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 (Kobs) of barakol degradation under alkaline conditions at pHs 12 and 13 were 3.0x10(-5) and 9.6x10(-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 degrees C. The major degradation product of barakol under both alkaline and thermal stress conditions was characterized by LC-MS and NMR as cassiachromone.

Determination of the barakol content of mature leaves, young flowers of Senna siamea (Lam.) Irwin and Barneby and in the herbal recipes

“…All identification data were similar to standard barakol reported in previous publications (Padumanonda et al 2007;Chantong et al 2009). The identification results indicated that the extracted chemical constituent from fresh young leaves of S. siamea was barakol.…”

“…Barakol exhibits hypnotic effect in both animals and human volunteers and has been used as a medicinal agent by insomniacs. But, the Food and Drug Administration of Thailand removed the products containing S. siamea leaves from the market due to their hepatotoxicity (Chantong et al 2009). …”

Barakol-induced apoptosis in P19 cells through generation of reactive oxygen species and activation of caspase-9

“…A decrease in the level of hepatic cytochrome P450 (CYP) in barakoltreated mice was observed (Devakul Na Ayutthaya et al, 2005) and CYP was found to be a key enzyme in controlling differentiation of P19 cells (Sonneveld et al, 1999). Barakol, which contains a phenolic moiety, might be metabolized by CYP isozymes into anhydrobarakol, a semi-quinone (Thongsaard et al, 2001) or cassiachromone, a chromone (Chantong et al, 2009) (Fig. 1).…”

“…1) as previously described (Chantong et al, 2009). Briefly, the leaves were boiled with 5% sulfuric acid for 15 min, filtered and alkalinized with sodium bicarbonate (10% w/v).…”

Perfil metabolômico e avaliação biológica de espécies de Senna e Cassia

“…As principais correlações observadas no mapa de contorno HMBC (Figuras 155−157; Tabela 29) entre δH 2,28 (H-14) com δC 164,5 (C-2) ( 2 JH→C) e δC 110,3 (C-3) ( 3 JH→C); entre δH 5,95 (H-3) com δC 164,5 (C-2) ( 2 JH→C), δC 113,9 (C-10) ( 3 JH→C) e δC 19,4 (C-14) ( 3 JH→C); permitiram confirmar o padrão de substituição do anel γ-pirona. Assim como as correlações entre δH 6,58 (H-6) com δC 161,1 (C-7) ( 2 JH→C), δC 101,3 (C-8) ( 3 JH→C), δC 113,9 (C-10) ( 3 JH→C) e δC 48,9 (C-11) ( 3 JH→C); entre δH 6,70 (H-8) com δ C 177,7 (C-4) ( 4 J H→C ), δ C 118,1 (C-6) ( 3 J H→C ), δ C 161,1 (C-7) ( 2 J H→C ), δ C 159,0 (C-9) ( 2 JH→C) e δC 113,9 (C-10) ( 3 JH→C); entre δH 4,11 (H-11) com δC 138,3 (C-5) ( 2 JH→C), δC 118,1 (C-6) ( 3 JH→C), δC 113,9 (C-10) ( 3 JH→C) e δC 204,5 (C-12) ( 2 JH→C); entre δH 2,18 (H-13) com δC 138,3 (C-5) ( 4 JH→C), δC 48,9 (C-11) ( 3 JH→C), δC 204,5 (C-12) ( 2 JH→C), que permitiram confirmar o padrão de substituição do anel aromático (Figura 148; Tabela 29).Os dados de RMN (Tabelas 28 e 29; Figuras 151−157), aliados aos dados de EM e UV-Vis foram similares aos publicados na literatura(CHANTONG et al, 2009;SINGH, 1982) e são consistentes com a estrutura da 5-acetonil-7-hidroxi-2-metilcromona (VII), também conhecida como cassiacromona.Tabela 28 -Dados de RMN de 1 H e 13 C (400/100 MHz, DMSO-d6) do composto VII em comparação com dados da literatura. Deslocamentos químicos estabelecidos em relação ao padrão interno TMS (δTMS = 0,0 ppm).…”