A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-κB Pathway

Bao, Zhenmin; Guan, Sheng-Uei; Chang, Cheng; Wu, Songlian; Wong, Siew Heng; Kemeny, David M.; Leung, Bernard P.; Wong, W.S. Fred

doi:10.1164/rccm.200809-1516oc

Cited by 189 publications

(189 citation statements)

References 56 publications

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“…in rats and found that the blood concentration of andrographolide was approximately 11 mg/mL ($30 mM). At this concentration, andrographolide was reported to possess anti-inflammatory, anti-tumor and anti-thrombotic properties in in vitro studies (Bao et al, 2009;Lu et al, 2011Lu et al, , 2012Zhou et al, 2008). In the present study, our data showed that andrographolide at 50 mM caused CEC death or apoptosis (Figures 1 and 2).…”

Section: Discussionsupporting

confidence: 62%

“…f.) Nees (Acanthaceae) (Coon & Ernst, 2004). Recent studies demonstrated that andrographolide possesses anticancer, anti-inflammatory and hepatoprotective activities (Bao et al, 2009;Negi et al, 2008). Recently, we also demonstrated that andrographolide enhanced nuclear factor (NF)-kB subunit p65 Ser 536 dephosphorylation through the activation of protein phosphatase 2A in vascular smooth muscle cells (Hsieh et al, 2011) and that andrographolide possesses anti-platelet activity via regulating the p38 MAPK-hydroxyl radical-ERK2 cascade (Lu et al, 2011(Lu et al, , 2012.…”

Section: Introductionmentioning

confidence: 93%

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A novel bioactivity of andrographolide fromAndrographis paniculataon cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis

Yen

Hsu

Huang

et al. 2013

Pharmaceutical Biology

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Context: Andrographolide, extracted from the leaves of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is a labdane diterpene lactone. It is widely reported to possess antiinflammatory and antitumorigenic activities. Cerebral endothelial cells (CECs) play a crucial role in supporting the integrity and the function of the blood-brain barrier (BBB). However, no data are available concerning the effects of andrographolide in CECs. The aim of this study was to examine the detailed mechanisms of andrographolide on CECs.Objective: This study investigated a novel bioactivity of andrographolide on cerebral ischemia/ reperfusion-induced brain injury. Materials and methods: CECs were treated with andrographolide (20-100 mL) for the indicated times (0-24 h). After the reactions, cell survival rate and cytotoxicity were tested by the MTT assay and the lactate dehydrogenase (LDH) test, respectively. Western blotting was used to detect caspase-3 expression. In addition, analysis of cell cycle and apoptosis using PI staining and annexin V-FITC/PI labeling, respectively, was performed by flow cytometry. We also investigated the effect of andrographolide on middle cerebral artery occlusion (MCAO)/reperfusion-induced brain injury in a rat model. Results: In the present study, we found that andrographolide (50-100 mL) markedly inhibited CEC growth according to an MTT assay and caused CEC damage according to a LDH test. Our data also revealed that andrographolide (50 mM) induced CEC apoptosis and caspase-3 activation as respectively detected by PI/annexin-V double staining and western blotting. Moreover, andrographolide arrested the CEC cell cycle at the G0/G1 phase by PI staining. In addition, andrographolide (5 mg/kg) caused deterioration of MCAO/reperfusion-induced brain injury in a rat model. Conclusions: These data suggest that andrographolide may disrupt BBB integrity, thereby deteriorating MCAO/reperfusion-induced brain injury, which are, in part, associated with its capacity to arrest cell-cycle and induce CEC apoptosis.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 93%

A novel bioactivity of andrographolide fromAndrographis paniculataon cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis

Yen

Hsu

Huang

et al. 2013

Pharmaceutical Biology

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“…Recent studies showed that a potential therapeutic value of Andrographolide in the treatment of asthma and it may act by inhibiting the NF-B pathway at the level of inhibitory B kinase- activation. Andrographolide blocked p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of OVA-challenged mice (8). But the drug may affect asthmatic inflammation and airway hyperreactivity has not been explored.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of NF-κB Expression and Allergen-induced Airway Inflammation in a Mouse Allergic Asthma Model by Andrographolide

Luo

Wang

et al. 2009

Cell Mol Immunol

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“…On stimulation, IKK complex phosphorylates IkBa, which then undergoes a rapid ubiquitin-induced degradation by 26S proteasome, leading to enhanced NF-kB nuclear translocation, kB oligonucleotide sequence binding, and transcriptional activation (5). Our laboratory has previously demonstrated increased phosphorylation of IKKb, degradation of IkBa, and nuclear translocation and DNA-binding activity of p65 subunit of NF-kB in lung tissues from OVA mouse asthma model (6). In mice deficient in NF-kB p50 subunit or IKKb, reduced pulmonary eosinophilia, Th2 cytokine and eotaxin levels, and mucus production were observed in response to OVA aerosol challenge (7,8).…”

mentioning

confidence: 98%

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Goh

Cook

Upton

et al. 2013

The Journal of Immunology

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Persistent activation of NF-κB has been associated with the development of asthma. Receptor-interacting protein 2 (Rip2) is a transcriptional product of NF-κB activation. It is an adaptor protein with serine/threonine kinase activity and has been shown to positively regulate NF-κB activity. We investigated potential protective effects of Rip2 gene silencing using small interfering RNA (siRNA) in an OVA-induced mouse asthma model. Rip2 protein level was found to be upregulated in allergic airway inflammation. A potent and selective Rip2 siRNA given intratracheally knocked down Rip2 expression in OVA-challenged lungs and reduced OVA-induced increases in total and eosinophil counts, and IL-4, IL-5, IL-13, IL-1β, IL-33, and eotaxin levels in bronchoalveolar lavage fluid. Rip2 silencing blocked OVA-induced inflammatory cell infiltration and mucus hypersecretion as observed in lung sections, and mRNA expression of ICAM-1, VCAM-1, E-selectin, RANTES, IL-17, IL-33, thymic stromal lymphopoietin, inducible NO synthase, and MUC5ac in lung tissues. In addition, elevation of serum OVA-specific IgE level in mouse asthma model was markedly suppressed by Rip2 siRNA, together with reduced IL-4, IL-5, and IL-13 production in lymph node cultures. Furthermore, Rip2 siRNA-treated mice produced significantly less airway hyperresponsiveness induced by methacholine. Mechanistically, Rip2 siRNA was found to enhance cytosolic level of IκBα and block p65 nuclear translocation and DNA-binding activity in lung tissues from OVA-challenged mice. Taken together, our findings clearly show that knockdown of Rip2 by gene silencing ameliorates experimental allergic airway inflammation, probably via interruption of NF-κB activity, confirming Rip2 a novel therapeutic target for the treatment of allergic asthma.

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A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-κB Pathway

Abstract: Our findings implicate a potential therapeutic value of andrographolide in the treatment of asthma and it may act by inhibiting the NF-kappaB pathway at the level of inhibitory kappaB kinase-beta activation.

Cited by 189 publications

References 56 publications

A novel bioactivity of andrographolide fromAndrographis paniculataon cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis

A novel bioactivity of andrographolide fromAndrographis paniculataon cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis

Inhibition of NF-κB Expression and Allergen-induced Airway Inflammation in a Mouse Allergic Asthma Model by Andrographolide

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

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