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Bupleurum chinense Roots: a Bioactivity-Guided Approach toward Saponin-Type NF-?B Inhibitors.

ABSTRACT: The roots of Bupleurum chinense have a long history in traditional medicine to treat infectious diseases and inflammatory disorders. Two major compounds, saikosaponins A and D, were reported to exert potent anti-inflammatory activity by inhibiting NF-?B. In the present study, we isolated new saikosaponin analogues from the roots of B. chinese interfering with NF-?B activity in vitro. The methanol-soluble fraction of the dichloromethane extract of Radix Bupleuri was subjected to activity-guided isolation yielding 18 compounds, including triterpenoids and polyacetylenes. Their structures were determined by spectroscopic methods as saikogenin D (1), prosaikogenin D (2), saikosaponins B₂ (3), W (4), B₁ (5), Y (6), D (7), A (8), E (9), B₄ (10), B₃ (11), and T (12), saikodiyne A (13), D (14), E (15) and F (16), falcarindiol (17), and 1-linoleoyl-sn-glycero-3-phosphorylcholine (18). Among them, 4, 15, and 16 are new compounds, whereas 6, previously described as a semi-synthetic compound, is isolated from a natural source for the first time, and 13-17 are the first reports of polyacetylenes from this plant. Nine saponins/triterpenoids were tested for inhibition of NF-?B signaling in a cell-based NF-?B-dependent luciferase reporter gene model in vitro. Five of them (1, 2, 4, 6, and 8) showed strong (>?50%, at 30?µM) NF-?B inhibition, but also varying degrees of cytotoxicity, with compounds 1 and 4 (showing no significant cytotoxicity) presenting IC₅₀ values of 14.0?µM and 14.1?µM in the cell-based assay, respectively.

SUBMITTER: Liu X

PROVIDER: S-EPMC6193276 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Bupleurum chinense Roots: a Bioactivity-Guided Approach toward Saponin-Type NF-κB Inhibitors.

Liu Xin X Latkolik Simone S Atanasov Atanas G AG Kunert Olaf O Pferschy-Wenzig Eva-Maria EM Heiss Elke H EH Malainer Clemens C Schinkovitz Andreas A Kollroser Manfred M Dirsch Verena M VM Bauer Rudolf R

Planta medica 20170908 14-15

The roots of Bupleurum chinense have a long history in traditional medicine to treat infectious diseases and inflammatory disorders. Two major compounds, saikosaponins A and D, were reported to exert potent anti-inflammatory activity by inhibiting NF-κB. In the present study, we isolated new saikosaponin analogues from the roots of B. chinese interfering with NF-κB activity in vitro. The methanol-soluble fraction of the dichloromethane extract of Radix Bupleuri ...[more]

PMID: 28902374

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Project description:OBJECTIVE:In developed countries with westernized diets, the excessive consumption of added sugar in beverages and highly refined and processed foods is associated with increased risk for obesity, diabetes, and cardiovascular diseases. As a major constituent of added sugars, fructose has been shown to cause a variety of adverse metabolic effects, such as impaired insulin sensitivity, hypertriglyceridemia, and oxidative stress. Recent studies have shown that ketohexokinase isoform C is the key enzyme responsible in fructose metabolism that drive's fructose's adverse effects. The objective of this study was to identify botanical ingredients with potential for inhibitory activity against ketohexokinase-C and fructose-induced metabolic effects by using a series of in vitro model systems. METHODS:Extracts from 406 botanicals and 1200 purified phytochemicals were screened (initial concentration of 50 ?g/mL and 50 ?M, respectively) for their inhibitory activity using a cell free, recombinant human ketohexokinase-C assay. Dose response evaluations were conducted on botanical extracts and phytochemicals that inhibited ketohexokinase-C by > 30% and > 40%, respectively. Two different extract lots of the top botanical candidates were further evaluated in lysates of HepG2 cells overexpressing ketohexokinase-C for inhibition of fructose-induced ATP depletion. In addition, extracts were evaluated in intact Hep G2 cells for inhibition of fructose-induced elevation of triglyceride and uric acid production. RESULTS:Among the botanical extracts, phloretin (Malus domestica) extracts were the most potent (IC50: 8.9-9.2 ?g/mL) followed by extracts of Angelica archangelica (IC50: 22.6 ?g/mL-57.3 ?g/mL). Among the purified phytochemicals, methoxy-isobavachalcone (Psoralea corylifolia, IC50 = 0.2 ?M) exhibited the highest potency against ketohexokinase isoform C activity followed by osthole (Angelica archangelica, IC50 = 0.7 ?M), cratoxyarborenone E (Cratoxylum prunifolium, IC50 = 1.0 ?M), and ?-/?-mangostin (Cratoxylum prunifolium, IC50 = 1.5 ?M). Extracts of Angelica archangelica, Garcinia mangostana, Petroselinum crispum, and Scutellaria baicalensis exhibited ketohexokinase inhibitory activity and blocked fructose-induced ATP depletion and fructose-induced elevation in triglyerides and uric acid. CONCLUSIONS:Angelica archangelica, Garcinia mangostana, Petroselinum crispum, and Scutellaria baicalensis were the top four botanical candidiates identified with inhibitory activity against ketohexokinase-C. Future studies are needed to show proof of mechanism and the efficacy of these botanical extracts in humans to blunt the negative metabolic effects of fructose-containing added sugars.

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Bupleurum chinense Roots: a Bioactivity-Guided Approach toward Saponin-Type NF-?B Inhibitors.

Publications

Bupleurum chinense Roots: a Bioactivity-Guided Approach toward Saponin-Type NF-κB Inhibitors.

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