Analgesic, antipyretic, anti-inflammatory and toxic effects of andrographolide derivatives in experimental animals

Abstract

Andrographolide (1) and 14-deoxy-11,12-didehydroandrographolide (2) are active constituents of Andrographis paniculata (Burm. f.), family Acanthaceae. A. paniculata extracts are reported to have antiviral, antipyretic, immunostimulant and anticancer activities. In this study, 1 and its 14-acetyl- (4) and 3,19-isopropylidenyl- (3) derivatives, as well as 2 and its 3,19-dipalmitoyl-derivative (5), were intraperitoneally tested for their analgesic, antipyretic, anti-inflammatory and acute toxicity effects in animal models. Analgesic effects were tested in mice using hot plate and writhing tests to distinguish the central and peripheral effects, respectively. The results showed that, at 4 mg/kg, all tested substances have significant analgesic effects, and the highest potency was seen with 3, 4 and 5. Increasing the dose of 3 and 5 to 8 mg/kg did not increase the analgesic effect. In the writhing test, 3 and 5, but not 1, showed significant results. In a baker's yeast-induced fever model, 3 and 5 significantly reduced rats' rectal temperature (p < 0.05). In a carrageenan-induced inflammation model, 1, 3 and 5 significantly reduced rats' paw volume. Doses of 3 and 5 up to 100 mg/kg did not show any serious toxic effects. From this study, 3 and 5 are the most interesting derivatives, showing much greater potency than their parent compounds. These could be further developed as analgesic, antipyretic and anti-inflammatory agents, without any serious toxicity.

Identification and evaluation of agents isolated from traditionally used herbs against Ophiophagus hannah venom

“…14-Deoxy-11,12-didehydro-andrographolide. The 1 H-NMR and 13 C-NMR data are identical with Suebsasana et al (7).…”

Evaluation of medicinal plant extracts against ticks and fluke

“…Similar studies carried out by Kamaraj et al (2010b) Control-nil mortality a Mean value of five replicates±SD been observed earlier by Bagavan et al (2009) that the potential of acaricidal and flukicidal activity of leaf hexane extract of Annona squamosa, methanol extracts of Gloriosa superba, and Phyllanthus emblica against H. bispinosa (LC 50 = 145.39, 225.57, and 256.08 ppm); methanol extracts of Centella asiatica and G. superba against P. cervi (LC 50 =77.61and 60.16 ppm). Andrographolide (1) and 14-deoxy-11, 12-didehydroandrographolide (2) were isolated from A. paniculata and reported to have antiviral, antipyretic, immunostimulant, and anticancer activities (Suebsasana et al 2009). Alkaloids isolated from A. squamosa have shown larvicidal growth-regulating and chemosterilant activities against Anopheles stephensi at concentrations of 50-200 ppm; the larvae, pupae, and adults produced about a 52-92% decrease in the laboratory experiment (Saxena et al 1993).…”

Andrographolide a New Potential Drug for the Long Term Treatment of Rheumatoid Arthritis Disease

“…Andrographolide is also a starting point for the semisynthesis of other labdane diterpenes [46][47][48]. …”