Original article
Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata)
- Open Access funded by Center for Food and Biomolecules, National Taiwan University
- Under a Creative Commons license
Abstract
Andrographolide is a major bioactive secondary plant metabolite isolated Andrographis paniculata (Burm. F.) Wall. Ex. Nees. (穿心蓮 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 11th day of treatment. Observations made during a pilot dose finding experiment revealed that, likeA. 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 5th 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.
Graphical abstract
Keywords
- andrographolide;
- foot-shock stress;
- hyperthermia;
- pentobarbital hypnosis;
- adaptogen
1. Introduction
Andrographis paniculata (Burm. F.) Wall. Ex. Nees. (穿心蓮 chuān xīn lián) is a herbaceous plant of the Acanthaceae family, often cultivated in India, China, and other countries for medicinal purposes. Due to its extremely bitter taste, it is often referred to as the “the king of bitters,” and is used as a bitter tonic in Ayurvedic and other traditionally known health care systems of India and many other Asian countries. In traditional Chinese medicine, Andrographis paniculata (Burm. F.) Wall. Ex. Nees. (A. paniculata) is indicated for conditions of “heat,” particularly in the lungs, throat, and urinary tract, as well as for manifestations of “fire poison” on the skin, such as sores and carbuncles. 1 During more recent decades, the plant has attracted considerable attention of modern drug discoverers and herbal researchers, and several reports revealing diverse therapeutic potentials of different types of A. paniculata extracts in properly controlled clinical trials have also appeared. 2, 3, 4 and 5 Andrographolide, structurally a labdane diterpenoid (Fig. 1), is quantitatively the major bitter-tasting secondary metabolite of the plant, and it is now often considered to be the major bioactive constituent of the plant involved in its observed therapeutically interesting bioactivities. 6, 7 and 8 Although a very broad spectrum of therapeutically interesting pharmacological properties of A. paniculataextracts and pure andrographolide have now been revealed, many questions concerning their pharmacological targets and sites of actions still remain unanswered. 9 and 10Available information on their medicinal chemistry and pharmacology suggest, though, that like various other bioactive secondary plant metabolites, andrographolide is also a pharmacologically pleiotropic or polyvalent agent, and that most probably several biological targets and mechanisms are involved in its modes of actions.
