Article

Barrier protective effects of withaferin A in HMGB1-induced inflammatory responses in both cellular and animal models.

College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
Toxicology and Applied Pharmacology (impact factor: 4.45). 04/2012; 262(1):91-8. DOI:10.1016/j.taap.2012.04.025
Source: PubMed

ABSTRACT Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. In this study, we first investigated the possible barrier protective effects of WFA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice induced by high mobility group box 1 protein (HMGB1) and the associated signaling pathways. The barrier protective activities of WFA were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that WFA inhibited lipopolysaccharide (LPS)-induced HMGB1 release and HMGB1-mediated barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of leukocytes to human endothelial cells. WFA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that WFA suppressed the production of interleukin 6, tumor necrosis factor-α (TNF-α) and activation of nuclear factor-κB (NF-κB) by HMGB1. Collectively, these results suggest that WFA protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

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  • Article: Molecular insight in the multifunctional activities of Withaferin A.
    Wim Vanden Berghe, Linde Sabbe, Mary Kaileh, Guy Haegeman, Karen Heyninck
    [show abstract] [hide abstract]
    ABSTRACT: Herbal medicine which involves the use of plants for their medicinal value, dates as far back as the origin of mankind and demonstrates an array of applications including cardiovascular protection and anti-cancer activities, via antioxidant, anti-inflammatory and metabolic activities. Even today the popularity of medicinal herbs is still growing like in traditional medicines such as the Indian medicine, Ayurveda. One of the Ayurvedic medicinal plants is Withania somnifera Dunal, of which the important constituents are the withanolides. Among them, Withaferin A is one of the most bioactive compounds, exerting anti-inflammatory, pro-apoptotic but also anti-invasive and anti-angiogenic effects. In the context of modern pharmacology, a better insight in the underlying mechanism of the broad range of bioactivities exerted by Withaferin A is compulsory. Therefore, a lot of effort was made to explore the intracellular effects of Withaferin A and to characterize its target proteins. This review provides a decisive insight on the molecular basis of the health-promoting potential of Withaferin A.
    Biochemical pharmacology 09/2012; 84(10):1282-91. · 4.25 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

active compound
 
barrier protective activities
 
carboxymethylcellulose-induced leukocytes migration
 
cell adhesion molecules
 
central nervous system effects
 
HMGB1-mediated barrier disruption
 
human endothelial cells
 
human umbilical vein endothelial cells
 
inhibiting hyperpermeability
 
interleukin 6
 
leukocytes adhesion
 
mobility group box 1 protein
 
nuclear factor-κB
 
possible barrier protective effects
 
pro-inflammatory responses
 
tumor necrosis factor-α
 
vascular barrier integrity
 
vascular inflammatory diseases
 
WFA inhibited lipopolysaccharide
 
WFA suppressed
 

Wonhwa Lee