Protective effects of Andrographis paniculata extract and pure andrographolide against chronic stress-triggered pathologies in rats

Abstract

This study was designed to experimentally verify the possibility that Andrographis paniculata could be another medicinal herb potentially useful for prevention of diverse spectrums of pathologies commonly associated with chronic unavoidable environmental stress, and whether andrographolide could as well be its quantitatively major bioactive secondary metabolite. Preventive effects of 21 daily oral 50, 100 and 200 mg/kg doses of a therapeutically used extract of the plant (AP) and 30 and 60 mg/kg/day of pure andrographolide were compared in rats subjected to 1-h daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, gastric ulcer, adrenal and spleen weights, and depressive state and sexual behavior in male rats were quantified. Other parameters quantified were plasma cortisol levels, and expressions of the cytokines TNF-α, IL-10 and IL-1β in blood and brain. All observed stress-induced pathological changes were less pronounced or completely prevented by both AP and pure andrographolide. Even the lowest tested doses of AP (50 mg/kg/day) or of andrographolide (30 mg/kg/day) suppressed almost maximally the blood IL-1β and IL-10 as well as brain TNF-α and IL-10 expressions induced by chronic stress. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both AP and andrographolide are pharmacologically polyvalent anti-stress agents, and that biological processes regulating corticosterone and cytokine homeostasis are involved in their modes of actions.

Fig. 1

HPLC fingerprint of Andrographis paniculata extract

Fig. 2

HPLC fingerprint and chemical structure of andrographolide

Fig. 3

HPLC fingerprint of Withania somnifera extract

Fig. 4

Summary of the experimental design used

Fig. 5

Effects of Andrographis paniculata extract (AP), andrographolide (Andro), and Withania somnifera extract (WS) treatments on a body weight and b body weight changes observed between day 1 and 21. Values are Mean ± SEM (n = 6), *p < 0.05 versus normal control; ^¥ p < 0.05 versus stress control

Fig. 6

Effects of Andrographis paniculata extract (AP), andrographolide (Andro), and Withania somnifera extract (WS) on a weight of adrenal glands and spleen, and b plasma corticosterone level of chronically stressed rats. Values are Mean ± SEM (n = 6), *p < 0.05 versus normal control; ^¥ p < 0.05 versus stressed control

Fig. 7

Effects of Andrographis paniculata extract (AP), andrographolide (Andro) and Withania somnifera extract (WS) on stressed rat a learned helpless test, b suppression in sexual behavior test, and c behavioral despair test. Values are Mean ± SEM (n = 6), *p < 0.05 versus normal control; ^¥ p < 0.05 versus stress control

Fig. 8

Effect of Andrographis paniculata extract (AP), andrographolide (Andro), and Withania somnifera extract (WS) on expressions of TNF-α, IL-10 and IL-1β in chronic stressed rats. a Gel picture showing expression of cytokines normalized with β-actin housekeeping gene in blood and brain, and b percentage change in mRNA expression of cytokines in blood (WBC), and c in frontal cortex. Values given are Mean ± SEM of three amplifications for each group. *p < 0.05 versus normal control, ^¥ p < 0.05 versus stress control