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Invited Symposium: Medicinal Plants and Drug Actions






Abstract

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Pharmacological Mechanisms of Cardiovascular Actions of Diterpenoids of Andrographis Paniculata


Contact Person: Benny K H TAN (phctankh@nus.edu.sg)


Introduction

Andrographis paniculata (Burm. f.) Nees (Acanthaceae), a common plant in Asia (Fig. 1) has been widely used in traditional Chinese medicine as an antiinflammatory and antipyretic drug for the treatment of cold, fever, laryngitis and diarrhoea (Deng et al., 1982). It also has a reputation as a potent folk medicine in the treatment of diabetes and hypertension (Ahmad & Asmawi, 1993). Chewing the fresh leaves is claimed to be effective against hypertension. Other reported pharmacological properties include antibacterial, immunological, antivenin, antithrombotic (Yeung et al., 1987), hepatoprotective (Handa & Sharma, 1990) and antifertility (Akbarsha et al., 1990) activities.

The chemical constituents of A. paniculata that have been identified include the diterpene lactones (Tang & Eiserbrand, 1992) and flavonoids (Zhu & Liu, 1984; Kuroyanagi et al., 1987). 14-deoxyandrographolide (DA, C20H30O4, plate crystal from methanol) and 14-deoxy-11,12-didehydroandrographolide (DDA, C20H28O4, needle crystal from methanol) are two main diterpenoids isolated from A. paniculata (Balmain et al., 1973). DDA has hydroxyl, alpha, beta-unsaturated-gamma-lactone and exo-methylene groups in its chemical structure (Matsuda et al., 1994). This is very similar to that of DA, with the exception of a double bond at C-11 and 12 (Fig. 2).



DA was reported to possess antipyretic and anti-inflammatory effects (Deng et al., 1982), and potent cell differentiation-inducing activity on mouse myeloid leukemia (M1) cells (Matsuda et al., 1994). There is however no known report on the effects of DA on blood pressure. There are also no known reports on the biological activities of DDA.

We performed preliminary dose response studies with a crude aqueous extract of A. paniculata in the spontaneously hypertensive rat (SHR) to determine whether it has a hypotensive effect. The optimum hypotensive dose of the extract was thus determined from this study. Semi-purification of the extract was done and the fractions were tested for bioactivity in the anaesthetised Sprague-Dawley (SD) rat. In order to elucidate the possible mechanism(s) of the hypotensive action, pharmacological antagonist studies were done in the anaesthetised rat with the crude extract and its bioactive fraction. Five diterpenoids from the plant were tested for hypotensive activity in the anaesthetised rat. Subsequently, 2 of these with bioactivity were identified and their possible mechanism(s) of action were investigated, using isolated rat thoracic aortae and right atria.

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Tan, BKH; Zhang, CY; (1998). Pharmacological Mechanisms of Cardiovascular Actions of Diterpenoids of Andrographis Paniculata. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/kwan/tan0674/index.html
© 1998 Author(s) Hold Copyright