Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata)

Abstract

Andrographolide is a major bioactive secondary plant metabolite isolated Andrographis paniculata (Burm. F.) Wall. Ex. Nees. ( chuān xīn lián), a well-known traditionally used medicinal herb. The aim of the study was to pharmacologically evaluate the beneficial effect of andrographolide on stress-induced thermoregulatory and other physiological responses in mice. A stress-induced hyperthermia test was conducted in mice. The test agents were orally administered once daily for 11 consecutive days, and treatment effects on body weight changes, basal rectal temperature, and foot-shock-triggered hyperthermic responses were quantified on Day 1, Day 5, Day 7, and Day 10 of the experiments. Pentobarbital-induced hypnosis was quantified on the 11(th) day of treatment. Observations made during a pilot dose finding experiment revealed that, like A. paniculata extracts, pure andrographolide also possess adaptogenic properties. Observed dose-dependent efficacies of 3 mg/kg/d, 10 mg/kg/d, and 30 mg/kg/d andrographolide in the pilot experiment were reconfirmed by conducting two further analogous experiments using separate groups of either male or female mice. In these confirmatory experiments, efficacies of andrographolide were compared with that of 5 mg/kg/d oral doses of the standard anxiolytic diazepam. Significantly reduced body weights and elevated core temperatures of the three vehicle-treated control groups observed on the 5(th) day and subsequent observational days were completely absent even in the groups treated with the lowest andrographolide dose (3 mg/kg/d) or diazepam (5 mg/kg/d). Benzodiazepine-like potentiation of pentobarbital hypnosis was observed in andrographolide-treated animals. These observations reveal that andrographolide is functionally a diazepam-like desensitizer of biological mechanisms, and processes involved in stress trigger thermoregulatory and other physiological responses.

Keywords: adaptogen; andrographolide; foot-shock stress; hyperthermia; pentobarbital hypnosis.

Graphical abstract

Fig. 1

HPLC fingerprint and chemical structure of andrographolide. HPLC = high-performance liquid chromatography.

Fig. 2

Mean (± SEM) of (A) body weights, (B) basal rectal temperatures, (C) foot-shock stress-induced hyperthermic responses, and (D) sleep onset periods and durations of sleep induced by pentobarbital in the vehicle-treated control groups used in the three reported experiments. The number of control animals used in the pilot experiment was 12, and that in each of the two confirmatory experiments was 6. No statistically significant differences (2-tailed t test) were detected between the values observed in separate groups of male and female animals used in the confirmatory experiments. SEM = standard error of mean.

Fig. 3

Effects of once-daily oral doses of andrographolide on the parameters quantified in the pilot experiment for 10 consecutive days observed. (A) Mean body weights (B) and basal core temperature were quantified on different days of the experiment. Andrographolide dose–response curves (C) in the foot-shock stress-induced hyperthermia test conducted on Day 1, Day 5, Day 7, and 10 of the experiment and (D) in the pentobarbital sleep test conducted on Day 11 of the test are shown in this figure. Observed statistically significant (p < 0.05) mean values of andrographolide-treated groups against the mean values of the control group on the same day are marked with *, and such differences (p < 0.05) between the mean values of a group on Day 1 and on subsequent days of the experiment are marked with the symbol ^¥. Percent response values used in the dose–response curves were calculated by considering the responses of the control group on the day of the experiment as 100%.

Fig. 4

Effects of intermittent foot-shocks and daily handling on (A and B) body weights and (C and D) basal rectal temperatures of male and female mice treated with vehicle, or andrographolide, or diazepam. * p < 0.05 versus control values on the same day. ^¥p < 0.05 versus Day 1 values of the same group.

Fig. 5

Effects of daily handling on foot-shock stress-triggered hyperthermia on Day 1, Day 5, Day 7, and Day 10 in (A) male and (B) female mice treated with vehicle, or andrographolide, or diazepam. * p < 0.05 versus control values on the same day. ^¥p < 0.05 versus Day 1 values of the same group.

Fig. 6

Effects of andrographolide or diazepam treatments on pentobarbital-induced sleep parameters quantified on Day 11 of treatments in (A) male and (B) female mice. * p < 0.05 versus control.

Fig. 7

Graphical summary.