A strategy for screening active lead compounds and functional compound combinations from herbal medicines based on pharmacophore filtering and knockout/knockin chromatography

Song, Hui‐Peng; Wu, Siqi; Qi, Lian‐Wen; Long, Fang; Jiang, Lifeng; Liu, Ke; Zeng, Hao; Xu, Zhimeng; Li, Ping; Yang, Hua

doi:10.1016/j.chroma.2016.06.009

Cited by 30 publications

(13 citation statements)

References 34 publications

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“…, 15. , 16. limonoids and targeted the A/B spiro-type limonoids based on the characteristic ultraviolet absorption distinction between cedrelones, including cedrelone, 11 β -acetoxycedrelone, 11 β -hydroxycedrelone ( Supporting Information Fig.…”

Section: Introductionmentioning

confidence: 99%

“…In our previous study, two novel limonoids with unprecedented 5-oxatricyclo[5.4.0.11., 4.]hendecane ring system were isolated and reported, and walrobsin A showed significant anti-inflammatory activity by inhibiting the expression of iNOS and IL-1 β 10 . In our efforts to discover novel bioactive limonoids in Walsura , we decided to rapidly filter “impurious”14., 15., 16. limonoids and targeted the A/B spiro-type limonoids based on the characteristic ultraviolet absorption distinction between cedrelones, including cedrelone, 11 β -acetoxycedrelone, 11 β -hydroxycedrelone (Supporting Information Fig. S1) and walrobsins to guide the isolation based on HPLC—DAD method for the first time.…”

Section: Introductionmentioning

confidence: 99%

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Bioactive A-ring rearranged limonoids from the root barks of Walsura robusta

Wang

Yang

et al. 2019

Acta Pharmaceutica Sinica B

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Screening active natural products, rapid identification, and accurate isolation are of great important for modern natural lead compounds discovery 1 . We hereby reported the isolation of seven new neotecleanin-type limonoids ( 1 — 7 ), seven new limonoids with 5-oxatricyclo[5.4.0.1 1. , 4. ]hendecane ring system ( 8 — 14 ), and two new precursors ( 15 — 16 ) together with four known limonoids ( 17 — 20 ) from the root barks of Walsura robusta . Their structures, including their absolute configurations, were elucidated based on analyses of HR-ESI-MS, 1D/2D NMR, ECD spectrum calculations and single-crystal X-ray diffraction techniques. Compounds 2 , 8 , 9 , 11 , 13 , 14 , 18 showed significant anti-inflammatory activities in LPS-induced RAW 264.7 cell line, BV2 microglial cells, and Propionibacterium acnes -stimulated THP-1 human monocytic cells. Walrobsin M ( 11 ) exhibited anti-inflammatory activity with IC 50 value of 7.96±0.36 μmol/L, and down-regulated phosphorylation levels of ERK and p38 in a dose-dependent manner.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bioactive A-ring rearranged limonoids from the root barks of Walsura robusta

Wang

Yang

et al. 2019

Acta Pharmaceutica Sinica B

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“…Removing constituents can be performed by preparative chromatographic techniques, including PTLC, preparative column chromatography, and preparative high performance liquid chromatography (PHPLC)10111213. Thereafter, in vivo and in vitro bioassays are used to screen the change in bioactivity.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, there have been reports of a new strategy to screen active compounds from herbal medicines by removing or adding constituents10111213. Yan et al 10.…”

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confidence: 99%

Using the “target constituent removal combined with bioactivity assay” strategy to investigate the optimum arecoline content in charred areca nut

Peng

Liu

et al. 2017

Sci Rep

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Charred areca nut (CAN) is used to treat dyspepsia and abdominal distension in children. However, reports revealed that arecoline, the most important active constituent of CAN, possesses potential toxicities. This study was designed to investigate the optimum arecoline content in CAN, using the “target constituent removal combined with bioactivity assay” strategy. Based on PTLC method, we prepared CAN lacking all arecoline (WAC-100R) and a series of different ratios of arecoline-removed CAN samples (WAC-Rx). MTT and acute toxicity assays indicated that decreasing content by 50% decreased CAN toxicity significantly. Animal results revealed arecoline contents over 50% could guarantee the beneficial effects of CAN on gastrointestinal tract. Additionally, decreasing arecoline content in CAN by 50% decreased its pro-apoptotic effects significantly. Furthermore, decreasing 50% arecoline content in CAN down-regulated the expressions of Cleaved-Caspase-3, c-jun, c-fos, COX-2, PGE2, and IL-1α. Thus, our results revealed that CAN with 50% arecoline content (WAC-50R) has similar beneficial effects on the gastrointestinal tract to CAN, whereas its toxicity was decreased significantly. Collectively, our study suggested that the strategy of “target constituent removal combined with bioactivity assay” is a promising method to identify the optimum arecoline content in CAN, which is approximately 0.12%.

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“…Traditional Chinese medicine has played a key role in the healthcare system in the past 12–14. The screening of candidate compounds from Chinese medicine is a good strategy for new drug development 15,16. Vine tea, a traditional Chinese materia medica, is composed of the tender stem and leaves of Ampelopsis grossedentata (Hand.-Mazz) W. T. Wang.…”

Section: Introductionmentioning

confidence: 99%

<p>Dihydromyricetin Attenuates Metabolic Syndrome And Improves Insulin Sensitivity By Upregulating Insulin Receptor Substrate-1 (Y612) Tyrosine Phosphorylation In db/db Mice</p>

Zhang

Dong

et al. 2019

DMSO

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PurposeDihydromyricetin (DHM), the main bioactive ﬂavonoid in vine tea, exerts multiple health beneficial effects. This work aimed to identify whether a naturally derived flavonoid product, DHM, can significantly attenuate metabolic syndrome and improve insulin sensitivity.Methods10-week-old db/db mice were randomly assigned to receive the antidiabetic agent metformin (Met, 50 mg/kg BW), DHM (1.0 g and 0.5 g/kg BW) or placebo and were simultaneously fed a high-fat diet for 8 weeks. The general status of the animals was observed and recorded daily, body weight and blood glucose levels were measured weekly, during the experimental period. On day 55, the oral glucose tolerance test (OGTT) was performed. After OGTT, all animals were anesthetized and sacrificed by cervical decapitation. Blood samples were collected in tubes to detect plasma insulin and the biochemical parameters of lipid metabolism. Pancreas histological changes and islet fibrosis were demonstrated by H&E staining and Masson staining, respectively. Moreover, the expression of insulin receptor substrate-1 and phosphorylated insulin receptor substrate-1 in the insulin signaling pathway was detected by Western blot assay.ResultsThe oral administration of DHM (1.0 g and 0.5 g/kg BW) reduced the fasting blood glucose, serum insulin, and glycated hemoglobin levels and the insulin resistance (HOMA-IR) index. Furthermore, DHM intervention decreased body weight and the serum lipid profile. In addition, DHM treatment also markedly decreased the relative abdominal fat weight. Western blot analysis indicated that DHM upregulated the IRS-1 (Y612) tyrosine phosphorylation, improving insulin resistance. Treatment with dihydromyricetin attenuated the progression of insulin resistance and pancreatic fibrosis in fatty db/db mice.ConclusionIn summary, we determined the antimetabolic syndrome effect of DHM in db/db obese mice. DHM upregulates the IRS-1 (Y612) tyrosine phosphorylation, improving insulin resistance. Therefore, DHM is a promising therapeutic candidate for the control of metabolic syndrome.

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A strategy for screening active lead compounds and functional compound combinations from herbal medicines based on pharmacophore filtering and knockout/knockin chromatography

Cited by 30 publications

References 34 publications

Bioactive A-ring rearranged limonoids from the root barks of Walsura robusta

Bioactive A-ring rearranged limonoids from the root barks of Walsura robusta

Using the “target constituent removal combined with bioactivity assay” strategy to investigate the optimum arecoline content in charred areca nut

<p>Dihydromyricetin Attenuates Metabolic Syndrome And Improves Insulin Sensitivity By Upregulating Insulin Receptor Substrate-1 (Y612) Tyrosine Phosphorylation In db/db Mice</p>

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