Catalpol downregulates vascular endothelial-cadherin expression and induces vascular hyperpermeability

Zhang, Caiqing; Liu, Qingfa; Fang, Dong; Li, Liqun; Du, Juan; Xie, Qi; Hu, Hesheng; Yan, Shi Fang; Zhou, Xia; Li, Changsheng; Lobe, Corrinne G.; Liu, Ju

doi:10.3892/mmr.2015.4522

Cited by 11 publications

(6 citation statements)

References 32 publications

(38 reference statements)

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“…The effect of aging-related hyperpermeability is also observed in blood vessels. Adherens junctions consisting of vascular endothelial cadherin (VE-cadherin) and β-catenin maintain intercellular permeability in both blood vessels and lymphatic vessels [16, 17, 66]. VE-cadherin is a type of trans-membrane protein which connects adjacent endothelial cells through calcium-dependent homophilic binding of its extracellular domain [67].…”

Section: Structure Of Lymphatic Vessels and Their Functions In Lymph mentioning

confidence: 99%

Pathophysiology of aged lymphatic vessels

Shang

Liang

Kapron

et al. 2019

Aging

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Lymphatic vessels maintain body homeostasis by recirculation of fluid and cells. Cell senescence induces lymphatic dysfunction. Impaired contractile function is caused by low muscle cell investiture and decrease of nitric oxide in aged lymphatic collectors, leading to poor drainage of lymph. Aging-induced loss of endothelial glycocalyx and production of inflammatory cytokines increases permeability of lymphatic vessels. In addition, aging-associated basal activation of mast cells delays immune response. In this review, we summarize the structural and pathological changes of aged lymphatic vessels, and discuss the underlying molecular mechanisms.

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Section: Structure Of Lymphatic Vessels and Their Functions In Lymph mentioning

confidence: 99%

Pathophysiology of aged lymphatic vessels

Shang

Liang

Kapron

et al. 2019

Aging

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“…Catalpol, the major active ingredient in Rehmannia glutinosa , plays a role in anti-inflammation [ 14 , 15 , 16 ], reducing capillary permeability [ 17 ], and reducing blood sugar [ 18 , 19 ]. Moreover, in vivo and in vitro studies have reported that catalpol exerts a protective role in LPS-induced trauma.…”

Section: Introductionmentioning

confidence: 99%

RhoA/ROCK-2 Pathway Inhibition and Tight Junction Protein Upregulation by Catalpol Suppresses Lipopolysaccaride-Induced Disruption of Blood-Brain Barrier Permeability

et al. 2018

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Lipopolysaccaride (LPS) directly or indirectly injures brain microvascular endothelial cells (BMECs) and damages the intercellular tight junction that gives rise to altered blood-brain barrier (BBB) permeability. Catalpol plays a protective role in LPS-induced injury, but whether catalpol protects against LPS-caused damage of BBB permeability and the underlying mechanism remain to be delineated. Prophylactic protection with catalpol (5 mg/kg, i.v.) consecutively for three days reversed the LPS-induced damage of BBB by decreased Evans Blue (EB) leakage and restored tight junctions in C57 mice. Besides, catalpol co-administrated with LPS increased BMECs survival, decreased their endothelin-1, TNF-Α and IL-6 secretion, improved transmembrane electrical resistance in a time-dependent manner, and in addition increased the fluorescein sodium permeability coefficient of BMECs. Also, transmission electron microscopy showed catalpol protective effects on tight junctions. Fluorescence staining displayed that catalpol reversed the rearrangement of the cytoskeleton protein F-actin and upregulated the tight junction protein of claudin-5 and ZO-1, which have been further demonstrated by the mRNA and protein expression levels of ZO-1, ZO-2, ZO-3, claudin-5, and occludin. Moreover, catalpol concurrently downregulated the mRNA and protein levels of RhoA, and ROCK2, the critical proteins in the RhoA/ROCK2 signaling pathway. This study thus indicated that catalpol, via inhibition of the RhoA/ROCK2 signaling pathway, reverses the disaggregation of cytoskeleton actin in BMECs and prevents down-regulation of junctional proteins, such as claudin-5, occludin, and ZO-1, and decreases endothelin-1 and inflammatory cytokine secretion, eventually alleviating the increase in LPS-induced BBB permeability.

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“…It has been demonstrated to exert anti-inflammatory, anti-oxidant, anti-apoptotic, and other neuroprotective properties, and has a role in neuroprotection against ischemic injuries and neurodegenerative diseases. Catalpol can reduce oxidative damage, regulate endocrine function, and enhance anti-inflammatory properties [17]. Catalpol can also protect against cardiovascular injuries by attenuating free radicals, lipid peroxidation, and cell apoptosis [18].…”

Section: Introductionmentioning

confidence: 99%

Catalpol Inhibits Homocysteine-induced Oxidation and Inflammation via Inhibiting Nox4/NF-κB and GRP78/PERK Pathways in Human Aorta Endothelial Cells

Wang

Jin

et al. 2018

Inflammation

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Hyperhomocysteinemia (HHCY) has been recognized as an independent risk factor for atherosclerosis and plays a vital role in the development of atherosclerosis. Catalpol, an iridoid glucoside extracted from the root of Rehmannia glutinosa , can produce anti-inflammatory, anti-oxidant, anti-tumor, and dopaminergic neurons protecting effects. This study aimed to determine the protecting effects of catalpol against homocysteine (HCY)-induced injuries in human aortic endothelial cells (HAECs) and uncover the underlying mechanisms: 1. HAECs were cultured with different concentrations of HCY (3 mM) and catalpol (7.5 μΜ, 15 μΜ, 30 μΜ) for 24 h. (1) The level of MDA and GSH as well as LDH release was measured with colorimetric assay. (2) Reactive oxygen species (ROS) were detected by flow cytometry analysis. (3) Western blotting analysis was performed to detect the expression of Nox4, p22 phox , ICAM-1, MCP-1, VCAM-1, IκB, nucleus p65, p65 phosphorylation, caspase-3, −9, bax, bcl-2, and ER stress-related proteins. (4) The expressions of CHOP, ATF4 were measured by qRT-PCR. (5) Mitochondrial membrane potential in HCY-treated HAECs was measured by rhodamine 123 staining, and the samples were observed by confocal laser scanning microscopy. 2. DPI, PDTC, and TUDCA were used to determine the interaction among Nox4/ROS, NF-κB, and endoplasmic reticulum stress. 3. TUDCA or Nox4 siRNA were used to investigate whether the effect of catalpol inhibiting the over-production of ROS were associated with inhibiting ER stress and Nox4 expression. Catalpol significantly suppressed LDH release, MDA level, and the reduction of GSH. Catalpol reduced HCY-stimulated ROS over-generation, inhibited the NF-κB transcriptional activation as well as the protein over-expressions of Nox4, ICAM-1, VCAM-1, and MCP-1. Catalpol elevated bcl-2 protein expression and reduced bax, caspase-3, −9 protein expressions in the HCY-treated HAECs. Simultaneously, catalpol could also inhibit the activation of ER stress-associated sensors GRP78, IRE1α, ATF6, P-PERK, P-eIF2α, CHOP, and ATF4 induced by HCY. In addition, the extent of catalpol inhibiting ROS over-generation and NF-κB signaling pathway was reduced after inhibiting Nox4 or ER stress with DPI or TUDCA. The inhibitor of NF-κB PDTC also reduced the effects of catalpol inhibiting the expressions of Nox4 and GRP78. Furthermore, the effect of catalpol inhibiting the over-generation of ROS was reduced by Nox4 siRNA. Catalpol could ameliorate HCY-induced oxidation, cells apoptosis and inflammation in HAECs possibly by inhibiting Nox4/NF-κB and ER stress.

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Catalpol downregulates vascular endothelial-cadherin expression and induces vascular hyperpermeability

Cited by 11 publications

References 32 publications

Pathophysiology of aged lymphatic vessels

Pathophysiology of aged lymphatic vessels

RhoA/ROCK-2 Pathway Inhibition and Tight Junction Protein Upregulation by Catalpol Suppresses Lipopolysaccaride-Induced Disruption of Blood-Brain Barrier Permeability

Catalpol Inhibits Homocysteine-induced Oxidation and Inflammation via Inhibiting Nox4/NF-κB and GRP78/PERK Pathways in Human Aorta Endothelial Cells

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