scholarly journals Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal Herbs

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4126
Author(s):  
Hassan Madkhali ◽  
Amer Tarawneh ◽  
Zulfiqar Ali ◽  
Hoang V. Le ◽  
Stephen J. Cutler ◽  
...  

The goal of this study was to assess the pharmacological effects of black tea (Camellia sinensis 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.

2017 ◽  
Vol 45 (01) ◽  
pp. 137-157 ◽  
Author(s):  
Jian-Jung Chen ◽  
Chung-Chun Huang ◽  
Heng-Yuan Chang ◽  
Pei-Ying Li ◽  
Yu-Chia Liang ◽  
...  

Scutellaria baicalensis has been widely used as both a dietary ingredient and traditional herbal medicine in Taiwan to treat inflammation, cancer, and bacterial and viral infections of the respiratory tract and gastrointestinal tract. This paper aims to investigate the in vitro and in vivo anti-inflammatory effects of S. baicalensis. In HPLC analysis, the fingerprint chromatogram of the water extract of S. baicalensis (WSB) was established. The anti-inflammatory effects of WSB were inverstigated using lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) in vitro and LPS-induced lung injury in vivo. WSB attenuated the production of LPS-induced nitric oxide (NO), tumor necrosis factor-alpha (TNF-[Formula: see text], interleukin-[Formula: see text] (IL-1[Formula: see text], and IL-6 in vitro and in vivo. Pretreatment with WSB markedly reduced the LPS-induced histological alterations in lung tissues. Furthermore, WSB significantly reduced the number of total cells and the protein concentration levels in the BALF. WSB blocked protein expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of I[Formula: see text]B-[Formula: see text] protein and MAPKs in LPS-stimulated RAW 264.7 cells and LPS-induce lung injury was also blocked. This study suggests that WSB possesses anti-inflammatory effects in vitro and in vivo, and the results suggested that WSB may be a potential therapeutic candidate for the treatment of inflammatory diseases.


2016 ◽  
Vol 44 (06) ◽  
pp. 1127-1143 ◽  
Author(s):  
Min-Jee Kim ◽  
Yung-Choon Yoo ◽  
Nak-Yun Sung ◽  
Julim Lee ◽  
Seok-Rae Park ◽  
...  

In the present study, the anti-inflammatory and antisepticemic activities of a water extract of Liriope platyphylla (LP) were investigated. We first estimated the scavenging activity of DPPH and the hydroxyl radical and total phenolic contents of LP. Results indicated that LP, a rich source of phenolic compounds, showed a remarkable radical scavenging capacity. A MTT assay showed that LP treatment did not affect the toxicity against the RAW 264.7 macrophage cells, up to the concentration of 500[Formula: see text][Formula: see text]g/mL. Treatment of LP significantly attenuated the production of inflammatory mediators, such as nitric oxide (NO), interleukin-6 (IL-6), tumor-necrosis factor (TNF)-[Formula: see text] and prostaglandin (PG)E2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages cells. Moreover, LP contributed to the down-regulation of inducible NO synthase (iNOS) and TNF-[Formula: see text] mRNA expression, as well as cyclooxygenase-2 (COX-2) protein expression. A western blotting assay further showed that LP inhibited activation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-[Formula: see text]B. In an animal experiment using an LPS-induced septicemia model in C57BL/6 mice, oral administration of LP (40[Formula: see text]mg/kg body weight) markedly reduced the level of TNF-[Formula: see text] and IL-6 in serum and protected against LPS-induced lethal shock in mice. Taken together, the results of treatments of LP on inhibited LPS-induced inflammatory responses in both in vitro and in vivo models and indicate it may be a promising neutraceutical or medicinal agent to prevent or cure inflammation-related disease.


Author(s):  
Joung-Woo Hong ◽  
Ga-Eun Yang ◽  
Yoon Bum Kim ◽  
Seok Hyun Eom ◽  
Jae-Hwan Lew ◽  
...  

KSBB Journal ◽  
2015 ◽  
Vol 30 (4) ◽  
pp. 148-154
Author(s):  
Bo-Kyeong Kang ◽  
Koth-Bong-Woo-Ri Kim ◽  
Na-Kyung Ahn ◽  
Yeon-Uk Choi ◽  
Min-ji Kim ◽  
...  

2017 ◽  
Vol 43 (08) ◽  
pp. 814-826 ◽  
Author(s):  
Clément Naudin ◽  
Elena Burillo ◽  
Stefan Blankenberg ◽  
Lynn Butler ◽  
Thomas Renné

AbstractContact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation–associated disease states.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Moran Wang ◽  
Pengcheng Luo ◽  
Wei Shi ◽  
Junyi Guo ◽  
Shengqi Huo ◽  
...  

Pulmonary hypertension (PH) is a progressive and life-threatening chronic disease in which increased pulmonary artery pressure (PAP) and pulmonary vasculature remodeling are prevalent. Inhaled nitric oxide (NO) has been used in newborns to decrease PAP in the clinic; however, the effects of NO endogenous derivatives, S-nitrosothiols (SNO), on PH are still unknown. We have reported that S-nitroso-L-cysteine (CSNO), one of the endogenous derivatives of NO, inhibited RhoA activity through oxidative nitrosation of its C16/20 residues, which may be beneficial for both vasodilation and remodeling. In this study, we presented data to show that inhaled CSNO attenuated PAP in the monocrotaline- (MCT-) induced PH rats and, moreover, improved right ventricular (RV) hypertrophy and fibrosis induced by RV overloaded pressure. In addition, aerosolized CSNO significantly inhibited the hyperactivation of signal transducers and activators of transduction 3 (STAT3) and extracellular regulated protein kinases (ERK) pathways in the lung of MCT-induced rats. CSNO also regulated the expression of smooth muscle contractile protein and improved aberrant endoplasmic reticulum (ER) stress and mitophagy in lung tissues following MCT induction. On the other hand, CSNO inhibited reactive oxygen species (ROS) production in vitro, which is induced by angiotensin II (AngII) as well as interleukin 6 (IL-6). In addition, CSNO inhibited excessive ER stress and mitophagy induced by AngII and IL-6 in vitro; finally, STAT3 and ERK phosphorylation was inhibited by CSNO in a concentration-dependent manner. Taken together, CSNO led to pulmonary artery relaxation and regulated pulmonary circulation remodeling through anti-ROS and anti-inflammatory pathways and may be used as a therapeutic option for PH treatment.


2008 ◽  
Vol 119 (1) ◽  
pp. 145-152 ◽  
Author(s):  
Se Eun Byeon ◽  
Joo Young Chung ◽  
Yong Gyu Lee ◽  
Byung Hun Kim ◽  
Kook Hyun Kim ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6951
Author(s):  
Norelhouda Abderrezag ◽  
Jose David Sánchez-Martínez ◽  
Ouahida Louaer ◽  
Abdeslam-Hassen Meniai ◽  
Jose A. Mendiola

Ammodaucus leucotrichus is a spontaneous plant endemic of the North African region. An efficient selective pressurized liquid extraction (PLE) method was optimized to concentrate neuroprotective extracts from A. leucotrichus fruits. Green solvents were tested, namely ethanol and water, within a range of temperatures between 40 to 180 °C. Total carbohydrates and total phenolics were measured in extracts, as well as in vitro antioxidant capacity (DPPH radical scavenging), anticholinesterase (AChE) and anti-inflammatory (LOX) activities. Metabolite profiling was carried out by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-q-TOF-MS/MS), identifying 94 compounds. Multivariate analysis was performed to correlate composition with bioactivity. A remarkable effect of the temperature using water was observed: the higher temperature, the higher extraction yield, the higher total phenolic content, as well as the higher total carbohydrates content. The water extract obtained at 180 °C, 10.34 MPa and 10 min showed meaningful anti-inflammatory (IC50LOX = 39.4 µg/mL) and neuroprotective activities (IC50AChE = 55.6 µg/mL). The Principal Components Analysis (PCA) and the cluster analysis correlated these activities with the presence of carbohydrates and phenolic compounds.


2009 ◽  
Vol 21 (7) ◽  
pp. 840 ◽  
Author(s):  
Hiroaki Kawato ◽  
Tsutomu Tabata ◽  
Hiroyuki Minoura ◽  
Nao Murabayashi ◽  
Ning Ma ◽  
...  

Decidualisation of endometrial stromal cells (ESC) is a prerequisite for the implantation of human embryos. Identification of genes that are upregulated or downregulated during decidualisation could lead to a better understanding of the molecular mechanisms involved in this process. In the present study, we examined differences in gene expression between decidualised and non-decidualised cells using microarray analysis and found that Factor XII (FXII) gene expression was upregulated during decidualisation. Furthermore, we also examined the expression of FXII by human ESC before and during pregnancy, as well as its expression by cells that had undergone decidualisation in vitro. Weak expression of FXII mRNA was detected in the non-pregnant endometrium that increased gradually from the proliferative to the secretory endometrium. During pregnancy, FXII mRNA expression was markedly increased in decidualised endometrium. When sex steroids (200 pg mL–1 of 17β-oestradiol and 100 ng mL–1 of progesterone) were used to induce in vitro decidualisation of ESC, the expression of FXII mRNA increased by approximately 25.3-fold compared with that in non-decidualised ESC. Using western blotting, we confirmed the presence of FXII protein (80 kDa) in ESC after in vitro decidualisation. Increased expression of FXII in ESC during decidualisation suggests that the kallikrein–kininogen–kinin system may be activated during the implantation of human embryos.


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