Acteoside: A new antihypertensive drug

August 20, 2017 | Autor: Mansoor Ahmad | Categoría: Phytopharmacology, Biological Sciences, Phytotherapy, CHEMICAL SCIENCES
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PHYTOTHERAPY RESEARCH, VOL. 9,525-527 (1995)

SHORT COMMUNICATION

Acteoside: a New Antihypertensive Drug Mansoor Ahmad* and Ghazala H. Rizwani Department of Pharmacognosy, University of Karachi, Karachi-75270, Pakistan

Khalid Aftab and Viqar Uddin Ahmad HEJ Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan

Anwarul Hasan Gilani The Aga Khan University and Medical College, Karachi, Pakistan

Shahida Perveen Ahmad Department of Pharmacology, University of Karachi, Karachi-75270, Pakistan

Acteoside is a phenylpropanoid, reported as a chemical constituent from ditrerent plant species, and was isolated as a pure compound on RP-HPLC from the violet Rowers of Syringa uulguris. On pharmacological evaluation this compound exhibited a dose-dependent decrease in sytolic, diastolic and mean arterial blood pressure in normotensive pentothal anaesthetized rats. The median effective dose was 10mglkg and lasted for 2-3min, whilst heart rate also decreased. Keywords: acteoside; Syringa vulgaris; Oleaceae; antihypertensive.

INTRODUCTION

MATERIALS AND METHODS

Acteoside is a phenylpropanoid glycoside of natural origin. Originally it was isolated from the flowers of Syringa vulgaris (Birkofer et al., 1968). Acteoside and similar compounds have also been reported from other sources, e.g. Martynia louisiana, Gelopsis pubescens, Cistanche tubulosa, Orobanche rapum-genistae, Forsythia suspensa, Hygrophila erecta, Buddleja dauidii (Sasaki et al., 1978; Andry et al. 1982; Nishibe et al., 1982; Galis et al., 1984; Ahmad, 1986; Henry et al., 1987; Kobayashi et al., 1984; 1987; Ahmad and Sticher, 1988; Yashizawa et al., 1990). Cardiovascular parameters have not been reported either for acteoside or for phenylpropanoid/phenylethanoids. However, cynarin, (a derivative of caffeic acid, 1,5dicaffeoylquinic acid), isolated from Cynara scolymus (Panizzi and Scarpati, 1965) in antihepatotoxic and caffeoyl derivatives (Konig and Dustmann, 1985) have antiviral actions. Syringa vulgaris (Oleaceae) is used to treat malaria (Hegi, 1926). Its two compounds, syringin and kaempferol-3-O-rutinoside,have been reported as antihypertensive compounds (Ahmad et al., 1993; Ahmad and Aftab, 1994). In continuation of our pharmacological studies on pure chemical constituents of S. vulgaris, acteoside (obtained from violet flowers) was used for cardiovascular studies and this communication deals with the effects of acteoside on mean arterial blood pressure.

Plant material. The crude extract of S. vulgaris was obtained from fresh violet flowers (4.5 kg). The fresh violet flowers were collected near Zurich, Switzerland in 1982. The plant material was identified by Professor Dr 0. Sticher, Department of Pharmacy, ETH-Zurich, Switzerland, and a voucher herbarium specimen was deposited in the Department of Pharmacy, ETH-Zurich. For TLC, silica gel FP254 type 60 plates and for column chromatography silica gel 60 particle size 0.063-0.200 mm (70-230 mesh ASTM, Merck) were used. Spray reagent: vanillin-H,SO, (1% vanillin in concentrated H2S04) after development heated at 120 "C in a hot air oven for 5 min. UV spectra were recorded on a Perkin-Elmer Spectrophotometer model 550 and IR spectra with KBr pellets on Perkin-Elmer grating IR-Spectrophotometer model 257. 'H- and 3C-NMR: Bruker Spectrospin (300 and 75.47 MHz), Mass spectrometer: Hitachi Perkin-Elmer RMU 6M. For blood pressure: Using transducer (Model P23ID), Gould Statham Instruments Inc., (USA), Grass Polygraph Model 7D (USA). The following reference materials were obtained from the sources specified: acetylcholine chloride (Sigma); atropine sulphate (Sigma); chloropheniraTable 1. Dose (mglkg)

* Author to whom correspondence should be addressed.

1 3 10

Number of observations

% Fall in MABP ~rnmHg)

3 5 5

14.33 f 2.33 26.08 k 2.65 39.40 f 2.38

CCC 095 1-418X/95/070525-03

0 1995 by John Wiley & Sons, Ltd.

Accepted 31 August 1994

M. AHMAD ET AL.

526 2Wl-

AUmine

Figure 1. Effect of acteoside in norrnotensive pentothal sodium anaesthetized rats along with acetylcholine, atropine, norepinephrine and phentolamine.

mine maleate (Sigma); histamine (Sigma); norepinephrine (Sigma); cimetidine (Ciba); phentolamine (Ciba) and pentothal sodium (Abbott Laboratories, Pakistan). Isolation and identification. From fresh violet flowers

(9.45 kg), acteoside was obtained as an impure compound by polyamide and silica gel column chromatography. It was purified on HPLC (semi-preparative RP-column) and its structure was elucidated by spectroscopy (UV, IR, MS, NMR) and comparison with an authentic sample (Ahmad, 1985). In uiuo experiments. Wistar rats of either sex (200-250 g)

were anaesthetized with pentothal sodium (40 mg/kg intraperitoneal injection). The trachea was exposed and cannulated with a polyethylene cannula to facilitate spontaneous respiration. Acteoside dissolved in distilled water was injected slowly via the cannula inserted into the external jugular vein. The maximum volume of injection was 0.2 mL. The systemic blood pressure was recorded from the carotid artery via an arterial cannula connected to a pressure transducer (model P,, ID, Gould Statham Instruments Inc. Hato Rey, Puerto Rico) and heart rate was recorded using tachograph (model 7P 44C, Grass Instruments Co., MA) driven by blood pressure waves. These were displayed on a Grass Polygraph Model 7D (Grass Instruments Co., MA). An equilibrium period of 30 min was allowed before administration of any drug (McLeod et al., 1970). Mean

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30 40

50 1

3

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Dose mg/kg Figure 2. Dose-dependent effect of acteoside on blood pressure and heart rate.

arterial blood pressure was measured in mm Hg and calculated by standard procedures (Steinmetz ef af., 1990). Responses were taken as O/O change in the control values obtained immediately before the addition of test substances. Results are expressed as mean f standard error of means (SEM). Student's f-test was used to test the significance in differences of means.

RESULTS AND DISCUSSION Table 1 and Figs 1 and 2 summarize the effects of acteoside on blood pressure and heart rate. The acteoside showed a definite antihypertensive effect, 39.40% f2.38%, at a high dose of 10 mg/kg and this was recorded for a period of 2-3 min, meanwhile heart rate was also decreased. On the whole, acteoside exhibited a dose dependent decrease in systolic, diastolic and mean arterial blood pressure (Fig. 1). The effects of two possible antagonists, atropine and chloropheniramine with cimetidine on the hypotensive effect of acteoside were determined. The substance was given 5 min after the administration of atropine (1mg/ kg) and chloropheniramine (10 mg/kg) with cimetidine (10 mg/kg). It was observed that atropine and chloropheniramine with cimetidine, which are well known for blocking the effect of acetylcholine (1 pg/kg) and histamine (1 pg/kg), did not block the hypotensive action of acteoside. Norepinephrine (1 pg/kg) produced a pronounced increase in mean arterial blood pressure, which was completely blocked by phentolamine (2 mg/ kg) but was not affected by acteoside (Fig. 1). In this study we demonstrated a dose dependent hypotensive effect of acteoside. An intravenous injection of 10 mg/kg of acteoside produced a significant decrease in systolic, diastolic and mean arterial blood pressure in pentothal anaesthetized rats. In model experiments it was also observed that the depressor effect was independent of muscarinic and histaminergic receptors, since it did not block the effect of atropine (antimuscarinic agent) and chloropheniramine/ cimetidine (antihistaminergic agent). In addition, mechanisms such as an a-adenoceptor interference with sympathetic transmission can be excluded, since acteoside did not block the pressor effect of noradrenaline completely blocked by phentolamine (aadenoceptor blocker). In structure-activity relationships, the effects of this

ACTEOSIDE: A NEW ANTIHYPERTENSIVE DRUG

drug on blood pressure were not different from our previous results reported for rutin, kaempferol-3-0rutinoside and syringin, obtained from the same plant (Ahmad et al. 1993; Ahmad and Aftab, 1994). The hypotensive effects of acteoside are completely in agreement with those proposed by Ahmad and Aftab (1994) on structure-activity, namely, that in those drugs showing hypotensive action, not mediated through histaminic and muscarinic receptors and having an aromatic ring in the structure, their efficacy is dependent on the occurrence of an OH group in the aromatic ring. Further support was obtained from the antihypertensive effects of oleuropein performed on blood pressure of anaesthetized rats (Petkov and Manolov, 1972). Oleuropein, a secoiridoid glucoside, is

527

a major chemical constituent of Olea europa (Oleaceae), but occurs also in S. vulgaris (Oleaceae) (Ahmad, 1985). It is a similar structure (aromatic ring with two OH group) to acteoside. It is also interesting to note that the antihypertensive results reported for experiment with oleuropein in oiuo (33% at 30 mg/kg dose) are similar to acteoside (39.40% k 2.38% at 10 mg/ kg dose). From the folk medicine use, as a fever reducing agent in malaria (Hegi, 1926), and the antihypertensive actions of rutin, kaempferol-3-o-rutinoside, syringin, acteoside, and oleuropein it can be concluded that Syringa vulgaris (Oleaceae) is a plant with hypotensive action and due to these activities it could be developed as an hypotensive drug.

REFERENCES Ahmad, M. (1986). Naturally occurring acteoside from Buddleja davidii. J. Pharm. Univ. Kar. 4(2), 65-68. Ahmad, M., and Sticher, 0. (1988). Isolation of acacetin-7-0rutinoside and martynoside from Buddleja davii. J. Chem. SOC.Pak. lO(1). 117-123. Ahmad, M., and Aftab, K. (1994). Hypotensive action of syringin from Syringa vulgaris. Phytother. Res. (in press). Ahmad, M., Gilani, A. U. H., Aftab, K., and Ahmad, V. U. (1993). Effects of kaempferol-3-0-rutinoside on rat blood pressure. Phytother. Res. 7, 314-316. Ahmad, M. (1985). The Chemical Constituents of Buddleja davidii and Syringa vulgaris, Ph.D. Thesis No. 7903, ETH-Zurich, Switzerland. p. 47. Andary, C., Wylde, R., Laffite, C., Privat, G., and Winternitz (1982). Structure of verbascoside and orobanchoside, caffeic acid sugar ester from Orobancho rapum-genistae. Phytochemistry 21(51, 1123-1 127. Birkofer, L., Kaiser, C., and Thomas, U. (1968). Acteoside and Syringa vulgaris. neoacteoside: Zuckerester aus Naturforschung 236,1051 -1 058. Calis, I., Lahloub, M. F., Rogenmoser, E., and Sticher, 0. (1984). Isomartynoside, a phenylpropanoid glycoside from Galeopsis pubescens. Phytochemistry 23(lo), 23 13-231 5. Hegi, G. (1926). lllustrierte Flora von Mitteleuropa, Vol. V, Part 3, pp. 1912-1917. Henry, M., Roussel, J. L., and Andary, C. (1987). Verbascoside production in callus and suspension culture of Hygrophila erecta. Phytochemistry 26 (7). 1961-1963. Kobayashi, H., Oguchi, H., Takizawa, N., Miyase, T., Ueno, A., Usmanghani, K., and Ahmad, M. (1987). New phenylethanoid glycoside from Cistanche tubulosa (Schrenk)Hook. f. 1. Chem. Pharm. Bull. 35, (8). 3309-3314.

Kobayashi, H., Karasawa, H., Miyase, T., and Fukushima (1984). Studies on the constituents of Cistanche Herba IV. Isolation and structures of two new phenylpropanoid glycosides, cistanoside C & D. Chem. Pharm. Bull. 32(10), 3880-3885. Konig, B., and Dustmann, J. H. (1985). The caffeoylics as a new family of natural antiviral compounds. Naturwissensschaften 72, 659-661. McLeod, L. J. et a/. (1970). Pharmacological Experiments on lntact Preparations, pp. 63-64. E & S Livingstone, Edinburgh. Nishibe, S., Okabe, K., Tsukamoto, H., Sakushima, A., and Hisada, S. (1982). The structure of forsythiaside isolated from Forsythia suspensa. Chem. Pharm. Bull. 30(3), 10481050. Panizzi, L., and Scarpati, M. L. (1965). 1.4- and 1.5Dicaffeoylquinic acids. Gizz. Chim. ltal. 95, 71-73. Petkov, V., and Manolov, P. (1972). Pharmacologicalanalysis of iridoid oleuropein. Arzneimittelforsch (Drug Res.) 22(9), 1476- 1479. Sasaki, H., Taguchi, H., Endo, T., and Yosioka, 1. (1978). The glycosides of Martynia lousiana Mill. A new phenyl propanoid glycoside, Martynoside. Chem. Pharm. Bull. 26(7), 21 11-2121. Steinmetz, M. D., Regli, P., Vial, M., Y., and Mourgue, M. (1990). Effect of aqueous leaf extracts of Cajanus cajan on blood pressure. Fitoterapia 61, 317-324. Yoshizwawa, F., Deyama,T., Takizawa, N., Usmamghani, K., and Ahmad, M. (1990). The constituents of Cistanche tubulosa (Schrenk) Hook. f. II. Isolation and structures of a new phenylethanoid glycoside and a new neolignan glycoside. Chem. Pharm. Bull. 38(7),1927-1930.

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