Dataset Information

Insight into the Hydrolytic Selectivity of ?-Glucosidase to Enhance the Contents of Desired Active Phytochemicals in Medicinal Plants.

ABSTRACT: Most glycosides in herbal medicines become pharmacologically active after hydrolysis or subsequent metabolism to respective aglycones. Hence, the hydrolytic efficiency of glycosidase is a crucial determinant of the pharmacological efficacy of herbal glycosides. In this study, we investigated the enzymatic conversion of the four herbal extracts and their glycosides using the glycoside hydrolase family 3 ?-glucosidase from Lactobacillus antri (rBGLa). We show that ?-glucosidase substrate specificity depends on the arrangements and linkage types of sugar residues in glycosides. The enzyme rBGLa showed higher hydrolytic selectivity for glucopyranoside than for glucuronide and rhamnopyranoside, and specificity for 1?6 rather than 1?2 linkages. In addition, in silico 3D structural models suggested that D243 and E426 of rBGLa act as catalytic nucleophile and acid/base residues, respectively. These experiments also suggested that substrate specificity is determined by interactions between the C6 residue of the sugar moiety of the substrate glycoside and the oxygen OD1 of D56 in rBGLa. Therefore, despite the broad substrate spectrum of ?-glucosidase, differences in hydrolytic selectivity of ?-glucosidases for glycoside structures could be exploited to enhance the hydrolysis of the desired medicinal glycosides in herbs using tailored ?-glucosidases, allowing for improvement of specific potencies of herbal medicines.

SUBMITTER: Kim YS

PROVIDER: S-EPMC6327262 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Insight into the Hydrolytic Selectivity of β-Glucosidase to Enhance the Contents of Desired Active Phytochemicals in Medicinal Plants.

Kim Young Soo YS Ma Jin Yeul JY

BioMed research international 20181227

Most glycosides in herbal medicines become pharmacologically active after hydrolysis or subsequent metabolism to respective aglycones. Hence, the hydrolytic efficiency of glycosidase is a crucial determinant of the pharmacological efficacy of herbal glycosides. In this study, we investigated the enzymatic conversion of the four herbal extracts and their glycosides using the glycoside hydrolase family 3 β-glucosidase from Lactobacillus antri (rBGLa). We show that β-glucosidas ...[more]

PMID: 30687743

Similar Datasets

Project description:BACKGROUND: Human African trypanosomiasis (HAT), a parasitic protozoal disease, is caused primarily by two subspecies of Trypanosoma brucei. HAT is a re-emerging disease and currently threatens millions of people in sub-Saharan Africa. Many affected people live in remote areas with limited access to health services and, therefore, rely on traditional herbal medicines for treatment. METHODS: A molecular docking study has been carried out on phytochemical agents that have been previously isolated and characterized from Nigerian medicinal plants, either known to be used ethnopharmacologically to treat parasitic infections or known to have in-vitro antitrypanosomal activity. A total of 386 compounds from 19 species of medicinal plants were investigated using in-silico molecular docking with validated Trypanosoma brucei protein targets that were available from the Protein Data Bank (PDB): Adenosine kinase (TbAK), pteridine reductase 1 (TbPTR1), dihydrofolate reductase (TbDHFR), trypanothione reductase (TbTR), cathepsin B (TbCatB), heat shock protein 90 (TbHSP90), sterol 14?-demethylase (TbCYP51), nucleoside hydrolase (TbNH), triose phosphate isomerase (TbTIM), nucleoside 2-deoxyribosyltransferase (TbNDRT), UDP-galactose 4' epimerase (TbUDPGE), and ornithine decarboxylase (TbODC). RESULTS: This study revealed that triterpenoid and steroid ligands were largely selective for sterol 14?-demethylase; anthraquinones, xanthones, and berberine alkaloids docked strongly to pteridine reductase 1 (TbPTR1); chromenes, pyrazole and pyridine alkaloids preferred docking to triose phosphate isomerase (TbTIM); and numerous indole alkaloids showed notable docking energies with UDP-galactose 4' epimerase (TbUDPGE). Polyphenolic compounds such as flavonoid gallates or flavonoid glycosides tended to be promiscuous docking agents, giving strong docking energies with most proteins. CONCLUSIONS: This in-silico molecular docking study has identified potential biomolecular targets of phytochemical components of antitrypanosomal plants and has determined which phytochemical classes and structural manifolds likely target trypanosomal enzymes. The results could provide the framework for synthetic modification of bioactive phytochemicals, de novo synthesis of structural motifs, and lead to further phytochemical investigations.

Project description:The number of patients with type 2 diabetes mellitus (T2DM) has increased worldwide. Although an instant cure was achieved with the standard treatment acabose, unsatisfactory symptoms associated with cardiovascular disease after acabose administration have been reported. Therefore, it is important to explore new treatments. A Thai folk recipe has long been used for T2DM treatment, and it effectively decreases blood glucose. However, the mechanism of this recipe has never been proven. Therefore, the potential anti-T2DM effect of this recipe, which is used in Thai hospitals, was determined to involve alpha-glucosidase (AG) inhibition with a half maximal inhibitory concentration (IC50). In vitro experiments showed that crude Cinnamomum verum extract (IC50 = 0.35 ± 0.12 mg/mL) offered excellent inhibitory activity, followed by extracts from Tinospora crispa (IC50 = 0.69 ± 0.39 mg/mL), Stephania suberosa (IC50 = 1.50 ± 0.17 mg/mL), Andrographis paniculate (IC50 = 1.78 ± 0.35 mg/mL), and Thunbergia laurifolia (IC50 = 4.66 ± 0.27 mg/mL). However, the potencies of these extracts were lower than that of acabose (IC50 = 0.55 ± 0.11 mg/mL). Therefore, this study investigated and developed a formulation of this recipe using computational docking. Among 61 compounds, 7 effectively inhibited AG, including chlorogenic acid (IC50 = 819.07 pM) through 5 hydrogen bonds (HBs) and 2 hydrophobic interactions (HIs); β-sitosterol (IC50 = 4.46 nM, 6 HIs); ergosterol peroxide (IC50 = 4.18 nM, 6 HIs); borapetoside D (IC50 = 508.63 pM, 7 HBs and 2 HIs); borapetoside A (IC50 = 1.09 nM, 2 HBs and 2 His), stephasubimine (IC50 = 285.37 pM, 6 HIs); and stephasubine (IC50 = 1.09 nM, 3 HBs and 4 HIs). These compounds bind with high affinity to different binding pockets, leading to additive effects. Moreover, the pharmacokinetics of six of these seven compounds (except ergosterol peroxide) showed poor absorption in the gastrointestinal tract, which would allow for competitive binding to AG in the small intestine. These results indicate that the development of these 6 compounds into oral antidiabetic agents is promising.

Dataset Information

Insight into the Hydrolytic Selectivity of ?-Glucosidase to Enhance the Contents of Desired Active Phytochemicals in Medicinal Plants.

Publications

Insight into the Hydrolytic Selectivity of <i>β</i>-Glucosidase to Enhance the Contents of Desired Active Phytochemicals in Medicinal Plants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets