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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.

Background: Patients with radiation-induced xerostomia produce little or no saliva. Several studies have demonstrated the efficacy of systemic administration of pilocarpine hydrochloride in individuals with post-radiation xerostomia. However, analysis of pilocarpine lozenges for treatment of post-radiation xerostomia in patients with head and neck cancer has not been reported. Methods:The aim of this study was to quantify improvement in clinical symptoms and salivary function after treatment of post-radiation xerostomia with pilocarpine lozenges. In a double-blinded, placebo-controlled trial, 33 head and neck cancer patients were assigned randomly to receive Salagen® tablet, pilocarpine hydrochloride lozenge (3 or 5mg) or placebo lozenge every 10 days. At each visit, a subjective evaluation was undertaken through the use of visual analog scales before and at 180 minutes after treatment. Whole resting saliva was collected before and at 0, 30, 60, 90, 120, 150 and 180 minutes after treatment. Results:The percentage of patients with decreased feeling of oral dryness, sore mouth or speaking difficulties after taking 5-mg pilocarpine lozenge was greater than Salagen® or placebo. There were statistically significant increases in salivary production in pilocarpine treatment groups vs. placebo (P<0.05). Conclusion:The 5-mg pilocarpine lozenge produced the best clinical results, but further investigation with a larger group of patients is required.

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Andrographolide (AD), and 14-deoxyandrographolide (DAD) isolated from Andrographis paniculata Nees, Acanthaceae, and 3,19-isopropylideneandrographolide (IPAD), a semi-synthetic compound of AD, were examined for anti-HSV-1 activity in vitro. The inhibitory effects of these compounds on viral entry and replication steps were determined using pre- and post-infection assays, respectively. All the three compounds exhibited less than 50% inhibitory act against viral entry. In the post-infection, IPAD displayed absolute inhibition, whereas AD and DAD gave moderate activity. IPAD was selected to determine for the stage of anti-replication by time-of-addition and time-of-removal assays. From the time of removal assay, IPAD activity began after 4 h and completed at 16 h post infection which corresponded to the early genes expression. Its ability to inhibit HSV-1 was confirmed by polymerase chain reaction and the expression of viral glycoproteins C and D by western blot analysis. No viral enveloped glycoproteins D and C expressions were found. IPAD exhibited anti-HSV-1 replication relating to the early step of replication. Structure-activity relationships of andrographolide against HSV-1 was proposed, it is the first report of this ent-labdane diterpene.