Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti‐inflammatory effect

Abstract

1 We have reported that andrographolide (ANDRO), an active component of Andrographis paniculata, inhibits in¯ammatory responses by rat neutrophils. To further elucidate the possible mechanism(s) underlying the ANDRO's e ect, N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion and transmigration of isolated peripheral human neutrophils were studied. 2 Pretreatment with ANDRO (0.1 ± 10 mM) concentration-dependently prevented fMLP-induced neutrophil adhesion and transmigration. We further examined the up-expression of surface Mac-1 (CD11b/CD18), an essential integrin mediated in neutrophil adhesion and transmigration. ANDRO pretreatment signi®cantly decreased fMLP-induced up-expression of both CD11b and CD18. 4 To clarify whether ROS production impeded by ANDRO could be an antagonism of fMLP binding, phorbol-12-myristate-13-acetate (PMA), a direct protein kinase C (PKC) activator, was introduced to activate ROS production. PMA triggered remarkable ROS production and adhesion, and were partially reversed by ANDRO. This indicated that a PKC-dependent mechanism might be interfered by ANDRO. 5 We conclude that the prevention of ROS production through, at least in part, modulation of PKC-dependent pathway could confer ANDRO the ability to down-regulate Mac-1 up-expression that is essential for neutrophil adhesion and transmigration.

Identification of a Rare Sulfonic Acid Metabolite of Andrographolide in Rats

“…It was found that andrographolide had wide bioactivities, such as anti-inflammatory antibiotic (Sinha et al, 2000;Shen et al, 2002), anti-platelet aggregation (Zhang and Tan, 1997;Amroyan et al, 1999), and anti-human immunodeficiency virus activities (Calabrese et al, 2000). Andrographolide was widely used in the clinic, but it was not effective in vitro.…”

Apoptosis Inducing Effect Of Andrographolide On TF-47 Human Breast Cancer Cell Line

“…It possesses antimicrobial (Prajjal et al, 2003), anti-inflammatory (Shen et al, 2002), hypotensive ( Zhang and Tan, 1996) , antihyperglycemic ( Yu et al, 2003;Borhanuddin et al ., 1994); oxygen radical scanvenging (Shen et al, 2002), atherosclerotic ( Wang and Zhao.,1994), anti-malarial activity (Dua et al,2000), anti-HIV (Calabrese et al,2000), antiplatelet aggregation (Amroyan et al,1999), hepatic lipid peroxidation protective (Choudhury and Poddar,1984), hepatoprotective (Handa and Sarma ,1990), choleretic effect (Shukla et al, 1992), and anticancer effects (Kumar et al,2004 ;Rajagopal et al 2003;Chang, 1987;Matsuda et al, 1994 ). One of the major constituents of A. paniculata Ness is diterpene lactone such as andrographolide, which has anticancer activity in vitro in many tumor cell lines including leukemia, myeloma, HeLa, colon (HT-29), human peripheral blood lymphocytes (HPBLs), and human breast cancer MCF-7 (Satyanaraya et al, 2004).…”

Pharmacological Aspects of Andrographis paniculata on Health and Its Major Diterpenoid Constituent Andrographolide

“…5) In Thailand, this plant was selected by the Ministry of Public Health as one of the medicinal plants to be included in "The National List of Essential Drugs A.D. 1999" (List of Herbal Medicinal Products). 6) Extensive research has revealed that Andrographis paniculata has a surprisingly broad range of pharmacological effects and some of them are extremely beneficial, such as antiinflammatory, [7][8][9][10][11] antidiarrhoeal, 12,13) antiviral, 14) anti-malarial, 15,16) hepatoprotective, [17][18][19][20][21][22][23][24][25][26][27][28][29] cardiovascular, 30,31) anticancer, [32][33][34][35][36][37][38][39] and immunostimulatory [40][41][42][43][44] activities. On the other hand, male reproductive toxicity 45) and cytotoxicity 46) of this plant have been reported as well.…”