Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models
Background Phytolaccagenin, a natural triterpenoid, is reported for various biological activities that indicate its potential role in the management of hypertension. Methods Phytolaccagenin was evaluated for its antihypertensive activity in rat models via in vivo and in vitro experiments using polye...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-08-01
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| Series: | Clinical and Experimental Hypertension |
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| Online Access: | http://dx.doi.org/10.1080/10641963.2022.2079671 |
| _version_ | 1797681034605625344 |
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| author | Imran Ul Haq Taseer Ahmad Taous Khan Abdul Jabbar Shah |
| author_facet | Imran Ul Haq Taseer Ahmad Taous Khan Abdul Jabbar Shah |
| author_sort | Imran Ul Haq |
| collection | DOAJ |
| description | Background Phytolaccagenin, a natural triterpenoid, is reported for various biological activities that indicate its potential role in the management of hypertension. Methods Phytolaccagenin was evaluated for its antihypertensive activity in rat models via in vivo and in vitro experiments using polyethylene tubings for cannulation, organ bath bubbled with carbogen gas, and a pressure transducer connected to a PowerLab data acquisition system. Results Intravenous administration of phytolaccagenin decreased mean arterial pressure (MAP), significantly, in normotensive and hypertensive anesthetized rats. Pretreatment of rats with atropine (2 mg/kg) partially reversed the decrease in blood pressure due to phytolaccagenin at first tested doses. However, Nω-nitro-L-arginine methyl ester (L-NAME) (100 mg/kg) pretreatment modified the effect of phytolaccagenin on blood pressure with greater response. In isolated rat aortic rings precontracted with phenylephrine, cumulative addition of phytolaccagenin induced relaxation that is ablated (50%) with denudation and pre-incubation with atropine (1 μM) and L-NAME (10 μM). Phytolaccagenin also partially inhibited high K+ precontraction at initial doses, while an inhibitory effect was observed at higher concentrations, confirming its effect on voltage-dependent calcium channels. In isolated spontaneously beating rat atrial strips, phytolaccagenin suppressed the atrial tone that was reduced with isoprenaline and atropine pre-incubation, suggesting the role of cardiac adrenergic and muscarinic receptors. Interestingly, atenolol (1 μM) pretreatment also ablated the cardiac effects of phytolaccagenin. Conclusion The antihypertensive effect of phytolaccagenin is due to a decrease in vascular resistance and cardiac depressant effects. These effects are mediated via muscarinic receptors-linked NO pathway, inhibitory effect on Ca2+ movements (vascular), and activation of cardiac muscarinic and blockade of β-adrenergic receptors. |
| first_indexed | 2024-03-11T23:39:02Z |
| format | Article |
| id | doaj.art-8f7c2a07a8fc473183582c11e5d31f94 |
| institution | Directory Open Access Journal |
| issn | 1064-1963 1525-6006 |
| language | English |
| last_indexed | 2024-03-11T23:39:02Z |
| publishDate | 2022-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Clinical and Experimental Hypertension |
| spelling | doaj.art-8f7c2a07a8fc473183582c11e5d31f942023-09-19T16:04:08ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062022-08-0144655756610.1080/10641963.2022.20796712079671Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat modelsImran Ul Haq0Taseer Ahmad1Taous Khan2Abdul Jabbar Shah3COMSATS University IslamabadCollege of Pharmacy, University of Sargodha, University RoadCOMSATS University IslamabadCOMSATS University IslamabadBackground Phytolaccagenin, a natural triterpenoid, is reported for various biological activities that indicate its potential role in the management of hypertension. Methods Phytolaccagenin was evaluated for its antihypertensive activity in rat models via in vivo and in vitro experiments using polyethylene tubings for cannulation, organ bath bubbled with carbogen gas, and a pressure transducer connected to a PowerLab data acquisition system. Results Intravenous administration of phytolaccagenin decreased mean arterial pressure (MAP), significantly, in normotensive and hypertensive anesthetized rats. Pretreatment of rats with atropine (2 mg/kg) partially reversed the decrease in blood pressure due to phytolaccagenin at first tested doses. However, Nω-nitro-L-arginine methyl ester (L-NAME) (100 mg/kg) pretreatment modified the effect of phytolaccagenin on blood pressure with greater response. In isolated rat aortic rings precontracted with phenylephrine, cumulative addition of phytolaccagenin induced relaxation that is ablated (50%) with denudation and pre-incubation with atropine (1 μM) and L-NAME (10 μM). Phytolaccagenin also partially inhibited high K+ precontraction at initial doses, while an inhibitory effect was observed at higher concentrations, confirming its effect on voltage-dependent calcium channels. In isolated spontaneously beating rat atrial strips, phytolaccagenin suppressed the atrial tone that was reduced with isoprenaline and atropine pre-incubation, suggesting the role of cardiac adrenergic and muscarinic receptors. Interestingly, atenolol (1 μM) pretreatment also ablated the cardiac effects of phytolaccagenin. Conclusion The antihypertensive effect of phytolaccagenin is due to a decrease in vascular resistance and cardiac depressant effects. These effects are mediated via muscarinic receptors-linked NO pathway, inhibitory effect on Ca2+ movements (vascular), and activation of cardiac muscarinic and blockade of β-adrenergic receptors.http://dx.doi.org/10.1080/10641963.2022.2079671phytolaccageninantihypertensivecalcium movementnitric oxidemuscarinicβ- receptors |
| spellingShingle | Imran Ul Haq Taseer Ahmad Taous Khan Abdul Jabbar Shah Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models Clinical and Experimental Hypertension phytolaccagenin antihypertensive calcium movement nitric oxide muscarinic β- receptors |
| title | Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models |
| title_full | Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models |
| title_fullStr | Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models |
| title_full_unstemmed | Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models |
| title_short | Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models |
| title_sort | antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models |
| topic | phytolaccagenin antihypertensive calcium movement nitric oxide muscarinic β- receptors |
| url | http://dx.doi.org/10.1080/10641963.2022.2079671 |
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