Stability of Barakol under Hydrolytic Stress Conditions and its Major Degradation Product

Abstract

The aim of the present study was to investigate the stability of barakol, an anxiolytic constituent extracted from leaves of Senna siamea (Lam.) Irwin & Barneby (syn. Cassia siamea Lam.), under the International Conference on Harmonisation suggested conditions using HPLC with photodiode array detection. Extensive degradation of barakol was found to occur under alkaline conditions through base-catalyzed hydrolysis. Mild degradation of barakol was observed under thermal and oxidative stress while it was stable under acidic conditions. The reaction rate constants (k _obs) of barakol degradation under alkaline conditions at pHs 12 and 13 were 3.0 × 10^– 5 and 9.6 × 10^– 3 min⁻¹, respectively. The activation energy according to the Arrhenius plot was calculated to be 26.9 ± 3.3 kcal/mol at pH 13 and temperatures between 12 and 51 °C. The major degradation product of barakol under both alkaline and thermal stress conditions was characterized by LC-MS and NMR as cassiachromone.

Key words

barakol - Senna siamea - Leguminosae-Caesalpinoideae - cassiachromone - stability study

References

• 1 Carlini E A. Plants and the central nervous system.  Pharmacol Biochem Behav. 2003;  75 501-12
• 2 Arunlakshana O. The pharmacological study of the leaves of Cassia siamea. .  Siriraj Hosp Gaz. 1949;  1 434-44
• 3 Deachapunya C, Thongsaard W, Poonyachoti S. Barakol suppresses norepinephrine-induced inhibition of spontaneous longitudinal smooth muscle contractions in isolated rat small intestine.  J Ethnopharmacol. 2005;  101 227-32
• 4 Hassanali-Walji A, King T J, Wallwork S C. Barakol, a novel dioxaphenalene derivative from Cassia siamea. .  J Chem Soc Chem Commun. 1969;  12 678
• 5 Sukma M, Chaichantipyuth C, Murakami Y, Tohda M, Matsumoto K, Watanabe H. CNS inhibitory effects of barakol, a constituent of Cassia siamia Lamk.  J Ethnopharmacol. 2002;  83 87-94
• 6 Thongsaard W, Deachapunya C, Pongsakorn S, Boyd E A, Bennett G W, Marsden C A. Barakol: a potential anxiolytic extracted from Cassia siamea. .  Pharmacol Biochem Behav. 1996;  53 753-8
• 7 Pooviboonsuk P, Tappayuthpijarn P, Hincheeranund T. Hypnotic effect and sleep qualities of modified herbal extract from Cassia siamea.  J Psychiatr Assoc Thai. 2000;  45 251-8
• 8 Hongsirinirachorn M, Threeprasertsuk S, Chutaputti A. Acute hepatitis associated with barakol.  J Med Assoc Thai. 2003;  86 S484-9
• 9 Bycroft B W, Hassaniali W A, Johnson A W, King T J. Structure and synthesis of barakol; a novel dioxaphenalene derivative from Cassia siamea. .  J Chem Soc. 1970;  12 1686-9
• 10 Thongsaard W, Chainakul S, Bennett G W, Marsden C A. Determination of barakol extracted from Cassia siamea by HPLC with electrochemical detection.  J Pharm Biomed Anal. 2001;  25 853-9
• 11 ICH Harmonised tripartite guideline: Stability testing of new drug substances and products Q1A (R2). Available at http://www.ich.org/cache/compo/363-272-1.html#Q1A(R2). Accessed February 11, 2005
• 12 ICH Harmonised tripartite guideline: Stability testing : photostability testing of new drug substances and products Q1B. Available at http://www.ich.org/cache/compo/363-272-1.html#Q1B. Accessed May 10, 2008
• 13 Connors K A. Chemical kinetics. The study of reaction rates in solution. New York; VCH Publishers, Inc 1990: 187-243
• 14 Arora S, Deymann H, Tiwari R D, Winterfeldt E. A new chromone from Cassia siamea. .  Tetrahedron. 1971;  27 981-4
• 15 Wagner H, El-Sayyad S M, Seligmann O, Chari V M. Chemical constituents of Cassia siamea Lam., 2-methyl-5-acetonyl-7-hydroxychromone (cassiachromone).  Planta Med. 1978;  33 258-61