Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

Roberts, Richard E.; Allen, Stephanie; Chang, An; Henderson, Holly; Hobson, G.C.; Karania, B.; Morgan, Kevin; Pek, A.S.Y.; Raghvani, K.; Shee, Cheng Yap; Shikotra, J.; Street, E.; Abbas, Zainab Sabri; Ellis, K. O.; Heer, J.K.; Alexander, Stephen P.H.

doi:10.1016/j.taap.2013.06.021

Cited by 26 publications

(20 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, neither soluble guanylate cyclase (sGC) nor adenylyl cyclase activation is involved in the mediation of vasorelaxant effects of (−)-α-bisabolol as they were unaffected following pre-incubation of aortic preparations with the sGC inhibitor ODQ and the cAMP-dependent protein kinase A inhibitor KT-5720, respectively. These data are consistent with a recent study showing vasodilatory effect of bioactive components from Matricaria recutita L., including the (−)-α-bisabolol, in porcine vessels [21].…”

Section: Discussionsupporting

confidence: 93%

(−)-α-Bisabolol inhibits preferentially electromechanical coupling on rat isolated arteries

Siqueira

Ribeiro-Filho

Freire

et al. 2014

Vascular Pharmacology

View full text Add to dashboard Cite

Previous findings enable us to hypothesize that (-)-α-bisabolol acts as inhibitor of voltage-dependent Ca(2+) channels in smooth muscle. The current study was aimed at consolidating such hypothesis through the recording of isometric tension, measurement of intracellular Ca(2+) as well as discovery of channel target using in silico analysis. In rat aortic rings, (-)-α-bisabolol (1-1000 µM) relaxed KCl- and phenylephrine-elicited contractions, but the IC50 differed significantly (22.8 [17.6-27.7] and 200.7 [120.4-334.6] µM, respectively). The relaxation of phenylephrine contractions remained unaffected by l-NAME, indomethacin, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, tetraethylammonium, glibenclamide or KT-5720. Under Ca(2+)-free conditions, (-)-α-bisabolol did not alter the contractions evoked by phenylephrine or caffeine whereas it reduced those evoked by CaCl2 in KCl-, but not in PHE-stimulated preparations. Furthermore, it did not significantly alter the contractions evoked by phorbol 12,13-dibutyrate or induced by the extracellular Ca(2+) restoration in cyclopiazonic acid-treated preparations. In mesenteric rings loaded with Fluo-4 AM, (-)-α-bisabolol blunted the tension and the cytosolic levels of Ca(2+) in response to K(+) but not to norepinephrine. Silico docking analysis of the Cavβ2a subunit of voltage-dependent Ca(2+) channel indicated putative docking sites for (-)-α-bisabolol. These findings reinforce the ability of (-)-α-bisabolol to inhibit preferentially contractile responses evoked by Ca(2+) influx through voltage-dependent Ca(2+) channels.

show abstract

Section: Discussionsupporting

confidence: 93%

(−)-α-Bisabolol inhibits preferentially electromechanical coupling on rat isolated arteries

Siqueira

Ribeiro-Filho

Freire

et al. 2014

Vascular Pharmacology

View full text Add to dashboard Cite

show abstract

“…Of the 15 plants, 10 were chosen for their purported hypotensive properties: the leaves and flowers of fresh lavender (Lavandula angustifolia) and German chamomile (Matricaria chamomilla); leaves of fresh basil (Ocimum basilicum), oregano (Origanum vulgaris), marjoram (Origanum majorana), and thyme (Thymus vulgaris); whole fennel seed (Foeniculum vulgare); dried rhizome of ginger (Zingiber officinale); dried roots of shrubby Sophora (Sophora flavescens; termed Ku Shen in Chinese traditional medicine); and dried Vietnamese Sophora (Sophora tonkinensis) root (VSR) and rhizome. We classified the plants as hypotensive based on historic and/or current usage to purportedly lower blood pressure, coupled with published clinical, preclinical, and/or ex vivo tissue studies demonstrating the capacity of the extracts to lower blood pressure and/or vasorelax (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52).…”

Section: Resultsmentioning

confidence: 99%

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

Manville

Horst

Redford

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Botanical folk medicines have been used throughout human history to treat common disorders such as hypertension, often with unknown underlying mechanisms. Here, we discovered that hypotensive folk medicines from a genetically diverse range of plant species each selectively activated the vascular-expressed KCNQ5 potassium channel, a feature lacking in the modern synthetic pharmacopeia, whereas nonhypotensive plant extracts did not. Analyzing constituents of the hypotensive Sophora flavescens root, we found that the quinolizidine alkaloid aloperine is a KCNQ-dependent vasorelaxant that potently and isoform-selectively activates KCNQ5 by binding near the foot of the channel voltage sensor. Our findings reveal that KCNQ5-selective activation is a defining molecular mechanistic signature of genetically diverse traditional botanical hypotensives, transcending plant genus and human cultural boundaries. Discovery of botanical KCNQ5-selective potassium channel openers may enable future targeted therapies for diseases including hypertension and KCNQ5 loss-of-function encephalopathy.

show abstract

“…Consistent with our results, Siqueira et al 46 have shown that tracheal rings of rats challenged with ovalbumin and treated previously with α-bis (aerosol) reduced the hyperresponsive phenotype, and they showed that α-bis may act as an inhibitor of voltagedependent Ca 2+ channels. Similarly, Roberts et al, 47 using a porcine isolated tissue bath (from coronary and splenic arteries), demonstrated that α-bis was able to inhibit calciuminduced contractions and that the removal of extracellular calcium inhibited its responses.…”

mentioning

confidence: 88%

α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

D'Almeida¹,

Oliveira²,

Souza³

et al. 2017

IJN

View full text Add to dashboard Cite

Acute respiratory distress syndrome (ARDS) is a severe clinical condition of respiratory failure due to an intense inflammatory response with different etiologies. Despite all efforts, therapy remains limited, and ARDS is still associated with high mortality and morbidity. Plants can provide a vast source of active natural products for the discovery of new drugs. α-bisabolol (α-bis), a constituent of the essential oil from chamomile, has elicited pharmacological interest. However, the molecule has some limitations to its biological application. This study was conducted to develop a drug delivery system using lipid-core nanocapsules (LNCs) to improve the anti-inflammatory effects of orally administered α-bis. α-bis-loaded LNCs (α-bis-LNCs) were prepared by interfacial deposition of poly(ε-caprolactone) and orally administered in a mouse model of ARDS triggered by an intranasal administration of lipopolysaccharide (LPS). We found that α-bis-LNCs (30, 50, and 100 mg kg −1 ) significantly reduced airway hyperreactivity (AHR), neutrophil infiltration, myeloperoxidase activity, chemokine levels (KC and MIP-2), and tissue lung injury 18 hours after the LPS challenge. By contrast, free α-bis failed to modify AHR and neutrophil accumulation in the bronchoalveolar lavage effluent and lung parenchyma and inhibited elevation in the myeloperoxidase and MIP-2 levels only at the highest dose. Furthermore, only α-bis-LNCs reduced LPS-induced changes in mitogen-activated protein kinase signaling, as observed by a significant reduction in phosphorylation levels of ERK1/2, JNK, and p38 proteins. Taken together, our results clearly show that by using LNCs, α-bis was able to decrease LPS-induced inflammation. These findings may be explained by the robust increase of α-bis concentration in the lung tissue that was achieved by the LNCs. Altogether, these results indicate that α-bis-LNCs should further be investigated as a potential alternative for the treatment of ARDS.

show abstract

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

Cited by 26 publications

References 17 publications

(−)-α-Bisabolol inhibits preferentially electromechanical coupling on rat isolated arteries

(−)-α-Bisabolol inhibits preferentially electromechanical coupling on rat isolated arteries

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

Contact Info

Product

Resources

About

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

Cited by 26 publications

References 17 publications

(−)-α-Bisabolol inhibits preferentially electromechanical coupling on rat isolated arteries

(−)-α-Bisabolol inhibits preferentially electromechanical coupling on rat isolated arteries

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

&alpha;-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

Contact Info

Product

Resources

About

α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice