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Fulltext Evaluation of vasodilatory effect and antihypertensive effect of chrysin through in vitro and sub-chronic in vivo study

Tew WY, Tan CS, Yan CS, Loh HW, Wen X, Wei X, et al.

Biomed Pharmacother, 2023 Jan;157:114020.
PMID: 36469968 DOI: 10.1016/j.biopha.2022.114020

Chrysin, a bioflavonoid belonging to the flavone, occurs naturally in plants such as the passionflower, honey and propolis. Few studies have demonstrated that chrysin can promote vasorelaxant activities in rats' aorta and mesenteric arteries. To date, no research has explored the signalling system routes that chrysin may utilise to produce its vasorelaxant action. Therefore, this study aimed to investigate the underlying mechanisms involved in chrysin-induced vasorelaxant in rats' aortic rings and assess the antihypertensive effect of chrysin in spontaneously hypertensive rats (SHRs). The findings revealed that chrysin utilised both endothelium-dependent and endothelium-independent mechanisms. The presence of L-NAME (endothelial NO synthase inhibitor), ODQ (sGC inhibitor), methylene blue (cGMP lowering agent), 4-AP (voltage-gated potassium channel inhibitor), atropine (muscarinic receptors inhibitor) and propranolol (β-adrenergic receptors inhibitor) significantly reduced the chrysin's vasorelaxant action. Furthermore, chrysin can reduce intracellular Ca2+ levels by limiting the extracellular intake of Ca2+ through voltage-operated calcium channels and blocking the intracellular release of Ca2+ from the sarcoplasmic reticulum via the IP3 receptor. These indicate that chrysin-induced vasorelaxants involved NO/sGC/cGMP signalling cascade, muscarinic and β-adrenergic receptors, also the potassium and calcium channels. Although chrysin had vasorelaxant effects in in vitro studies, the in vivo antihypertensive experiment discovered chrysin does not significantly reduce the blood pressure of SHRs following 21 days of oral treatment. This study proved that chrysin utilised multiple signalling pathways to produce its vasorelaxant effect in the thoracic aorta of rats; however, it had no antihypertensive effect on SHRs.

Matched MeSH terms: Receptors, Adrenergic, beta/metabolism
Anti-diarrheal activities of phytol along with its possible mechanism of action through in-vivo and in-silico models

Islam MT, Rahman MA, Saeed M, Ul-Haq Z, Alam MJ, Mondal M, et al.

Cell Mol Biol (Noisy-le-grand), 2020 Jun 25;66(4):243-249.
PMID: 32583783

Phytol (PHY), a chlorophyll-derived diterpenoid, exhibits numerous pharmacological properties, including antioxidant, antimicrobial, and anticancer activities. This study evaluates the anti-diarrheal effect of phytol (PHY) along with its possible mechanism of action through in-vivo and in-silico models. The effect of PHY was investigated on castor oil-induced diarrhea in Swiss mice by using prazosin, propranolol, loperamide, and nifedipine as standards with or without PHY. PHY at 50 mg/kg (p.o.) and all other standards exhibit significant (p < 0.05) anti-diarrheal effect in mice. The effect was prominent in the loperamide and propranolol groups. PHY co-treated with prazosin and propranolol was found to increase in latent periods along with a significant reduction in diarrheal section during the observation period than other individual or combined groups. Furthermore, molecular docking studies also suggested that PHY showed better interactions with the α- and β-adrenergic receptors, especially with α-ADR1a and β-ADR1. In the former case, PHY showed interaction with hydroxyl group of Ser192 at a distance of 2.91Å, while in the latter it showed hydrogen bond interactions with Thr170 and Lys297 with a distance of 2.65 and 2.72Å, respectively. PHY exerted significant anti-diarrheal effect in Swiss mice, possibly through blocking α- and β-adrenergic receptors.

Matched MeSH terms: Receptors, Adrenergic, beta/metabolism
Mechanisms of β-adrenergic receptors agonists in mediating pro and anti-apoptotic pathways in hyperglycemic Müller cells

Safi SZ, Saeed L, Shah H, Latif Z, Ali A, Imran M, et al.

Mol Biol Rep, 2022 Oct;49(10):9473-9480.
PMID: 35925485 DOI: 10.1007/s11033-022-07816-0

BACKGROUND: The current study aimed to investigate the stimulatory effect of beta-adrenergic receptors (β-ARs) on brain derived neurotropic factor (BDNF) and cAMP response element binding protein (CREB).
METHODS: Human Müller cells were cultured in low and high glucose conditions. Cells were treated with xamoterol (selective agonist for β1-AR), salmeterol (selective agonist for β2-AR), isoproterenol (β-ARs agonist) and propranolol (β-ARs antagonist), at 20 µM concentration for 24 h. Western Blotting assay was performed for the gene expression analysis. DNA damage was evaluated by TUNEL assay. DCFH-DA assay was used to check the level of reactive oxygen species (ROS). Cytochrome C release was measured by ELISA.
RESULTS: Xamoterol, salmeterol and isoproterenol showed no effect on Caspase-8 but it reduced the apoptosis and increased the expression of BDNF in Müller cells. A significant change in the expression of caspase-3 was observed in cells treated with xamoterol and salmeterol as compared to isoproterenol. Xamoterol, salmeterol and isoproterenol significantly decreased the reactive oxygen species (ROS) when treated for 24 hours. Glucose-induced cytochrome c release was disrupted in Müller cells.
CONCLUSION: β-ARs, stimulated by agonist play a protective role in hyperglycemic Müller cells, with the suppression of glucose-induced caspase-3 and cytochrome c release. B-Ars may directly mediate the gene expression of BDNF.

Matched MeSH terms: Receptors, Adrenergic, beta/metabolism
Effects of various nonopioid receptor antagonists on the antinociceptive activity of Muntingia calabura extracts in mice

Zakaria ZA, Hassan MH, Nurul Aqmar MN, Abd Ghani M, Mohd Zaid SN, Sulaiman MR, et al.

Methods Find Exp Clin Pharmacol, 2007 Oct;29(8):515-20.
PMID: 18040526

This study was carried out in mice to determine the nonopioid receptor signaling pathway(s) that might modulate the antinociceptive activity of the aqueous and chloroform extracts of Muntingia calabura (M. calabura) leaves, using the hot-plate test. The leaves of M. calabura were sequentially soaked [1:2 (w/v); 72 h] in distilled water (dH(2)O) and chloroform. The 50% concentration extracts were selected for this study based on the plant's previously established antinociceptive profiles. The mice (n = 7) were pretreated (s.c.) for 10 min with the selected nonopioid receptor antagonists, followed by the (s.c.) administration of the respective extract. The latency of discomfort was recorded at the interval time of 0.5, 1, 2, 3, 4 and 5 h after the extract administration. The 5 mg/kg atropine, 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol, 1 mg/kg haloperidol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the aqueous extract-induced antinociceptive activity. The 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the chloroform extract-induced antinociceptive activity. In conclusion, the central antinociceptive activity of M. calabura leaves appears to be involved in the modulation of various nonopioid receptor signaling pathways. Its aqueous extract antinociceptive activity is mediated via modulation of the muscarinic, alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic, dopaminergic and GABAergic receptors, while its chloroform extract activity is mediated via modulation of the alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic and GABAergic receptors.

Matched MeSH terms: Receptors, Adrenergic, beta/metabolism