Studies on Cardio-suppressant, Vasodilator and Tracheal Relaxant Effects of Sarcococca saligna

  • Ghayur, Muhammad Nabeel (Department of Biological and Biomedical Sciences, The Aga Khan University Medical College) ;
  • Gilani, Anwarul Hassan (Department of Biological and Biomedical Sciences, The Aga Khan University Medical College)
  • Published : 2006.11.30

Abstract

Sarcococca saligna is a shrub that is traditionally used for its medicinal properties in Pakistan. In this study we report the cardio-suppressant, vasodilator and tracheal relaxant activities of the aqueous-methanolic extract (Ss.Cr) of the plant. Ss.Cr, that tested positive for the presence of saponins, flavonoids, tannins, phenols, and alkaloids, exhibited a dose-dependent (0.3-5 mg/mL) negative inotropic and chronotropic effect on the isolated guinea-pig atrium which was resistant to atropine ($1\;{\mu}M$) and aminophylline ($10\;{\mu}M$) pretreatment. In rabbit thoracic aorta, Ss.Cr dose-dependently (0.1-3 mg/mL) relaxed the high $K^{+}$ (80 mM) and phenylephrine ($PE,\;1\;{\mu}M$)-induced contractions, indicating a possible $Ca^{++}$ channel blocking (CCB) effect. When tested against PE ($1\;{\mu}M$) control peaks in normal $Ca^{++}\;and\;Ca^{++}$-free Kreb's solution, Ss.Cr exhibited dose-dependent (0.1-3 mg/mL) inhibition, being more potent in relaxing the PE responses in $Ca^{++}$-free Kreb's solution, thus indicating specific blockade of $Ca^{++}$ release from the intracellular stores. Ss.Cr also relaxed the agonist-induced contractions in: a) rat aorta irrespective of the presence of endothelium or nitric oxide synthase inhibitor L-NAME and b) rabbit and guinea-pig tracheal strips. The data shows that Ss.Cr possesses possible $Ca^{++}$ channel blocking activity which might be responsible for its observed cardio-suppressant, vasodilator and tracheal relaxant effects though more tests are required to confirm this $Ca^{++}$ channel blocking effect.

Keywords

References

  1. Ajay, M., Gilani, A. H., and Mustafa, M. R., Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sci., 74, 603-612 (2003) https://doi.org/10.1016/j.lfs.2003.06.039
  2. Arunlakhshana, O. and Schild, H. O., Some quantitative uses of drug antagonists. Br. J. Pharmacol., 14, 48-58 (1959)
  3. Benham, C. D., Bolton, T. B., Lang, R. J., and Takewaki, T., Calcium-activated potassium channels in single smooth muscle cells of rabbit jejunum and guinea-pig mesenteric artery. J. Physiol., 371, 45-67 (1986) https://doi.org/10.1113/jphysiol.1986.sp015961
  4. Fredholm, B. B. and Persson, C. G., Xanthine derivatives as adenosine receptor antagonists. Eur. J. Pharmacol., 81, 673- 676 (1982) https://doi.org/10.1016/0014-2999(82)90359-4
  5. Furchgott, R. F. and Zawadski, J. V., The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 299, 373-376 (1980)
  6. Gilani, A. H. and Cobbin, L.B., Cardioselectivity of himbacine: a muscarinic receptor antagonist. Naunyn-Schmiedeberg's Arch. Pharmacol., 332, 16-20 (1986) https://doi.org/10.1007/BF00633191
  7. Gilani, A. H., Ghayur, M. N., Khalid, A., Haq, Z., Choudhary, M. I., and Rahman, A., The presence of antispasmodic, antidiarrhoeal, antisecretory and acetylcholinesterase inhibitory constituents in Sarcococca saligna. Planta Med., 71, 120- 125 (2005) https://doi.org/10.1055/s-2005-837777
  8. Gilani, A. H., Shaheen, F., and Saeed, S. A., Cardiovascular actions of Daucus carota. Arch. Pharmacal Res., 17, 150- 153 (1994) https://doi.org/10.1007/BF02974250
  9. Guan, Y. Y., Kwan, C. Y., and Daniel, E. E., The effects of EGTA on vascular smooth muscle contractility in calcium free medium. Can. J. Physiol. Pharmacol., 66, 1053-1056 (1988) https://doi.org/10.1139/y88-172
  10. Hashimoto, T., Hirata, M., Itoh, T., Kanmura, Y., and Kuriyama, H., Inositol 1,4,5-triphosphate activates pharmaco-mechanical coupling in smooth muscle of rabbit mesenteric artery. J. Physiol., 370, 605-618 (1986) https://doi.org/10.1113/jphysiol.1986.sp015953
  11. Kamei, J. and Kasuya, Y., Antitussive effects of $Ca^{++}$ channel antagonists. Eur. J. Pharmacol., 212, 61-66 (1992) https://doi.org/10.1016/0014-2999(92)90072-C
  12. Karaki, H., Ozaki, H., Hori, M., Mitsui-Saito, M., Amano, K., Harada, K., Miyamoto, S., Nakazawa, H., Won, K. J., and Sato, K., Calcium movements, distribution, and functions in smooth muscle. Pharmacol. Rev., 49, 157-230 (1997)
  13. Kirtikar, K. R. and Basu, B. D., Indian Medicinal Plants. Prabasi Press, Calcutta, pp. 2211-2212 (1933)
  14. Knekt, P., Jarvinen, R., Reunanen, A., and Maatela, J., Flavonoid intake and coronary mortality in Finland: a comparative study. Br. Med. J., 312, 478-481 (1996) https://doi.org/10.1136/bmj.312.7029.478
  15. Kohli, J. M., Zaman, A., and Kidwai, A. R., Separation and characterization of the alkaloids of Sarcococca pruniformis. Tetrahedron, 23, 3829-3835 (1967) https://doi.org/10.1016/0040-4020(67)80030-9
  16. Miana, G. A. and Kaimuddin, M., Alkaloids of Sarcococca saligna Muel: salignine. Pak. J. Sci. Ind. Res., 12, 161-163 (1969)
  17. NRC (National Research Council), Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, D.C., pp. 1-7 (1996)
  18. Qiu, M. H., Nie, R. L., and Li, R., Chemical structures and bioactive screening of Pachysandra alkaloids. Yunnan Zhiwu Yanjiu, 16, 296-300 (1994)
  19. Rahman, A., Anjum, S., Farooq, A., Khan, M. R., and Choudhary, M. I., Two new pregnane-type steroidal alkaloids from Sarcococca saligna. Phytochemistry, 46, 771-775 (1997) https://doi.org/10.1016/S0031-9422(97)00347-6
  20. Rahman, A., Anjum, S., Farooq, A., Khan, M. R., and Choudhary, M. I., Phytochemical studies on steroidal alkaloids of Sarcococca saligna. Nat. Prod. Lett., 11, 297-304 (1998) https://doi.org/10.1080/10575639808044963
  21. Rahman, A., Anjum, S., Farooq, A., Khan, M. R., Perveen, Z., and Choudhary, M. I., Antibacterial steroidal alkaloids from Sarcococca saligna. J. Nat. Prod., 61, 202 -206 (1998a) https://doi.org/10.1021/np970294a
  22. Rahman, A., Choudhary, M. I., Khan, M. R., Anjum, S., Farooq, A., and Iqbal, M. Z., New steroidal alkaloids from Sarcococca saligna. J. Nat. Prod., 63, 1364-1368 (2000) https://doi.org/10.1021/np990108w
  23. Rahman, A., Feroz, F., Haq, Z., Nawaz, S. A., Khan, M. R., and Choudhary, M. I., New steroidal alkaloids from Sarcococca saligna. Nat. Prod. Res., 17, 235-241 (2003) https://doi.org/10.1080/1057563021000051086
  24. Shinwari, Z. K., Khan, A. A., and Nakaike, T., Medicinal and Other Useful Plants of District Swat Pakistan. Al-Aziz Communications, Peshawar, pp. 97-98 (2003)
  25. Taggart, M. J., Menice, C. B., Morgan, K. G., and Wray, S., Effects of metabolic inhibition on intracellular $Ca^{++}$, phosphorylation of myosin regulatory light chain and force in rat smooth muscle. J. Physiol., 499, 485-496 (1997) https://doi.org/10.1113/jphysiol.1997.sp021943
  26. Thorin, E., Huang, P. L., Fishman, M. C., and Bevan, J. A., Nitric oxide inhibits alpha2-adrenoceptor-mediated endotheliumdependent vasodilation. Circ. Res., 82, 1323-1329 (1998) https://doi.org/10.1161/01.RES.82.12.1323
  27. Tona, L., Kambu, K., Ngimbi, N., Cimanga, K., and Vlietinck, A. J., Antiamoebic and phytochemical screening of some Congolese medicinal plants. J. Ethnopharmacol., 61, 57-65 (1998) https://doi.org/10.1016/S0378-8741(98)00015-4
  28. Vanhoutte, P. M., Rubanyi, G. M., Miller, V. M., and Houston, D. S., Modulation of vascular smooth muscle contraction by endothelium. Ann. Rev. Physiol., 48, 307-330 (1986) https://doi.org/10.1146/annurev.ph.48.030186.001515