating chalcone moieties on isolated rat aorta. The mechanism of vasorelaxation by these molecules was investigated by performing in vitro cGMP mediated sGC activation assay and using Tetraethylammonium chloride (TEA) as a potassium channel blocker and Methylene blue as NO blocker. RESULTS Both NO and H2S donating chalcone moieties were found to be potent vasorelaxant. The compound G4 and G5 produce the highest vasorelaxation with 3.716 and 3.789 M of pEC50, respectively. After the addition of TEA, G4 and G5 showed 2.772 and 2.796 M of pEC50, respectively. The compounds Ca1, Ca2, and D7 produced significant activation and release of cGMP mediated sGC which was 1.677, 1.769 and 1.768 M of pEC50, respectively. CONCLUSION The vasorelaxation by NO-donating chalcones was blocked by Methylene blue but it did not show any effect on H2S donating chalcones. The vasorelaxing potency of NO-donating molecules was observed to be less affected by the addition of TEA but H2S donors showed a decrease in both efficacy and potency. The cGMP release was more in the case of NO-donating molecules. The tested compounds were found potent for relaxing vasculature of rat aorta.
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Affiliation(s)
- Amol Sherikar
- Department of Pharmaceutical Chemistry, Tatyasaheb Kore College of Pharmacy, Warananagar, Tal-Panhala, Dist- Kolhapur-416 113 (MS), India
| | - Rakesh Dhavale
- Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, Near Chitranagri, Kolhapur-416 013 (MS), India
| | - Manish Bhatia
- Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, Near Chitranagri, Kolhapur-416 013 (MS), India
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Zheng CB, Gao WC, Pang PP, Ma X, Peng LC, Yang L, Li X. Synthesis and vasorelaxant evaluation of novel 7-methoxyl-2,3-disubstituted-quinoxaline derivatives. Bioorg Med Chem Lett 2021; 36:127785. [PMID: 33444740 DOI: 10.1016/j.bmcl.2021.127785] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/11/2020] [Accepted: 01/05/2021] [Indexed: 01/02/2023]
Abstract
An array of novel 7-methoxyl-2,3-disubstituted quinoxaline derivatives was designed, synthesized and their potential antihypertensive activities were examined, in an attempt to discover potent small molecules with vasorelaxant effects. The vasoactivities of these compounds on vascular tone, as well as underlying mechanisms were hereby explored. Results showed that five compounds (7s, 7t, 7v, 7w, 7γ) could induce endothelium-independent relaxation in high extracellular K+- and phenylephrine-precontracted C57 mice aortic rings. These five compounds, unlike other commonly used vasodilators, could slowly but effectively inhibit vasoconstriction.
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Affiliation(s)
- Chang-Bo Zheng
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China
| | - Wen-Cong Gao
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China
| | - Pan-Pan Pang
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China
| | - Xin Ma
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China
| | - Li-Chun Peng
- School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China
| | - Liang Yang
- Key Laboratory of Chemical Biology (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Science, Shandong University, Ji'nan, Shandong 250012, China
| | - Xun Li
- Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan, Shandong 250002, China.
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Secondary Metabolites of Plants as Modulators of Endothelium Functions. Int J Mol Sci 2021; 22:ijms22052533. [PMID: 33802468 PMCID: PMC7959468 DOI: 10.3390/ijms22052533] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/20/2021] [Accepted: 02/25/2021] [Indexed: 12/31/2022] Open
Abstract
According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time—from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide–cyclic guanosine monophosphate activation, prostacyclin–cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.
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Natural Compounds for the Prevention and Treatment of Cardiovascular and Neurodegenerative Diseases. Foods 2020; 10:foods10010029. [PMID: 33374186 PMCID: PMC7824130 DOI: 10.3390/foods10010029] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 12/15/2020] [Accepted: 12/22/2020] [Indexed: 12/12/2022] Open
Abstract
Secondary metabolites from plants and fungi are stimulating growing interest in consumers and, consequently, in the food and supplement industries. The beneficial effects of these natural compounds are being thoroughly studied and there are frequent updates about the biological activities of old and new molecules isolated from plants and fungi. In this article, we present a review of the most recent literature regarding the recent discovery of secondary metabolites through isolation and structural elucidation, as well as the in vitro and/or in vivo evaluation of their biological effects. In particular, the possibility of using these bioactive molecules in the prevention and/or treatment of widely spread pathologies such as cardiovascular and neurodegenerative diseases is discussed.
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In vitro study and structure-activity relationship analysis of stilbenoid derivatives as powerful vasorelaxants: Discovery of new lead compound. Bioorg Chem 2020; 104:104239. [DOI: 10.1016/j.bioorg.2020.104239] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 08/03/2020] [Accepted: 08/09/2020] [Indexed: 12/17/2022]
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Dias FCR, Gomes MDLM, Melo FCSAD, Menezes TP, Martins AL, Cupertino MDC, Otoni WC, Matta SLPD. Pfaffia glomerata hydroalcoholic extract stimulates penile tissue in adult Swiss mice. JOURNAL OF ETHNOPHARMACOLOGY 2020; 261:113182. [PMID: 32730872 DOI: 10.1016/j.jep.2020.113182] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/15/2020] [Accepted: 07/12/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Roots of Pfaffia glomerata are used in traditional medicine as aphrodisiacs and sexual stimulants. AIM OF THE STUDY The aim of this study was to evaluate the action of the hydroalcoholic extract from the roots of Pfaffia glomerata on the Leydig cells, cavernous bodies and other penile constituents, as well as on serum testosterone and 17β-estradiol levels of adult mice. MATERIALS AND METHODS Mature male Swiss mice were divided into 6 groups: control (water), sildenafil citrate, 3 groups receiving daily doses of P. glomerata extract (100, 200 and 400 mg/kg) and one group receiving intermittent doses of P. glomerata (200 mg/kg/3-3d). RESULTS The proportions of blood vessels, lymphatic space and estradiol levels were increased. On the other hand, reduction of testosterone levels due to Leydig cells death was observed. As for penile parameters, volumetric proportions of cavernous bodies, collagen and nitric oxide were increased, while smooth muscle content was decreased. CONCLUSIONS Despite that the long term intake of P. glomerata extract was related to a stimulant action, reduction on Leydig cell viability induced decreased testosterone production.
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Affiliation(s)
- Fernanda Carolina Ribeiro Dias
- Department of General Biology, Federal University of Viçosa, Peter Henry Rolfs Avenue S/n, 36570-900, Viçosa, MG, Brazil; Department of Structural Biology, Federal University of Triângulo Mineiro, Praça Manoel Terra, 330, 38025-015, Uberaba, MG, Brazil
| | - Marcos de Lucca Moreira Gomes
- Department of Structural Biology, Federal University of Triângulo Mineiro, Praça Manoel Terra, 330, 38025-015, Uberaba, MG, Brazil.
| | | | - Tatiana Prata Menezes
- Department of General Biology, Federal University of Viçosa, Peter Henry Rolfs Avenue S/n, 36570-900, Viçosa, MG, Brazil
| | - Ana Luiza Martins
- Department of General Biology, Federal University of Viçosa, Peter Henry Rolfs Avenue S/n, 36570-900, Viçosa, MG, Brazil
| | - Marli do Carmo Cupertino
- Department of General Biology, Federal University of Viçosa, Peter Henry Rolfs Avenue S/n, 36570-900, Viçosa, MG, Brazil
| | - Wagner Campos Otoni
- Department of Plant Biology, Federal University of Viçosa, Peter Henry Rolfs Avenue S/n, 36570-900, Viçosa, MG, Brazil
| | - Sérgio Luis Pinto da Matta
- Department of General Biology, Federal University of Viçosa, Peter Henry Rolfs Avenue S/n, 36570-900, Viçosa, MG, Brazil
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Moringa oleifera leaf extract enhances endothelial nitric oxide production leading to relaxation of resistance artery and lowering of arterial blood pressure. Biomed Pharmacother 2020; 130:110605. [PMID: 32781358 DOI: 10.1016/j.biopha.2020.110605] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 08/02/2020] [Accepted: 08/02/2020] [Indexed: 12/14/2022] Open
Abstract
A mass of evidence has identified a promoting of nitric oxide (NO) production in endothelial cells using natural products as a potential strategy to prevent and treat hypertension. This study investigated whether the aqueous extract of Moringa oleifera leaves (MOE) could lower mean arterial pressure (MAP) and relax mesenteric arterial beds in rats via stimulating endothelium-derived NO production. Intravenous administration of MOE (1-30 mg/kg) caused a dose-dependent reduction in MAP in anesthetized rats. In rats pretreated with the NO-synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg, i.v.), the effect of MOE on MAP was significantly reduced. MOE (0.001-3 mg) induced relaxation in methoxamine (10 μM) pre-contracted mesenteric arterial beds, which was abolished by endothelium denudation. This endothelium-dependent vasorelaxation was reduced by L-NAME (100 μM) or the NO-sensitive guanylyl cyclase inhibitor, 1H- [1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (10 μM). In primary human pulmonary artery endothelial cells, MOE (3-30 μg/mL) induced NO production, which was inhibited by L-NAME (100 μM) pretreatment. These findings show that MOE stimulates the endothelium-derived NO release for driving its vasorelaxation to lower arterial blood pressure. These suggest the development of MOE as a natural antihypertensive supplement.
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Septembre-Malaterre A, Lalarizo Rakoto M, Marodon C, Bedoui Y, Nakab J, Simon E, Hoarau L, Savriama S, Strasberg D, Guiraud P, Selambarom J, Gasque P. Artemisia annua, a Traditional Plant Brought to Light. Int J Mol Sci 2020; 21:E4986. [PMID: 32679734 PMCID: PMC7404215 DOI: 10.3390/ijms21144986] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/10/2020] [Accepted: 07/13/2020] [Indexed: 12/23/2022] Open
Abstract
Traditional remedies have been used for thousand years for the prevention and treatment of infectious diseases, particularly in developing countries. Of growing interest, the plant Artemisia annua, known for its malarial properties, has been studied for its numerous biological activities including metabolic, anti-tumor, anti-microbial and immunomodulatory properties. Artemisia annua is very rich in secondary metabolites such as monoterpenes, sesquiterpenes and phenolic compounds, of which the biological properties have been extensively studied. The purpose of this review is to gather and describe the data concerning the main chemical components produced by Artemisia annua and to describe the state of the art about the biological activities reported for this plant and its compounds beyond malaria.
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Affiliation(s)
- Axelle Septembre-Malaterre
- Unité de recherche Etudes Pharmaco-Immunologie (EPI), Université de La Réunion, CHU La Réunion site Félix Guyon, Allée des Topazes, CS11021, 97400 Saint Denis de La Réunion, France; (P.G.); (J.S.); (P.G.)
| | - Mahary Lalarizo Rakoto
- Faculté de Médecine, Université d’Antananarivo, Campus Universitaire Ambohitsaina, BP 375, Antananarivo 101, Madagascar;
| | - Claude Marodon
- APLAMEDOM Réunion, 1, rue Emile Hugot, Batiment B, Parc Technologique de Saint Denis, 97490 Sainte Clotilde, La Réunion, France; (C.M.); (J.N.); (E.S.); (L.H.)
| | - Yosra Bedoui
- INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Université de La Réunion, 97400 Saint Denis de La Réunion, France;
| | - Jessica Nakab
- APLAMEDOM Réunion, 1, rue Emile Hugot, Batiment B, Parc Technologique de Saint Denis, 97490 Sainte Clotilde, La Réunion, France; (C.M.); (J.N.); (E.S.); (L.H.)
| | - Elisabeth Simon
- APLAMEDOM Réunion, 1, rue Emile Hugot, Batiment B, Parc Technologique de Saint Denis, 97490 Sainte Clotilde, La Réunion, France; (C.M.); (J.N.); (E.S.); (L.H.)
| | - Ludovic Hoarau
- APLAMEDOM Réunion, 1, rue Emile Hugot, Batiment B, Parc Technologique de Saint Denis, 97490 Sainte Clotilde, La Réunion, France; (C.M.); (J.N.); (E.S.); (L.H.)
| | - Stephane Savriama
- EA929 Archéologie Industrielle, Histoire, Patrimoine/Géographie-Développement Environnement de la Caraïbe (AIHP-GEODE), Université des Antilles, Campus Schoelcher, BP7207, 97275 Schoelcher Cedex Martinique, France;
| | - Dominique Strasberg
- Unité Mixte de Recherche Peuplements Végétaux et Bio-agresseurs en Milieu Tropical (PVBMT), Pôle de Protection des Plantes, Université de La Réunion, 7 Chemin de l’IRAT, 97410 Saint-Pierre, La Réunion, France;
| | - Pascale Guiraud
- Unité de recherche Etudes Pharmaco-Immunologie (EPI), Université de La Réunion, CHU La Réunion site Félix Guyon, Allée des Topazes, CS11021, 97400 Saint Denis de La Réunion, France; (P.G.); (J.S.); (P.G.)
| | - Jimmy Selambarom
- Unité de recherche Etudes Pharmaco-Immunologie (EPI), Université de La Réunion, CHU La Réunion site Félix Guyon, Allée des Topazes, CS11021, 97400 Saint Denis de La Réunion, France; (P.G.); (J.S.); (P.G.)
| | - Philippe Gasque
- Unité de recherche Etudes Pharmaco-Immunologie (EPI), Université de La Réunion, CHU La Réunion site Félix Guyon, Allée des Topazes, CS11021, 97400 Saint Denis de La Réunion, France; (P.G.); (J.S.); (P.G.)
- Laboratoire d’immunologie clinique et expérimentale de la zone de l’océan indien (LICE-OI) CHU La Réunion site Félix Guyon, Allée des Topazes, CS11021, 97400 Saint Denis de La Réunion, France
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The bioflavonoid quercetin improves pathophysiology in a rat model of preeclampsia. Biomed Pharmacother 2020; 127:110122. [DOI: 10.1016/j.biopha.2020.110122] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 03/19/2020] [Accepted: 03/27/2020] [Indexed: 01/12/2023] Open
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(-)-Epicatechin Modulates Mitochondrial Redox in Vascular Cell Models of Oxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:6392629. [PMID: 32587663 PMCID: PMC7301192 DOI: 10.1155/2020/6392629] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 03/20/2020] [Accepted: 04/25/2020] [Indexed: 02/07/2023]
Abstract
Diabetes mellitus affects 451 million people worldwide, and people with diabetes are 3-5 times more likely to develop cardiovascular disease. In vascular tissue, mitochondrial function is important for vasoreactivity. Diabetes-mediated generation of excess reactive oxygen species (ROS) may contribute to vascular dysfunction via damage to mitochondria and regulation of endothelial nitric oxide synthase (eNOS). We have identified (–)-epicatechin (EPICAT), a plant compound and known vasodilator, as a potential therapy. We hypothesized that mitochondrial ROS in cells treated with antimycin A (AA, a compound targeting mitochondrial complex III) or high glucose (HG, global perturbation) could be normalized by EPICAT, and correlate with improved mitochondrial dynamics and cellular signaling. Human umbilical vein endothelial cells (HUVEC) were treated with HG, AA, and/or 0.1 or 1.0 μM of EPICAT. Mitochondrial and cellular superoxide, mitochondrial respiration, and cellular signaling upstream of mitochondrial function were assessed. EPICAT at 1.0 μM significantly attenuated mitochondrial superoxide in HG-treated cells. At 0.1 μM, EPICAT nonsignificantly increased mitochondrial respiration, agreeing with previous reports. EPICAT significantly increased complex I expression in AA-treated cells, and 1.0 μM EPICAT significantly decreased mitochondrial complex V expression in HG-treated cells. No significant effects were seen on either AMPK or eNOS expression. Our study suggests that EPICAT is useful in mitigating moderate ROS concentrations from a global perturbation and may modulate mitochondrial complex activity. Our data illustrate that EPICAT acts in the cell in a dose-dependent manner, demonstrating hormesis.
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Loh YC, Chan SY, Tew WY, Oo CW, Yam MF. New flavonoid-based compound synthesis strategy for antihypertensive drug development. Life Sci 2020; 249:117512. [PMID: 32145305 DOI: 10.1016/j.lfs.2020.117512] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 02/22/2020] [Accepted: 03/02/2020] [Indexed: 12/27/2022]
Abstract
Hypertension is one of the leading causes of mortality in relation to the cardiovascular conditions and easily the most overlooked and poorly managed disease in mankind. With well over 200 drugs available in the market globally, there is still an urgency to search for antihypertensive alternatives due to the subpar efficacy and unwarranted side effects of the current choices. Present studies reported over 250 types of plant-derived compounds were being investigated for potential pharmacological effects on the vasculature in the last 3 decades. There were numerous literatures that claimed various compounds exhibiting vasorelaxant properties to a certain extent with low numbers of these compounds being successfully adapted into the current medicinal practice for treatment of hypertension. The issue is the scarcity of reviews that summarizes the discovery of this field and the lack of thorough comparison of these compounds to identify which of these vasodilators should be the next face of hypertension management. Thus, this review is aiming towards identifying the relationship between a major class of plant-derived compounds, flavonoid's activity as a vasodilator with their signalling pathways and their structural characteristics according to their vasorelaxant properties. Interestingly, we found that both nitric oxide and voltage-operated calcium channels pathways, and two of the flavonoid's structural characteristics play crucial roles in eliciting strong vasorelaxant effects. We have faith that the insights of this review will serve as a reference for those researching similar topics in the future and potentially lead to the development of more promising antihypertensive alternative.
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Affiliation(s)
- Yean Chun Loh
- Department of Organic Chemistry, School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
| | - Sock Ying Chan
- Department of Organic Chemistry, School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
| | - Wan Yin Tew
- Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
| | - Chuan Wei Oo
- Department of Organic Chemistry, School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
| | - Mun Fei Yam
- Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
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Fusi F, Trezza A, Tramaglino M, Sgaragli G, Saponara S, Spiga O. The beneficial health effects of flavonoids on the cardiovascular system: Focus on K+ channels. Pharmacol Res 2020; 152:104625. [DOI: 10.1016/j.phrs.2019.104625] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 12/14/2019] [Accepted: 12/31/2019] [Indexed: 01/17/2023]
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Abdallah HM, Hassan NA, El-Halawany AM, Mohamed GA, Safo MK, El-Bassossy HM. Major flavonoids from Psiadia punctulata produce vasodilation via activation of endothelial dependent NO signaling. J Adv Res 2020; 24:273-279. [PMID: 32382447 PMCID: PMC7200196 DOI: 10.1016/j.jare.2020.01.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 01/01/2020] [Accepted: 01/02/2020] [Indexed: 12/11/2022] Open
Abstract
Methanol extract of Psiadia punctulata (MAPP) produced a significant vasodilation. Chloroform fraction and its methylated flavonoids were responsible for this effect. Vasodilation is referred to endothelial nitric oxide and, Ca2+ dependent eNOS. Interference with calcium entrance is another possible mechanism of vasodilation. Vasodilators are important pharmacologic agents for managing and/or treating hypertension. Medicinal plants are considered as valuable source of bioactive compounds. We used a bioguided approach to isolate, identify, and investigate the possible vasodilation activities and mechanism(s) of the prepared methanol extract from aerial parts of Psiadia punctulata (MAPP), its bioactive fraction and active compounds. Vascular effects of MAPP were studied using isolated artery technique in the presence or absence of specific candidate pathways inhibitors, and found to produce a significant vasodilation of phenylephrine preconstricted rat aortae. The bioactive chloroform fraction yielded five methoxylated flavonoids: umuhengerin (1), gardenin A (2), gardenin B (3), luteolin-3′,4′ -dimethyl ether (4), and 5,3′-dihydroxy-6,7,4′,5′-tetramethoxyflavone (5). Metabolites 1, 4, and 5 produced a significant vasodilation. Removal of the endothelium significantly inhibited MAPP vasodilation. Nitric oxide synthase inhibition and not prostacycline inhibition or K+ channel blocking, was found to cause the observed vasodilation inhibition. Both guanylate cyclase and adenylate cyclase inhibitions markedly inhibited MAPP vasodilation. In conclusion MAPP possesses vasodilation activities that is mediated through endothelial nitric oxide pathway, calcium dependent endothelial nitric oxide synthase activation, and interference with the depolarization process through calcium channel blocking activity.
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Key Words
- AC, adenylate cyclase
- Ca2+, calcium
- CaM, calmodulin
- CaMKII, Ca2+/calmodulin-dependent protein kinase II
- Endothelial nitric oxide
- Flavonoids
- GTP, guanosine triphosphate
- Hypertension
- L-NAME, Nω-nitro-L-arginine methyl ester
- MAPP, methanol extract from aerial parts of Psiadia punctulata
- MDL, cis-N-(2-Phenylcyclopentyl)azacyclotridec-1-en-2-amine.HCl (MDL-12, 330A)
- NO, nitric oxide
- NOS, nitric oxide synthase
- ODQ, 1H-(1,2,4)-oxadiazolo(4,3-a)quinoxalin-1-one
- PE, phenylephrine
- PI3K, phosphoinositide 3-kinase
- PKG, protein kinase G
- PP, Psiadia punctulata
- Psiadia punctulata
- TEA, tetraethylammonium chloride
- VSMCs, vascular smooth muscle cells
- Vasodilator
- cGMP, cyclic guanosine monophosphate
- eNOS, endothelial nitric oxide synthase
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Affiliation(s)
- Hossam M Abdallah
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.,Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Noura A Hassan
- Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Ali M El-Halawany
- Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Gamal A Mohamed
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.,Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assuit Branch, Assuit 71524, Egypt
| | - Martin K Safo
- Department of Medicinal Chemistry, Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy, Virginia Commonwealth University, VA 23219, USA
| | - Hany M El-Bassossy
- Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
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Cherfia R, Zaiter A, Akkal S, Chaimbault P, Abdelwahab AB, Kirsch G, Kacem Chaouche N. New approach in the characterization of bioactive compounds isolated from Calycotome spinosa (L.) Link leaves by the use of negative electrospray ionization LITMS n, LC-ESI-MS/MS, as well as NMR analysis. Bioorg Chem 2019; 96:103535. [PMID: 32000017 DOI: 10.1016/j.bioorg.2019.103535] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 12/13/2019] [Accepted: 12/20/2019] [Indexed: 02/06/2023]
Abstract
Two novel compounds were isolated for the first time from Calycotome spinosa (L.) Link, an alkaloid 5-Hydroxy-1H-indole (4) and a cyclitol D-pinitol (5), together with the three well-known flavonoids; Chrysin-7-O-(β-D-glucopyranoside) (1), Chrysin-7-O-β-D-(6″-acetyl)glycopyranoside (2) and Apigenin-7-O-β-D-glycopyranoside (3). The chemical structures of the isolated compounds were elucidated by spectroscopic data and mass spectrometric analyses; including a fresh approach 1D-NMR, 2D-NMR with LC-ESI-MS/MS. In this study, the new compound (4) that has been obtained from the leaves MeOH extract presented the best radical scavenging activity (DPPH) (IC50 < 10 µg/mL) compared to the standard butylated hydroxytoluene (BHT, IC50 = 34.73 ± 0.23 μg/mL) and showed the highest total antioxidant capacity (TAC = 985.54 ± 0.13 mg AAE/g extract) in contrast to ascorbic acid (TAC = 905.95 ± 0.07 mg AAE/g extract). Furthermore, the strongest reducing power (EC50 = 344.82 ± 0.02 µg/mL), as well as the remarkable scavenging potential by ABTS assay (IC50 = 7.8 ± 0.43 µg/mL), were exhibited by the same composite (4). Followed by the methanol crude extract and the compound (3) that also showed a potent antioxidant (DPPH; IC50 = 41.04 ± 0.15 and 47.36 ± 0.21 µg/mL, TAC; 671.02 ± 0.21 and 608.67 ± 0.34 mg AAE/g extract, FRAP; EC50 = 763.73 ± 0.32 and 814.61 ± 0.31 µg/mL, ABTS; IC50 = 19.18 ± 0.06 and 63.72 ± 0.64 µg/mL, respectively), but less than the previous samples. On the opposite side, compound (5) had the lowest activity, in which its values were less interesting to determine. Moreover, compound (4) has equally exerted an attractive antibacterial activity against Staphylococcus aureus (ATTC-25923), Pseudomonas aeruginosa (ATTC- 27853) and Salmonella abony (NCTC 6017), as measured by the disc diffusion assay, with inhibition zones of 16 ± 0.5, 9.83 ± 0.29 and 8 ± 0.28 mm, in that order. To the best of our knowledge, 5-Hydroxy-1H-indole was isolated from plants for the second time in our current work. Thus, the obtained results from this investigation propose that the leaves of C. spinosa are a rich natural source for value molecules as potential antioxidants and antimicrobial agents for best human health.
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Affiliation(s)
- Radia Cherfia
- Laboratoire de Mycologie, de Biotechnologie et de l'Activité Microbienne (LaMyBAM), Département de Biologie Appliquée, Université des Frères Mentouri, Constantine1, BP, 325 Route de Aïn El Bey, Constantine 25017, Algeria.
| | - Ali Zaiter
- Laboratoire de Chimie et Physique-Approche Multi-échelles des Milieux Complexes (LCP-A2MC), Université de Lorraine -METZ- France Boulevard Arago, Metz Technopole Cedex 03 F-57078, France
| | - Salah Akkal
- Laboratoire de Phytochimie et Analyses Physico-chimiques et Biologiques, Université des Frères Mentouri, Constantine 1, Route de Aïn El Bey, Constantine 25017, Algeria
| | - Patrick Chaimbault
- Laboratoire de Chimie et Physique-Approche Multi-échelles des Milieux Complexes (LCP-A2MC), Université de Lorraine -METZ- France Boulevard Arago, Metz Technopole Cedex 03 F-57078, France
| | - Ahmed Bakr Abdelwahab
- Laboratoire de Chimie et Physique-Approche Multi-échelles des Milieux Complexes (LCP-A2MC), Université de Lorraine -METZ- France Boulevard Arago, Metz Technopole Cedex 03 F-57078, France
| | - Gilbert Kirsch
- Laboratoire de Chimie et Physique-Approche Multi-échelles des Milieux Complexes (LCP-A2MC), Université de Lorraine -METZ- France Boulevard Arago, Metz Technopole Cedex 03 F-57078, France
| | - Noreddine Kacem Chaouche
- Laboratoire de Mycologie, de Biotechnologie et de l'Activité Microbienne (LaMyBAM), Département de Biologie Appliquée, Université des Frères Mentouri, Constantine1, BP, 325 Route de Aïn El Bey, Constantine 25017, Algeria
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Romero F, Palacios J, Jofré I, Paz C, Nwokocha CR, Paredes A, Cifuentes F. Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta. Molecules 2019; 24:molecules24152748. [PMID: 31362388 PMCID: PMC6695676 DOI: 10.3390/molecules24152748] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 05/08/2019] [Accepted: 05/11/2019] [Indexed: 11/16/2022] Open
Abstract
Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. Aristotelia chilensis (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 μM). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 μM) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p < 0.05) decreased. Interestingly, the potassium channel blockade with 10 μM BaCl2 (Kir), 10 μM glibenclamide (KATP), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (p < 0.05) reduced the ARI-induced relaxation. ARI significantly (p < 0.05) reduced the contractile response to agonist of CaV1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway.
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Affiliation(s)
- Fernando Romero
- Vicerrectoría de Investigación y Postgrado, Programa de Doctorado en Ciencias Médicas, Universidad de la Frontera, Temuco 4780000, Chile.
| | - Javier Palacios
- Laboratorio de Bioquímica Aplicada, Departamento de Química y Farmacia, Facultad Ciencias de la Salud, Universidad Arturo Prat, Iquique 1110939, Chile.
| | - Ignacio Jofré
- Laboratorio de Neurociencias y Biología de Péptidos, Centro de Excelencia en Biotecnología de La Reproducción, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile
| | - Cristian Paz
- Laboratorio de Productos Naturales y Descubrimiento de Fármacos, Departamento de Ciencias básicas, Universidad de La Frontera, Temuco 4811230, Chile
| | - Chukwuemeka R Nwokocha
- Department of Basic Medical Sciences Physiology Section, Faculty of Medical Sciences, The University of the West Indies, Mona, Kingston 7, KGN, Jamaica (W.I.)
| | - Adrián Paredes
- Laboratorio de Química Biológica, Instituto Antofagasta, Universidad de Antofagasta, Antofagasta 1270300, Chile
| | - Fredi Cifuentes
- Laboratorio de Fisiología Experimental, Instituto Antofagasta, Universidad de Antofagasta, Antofagasta 1270300, Chile
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Samaha AA, Fawaz M, Salami A, Baydoun S, Eid AH. Antihypertensive Indigenous Lebanese Plants: Ethnopharmacology and a Clinical Trial. Biomolecules 2019; 9:biom9070292. [PMID: 31330767 PMCID: PMC6681041 DOI: 10.3390/biom9070292] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Revised: 07/03/2019] [Accepted: 07/10/2019] [Indexed: 12/14/2022] Open
Abstract
Hypertension is highly prevalent among the Lebanese adult population and is indeed the major cause of mortality in Lebanon. Traditional use of antihypertensive medicinal plants has long been practiced. The aim of this study is to document this traditional knowledge and clinically test the antihypertensive capacity of three of the most commonly used wild plant species Mentha longifolia, Viola odorata and Urtica dioica. Ethno-pharmacological data was collected by personal interviews with herbalists and traditional healers using a semi structured survey questionnaire and assessing relative frequency of citation (RFC). The clinical study was conducted by a randomized, blind, placebo-controlled trial in 29 subjects with mild hypertension distributed in four groups, three plant extract treatments and one placebo. Systolic (SBP) and diastolic blood pressures (DBP) as well as mean arterial blood pressures (MAP) were monitored at weeks 4, 8, 12 and 16 during the treatment with 300 mL/day of plant extract. Results showed that M. longifolia, U. dioica and V. odorata exhibited the highest values of RCF (0.95) followed by Allium ampeloprasum (0.94), Apium graveolens (0.92) and Crataegus azarolus (0.90). The clinical trial revealed dose- and duration-dependent significant reductions in SBP, DBP and MAP of subjects treated with M. longifolia, U. dioica or V. odorata. Our findings indicate that extracts of these plants present an effective, safe and promising potential as a phyto-therapuetical approach for the treatment of mild hypertension. More research on the phytochemistry, pharmacological effects and the underlying mechanisms is necessary.
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Affiliation(s)
- Ali A Samaha
- Lebanese International University, Beirut, P.O. Box 146404, Lebanon
- Faculty of Health Sciences, Beirut Arab University, Beirut, P.O. Box 11-5020, Lebanon
- Lebanese University, Faculty of Public Health IV, Zahle, P.O. Box 6573/14, Lebanon
- Rayak University Hospital, Rayak, P.O. Box 1200, Lebanon
| | - Mirna Fawaz
- Faculty of Health Sciences, Beirut Arab University, Beirut, P.O. Box 11-5020, Lebanon
| | - Ali Salami
- Lebanese University, Rammal Hassan Rammal Research Laboratory, Physio-toxicity (PhyTox) Research Group, Faculty of Sciences (V), Nabatieh, P.O. Box 6573/14, Lebanon
| | - Safaa Baydoun
- Research Center for Environment and Development, Beirut Arab University, Bekaa, P.O. Box 11-5020, Lebanon.
| | - Ali H Eid
- Department of Pharmacology and Toxicology, American University of Beirut, Beirut, P.O. Box 11-0236, Lebanon.
- Department of Biomedical Sciences, Qatar University, Doha, P.O. Box 2713, Qatar.
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Mali DP, Bhatia NM. Hetero-Tricyclic Lead Scaffold as Novel PDE5A Inhibitor for Antihypertensive Activity: In Silico Docking Studies. Curr Comput Aided Drug Des 2019; 15:318-333. [DOI: 10.2174/1573409915666190214161221] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 12/14/2018] [Accepted: 02/07/2019] [Indexed: 12/11/2022]
Abstract
Objective:To screen the phytochemicals for phosphodiesterase 5A (PDE5A) inhibitory potential and identify lead scaffolds of antihypertensive phytochemicals using in silico docking studies.Methods:In this perspective, reported 269 antihypertensive phytochemicals were selected. Sildenafil, a PDE5A inhibitor was used as the standard. In silico docking study was carried out to screen and identify the inhibiting potential of the selected phytochemicals against PDE5A enzyme using vLife MDS 4.4 software.Results:Based on docking score, π-stacking, H-bond and ionic interactions, 237 out of 269 molecules were selected which have shown one or more interactions. Protein residue Gln817A was involved in H-boding whereas Val782A, Phe820A and Leu804A were involved in π-stacking interaction with ligand. The selected 237 phytochemicals were structurally diverse, therefore 82 out of 237 molecules with one or more tricycles were filtered out for further analysis. Amongst tricyclic molecules, 14 molecules containing nitrogen heteroatom were selected for lead scaffold identification which finally resulted in three different basic chemical backbones like pyridoindole, tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline as lead scaffolds.Conclusion:In silico docking studies revealed that nitrogen-containing tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline tricyclic lead scaffolds have emerged as novel PDE5A inhibitors for antihypertensive activity. The identified lead scaffolds may provide antihypertensive lead molecules after its optimization.
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Affiliation(s)
- Dipak P. Mali
- Department of Quality Assurance, Bharati Vidyapeeth College of Pharmacy, Kolhapur, 416013, Maharashtra, India
| | - Neela M. Bhatia
- Department of Quality Assurance, Bharati Vidyapeeth College of Pharmacy, Kolhapur, 416013, Maharashtra, India
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Aguilera-Méndez A, Espino-García R, Toledo-López ZJ, Hernández-Gallegos Z, Villafaña-Rauda S, Nieto-Aguilar R, Serrato-Ochoa D, Manuel-Jacobo GC. Biotin improves relaxation of rat aortic rings in combination with antihypertensive drugs. PHARMANUTRITION 2019. [DOI: 10.1016/j.phanu.2019.100147] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Sherikar A, Dhavale R, Bhatia M. Investigation of anti-inflammatory, nitric oxide donating, vasorelaxation and ulcerogenic activities of 1, 3-diphenylprop-2-en-1-one derivatives in animal models. Clin Exp Pharmacol Physiol 2019; 46:483-495. [PMID: 30714176 DOI: 10.1111/1440-1681.13069] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 12/26/2018] [Accepted: 01/29/2019] [Indexed: 12/16/2022]
Abstract
The main aim of this work is to find out novel chemical moieties with potent anti-inflammatory and vasorelaxant activities with reduced gastric toxicities. For fulfilling the above aim, here we investigated novel chalcones (1, 3-diphenylprop-2-en-1-one derivatives) with nitric oxide (NO) and hydrogen sulphide (H2 S) donating potency for anti-inflammatory activity by carrageenan-induced rat paw oedema. These molecules then further evaluated for in-vitro NO-releasing potency and vasorelaxation effect on isolated adult goat aortic tissue. The promising molecules were further screened for ulcerogenic activity in the rat model. The tested compounds produced % inhibition in paw oedema ranging from 29.16% to 79.69% and standard drug Diclofenac sodium produced 85.30% reduction in paw oedema after 5 hours. Out of this dataset, compounds AI1, AI7, Ca1, B2, B10, D2, and E8 showed 73.01%, 79.69%, 75.02%, 75.46%, 74.35%, 73.9% and 74.35% reduction in paw oedema respectively, which is approximately 80%-90% to that of standard Diclofenac sodium. The compound Ca1 was found to release 0.870 ± 0.025 mol/mol of NO and standard Glyceryl trinitrate (GTN) was found to release 0.983 ± 0.063 mol/mol of NO. The compound Ca1 produced 950.2 μmol/L of EC50 whereas standard GTN produced 975.8 μmol/L of EC50 for aortic smooth relaxation. The compounds Ca1 produced 0.1117 of ulcer index which is far less than that of standard Diclofenac sodium (1.148). The potent lead molecules were further evaluated to understand the mechanism of vasorelaxation by using specific antagonists or blockers of NO and H2 S.
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Affiliation(s)
- Amol Sherikar
- Department of Pharmaceutical Chemistry, Tatyasaheb Kore College of Pharmacy, Warananagar, India
| | - Rakesh Dhavale
- Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, India
| | - Manish Bhatia
- Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, India
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8-Oxo-9-Dihydromakomakine Isolated from Aristotelia chilensis Induces Vasodilation in Rat Aorta: Role of the Extracellular Calcium Influx. Molecules 2018; 23:molecules23113050. [PMID: 30469451 PMCID: PMC6278248 DOI: 10.3390/molecules23113050] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 11/15/2018] [Accepted: 11/17/2018] [Indexed: 02/06/2023] Open
Abstract
8-Oxo-9-dihydromakomakine is a tetracyclic indole alkaloid extracted from leaves of the Chilean tree Aristotelia chilensis. The present study investigated the effects of this alkaloid on vascular response in tissues isolated from aortic segments obtained from normotensive rats. Our results showed that 8-oxo-9-dihydromakomakine induced a dose-dependent relaxation of aortic rings pre-contracted with phenylephrine (PE; 10−6 M). The vasorelaxation induced by 8-oxo-9-dihydromakomakine in rat aortic rings is independent of endothelium. The pre-incubation of aortic rings with 8-oxo-9-dehydromakomakine (10−4 M) significantly reduced the contractile response to KCl (p < 0.001) more than PE (p < 0.05). The highest dose of 8-oxo-9-dehydromakomakine (10−4 M) drastically reduced the contraction to KCl (6·10−2 M), but after that, PE (10−6 M) caused contraction (p < 0.05) in the same aortic rings. The addition of 8-oxo-9-dihydromakomakine (10−5 M) decreased the contractile response to tetraethylammonium (a voltage-dependent potassium channels blocker; TEA; 5 × 10−3 M; p < 0.01) and BaCl2 (a non-selective inward rectifier potassium channel blocker; 5 × 10−3 M; p < 0.001) in rat aorta. 8-oxo-9-dihydromakomakine (10−5 M) decreased the contractile response to PE in rat aorta in the presence or absence of ouabain (an inhibitor of Na,K-ATPase; 10−3 M; p < 0.05). These results could indicate that 8-oxo-9-dihydromakomakine partially reduces plasma membrane depolarization-induced contraction. In aortic rings depolarized by PE, 8-oxo-9-dihydromakomakine inhibited the contraction induced by the influx of extracellular Ca2+ in a Ca2+ free solution (p < 0.01). 8-oxo-9-dihydromakomakine reduced the contractile response to agonists of voltage-dependent calcium channels type L (Bay K6844; 10−8 M; p < 0.01), likely decreasing the influx of extracellular Ca2+ through the voltage-dependent calcium channels. This study provides the first qualitative analysis indicating that traditional folk medicine Aristotelia chilensis may be protective in the treatment of cardiovascular pathologies.
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Luna-Vázquez FJ, Ibarra-Alvarado C, Camacho-Corona MDR, Rojas-Molina A, Rojas-Molina JI, García A, Bah M. Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine. Molecules 2018; 23:molecules23061474. [PMID: 29912156 PMCID: PMC6100030 DOI: 10.3390/molecules23061474] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 06/11/2018] [Accepted: 06/12/2018] [Indexed: 12/31/2022] Open
Abstract
Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC50), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC50, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4′-trihydroxy-3,7-dimethoxyflavone (EC50, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H2S/ATP-sensitive potassium channel (KATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4′-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4′-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.
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Affiliation(s)
- Francisco J Luna-Vázquez
- Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, C.P. 76010 Querétaro, Mexico.
| | - César Ibarra-Alvarado
- Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, C.P. 76010 Querétaro, Mexico.
| | - María Del Rayo Camacho-Corona
- Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Ciudad Universitaria, San Nicolás de los Garza, CP 66451 Nuevo León, Mexico.
| | - Alejandra Rojas-Molina
- Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, C.P. 76010 Querétaro, Mexico.
| | - J Isela Rojas-Molina
- Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, C.P. 76010 Querétaro, Mexico.
| | - Abraham García
- Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Ciudad Universitaria, San Nicolás de los Garza, CP 66451 Nuevo León, Mexico.
| | - Moustapha Bah
- Laboratorio de Investigación Química y Farmacológica de Productos Naturales, Facultad de Química, Universidad Autónoma de Querétaro, C.P. 76010 Querétaro, Mexico.
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Yuan TY, Niu ZR, Chen D, Chen YC, Zhang HF, Fang LH, Du GH. Vasorelaxant effect of quercetin on cerebral basilar artery in vitro and the underlying mechanisms study. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2018; 20:477-487. [PMID: 29693418 DOI: 10.1080/10286020.2018.1463995] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 04/09/2018] [Indexed: 06/08/2023]
Abstract
The aim of this study is to investigate the vasorelaxant effect of quercetin on cerebral basilar artery in vitro and provide a preliminary discussion concerning the underlying mechanisms. Using a DMT-isolated micro vessel system, quercetin was found to exhibit a vasodilatory effect on basilar arteries contracted by potassium chloride (KCl), endothelin-1 (ET-1), and 5-hydroxytryptamine (5-HT). The vasorelaxant effect of quercetin was partially attenuated when endothelium cells were removed. L-NAME, indomethacin, and ODQ treatment also decreased the potency of quercetin. In endothelium-denuded rings, the vasorelaxant effect of quercetin was not influenced by K+ channel inhibitors. However, quercetin inhibited KCl induced extracellular calcium influx and ET-1 induced transient intracellular calcium release in a Ca2+-free solution. In conclusion, quercetin induced relaxation of the basilar artery in vitro is partially dependent on endothelium, which is mainly related to NO and COX pathways. It also induces relaxation through blockage of calcium channels.
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Affiliation(s)
- Tian-Yi Yuan
- a Beijing Key Laboratory of Drug Targets Identification and Drug Screening , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
- b State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
| | - Zi-Ran Niu
- a Beijing Key Laboratory of Drug Targets Identification and Drug Screening , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
- b State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
| | - Di Chen
- a Beijing Key Laboratory of Drug Targets Identification and Drug Screening , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
- b State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
| | - Yu-Cai Chen
- a Beijing Key Laboratory of Drug Targets Identification and Drug Screening , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
- b State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
| | - Hui-Fang Zhang
- a Beijing Key Laboratory of Drug Targets Identification and Drug Screening , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
- b State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
| | - Lian-Hua Fang
- a Beijing Key Laboratory of Drug Targets Identification and Drug Screening , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
- b State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
| | - Guan-Hua Du
- a Beijing Key Laboratory of Drug Targets Identification and Drug Screening , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
- b State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China
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Singh D, Chaudhuri PK. Structural characteristics, bioavailability and cardioprotective potential of saponins. Integr Med Res 2018; 7:33-43. [PMID: 29629289 PMCID: PMC5884006 DOI: 10.1016/j.imr.2018.01.003] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2017] [Revised: 12/08/2017] [Accepted: 01/15/2018] [Indexed: 12/19/2022] Open
Abstract
Cardiovascular diseases are the leading cause of death, accounting about 31% deaths globally in 2012. The major risk factors causing cardiovascular diseases are coronary atherosclerosis, hyperlipidemia, myocardial infarction, and stroke. The dominating cause of cardiovascular diseases is accredited to our modern lifestyle and diet. Medicinal plants have been used for the prevention and treatment of cardiovascular diseases from centuries. The in built chirality and chemical space of natural products have been playing an important role in providing leads and templates for pharmacophore synthesis. This review highlights one of the important naturally occurring class saponins and their role in cardioprotection along with structural characteristics and pharmacological effects such as antioxidant, Ca2+ ion regulation, antiapoptotic, antiatherosclerosis, antihyperlipidemic, hypocholesterolemic, angiogenic, vasodilatory, and hypotensive. The characteristic cholesterol lowering, hemolytic, and anticoagulant properties of the saponins prompted us to select as one of the natural products class for cardioprotection. This review covers the most updated information on saponins related to their cardioprotective effects, mechanism of action, bioavailability, and structure activity relationship.
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Affiliation(s)
- Deepika Singh
- Medicinal Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CIMAP-CSIR), Lucknow, India
| | - Prabir Kumar Chaudhuri
- Medicinal Chemistry Division, Central Institute of Medicinal and Aromatic Plants (CIMAP-CSIR), Lucknow, India
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Chen GH, Li YC, Lin NH, Kuo PC, Tzen JTC. Characterization of Vasorelaxant Principles from the Needles of Pinus morrisonicola Hayata. Molecules 2017; 23:molecules23010086. [PMID: 29301239 PMCID: PMC6017640 DOI: 10.3390/molecules23010086] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Revised: 12/29/2017] [Accepted: 12/30/2017] [Indexed: 12/18/2022] Open
Abstract
Pinus morrisonicola Hayata, usually called Taiwan five-leaf pine (5LP), is an endemic species in Taiwan and is traditionally used to relieve hypertension symptoms and improve cardiovascular function. In this study, the needle extract of 5LP was fractionated and analyzed by LC/MS/MS to search for possible antihypertensive candidates. In addition, bioassay-guided purification of the bioactive components was performed by Ca2+ fluorescent signal (Fluo 4-AM) assays. Two dihydrobenzofuran lignans, pinumorrisonide A (1) and icariside E4 (2), and one acylated flavonoid glycoside, kaempferol 3-O-α-(6‴-p-coumaroylglucosyl-β-1,4-rhamnoside) (3) were characterized from the active fractions. The structure of a new compound 1 was established on the basis of 2D NMR spectroscopic and mass spectrometric analyses, and the known compounds 2 and 3 were identified by comparison of their physical and spectroscopic data with those reported in the literature. The purified compounds 1–3 exhibited significant inhibition of Ca2+ fluorescence with IC50 values of 0.71, 0.36, and 0.20 mM, respectively. A mechanism study showed that these compounds showed vasorelaxant effects by blocking the voltage-operated Ca2+ channel (VOCC) and inhibiting Ca2+ influx to the cytoplasmic. These results suggested that 5LP and the three characterized components could be promising antihypertensive candidates for the use as VOCC blockers.
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Affiliation(s)
- Guan-Heng Chen
- Graduate Institute of Biotechnology, National Chung-Hsing University, Taichung 402, Taiwan.
| | - Yue-Chiun Li
- Graduate Institute of Biotechnology, National Chung-Hsing University, Taichung 402, Taiwan.
| | - Nan-Hei Lin
- Graduate Institute of Biotechnology, National Chung-Hsing University, Taichung 402, Taiwan.
| | - Ping-Chung Kuo
- School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
| | - Jason T C Tzen
- Graduate Institute of Biotechnology, National Chung-Hsing University, Taichung 402, Taiwan.
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Marinko M, Jankovic G, Nenezic D, Milojevic P, Stojanovic I, Kanjuh V, Novakovic A. (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K + and Ca 2+ channels. Phytother Res 2017; 32:267-275. [PMID: 29193528 DOI: 10.1002/ptr.5969] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 10/02/2017] [Accepted: 10/09/2017] [Indexed: 01/05/2023]
Abstract
In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K+ , whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca2+ -free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+ -ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive KV channels, BKCa channels, and at least partly, KATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+ -ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.
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Affiliation(s)
- Marija Marinko
- Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Goran Jankovic
- Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Dragoslav Nenezic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia.,Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia
| | - Predrag Milojevic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia.,Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia
| | - Ivan Stojanovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia.,Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia
| | | | - Aleksandra Novakovic
- Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
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Feyzabadi Z, Ghorbani F, Vazani Y, Zarshenas MM. A Critical Review on Phytochemistry, Pharmacology of Viola odorata L. and Related Multipotential Products in Traditional Persian Medicine. Phytother Res 2017; 31:1669-1675. [PMID: 28948657 DOI: 10.1002/ptr.5909] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Revised: 06/27/2017] [Accepted: 08/10/2017] [Indexed: 11/09/2022]
Abstract
Common violet (Viola odorata L., Violaceae) has shown various medical applications. Current study aimed to compile a review over chemical composition and medicinal properties of this plant in modern phytotherapy and its related multipotential products from traditional Persian medicine (TPM). Medicinal applications of V. odorata and respective products were derived from credible pharmaceutical textbooks of TPM (10th-18th century AD). In parallel, electronic databases including PubMed, Scopus, and ScienceDirect were explored for targeted purposes. Management of cough, fever, common cold, headache, insomnia, epilepsy, constipation, palpitation, dyspnea, dysuria, and skin diseases is of most applications of V. odorata, reported in TPM. On the other side, this herb plant has exerted antiinflammatory, analgesic, antioxidant, diuretic, antihypertensive, and antibacterial activities in modern phytotherapy. Violet TPM therapeutic preparations are including violet oil in the form of nasal or topical application for neurologic and skin disorders as well as pill, decoction, sweet syrup, and confection or semisolid oral preparations for skin, respiratory, gastrointestinal, and urinary ailments. Flavonoids, saponins, and alkaloids are responsible for pharmacological activities. Some medical applications of V. odorata in TPM have been proven by recent studies. However, more studies are needed to confirm these medicinal properties. Copyright © 2017 John Wiley & Sons, Ltd.
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Affiliation(s)
- Zohre Feyzabadi
- Department of Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fariba Ghorbani
- Department of Persian Medicine, School of Persian and Complementary Medicine, Research Institute for Islamic and Complementary Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Yasaman Vazani
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad M Zarshenas
- Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Phytopharmaceuticals (Traditional Pharmacy), School of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Rodrigues AMG, Guimarães DO, Konno TUP, Tinoco LW, Barth T, Aguiar FA, Lopes NP, Leal ICR, Raimundo JM, Muzitano MF. Phytochemical Study of Tapirira guianensis Leaves Guided by Vasodilatory and Antioxidant Activities. Molecules 2017; 22:molecules22020304. [PMID: 28218702 PMCID: PMC6155791 DOI: 10.3390/molecules22020304] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 01/31/2017] [Accepted: 02/01/2017] [Indexed: 01/28/2023] Open
Abstract
The aim of this research was to perform a phytochemical study of the methanol leaves extract of T. guianensis (MET) guided by vasodilatory and antioxidant activities. The chemical profile of MET and the ethyl acetate fraction (EA fraction) was determined by HPLC-UV-MS and EA fraction guided fractionation by reverse-phase chromatography. The vasorelaxant effects of MET, fractions, sub-fractions and constituents were assessed on rat aorta pre-contracted with phenylephrine. Antioxidant activity was evaluated by using a DPPH assay. The results show that MET-induced vasodilation was dependent on NO/cGMP; and that the PI3K/Akt pathway seems to be the main route involved in eNOS activation. The EA fraction showed greater vasodilatory and antioxidant potency and was submitted to further fractionation. This allowed the isolation and characterization of quercetin, quercetin 3-O-(6″-O-galloyl)-β-d-galactopyranoside and 1,4,6-tri-O-galloyl-β-d-glucose. Also, galloyl-HHDP-hexoside and myricetin deoxyhexoside were identified by HPLC-UV-MS. These compounds are being described for the first time for T. guianensis. 1,4,6-tri-O-galloyl-β-d-glucose and quercetin 3-O-(6″-O-galloyl)-β-d-galactopyranoside showed no vasodilatory activity. Quercetin and myricetin glycoside seems to contribute to the MET activity, since they have been reported as vasodilatory flavonoids. MET-induced vasodilation could contribute to the hypotensive effect of T. guianensis previously reported.
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Affiliation(s)
- Amélia M G Rodrigues
- Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Av. Alberto Lamego, 2000, Parque Califórnia, Campos dos Goytacazes, 28013-602 Rio de Janeiro, Brazil.
- Laboratório Integrado de Pesquisa, Universidade Federal do Rio de Janeiro, Campus Macaé, Av. Aluízio da Silva Gomes, 50, Novo Cavaleiros, Macaé, 27930-560 Rio de Janeiro, Brazil.
- Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Polo Novo Cavaleiro-IMCT, R. Alcides da Conceição, 159, Novo Cavaleiros, Macaé, 27933-378 Rio de Janeiro, Brazil.
| | - Denise O Guimarães
- Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Polo Novo Cavaleiro-IMCT, R. Alcides da Conceição, 159, Novo Cavaleiros, Macaé, 27933-378 Rio de Janeiro, Brazil.
| | - Tatiana U P Konno
- Núcleo de Estudos em Ecologia e Desenvolvimento Sócio-Ambiental de Macaé, Universidade Federal do Rio de Janeiro, Av. São José Barreto, 764-São José do Barreto. Macaé, 27965-045 Rio de Janeiro, Brazil.
| | - Luzineide W Tinoco
- Instituto de Pesquisa de Produtos Naturais Walter Mors, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.
| | - Thiago Barth
- Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Polo Novo Cavaleiro-IMCT, R. Alcides da Conceição, 159, Novo Cavaleiros, Macaé, 27933-378 Rio de Janeiro, Brazil.
| | - Fernando A Aguiar
- Núcleo de Pesquisa em Produtos Naturais e Sintéticos, Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n. 14040-020 Ribeirão Preto, Brazil.
- Laboratório de Química, Universidade Federal do Rio de Janeiro-Campus Macaé, Av. Aluízio da Silva Gomes, 50, Novo Cavaleiros. Macaé, 27930-560 Rio de Janeiro, Brazil.
| | - Norberto P Lopes
- Núcleo de Pesquisa em Produtos Naturais e Sintéticos, Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n. 14040-020 Ribeirão Preto, Brazil.
| | - Ivana C R Leal
- Laboratório de Produtos Naturais e Ensaios Biológicos, Departamento De Produtos Naturais e Alimentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.
| | - Juliana M Raimundo
- Laboratório Integrado de Pesquisa, Universidade Federal do Rio de Janeiro, Campus Macaé, Av. Aluízio da Silva Gomes, 50, Novo Cavaleiros, Macaé, 27930-560 Rio de Janeiro, Brazil.
| | - Michelle F Muzitano
- Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Polo Novo Cavaleiro-IMCT, R. Alcides da Conceição, 159, Novo Cavaleiros, Macaé, 27933-378 Rio de Janeiro, Brazil.
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The Effects of Satureja hortensis L. Dried Leaves on Serum Sugar, Lipid Profiles, hs-CRP, and Blood Pressure in Metabolic Syndrome Patients: A Double-Blind Randomized Clinical Trial. IRANIAN RED CRESCENT MEDICAL JOURNAL 2016. [DOI: 10.5812/ircmj.34931] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Novakovic A, Marinko M, Vranic A, Jankovic G, Milojevic P, Stojanovic I, Nenezic D, Ugresic N, Kanjuh V, Yang Q, He GW. Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin. Eur J Pharmacol 2015; 762:306-12. [PMID: 26049011 DOI: 10.1016/j.ejphar.2015.05.066] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Revised: 05/03/2015] [Accepted: 05/21/2015] [Indexed: 02/05/2023]
Abstract
Evidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Among the K(+) channel blockers, 4-aminopyridine (4-AP) and margatoxin, blockers of voltage-gated K(+) (KV) channels, and glibenclamide, a selective ATP-sensitive K(+) (KATP) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca(2+)-activated K(+) channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80mM K(+), (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca(2+)-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium-independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and margatoxin-sensitive KV channels, as well as BKCa and KATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca(2+), interfere with intracellular Ca(2+) release and re-uptake by the sarcoplasmic reticulum.
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Affiliation(s)
- Aleksandra Novakovic
- Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
| | - Marija Marinko
- Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Vranic
- Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Goran Jankovic
- Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Predrag Milojevic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia
| | - Ivan Stojanovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia
| | - Dragoslav Nenezic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Institute for Cardiovascular Diseases "Dedinje", Belgrade, Serbia
| | - Nenad Ugresic
- Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | | | - Qin Yang
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong; TEDA International Cardiovascular Hospital, Tianjin, China
| | - Guo-Wei He
- TEDA International Cardiovascular Hospital, Tianjin, China
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Qu Z, Zhang J, Huo L, Chen H, Li H, Fan Y, Gao W. Antihypertensive and vasorelaxant effects of Rhizoma corydalis and its active component tetrahydropalmatine via NO/cGMP pathway and calcium channel blockade in isolated rat thoracic aorta. RSC Adv 2015. [DOI: 10.1039/c5ra17756a] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
The vasorelaxant effects of RC and THPviathe NO/cGMP pathway and calcium channel blockade in isolated rat thoracic aorta are explored.
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Affiliation(s)
- Zhuo Qu
- Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency
- School of Pharmaceutical Science and Technology
- Tianjin University
- Tianjin 300072
- China
| | - Jingze Zhang
- Department of Pharmacy
- Logistics College of Chinese People’s Armed Police Forces
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury
- Tianjin 300162
- China
| | - Liqin Huo
- Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency
- School of Pharmaceutical Science and Technology
- Tianjin University
- Tianjin 300072
- China
| | - Hong Chen
- Department of Pharmacy
- Logistics College of Chinese People’s Armed Police Forces
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury
- Tianjin 300162
- China
| | - Hongfa Li
- Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency
- School of Pharmaceutical Science and Technology
- Tianjin University
- Tianjin 300072
- China
| | - Yaya Fan
- Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency
- School of Pharmaceutical Science and Technology
- Tianjin University
- Tianjin 300072
- China
| | - Wenyuan Gao
- Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency
- School of Pharmaceutical Science and Technology
- Tianjin University
- Tianjin 300072
- China
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Qu Z, Zhang J, Gao W, Chen H, Guo H, Wang T, Li H, Liu C. Vasorelaxant effects of Cerebralcare Granule® are mediated by NO/cGMP pathway, potassium channel opening and calcium channel blockade in isolated rat thoracic aorta. JOURNAL OF ETHNOPHARMACOLOGY 2014; 155:572-579. [PMID: 24924524 DOI: 10.1016/j.jep.2014.05.062] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 05/26/2014] [Accepted: 05/31/2014] [Indexed: 06/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cerebralcare Granule (CG), one of the famous classical recipes in traditional Chinese medicine, is developed from the "Decoction of Four Drugs". It has been used for treatment of cerebrovascular related diseases, such as hypertension. It is well known that vasodilatation plays a very important role in hypertensive. Despite the popular medicinal use of CG, little data was available to its activity and mechanism involved in vasodilatation. Therefore, we aimed to investigate the vasorelaxant effects of CG on isolated rat thoracic aorta so as to assess some of the possible mechanisms. The present study was performed to examine the vasodilative activity of CG and its mechanisms in isolated rat thoracic aorta. MATERIALS AND METHODS CG was studied on isolated rat thoracic aorta in vitro, including endothelium-intact and endothelium-denuded aortic rings. In present study, specific inhibitors including NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), cyclooxygenase (COX) inhibitor indomethacin (INDO), non-selective K+ channel inhibitor tetraethylammonium chloride (TEA), Kir channel inhibitor BaCl2, KATP channel inhibitor Glibenclamide (Gli) and cholinergic receptor antagonist atropine were used, they were added 20 min before NE contraction and then added CG-induced vasodilation. RESULTS Removal of endothelium or pretreatment of aortic rings (intact endothelium) with L-NAME (0.1 mM) or INDO (0.01 mM) significantly blocked the CG induced relaxation. Pretreatment with the non-selective K+ channel inhibitor TEA (1 mM), or the Kir channel inhibitor BaCl2 (0.1 mM), neither of them had no influence on the CG-induced response (p>0.05). However, pretreatment with the KATP channel inhibitor Gli (0.01 mM) produced significant inhibition on the CG-induced response (p<0.01). Besides, CG also inhibited the contraction triggered by NE in endothelium-denuded rings in Ca2+-free medium. CG (0.4, 0.8 and 3.2 mg/mL) produced rightward parallel displacement of CaCl2 curves and reduced the maximum contraction induced by 30 mM CaCl2 to 31.1±9.3%, 18.8±6.9% and 9.4±4.5%, respectively. The relaxation, induced by CG on endothelium-intact rat aortic rings pre-contracted with NE, was significantly attenuated in the presence of atropine (EC50=3.7 mg/mL, p<0.01). CONCLUSIONS Our results suggest that CG induces relaxation in rat aortic rings through an endothelium-dependent pathway mediated by NO/cGMP pathway and an endothelium-independent pathway involving blockade of Ca2+ channels, inhibition of Ca2+ mobilization from intracellular stores, opening of KATP channel. In addition, the muscarinic receptor stimulation is also one of the vasorelaxant mechanisms.
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Affiliation(s)
- Zhuo Qu
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
| | - Jingze Zhang
- Department of Pharmacy, Logistics College of Chinese People׳s Armed Police Forces, Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Tianjin 300162, China
| | - Wenyuan Gao
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
| | - Hong Chen
- Department of Pharmacy, Logistics College of Chinese People׳s Armed Police Forces, Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Tianjin 300162, China
| | - Huimin Guo
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
| | - Tingting Wang
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
| | - Hongfa Li
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
| | - Changxiao Liu
- The State Key Laboratories of Pharmacodynamics and Pharmacokinetics, Tianjin, China
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Arcanjo DDR, Costa-Júnior JSD, Moura LHP, Ferraz ABF, Rossatto RR, David JM, Quintans-Júnior LJ, Oliveira RDCM, Citó AMDGL, Oliveira APD. Garcinielliptone FC, a polyisoprenylated benzophenone fromPlatonia insignisMart., promotes vasorelaxant effect on rat mesenteric artery. Nat Prod Res 2014; 28:923-7. [DOI: 10.1080/14786419.2014.889136] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Sen T, Samanta SK. Medicinal plants, human health and biodiversity: a broad review. ADVANCES IN BIOCHEMICAL ENGINEERING/BIOTECHNOLOGY 2014; 147:59-110. [PMID: 25001990 DOI: 10.1007/10_2014_273] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Biodiversity contributes significantly towards human livelihood and development and thus plays a predominant role in the well being of the global population. According to WHO reports, around 80 % of the global population still relies on botanical drugs; today several medicines owe their origin to medicinal plants. Natural substances have long served as sources of therapeutic drugs, where drugs including digitalis (from foxglove), ergotamine (from contaminated rye), quinine (from cinchona), and salicylates (willow bark) can be cited as some classical examples.Drug discovery from natural sources involve a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Accordingly, medicinal-plant-based drug discovery still remains an important area, hitherto unexplored, where a systematic search may definitely provide important leads against various pharmacological targets.Ironically, the potential benefits of plant-based medicines have led to unscientific exploitation of the natural resources, a phenomenon that is being observed globally. This decline in biodiversity is largely the result of the rise in the global population, rapid and sometimes unplanned industrialization, indiscriminate deforestation, overexploitation of natural resources, pollution, and finally global climate change.Therefore, it is of utmost importance that plant biodiversity be preserved, to provide future structural diversity and lead compounds for the sustainable development of human civilization at large. This becomes even more important for developing nations, where well-planned bioprospecting coupled with nondestructive commercialization could help in the conservation of biodiversity, ultimately benefiting mankind in the long run.Based on these findings, the present review is an attempt to update our knowledge about the diverse therapeutic application of different plant products against various pharmacological targets including cancer, human brain, cardiovascular function, microbial infection, inflammation, pain, and many more.
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Affiliation(s)
- Tuhinadri Sen
- Department of Pharmaceutical Technology and School of Natural Product Studies, Jadavpur University, Kolkata, 700032, India,
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