1. Estrogenic and anti-estrogenic activities of Cassia tora phenolic constituents
Masao Hattori,Mi Hwa Chung,Chao-Mei Ma,Tsutomu Nishihara,Norio Nakamura,Ali Mahmoud El-Halawany Chem Pharm Bull (Tokyo) . 2007 Oct;55(10):1476-82. doi: 10.1248/cpb.55.1476.
Through an estrogenic activity bioassay-guided fractionation of the 70% ethanolic extract of Cassia tora seeds two new phenolic triglucosides, torachrysone 8-O-[beta-D-glucopyranosyl(1-->3)-O-beta-D-glucopyranosyl(1-->6)-O-beta-D-glucopyranoside] (1) and toralactone 9-O-[beta-D-glucopyranosyl-(1-->3)-O-beta-D-glucopyranosyl-(1-->6)-O-beta-D-glucopyranoside] (2), along with seven known compounds were isolated. The structures of the new compounds were elucidated on the basis of spectroscopic and chemical evidence. The estrogenic activity of the fractions and the isolated compounds were investigated using the estrogen-dependent proliferation of MCF-7 cells. In addition, the yeast two hybrid assay expressing estrogen receptor alpha (ERalpha) and beta (ERbeta) and the ERalpha competitor screening assay (ligand binding screen) were used to verify the binding affinities of the isolated compounds to ER. Furthermore, a naringinase pre-treatment of the 70% alcoholic extract of Cassia tora seeds resulted in a significant increase in its estrogenic activity. From the naringinase pre-treated extract six compounds were isolated, among which 6-hydroxymusizin and aurantio-obtusin showed the most potent estrogenic activity, while torachrysone, rubrofusarin and toralactone showed a significant anti-estrogenic activity. Finally, the structure requirements responsible for the estrogenic activity of the isolated compounds were studied by investigating the activity of several synthetic compounds and chemically modifying the isolated compounds. The basic nucleus 1,3,8-trihyroxynaphthalene (T(3)HN) was found to play a principal role in the binding affinity of these compounds to ER.
2. Phenolic constituents of Cassia seeds and antibacterial effect of some naphthalenes and anthraquinones on methicillin-resistant Staphylococcus aureus
H Ito,T Tsuchiya,T Yoshida,T Hatano,H Uebayashi,S Shiota Chem Pharm Bull (Tokyo) . 1999 Aug;47(8):1121-7. doi: 10.1248/cpb.47.1121.
Thirteen phenolic glycosides including six new compounds were isolated from seeds of Cassia tora (Leguminosae). The structures of the new compounds, rubrofusarin triglucoside (7), nor-rubrofusarin gentiobioside (9), demethylflavasperone gentiobioside (10), torachrysone gentiobioside (11), torachrysone tetraglucoside (12) and torachrysone apioglucoside (13), were elucidated on the basis of spectroscopic and chemical evidence. The effects of the phenolic glycosides, their aglycones and several other compounds structurally related to them on Escherichia coli K12, Pseudomonas aeruginosa PAO1 and some strains of Staphylococcus aureus were then examined. Among them, torachrysone (15), toralactone (16), aloe-emodin (18), rhein (19) and emodin (20) showed noticeable antibacterial effects on four strains of methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 2-64 micrograms/ml. On the other hand, the phenolic compounds tested did not show strong antibacterial effects on E. coli and P. aeruginosa.
3. Structure Related Inhibition of Enzyme Systems in Cholinesterases and BACE1 In Vitro by Naturally Occurring Naphthopyrone and Its Glycosides Isolated from Cassia obtusifolia
Su Hui Seong,Pradeep Paudel,Jae Sue Choi,Hyun Ah Jung,Srijan Shrestha Molecules . 2017 Dec 28;23(1):69. doi: 10.3390/molecules23010069.
Cassia obtusifoliaLinn. have been used to improve vision, inflammatory diseases, and as hepatoprotective agents and to promote urination from ancient times. In the present study, we investigated the influence of glycosylation of components ofC. obtusifoliaand structure-activity relationships (SARs) with respect to the inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), which are related to Alzheimer's disease (AD). All sixC. obtusifolia-derived compounds, rubrofusarin (1), rubrofusarin 6-O-β-d-glucopyranoside (2), rubrofusarin 6-O-β-d-gentiobioside (3), nor-rubrofusarin 6-O-β-d-glucoside (4), isorubrofusarin 10-O-β-d-gentiobioside (5), and rubrofusarin 6-O-β-d-triglucoside (6) showed promising inhibitory activity against AChE/BACE1. Compounds3and4showed most significant inhibition against AChE and BACE1, respectively. The SARs results emphasized the importance of gentiobiosyl moiety in the rubrofusarin for AChE inhibition, whereas the presence of hydroxyl group at C-8 and the glucosyl moiety at the C-6 position in the nor-rubrofusarin appeared to largely determine BACE1 inhibition. Kinetics and docking studies showed the lowest binding energy and highest affinity for mixed-type inhibitors,3and4. Hydrophobic bonds interactions and the number of hydrogen bonds determined the strength of the protein-inhibitor interaction. These results suggest thatC. obtusifoliaand its constituents have therapeutic potential, and that the SARs of its active components are further explored with a view towards developing a treatment for AD.
4. Rubrofusarin as a Dual Protein Tyrosine Phosphate 1B and Human Monoamine Oxidase-A Inhibitor: An in Vitro and in Silico Study
Pradeep Paudel,Hyun Ah Jung,Jae Sue Choi,Su Hui Seong ACS Omega . 2019 Jul 3;4(7):11621-11630. doi: 10.1021/acsomega.9b01433.
A number of nature-derived biologically active compounds comprise glycosides. In some cases, the glycosidic residue is needed for bioactivity; however, in other cases, glycosylation just improves some pharmaco*kinetic/dynamic parameters. The patterns of protein tyrosine phosphatase 1B (PTP1B) and human monoamine oxidase A (hMAO-A) inhibition by rubrofusarin 6-O-β-d-glucopyranoside (1), rubrofusarin 6-O-β-d-gentiobioside (2), rubrofusarin triglucoside (3), and cassiaside B2 (4) were compared with the aglycone, rubrofusarin, isolated fromCassia obtusifoliaseeds. Rubrofusarin showed potent inhibition against the PTP1B enzyme (IC50; 16.95 ± 0.49 μM), and its glycosides reduced activity (IC50; 87.36 ± 1.08 μM for1and >100 μM for2-4) than did the reference drug, ursolic acid (IC50; 2.29 ± 0.04 μM). Similarly, in hMAO-A inhibition, rubrofusarin displayed the most potent activity with an IC50value of 5.90 ± 0.99 μM, which was twice better than the reference drug, deprenyl HCl (IC50; 10.23 ± 0.82 μM). An enzyme kinetic and molecular docking study revealed rubrofusarin to be a mixed-competitive inhibitor of both these enzymes. In a western blot analysis, rubrofusarin increased glucose uptake significantly and decreased the PTP1B expression in a dose-dependent manner in insulin-resistant HepG2 cells, increased the expression of phosphorylated protein kinase B (p-Akt) and phosphorylated insulin receptor substrate-1 (p-IRS1) (Tyr 895), and decreased the expression of glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase (PEPCK), key enzymes of gluconeogenesis. Our overall results show that glycosylation retards activity; however, it reduces toxicity. Thus,Cassiaseed as functional food and rubrofusarin as a base can be used for the development of therapeutic agents against comorbid diabetes and depression.
