title: 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.
authors.affiliation: Neuropharmacology Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221 005, India.
authors.forename: Ajit Kumar
authors.initials: AK
authors.lastname: Thakur
authors.forename: Upendra Kumar
authors.initials: UK
authors.lastname: Soni
authors.forename: Geeta
authors.initials: G
authors.lastname: Rai
authors.forename: Shyam Sunder
authors.initials: SS
authors.lastname: Chatterjee
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology; D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007858:Learning / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000188:drug therapy / Q000473:pathology; D013315:Stress, Psychological / Q000188:drug therapy*; D032341:Withania / Q000737:chemistry
chemical_list: D016207:Cytokines; D004224:Diterpenes; D010936:Plant Extracts; D020011:Protective Agents; C030419:andrographolide; D003345:Corticosterone