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Paudel KR, Panth N, Kim DW, Karki R. Chungtaejeon (CTJ) inhibits adhesion and migration of VSMC through cytoskeletal remodeling pathway. Heliyon 2024; 10:e38508. [PMID: 39397925 PMCID: PMC11471206 DOI: 10.1016/j.heliyon.2024.e38508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 09/08/2024] [Accepted: 09/25/2024] [Indexed: 10/15/2024] Open
Abstract
Introduction Vascular remodeling is crucial for the progression of vascular disease such as atherosclerosis. We utilize the in vitro experimental model of atherosclerosis to elucidate the activity of Chungtaejeon (CTJ), a Korean fermented tea on adhesion and migration of human aortic vascular smooth muscle cells (HASMC). Materials and methods Various in vitro assays such as cell viability, cell adhesion, Western blot, immunofluorescence, were carried out on HASMC to explore pathway associated with cytoskeletal remodeling during the progression of atherosclerosis. Results In result, CTJ significantly inhibited adhesion of HASMC as revealed by collagen assay. Similarly, CTJ inhibited the β1-integrin protein expression as well as FAK phosphorylation. Treatment of CTJ also inhibited stress fiber formation. Likewise, adherence of cells on collagen optimally increased the expression of both RhoA and Cdc42, however, treatment of CTJ dose dependently decreased their expression. The lysophosphatidic acid stimulation of HASMC rapidly increased the level of phosphorylated forms of MLC20 within 15 min, followed by an extended level of MLC20 phosphorylation. The treatment of CTJ at a dose of 50, 100 and 250 μg/ml remarkably reduced the diphosphorylated form while decreased the level of monophosphorylated form of MLC20. Conclusions Our results suggests that, with further validation CTJ could be a promising herbal resource for prevention of atherosclerosis.
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Affiliation(s)
- Keshav Raj Paudel
- Department of Oriental Medicine Resource, Mokpo National University, Muan-gun, Jeonnam, 58554, Republic of Korea
| | - Nisha Panth
- College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam, 58554, Republic of Korea
| | - Dong Wook Kim
- Department of Oriental Medicine Resource, Mokpo National University, Muan-gun, Jeonnam, 58554, Republic of Korea
| | - Rajendra Karki
- Department of Biological Sciences, College of Natural Science, Seoul National University, Seoul, 08826, Republic of Korea
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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: 0] [Impact Index Per Article: 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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Zhang X, Dong Z, Yang Y, Liu C, Li J, Sun W, Zhu Y, Shen Y, Wang Z, Lü M, Cui H. Morusinol Extracted from Morus alba Inhibits Cell Proliferation and Induces Autophagy via FOXO3a Nuclear Accumulation-Mediated Cholesterol Biosynthesis Obstruction in Colorectal Cancer. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:16016-16031. [PMID: 37870273 DOI: 10.1021/acs.jafc.3c01244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
The incidence rate of colorectal cancer (CRC) has been increasing significantly in recent years, and it is urgent to develop novel drugs that have more effects for its treatment. It has been reported that many molecules extracted from the root bark of Morus alba L. (also known as Cortex Mori) have antitumor activities. In our study, we identified morusinol as a promising anticancer agent by selecting from 30 molecules extracted from Morus alba L. We found that morusinol treatment suppressed cell proliferation and promoted apoptosis of CRC cells in vitro. Besides this, we observed that morusinol induced cytoprotective autophagy. The GO analysis of differentially expressed genes from RNA-seq data showed that morusinol affected cholesterol metabolism. Then we found that key enzyme genes in the cholesterol biosynthesis pathway as well as the sterol regulatory element binding transcription factor 2 (SREBF2) were significantly downregulated. Furthermore, additional cholesterol treatment reversed the anti-CRC effect of morusinol. Interestingly, we also found that morusinol treatment could promote forkhead box O3 (FOXO3a) nuclear accumulation, which subsequently suppressed SREBF2 transcription. Then SREBF2-controlled cholesterol biosynthesis was blocked, resulting in the suppression of cell proliferation, promotion of apoptosis, and production of autophagy. The experiments in animal models also showed that morusinol significantly impeded tumor growth in mice models. Our results suggested that morusinol may be used as a candidate anticancer drug for the treatment of CRC.
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Affiliation(s)
- Xiaolin Zhang
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
| | - Zhen Dong
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
- Jinfeng Laboratory, Chongqing 401329, China
- Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Beibei, Chongqing 400716, China
- Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Beibei, Chongqing 400716, China
| | - Yuanmiao Yang
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
| | - Chaolong Liu
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
| | - Jisheng Li
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
| | - Wenli Sun
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
| | - Yikang Zhu
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
| | - Yang Shen
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
| | - Zhi Wang
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
| | - Muhan Lü
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Hongjuan Cui
- State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, China
- Jinfeng Laboratory, Chongqing 401329, China
- Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Beibei, Chongqing 400716, China
- Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Beibei, Chongqing 400716, China
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Batiha GES, Al-Snafi AE, Thuwaini MM, Teibo JO, Shaheen HM, Akomolafe AP, Teibo TKA, Al-kuraishy HM, Al-Garbeeb AI, Alexiou A, Papadakis M. Morus alba: a comprehensive phytochemical and pharmacological review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:1399-1413. [PMID: 36877269 PMCID: PMC10244279 DOI: 10.1007/s00210-023-02434-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 02/16/2023] [Indexed: 03/07/2023]
Abstract
Morus alba is a fast-growing shrub or medium-sized tree with a straight, cylindrical trunk. Medicinally, whole plants, leaves, fruits, branches, and roots have been employed. Google Scholar, PubMed, Scopus, and Web of Science were used to search for relevant material on the phytochemical components and pharmacologic and mechanism of action of the Morus alba. This was reviewed to assess important updates about Morus alba. The fruits of Morus alba have traditionally been used as an analgesic, anthelmintic, antibacterial, anti-rheumatic, diuretic, hypotensive, hypoglycemia, purgative, restorative, sedative tonic, and blood stimulant. Various plant parts were used as a cooling, sedating, diuretic, tonic, and astringent agent to treat nerve disorders. The plant contained tannins, steroids, phytosterols, sitosterol, glycosides, alkaloids, carbohydrates, proteins, and amino acids, as well as saponins, triterpenes, phenolics, flavonoids, benzofuran derivatives, anthocyanins, anthraquinones, glycosides, vitamins, and minerals. Previous pharmacological research identified antimicrobial, anti-inflammatory, immunological, analgesic, antipyretic, antioxidant, anti-cancer, antidiabetic, gastrointestinal, respiratory, cardiovascular, hypolipidemic, anti-obesity, dermatological, neurological, muscular, and protecting effects. This study looked at Morus alba's traditional uses, chemical components, and pharmacological effects.
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Affiliation(s)
- Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511 El Beheira Egypt
| | - Ali Esmail Al-Snafi
- Department of Pharmacology, College of Medicine, University of Thi-Qar, Nasiriyah, Iraq
| | - Mahdi M. Thuwaini
- College of Medical and Healthy Techniques, Southern Technique University, Basra, Iraq
| | - John Oluwafemi Teibo
- Department of Biochemistry and Immunology, Ribeirão, Preto Medical School
, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Hazem M. Shaheen
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511 El Beheira Egypt
| | | | - Titilade Kehinde Ayandeyi Teibo
- Department of Maternal-Infant and Public Health Nursing, College of Nursing, University of São Paulo, Ribeirão PretoRibeirão Preto, São Paulo, Brazil
| | - Hayder M. Al-kuraishy
- Department of Clinical Pharmacologyand, Therapeutic Medicine, College of Medicine
, Almustansiriyah University, Baghdad, Iraq
| | - Ali I. Al-Garbeeb
- Department of Clinical Pharmacologyand, Therapeutic Medicine, College of Medicine
, Almustansiriyah University, Baghdad, Iraq
| | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770 Australia
- AFNP Med, 1030 Vienna, Austria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283 Wuppertal, Germany
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Sahinturk S. Metformin relaxes rat thoracic aorta via nitric oxide, AMPK, potassium channels, and PKC. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2023; 26:1030-1040. [PMID: 37605728 PMCID: PMC10440136 DOI: 10.22038/ijbms.2023.69728.15179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 04/10/2023] [Indexed: 08/23/2023]
Abstract
Objectives The present research aimed to identify the functional effects and underlying mechanisms of metformin on the rat thoracic aorta. Materials and Methods Thoracic aorta segments of Wistar Albino rats were put in the chambers of an isolated tissue bath system. The resting tone was adjusted to 1 g. Following the equilibration time, potassium chloride or phenylephrine was used to contract the vascular segments. The vessel segments were cumulatively treated with metformin (10-7-10-3 M) when a steady contraction was achieved. The described experimental approach was repeated after incubations with signaling pathway inhibitors and selective blockers of potassium channels to identify the effect mechanisms of metformin. Results Metformin had a potent vasorelaxant effect in a concentration-dependent way (P<0.001). After the endothelium was removed, the vasorelaxant effect level of metformin was significantly reduced. The level of vasorelaxant effect of metformin was increased by the maintenance of perivascular adipose tissue. Following administrations of L-NAME, methylene blue, compound C, BIM-I, and potassium channel blockers, the level of vasodilatory action of metformin was significantly reduced (P<0.001). Conclusion According to the results of this investigation, metformin significantly relaxes the thoracic aorta segments of rats. Metformin-mediated vasorelaxation involves the activation of numerous subtypes of potassium channels, including BKCa, IKCa, Kv, Kir, and K2p channels, as well as endothelium-dependent processes, including AMPK and eNOS/NO/sGS signaling pathways. Moreover, metformin-induced vasorelaxation is mediated through PVAT activation and the PKC signaling pathway.
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Affiliation(s)
- Serdar Sahinturk
- Bursa Uludag University Medicine School, Physiology Department, Bursa, Turkey
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Lamichhane G, Pandey J, Devkota HP. Bioactive Chemical Constituents and Pharmacological Activities of Ponciri Fructus. Molecules 2022; 28:255. [PMID: 36615447 PMCID: PMC9821892 DOI: 10.3390/molecules28010255] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/15/2022] [Accepted: 12/22/2022] [Indexed: 12/31/2022] Open
Abstract
Ponciri Fructus is a crude drug obtained from the dried immature fruits of Poncirus trifoliata (L). Raf. (Syn. Citrus trifoliata L.). This study aims to compile and analyze the ethnomedicinal uses, bioactive constituents, and pharmacological activities of Ponciri Fructus. Various online bibliographic databases namely, SciFinder, PubMed, Google Scholar, and Web of Science were used for collecting information on traditional uses, biological activities, and bioactive constituents. Concerning ethnomedicinal uses, Ponciri Fructus is extensively used in traditional Korean, Chinese, and Kampo medicines to mitigate allergic reactions, inflammation, edema, digestive complications, respiratory problems, spleen-related problems, liver complications, neuronal pain, hyperlipidemia, rheumatoid arthritis, cardiovascular problems, hernia, sinusitis, and insomnia. Several studies have shown that Ponciri Fructus is a major source of diverse classes of bioactive compounds namely flavonoids, terpenoids, coumarins, phytosterols, and alkaloids. Several in vivo and in vitro pharmacological activity evaluations such as antidiabetic, anti-obesity, anti-inflammatory, antiallergic, antimelanogenic, gastroprotective, anticancer, and neuroprotective effects have been conducted from Ponciri Fructus. However, scientific investigations focusing on bioassay-guided isolation and identification of specific bioactive constituents are limited. Therefore, an in-depth scientific investigation of Ponciri Fructus focusing on bioassay-guided isolation, mechanism based pharmacological studies, pharmacokinetic studies, and evaluation of possible toxicities is necessary in the future.
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Affiliation(s)
- Gopal Lamichhane
- Department of Oriental Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 570-749, Republic of Korea
| | - Jitendra Pandey
- Department of Pharmacy, Crimson College of Technology, Pokhara University, Devinagar-11, Butwal 32900, Nepal
| | - Hari Prasad Devkota
- Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
- Headquarters for Admissions and Education, Kumamoto University, Kurokami, 2-39-1, Chuo-ku, Kumamoto 860-8555, Japan
- Pharmacy Program, Gandaki University, Pokhara 33700, Nepal
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Stinging Nettle (Urtica dioica L.): Nutritional Composition, Bioactive Compounds, and Food Functional Properties. Molecules 2022; 27:molecules27165219. [PMID: 36014458 PMCID: PMC9413031 DOI: 10.3390/molecules27165219] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/09/2022] [Accepted: 08/12/2022] [Indexed: 11/17/2022] Open
Abstract
Stinging nettle (Urtica dioica L., Urticaceae) is commonly found in Asia, Africa, and Europe and has a long history of being used as food and traditional medicine. Recently, this plant is gaining attention as a highly nutritious food, where fresh leaves are dried and used as powder or in other forms. Leaves are rich in many bioactive compounds. This review aims to cover the traditional uses in food and medicine, as well as its nutritional composition, including its bioactive chemical constituents and reported food functional activities. Various bioactive chemical constituents have been isolated from stinging nettle to date, such as flavonoids, phenolic acids, amino acid, carotenoids, and fatty acids. Stinging nettle extracts and its compounds, such as rutin, kaempferol, and vitamin A, are also used for their nutritional properties and as anti-inflammatory and antioxidant agents. Future studies should focus on the proper formulation and stability testing of the functional foods containing stinging nettle and their detailed activities in clinical studies.
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Seong EH, Gong DS, Shiwakoti S, Adhikari D, Kim HJ, Oak MH. Taxifolin as a Major Bioactive Compound in the Vasorelaxant Effect of Different Pigmented Rice Bran Extracts. Front Pharmacol 2022; 13:799064. [PMID: 35387354 PMCID: PMC8979019 DOI: 10.3389/fphar.2022.799064] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 03/04/2022] [Indexed: 11/25/2022] Open
Abstract
Cardiovascular disease is one of the leading causes of morbidity and mortality in recent years. The intake of polyphenol rich diets has been associated with improved cardiovascular function and reduced cardiovascular risks. Oryza sativa L. is one of the most common cereals worldwide. Rice bran, a byproduct of the rice milling process, contains many bioactive ingredients, including polyphenols, polysaccharides, proteins, and micronutrients. It is also consumed as a healthy diet in the form of rice bran oil and powder in many Asian countries like Japan, South Korea, and India for its several health benefits as a natural antioxidant. Thus, this study evaluated the vasorelaxant effect of ethanolic extracts of brown, green, red, and black rice bran and investigated its underlying vasorelaxant mechanism. Among the four rice bran extracts (RBEs) examined, the red rice bran extract (RRBE) had a strong endothelium-dependent vasorelaxant effect, which was markedly prevented by N-ω-nitro-L-arginine [endothelial nitric oxide synthase (eNOS) inhibitor], wortmannin [phosphoinositide-3 kinase (PI3K) inhibitor], and 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one (inhibitor of guanylate cyclase). Likewise, RRBE induced the phosphorylation of eNOS and Src in cultured endothelial cells, thereby stimulating NO formation. Altogether, these findings propose that RRBE induces endothelium-dependent relaxation, involving at least in part, NO-mediated signaling through the PI3K/eNOS pathway. Further, LC-PDA analysis conducted on the four RBEs also revealed that RRBE highly contained taxifolin, which is an active flavanonol that induces endothelium-dependent vasorelaxation, compared to other RBEs. Subsequently, the underlying mechanism of taxifolin was assessed through vascular reactivity studies with pharmacological inhibitors similar to that of RRBE. These findings deciphered a distinct difference in vasorelaxant effects between RRBE and the other RBEs. We also observed that RRBE induced a potent endothelium-dependent NO-mediated relaxation in coronary artery rings, which involved the Src/PI3K pathway that activates eNOS. Additionally, taxifolin exhibited, at least in part, similar vasoprotective effects of RRBE. Therefore, we propose that RRBE may serve as natural sources of functional phytochemicals that improve cardiovascular diseases associated with disturbed NO production and endothelial dysfunction.
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Affiliation(s)
- Eun-Hee Seong
- College of Pharmacy, Mokpo National University, Mokpo, South Korea
| | - Dal-Seong Gong
- College of Pharmacy, Mokpo National University, Mokpo, South Korea
| | - Saugat Shiwakoti
- College of Pharmacy, Mokpo National University, Mokpo, South Korea
| | - Deepak Adhikari
- College of Pharmacy, Mokpo National University, Mokpo, South Korea
| | - Hyun Jung Kim
- College of Pharmacy, Mokpo National University, Mokpo, South Korea
| | - Min-Ho Oak
- College of Pharmacy, Mokpo National University, Mokpo, South Korea
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Mukherjee PK, Efferth T, Das B, Kar A, Ghosh S, Singha S, Debnath P, Sharma N, Bhardwaj PK, Haldar PK. Role of medicinal plants in inhibiting SARS-CoV-2 and in the management of post-COVID-19 complications. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 98:153930. [PMID: 35114450 PMCID: PMC8730822 DOI: 10.1016/j.phymed.2022.153930] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 12/30/2021] [Accepted: 01/03/2022] [Indexed: 05/07/2023]
Abstract
BACKGROUND The worldwide corona virus disease outbreak, generally known as COVID-19 pandemic outbreak resulted in a major health crisis globally. The morbidity and transmission modality of COVID-19 appear more severe and uncontrollable. The respiratory failure and following cardiovascular complications are the main pathophysiology of this deadly disease. Several therapeutic strategies are put forward for the development of safe and effective treatment against SARS-CoV-2 virus from the pharmacological view point but till date there are no specific treatment regimen developed for this viral infection. PURPOSE The present review emphasizes the role of herbs and herbs-derived secondary metabolites in inhibiting SARS-CoV-2 virus and also for the management of post-COVID-19 related complications. This approach will foster and ensure the safeguards of using medicinal plant resources to support the healthcare system. Plant-derived phytochemicals have already been reported to prevent the viral infection and to overcome the post-COVID complications like parkinsonism, kidney and heart failure, liver and lungs injury and mental problems. In this review, we explored mechanistic approaches of herbal medicines and their phytocomponenets as antiviral and post-COVID complications by modulating the immunological and inflammatory states. STUDY DESIGN Studies related to diagnosis and treatment guidelines issued for COVID-19 by different traditional system of medicine were included. The information was gathered from pharmacological or non-pharmacological interventions approaches. The gathered information sorted based on therapeutic application of herbs and their components against SARSCoV-2 and COVID-19 related complications. METHODS A systemic search of published literature was conducted from 2003 to 2021 using different literature database like Google Scholar, PubMed, Science Direct, Scopus and Web of Science to emphasize relevant articles on medicinal plants against SARS-CoV-2 viral infection and Post-COVID related complications. RESULTS Collected published literature from 2003 onwards yielded with total 625 articles, from more than 18 countries. Among these 625 articles, more than 95 medicinal plants and 25 active phytomolecules belong to 48 plant families. Reports on the therapeutic activity of the medicinal plants belong to the Lamiaceae family (11 reports), which was found to be maximum reported from 4 different countries including India, China, Australia, and Morocco. Other reports on the medicinal plant of Asteraceae (7 reports), Fabaceae (8 reports), Piperaceae (3 reports), Zingiberaceae (3 reports), Ranunculaceae (3 reports), Meliaceae (4 reports) were found, which can be explored for the development of safe and efficacious products targeting COVID-19. CONCLUSION Keeping in mind that the natural alternatives are in the priority for the management and prevention of the COVID-19, the present review may help to develop an alternative approach for the management of COVID-19 viral infection and post-COVID complications from a mechanistic point of view.
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Affiliation(s)
- Pulok K Mukherjee
- Institute of Bioresources and Sustainable Development, Imphal-795001, India; School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India.
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Bhaskar Das
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
| | - Amit Kar
- Institute of Bioresources and Sustainable Development, Imphal-795001, India
| | - Suparna Ghosh
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
| | - Seha Singha
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
| | - Pradip Debnath
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
| | - Nanaocha Sharma
- Institute of Bioresources and Sustainable Development, Imphal-795001, India
| | | | - Pallab Kanti Haldar
- School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata -700 032, India
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Memete AR, Timar AV, Vuscan AN, Miere (Groza) F, Venter AC, Vicas SI. Phytochemical Composition of Different Botanical Parts of Morus Species, Health Benefits and Application in Food Industry. PLANTS (BASEL, SWITZERLAND) 2022; 11:plants11020152. [PMID: 35050040 PMCID: PMC8777750 DOI: 10.3390/plants11020152] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 12/31/2021] [Accepted: 01/03/2022] [Indexed: 05/05/2023]
Abstract
In recent years, mulberry has acquired a special importance due to its phytochemical composition and its beneficial effects on human health, including antioxidant, anticancer, antidiabetic and immunomodulatory effects. Botanical parts of Morus sp. (fruits, leaves, twigs, roots) are considered a rich source of secondary metabolites. The aim of our study was to highlight the phytochemical profile of each of the botanical parts of Morus tree, their health benefits and applications in food industry with an updated review of literature. Black and white mulberries are characterized in terms of predominant phenolic compounds in correlation with their medical applications. In addition to anthocyanins (mainly cyanidin-3-O-glucoside), black mulberry fruits also contain flavonols and phenolic acids. The leaves are a rich source of flavonols, including quercetin and kaempferol in the glycosylated forms and chlorogenic acid as predominant phenolic acids. Mulberry bark roots and twigs are a source of prenylated flavonoids, predominantly morusin. In this context, the exploitation of mulberry in food industry is reviewed in this paper, in terms of developing novel, functional food with multiple health-promoting effects.
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Affiliation(s)
- Adriana Ramona Memete
- Doctoral School of Biomedical Science, University of Oradea, 410087 Oradea, Romania;
| | - Adrian Vasile Timar
- Faculty of Environmental Protection, University of Oradea, 410048 Oradea, Romania; (A.V.T.); (A.N.V.)
| | - Adrian Nicolae Vuscan
- Faculty of Environmental Protection, University of Oradea, 410048 Oradea, Romania; (A.V.T.); (A.N.V.)
| | - Florina Miere (Groza)
- Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (F.M.); (A.C.V.)
| | - Alina Cristiana Venter
- Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (F.M.); (A.C.V.)
| | - Simona Ioana Vicas
- Faculty of Environmental Protection, University of Oradea, 410048 Oradea, Romania; (A.V.T.); (A.N.V.)
- Correspondence:
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Chang BY, Koo BS, Kim SY. Pharmacological Activities for Morus alba L., Focusing on the Immunostimulatory Property from the Fruit Aqueous Extract. Foods 2021; 10:foods10081966. [PMID: 34441742 PMCID: PMC8393821 DOI: 10.3390/foods10081966] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/11/2021] [Accepted: 08/20/2021] [Indexed: 12/21/2022] Open
Abstract
Depending on the extraction method, numerous compounds that have specific pharmacological effects can be obtained from M. alba L. There is a growing scientific interest in health problems related to aging. Efforts to develop safe immune-enhancing pharmaceuticals are increasing. This review aims to summarize and critically discuss the immunity enhancement effects and pharmaceutical efficacy of M. alba L. extracts. The scientific database search was conducted using Google Scholar, Web of Science, and PubMed until May 2021. Additional articles were identified and obtained from references in the retrieved articles. Ethanol or methanol extraction of various parts of M. alba L. identified a large amount of phenols and flavonoids, which are effective for immunosuppression, antioxidants, and cardiovascular diseases, and are antibacterial, and anticancer. Water extraction of M. alba L. enhanced the innate immune response based on immune cell activation. A polysaccharide and an alkaloid related to increased macrophage activity were isolated from M. alba L. fruit extracts. M. alba L. fruit water extracts primarily induced the production of pro-inflammatory substances, in model organisms, via TLR4 in immune cells. Water extracts have been shown to be effective in pathogen defense and tumor suppression by enhancing macrophage activity. Based on our literature review on the bioactivity of M. alba L. fruit extracts, particularly in relation to their immunity enhancement activity, we anticipate that M. alba-derived pharmaceuticals will have excellent potential in future medical research.
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Affiliation(s)
- Bo-Yoon Chang
- Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Jeonbuk, Iksan 54538, Korea;
| | - Bong-Seong Koo
- ForBioKorea Co., Ltd., Geumcheon-gu, Seoul 08592, Korea;
| | - Sung-Yeon Kim
- Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Jeonbuk, Iksan 54538, Korea;
- Correspondence: ; Tel.: +82-63-850-6806
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In Vitro Antiplatelet Activity of Mulberroside C through the Up-Regulation of Cyclic Nucleotide Signaling Pathways and Down-Regulation of Phosphoproteins. Genes (Basel) 2021; 12:genes12071024. [PMID: 34209363 PMCID: PMC8305937 DOI: 10.3390/genes12071024] [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: 04/26/2021] [Revised: 06/21/2021] [Accepted: 06/29/2021] [Indexed: 11/16/2022] Open
Abstract
Physiological agonists trigger signaling cascades, called "inside-out signaling", and activated platelets facilitate adhesion, shape change, granule release, and structural change of glycoprotein IIb/IIIa (αIIb/β3). Activated αIIb/β3 interacts with fibrinogen and begins second signaling cascades called "outside-in signaling". These two signaling pathways can lead to hemostasis or thrombosis. Thrombosis can occur in arterial and venous blood vessels and is a major medical problem. Platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, controlling platelet activity is important for platelet-mediated thrombosis and cardiovascular diseases. In this study, focus on Morus Alba Linn, a popular medicinal plant, to inhibit the function of platelets and found the containing component mulberroside C. We examine the effect of mulberroside C on the regulation of phosphoproteins, platelet-activating factors, and binding molecules. Agonist-induced human platelet aggregation is dose-dependently inhibited by mulberroside C without cytotoxicity, and it decreased Ca2+ mobilization and p-selectin expression through the upregulation of inositol 1, 4, 5-triphosphate receptor I (Ser1756), and downregulation of extracellular signal-regulated kinase (ERK). In addition, mulberroside C inhibited thromboxane A2 production, fibrinogen binding, and clot retraction. Our results show antiplatelet effects and antithrombus formation of mulberroside C in human platelets. Thus, we confirm that mulberroside C could be a potential phytochemical for the prevention of thrombosis-mediated CVDs.
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Yun W, Dan W, Liu J, Guo X, Li M, He Q. Investigation of the Mechanism of Traditional Chinese Medicines in Angiogenesis through Network Pharmacology and Data Mining. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:5539970. [PMID: 34007289 PMCID: PMC8102115 DOI: 10.1155/2021/5539970] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 03/20/2021] [Accepted: 04/15/2021] [Indexed: 12/11/2022]
Abstract
Although traditional Chinese medicine is effective and safe for the treatment of angiogenesis, the in vivo intervention mechanism is diverse, complex, and largely unknown. Therefore, we aimed to explore the active ingredients of traditional Chinese medicine and their mechanisms of action against angiogenesis. Data on angiogenesis-related targets were collected from GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, DrugBank, and DisGeNET. These were matched to related molecular compounds and ingredients in the traditional Chinese medicine system pharmacology platform. The data were integrated and based on the condition of degree > 1, and relevant literature, target-compound, compound-medicine, and target-compound-medicine networks were constructed using Cytoscape. Molecular docking was used to predict the predominant binding combination of core targets and components. We obtained 79 targets for angiogenesis; 41 targets were matched to 3839 compounds, of which 110 compounds were selected owing to their high correlation with angiogenesis. Fifty-five combinations in the network were obtained by molecular docking, among which PTGS2-astragalin (-9.18 kcal/mol), KDR-astragalin (-7.94 kcal/mol), PTGS2-quercetin (-7.41 kcal/mol), and PTGS2-myricetin (-7.21 kcal/mol) were top. These results indicated that the selected potential core compounds have good binding activity with the core targets. Eighty new combinations were obtained from the network, and the top combinations based on affinity were KDR-beta-carotene (-10.13 kcal/mol), MMP9-beta-sitosterol (-8.04 kcal/mol), MMP9-astragalin (-7.82 kcal/mol), and MMP9-diosgenin (-7.51 kcal/mol). The core targets included PTGS2, KDR, VEGFA, and MMP9. The essential components identified were astragalin, kaempferol, myricetin, quercetin, and β-sitosterol. The crucial Chinese medicines identified included Polygoni Cuspidati Rhizoma et Radix, Morus alba Root Bark, and Forsythiae Fructus. By systematically analysing the ingredients of traditional Chinese medicine and their targets, it is possible to determine their potential mechanisms of action against pathological angiogenesis. Our study provides a basis for further research and the development of new therapeutics for angiogenesis.
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Affiliation(s)
- Wingyan Yun
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
- Graduate School of Beijing University of Chinese Medicine, Beijing 100029, China
| | - Wenchao Dan
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
- Graduate School of Beijing University of Chinese Medicine, Beijing 100029, China
| | - Jinlei Liu
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Xinyuan Guo
- Cancer Hospital Chinese Academy of Medical Sciences, Beijing 100021, China
| | - Min Li
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qingyong He
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Microparticles-Mediated Vascular Inflammation and its Amelioration by Antioxidant Activity of Baicalin. Antioxidants (Basel) 2020; 9:antiox9090890. [PMID: 32962240 PMCID: PMC7555600 DOI: 10.3390/antiox9090890] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 09/14/2020] [Accepted: 09/18/2020] [Indexed: 02/07/2023] Open
Abstract
Microparticles (MPs) are extracellular vesicles (0.1–1.0 μm in size), released in response to cell activation or apoptosis. Endothelial microparticles (EC-MP), vascular smooth muscle cell microparticles (VSMC-MP), and macrophage microparticles (MØ-MP) are key hallmarks of atherosclerosis progression. In our current study, we investigated the potent antioxidant activity of baicalin to ameliorate MP-induced vascular smooth muscle cell (VSMC) dysfunction and endothelial cell (EC) dysfunction, as well as the production of inflammatory mediators in macrophage (RAW264.7). In our study, baicalin suppressed the apoptosis, reactive oxygen species (ROS) generation, NO production, foam cell formation, protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in MØ-MP-induced RAW264.7. In addition, VSMC migration induced by VSMC-MP was dose-dependently inhibited by baicalin. Likewise, baicalin inhibits metalloproteinase-9 expression and suppresses VSMC-MP-induced VSMC proliferation by down-regulation of mitogen-activated protein kinase and proliferating cell nuclear antigen protein expressions. Baicalin also inhibited ROS production and apoptosis in VSMC. In EC, the marker of endothelial dysfunction (endothelial senescence, upregulation of ICAM, and ROS production) induced by EC-MP was halted by baicalin. Our results suggested that baicalin exerts potent biological activity to restore the function of EC and VSMC altered by their corresponding microparticles and inhibits the release of inflammation markers from activated macrophages.
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Park HJ, Chi GY, Choi YH, Park SH. The root bark of Morus alba L. regulates tumor-associated macrophages by blocking recruitment and M2 polarization of macrophages. Phytother Res 2020; 34:3333-3344. [PMID: 32677743 DOI: 10.1002/ptr.6783] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 05/24/2020] [Accepted: 06/04/2020] [Indexed: 12/15/2022]
Abstract
Tumor-associated macrophages (TAMs) promote tumor growth and metastasis, and are closely related with poor prognosis of cancers. Therefore, TAMs have been an attractive target in cancer therapy. This study investigated whether the root bark of Morus alba L. (MA) regulates TAMs. Methylene chloride extract of MA (MEMA) decreased the migration of RAW264.7 cells and THP-1 macrophages toward cancer cells via inhibition of focal adhesion kinase and Src activity. In addition, MEMA inhibited the phorbol myristate acetate-stimulated secretion of plasminogen activator inhibitor-1 from cancer cells, leading to the decreased chemotaxis of macrophages. Finally, MEMA-suppressed M2 macrophage polarization induced by interleukin (IL)-4/IL-13 or IL-6. MEMA downregulated the mRNA expression of M2 macrophage markers and decreased the phosphorylation of signal transducer and activator of transcription (STAT) 6 and STAT3 in RAW264.7 cells. Suppression of M2 polarization of macrophages by MEMA resulted in the reduced migration of Lewis lung carcinoma cells when the conditioned media from RAW264.7 cells was used as a chemoattractant. Taken together, our results demonstrate that MEMA regulates TAMs by blocking the recruitment of macrophages into tumor microenvironments and by inhibiting M2 polarization of macrophages.
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Affiliation(s)
- Hyun-Ji Park
- Department of Pathology, College of Korean Medicine, Dong-eui University, Busan, Republic of Korea
| | - Gyoo-Yong Chi
- Department of Pathology, College of Korean Medicine, Dong-eui University, Busan, Republic of Korea
| | - Yung-Hyun Choi
- Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan, Republic of Korea
| | - Shin-Hyung Park
- Department of Pathology, College of Korean Medicine, Dong-eui University, Busan, Republic of Korea
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Arraki K, Totoson P, Attia R, Zedet A, Pudlo M, Messaoud C, Demougeot C, Girard C. Arginase inhibitory properties of flavonoid compounds from the leaves of Mulberry (Morus alba, Moraceae). J Pharm Pharmacol 2020; 72:1269-1277. [PMID: 32496585 DOI: 10.1111/jphp.13297] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 04/25/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVES We aimed to isolate and identify bioactive molecules from Morus alba (Moraceae) leaves having arginase inhibitory activity towards the combat of clinical outcomes related to endothelial dysfunction. METHOD Extraction and isolation were carried out by successive macerations, prepurification by using a Solid Phase Extraction (SPE) and separation using preparative PLC. The structures of the isolated components were established and confirmed by spectroscopic analyses, including the ESI-HRMS and NMR spectroscopic investigations. Biological evaluation was performed by using an in vitro assay with liver bovine purified arginase and by an ex vivo aortic ring study. KEY FINDINGS We demonstrated that a phenolic extract from the leaves of M. alba possesses mammalian arginase inhibitory capacities. Investigation of the chemical constituents of its leaves results in the isolation and identification of ten compounds investigated in vitro for their arginase inhibitory capacities. Four compounds showed significant inhibition of arginase, with percentage inhibition ranging from 54% to 83% at 100 µm. In isolated rat aortic rings incubated with NO synthase inhibitor, Luteolin-7-diglucoside compound (2) was able to increase acetylcholine-induced relaxation. CONCLUSIONS These results demonstrated the attractive ability of M. alba to be a potential source for the discovery of new active products on vascular system.
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Affiliation(s)
- Kamel Arraki
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, Besançon, France
| | - Perle Totoson
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, Besançon, France
| | - Rym Attia
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, Besançon, France.,Laboratory of Nanobiotechnology and Medicinal Plants, Department of Biology, National Institute of Applied Science and Technology (INSAT), University of Carthage, Tunis Cedex, Tunisia
| | - Andy Zedet
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, Besançon, France
| | - Marc Pudlo
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, Besançon, France
| | - Chokri Messaoud
- Laboratory of Nanobiotechnology and Medicinal Plants, Department of Biology, National Institute of Applied Science and Technology (INSAT), University of Carthage, Tunis Cedex, Tunisia
| | | | - Corine Girard
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, Besançon, France
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A Review of Endothelium-Dependent and -Independent Vasodilation Induced by Phytochemicals in Isolated Rat Aorta. Animals (Basel) 2019; 9:ani9090623. [PMID: 31470540 PMCID: PMC6769919 DOI: 10.3390/ani9090623] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 08/17/2019] [Accepted: 08/21/2019] [Indexed: 12/27/2022] Open
Abstract
Simple Summary Cardiovascular diseases are the leading cause of death worldwide, so the investigation of new therapeutic tools is a priority for their prevention and treatment. This review shows the relevant contribution of the isolated rat aorta as an in vitro experimental model to validate the therapeutic potential of phytochemicals, mainly those present in plants traditionally used in folk medicine to relieve hypertension. The results of the assays carried out in this model show that a variety of plant extracts and their isolated compounds produce vasodilation, which may explain their use, especially to treat hypertension. Abstract This review discusses the contribution of the use of the isolated rat aorta (IRA) as a model for the evaluation of extracts and metabolites produced by plants with a vasodilator effect in animals. This model continues to be a valuable approach for the search and development of new phytochemicals consumed as medicinal plants or foods. In most cases, the sources of phytochemicals have been used in folk medicine to treat ailments that include hypertension. In this model, the endothelium is emphasized as a key component that modulates the vessel contractility, and therefore the basal tone and blood pressure. Based on the functional nature of the model, we focused on studies that determined the endothelium-dependent and -independent vasodilatory activity of phytochemicals. We describe the mechanisms that account for aorta contraction and relaxation, and subsequently show the vasoactive effect of a series of phytochemicals acting as vasodilators and its endothelium dependence. We highlight information regarding the cardiovascular benefits of phytochemicals, especially their potential antihypertensive effect. On this basis, we discuss the advantages of the IRA as a predictive model to support the research and development of new drugs that may be of help in the prevention and treatment of cardiovascular diseases, the number one cause of death worldwide.
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