Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal Herbs
The goal of this study was to assess the pharmacological effects of black tea (<i>Camellia sinensis</i> var. assamica) water extract on human kinin-forming enzymes in vitro. Tea is a highly consumed beverage in the world. Factor XII (FXII, Hageman factor)-independent- and -dependent acti...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/14/4126 |
| _version_ | 1827687308701204480 |
|---|---|
| author | Hassan Madkhali Amer Tarawneh Zulfiqar Ali Hoang V. Le Stephen J. Cutler Ikhlas A. Khan Zia Shariat-Madar |
| author_facet | Hassan Madkhali Amer Tarawneh Zulfiqar Ali Hoang V. Le Stephen J. Cutler Ikhlas A. Khan Zia Shariat-Madar |
| author_sort | Hassan Madkhali |
| collection | DOAJ |
| description | The goal of this study was to assess the pharmacological effects of black tea (<i>Camellia sinensis</i> var. assamica) water extract on human kinin-forming enzymes in vitro. Tea is a highly consumed beverage in the world. Factor XII (FXII, Hageman factor)-independent- and -dependent activation of prekallikrein to kallikrein leads to the liberation of bradykinin (BK) from high-molecular-weight kininogen (HK). The excessive BK production causes vascular endothelial and nonvascular smooth muscle cell permeability, leading to angioedema. The prevalence of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema appears to be through BK. Both histamine and BK are potent inflammatory mediators. However, the treatments for histamine-mediated angioedema are unsuitable for BK-mediated angioedema. We hypothesized that long-term consumption of tea would reduce bradykinin-dependent processes within the systemic and pulmonary vasculature, independent of the anti-inflammatory actions of polyphenols. A purified fraction of the black tea water extract inhibited both kallikrein and activated FXII. The black tea water extracts inhibited factor XII-induced cell migration and inhibited the production of kallikrein on the endothelial cell line. We compared the inhibitory effects of the black tea water extract and twenty-three well-known anti-inflammatory medicinal herbs, in inhibiting both kallikrein and FXII. Surprisingly, arjunglucoside II specifically inhibited the activated factor XII (FXIIa), but not the kallikrein and the activated factor XI. Taken together, the black tea water extract exerts its anti-inflammatory effects, in part, by inhibiting kallikrein and activated FXII, which are part of the plasma kallikrein–kinin system (KKS), and by decreasing BK production. The inhibition of kallikrein and activated FXII represents a unique polyphenol-independent anti-inflammatory mechanism of action for the black tea. |
| first_indexed | 2024-03-10T09:31:41Z |
| format | Article |
| id | doaj.art-a9438bbbe1104c2fa66e09607a64ad92 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:31:41Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a9438bbbe1104c2fa66e09607a64ad922023-11-22T04:28:57ZengMDPI AGMolecules1420-30492021-07-012614412610.3390/molecules26144126Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal HerbsHassan Madkhali0Amer Tarawneh1Zulfiqar Ali2Hoang V. Le3Stephen J. Cutler4Ikhlas A. Khan5Zia Shariat-Madar6Department of Pharmacology, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 16278, Saudi ArabiaDepartment of Chemistry, Tafila Technical University, Tafila 66110, JordanNational Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USADepartment of BioMolecular Sciences, Division of Medicinal Chemistry, University of Mississippi, Oxford, MS 38677, USACollege of Pharmacy, University of South Carolina, Columbia, SC 29208, USANational Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USADepartment of BioMolecular Sciences, Division of Pharmacology, University of Mississippi, Oxford, MS 38677, USAThe goal of this study was to assess the pharmacological effects of black tea (<i>Camellia sinensis</i> var. assamica) water extract on human kinin-forming enzymes in vitro. Tea is a highly consumed beverage in the world. Factor XII (FXII, Hageman factor)-independent- and -dependent activation of prekallikrein to kallikrein leads to the liberation of bradykinin (BK) from high-molecular-weight kininogen (HK). The excessive BK production causes vascular endothelial and nonvascular smooth muscle cell permeability, leading to angioedema. The prevalence of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema appears to be through BK. Both histamine and BK are potent inflammatory mediators. However, the treatments for histamine-mediated angioedema are unsuitable for BK-mediated angioedema. We hypothesized that long-term consumption of tea would reduce bradykinin-dependent processes within the systemic and pulmonary vasculature, independent of the anti-inflammatory actions of polyphenols. A purified fraction of the black tea water extract inhibited both kallikrein and activated FXII. The black tea water extracts inhibited factor XII-induced cell migration and inhibited the production of kallikrein on the endothelial cell line. We compared the inhibitory effects of the black tea water extract and twenty-three well-known anti-inflammatory medicinal herbs, in inhibiting both kallikrein and FXII. Surprisingly, arjunglucoside II specifically inhibited the activated factor XII (FXIIa), but not the kallikrein and the activated factor XI. Taken together, the black tea water extract exerts its anti-inflammatory effects, in part, by inhibiting kallikrein and activated FXII, which are part of the plasma kallikrein–kinin system (KKS), and by decreasing BK production. The inhibition of kallikrein and activated FXII represents a unique polyphenol-independent anti-inflammatory mechanism of action for the black tea.https://www.mdpi.com/1420-3049/26/14/4126kininsinflammationangioedema |
| spellingShingle | Hassan Madkhali Amer Tarawneh Zulfiqar Ali Hoang V. Le Stephen J. Cutler Ikhlas A. Khan Zia Shariat-Madar Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal Herbs Molecules kinins inflammation angioedema |
| title | Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal Herbs |
| title_full | Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal Herbs |
| title_fullStr | Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal Herbs |
| title_full_unstemmed | Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal Herbs |
| title_short | Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal Herbs |
| title_sort | identification of human kinin forming enzyme inhibitors from medicinal herbs |
| topic | kinins inflammation angioedema |
| url | https://www.mdpi.com/1420-3049/26/14/4126 |
| work_keys_str_mv | AT hassanmadkhali identificationofhumankininformingenzymeinhibitorsfrommedicinalherbs AT amertarawneh identificationofhumankininformingenzymeinhibitorsfrommedicinalherbs AT zulfiqarali identificationofhumankininformingenzymeinhibitorsfrommedicinalherbs AT hoangvle identificationofhumankininformingenzymeinhibitorsfrommedicinalherbs AT stephenjcutler identificationofhumankininformingenzymeinhibitorsfrommedicinalherbs AT ikhlasakhan identificationofhumankininformingenzymeinhibitorsfrommedicinalherbs AT ziashariatmadar identificationofhumankininformingenzymeinhibitorsfrommedicinalherbs |