Discovery of hyaluronidase inhibitors from natural products and their mechanistic characterization under DMSO-perturbed assay conditions

Tomohara, Keisuke; Ito, Tomohiro; Onikata, Saika; Kato, Atsushi; Adachi, Isao

doi:10.1016/j.bmcl.2017.01.083

Cited by 15 publications

(26 citation statements)

References 41 publications

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“…The inhibition by BC and CA extracts was lower; 64% and 60%, respectively. These differences in inhibition effect towards hyaluronidase are mainly correlated to the subclasses of polyphenols and flavonoids identified in each extract [ 57 , 58 , 59 ] and not to the sum of TPC and TFC extracted mass. This is clearly observed with BC leaves which demonstrated the lowest hyaluronidase inhibition despite having the highest TPC and TFC amongst all extracts.…”

Section: Resultsmentioning

confidence: 99%

Water-Based Extraction of Bioactive Principles from Blackcurrant Leaves and Chrysanthellum americanum: A Comparative Study

Cao-Ngoc

Leclercq

Rossi

et al. 2020

Foods

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The water-based extraction of bioactive components from flavonoid-rich medicinal plants is a key step that should be better investigated. This is especially true when dealing with easy-to-use home-made conditions of extractions, which are known to be a bottleneck in the course for a better control and optimization of the daily uptake of active components from medicinal plants. In this work, the water-based extraction of Blackcurrant (Ribes nigrum) leaves (BC) and Chrysanthellum americanum (CA), known to have complementary pharmacological properties, was studied and compared with a previous work performed on the extraction of Hawthorn (Crataegus, HAW). Various extraction modes in water (infusion, percolation, maceration, ultrasounds, microwaves) were compared for the extraction of bioactive principles contained in BC and CA in terms of extraction yield, of amount of flavonoids, phenolic compounds, and proanthocyanidin oligomers, and of UHPLC profiles of the extracted compounds. The qualitative and quantitative aspects of the extraction, in addition to the kinetic of extraction, were studied. The optimized easy-to-use-at-home extraction protocol developed for HAW was found very efficient to easily extract bioactive components from BC and CA plants. UHPLC-ESI-MS and high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) were also implemented to get more qualitative information on the specific and common chemical compositions of the three plants (including HAW). Their antihyaluronidase, antioxidant, and antihypertensive activities were also determined and compared, demonstrating similar activities as the reference compound for some of these plants.

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Section: Resultsmentioning

confidence: 99%

Water-Based Extraction of Bioactive Principles from Blackcurrant Leaves and Chrysanthellum americanum: A Comparative Study

Cao-Ngoc

Leclercq

Rossi

et al. 2020

Foods

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“…Alternatively, instead of adding detergents, the addition of bovine serum albumin to the assay medium has been utilized as a means of attenuating the inhibition of proteins/enzymes by SCAMs through a competing adsorption mechanism at the aggregate's surface 58 . More recently, Adachi and co-workers 59 have developed a DMSO-perturbed assay to identify SCAMs among natural products. In short, the addition of DMSO to the assay mixture leads to conformational changes in the protein, and the formation of two distinct protein populations -one productive (folded) and another that is non-productive (partly unfolded).…”

Section: Experimental Scam Detection Methodsmentioning

confidence: 99%

Computational advances in combating colloidal aggregation in drug discovery

2019

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Small molecule effectors are essential for drug discovery. Specific molecular recognition, reversible binding, and dose-dependency are usually key requirements to ensure utility of a novel chemical entity. However, artefactual frequent-hitter and assay interference compounds may divert lead optimization and screening programs towards attrition-prone chemical matter. Colloidal aggregates are the prime source of false positive readouts, either through protein sequestration or protein-scaffold mimicry. Nevertheless, assessment of colloidal aggregation remains somewhat overlooked and under-appreciated. In this Review we discuss the impact of aggregation on drug discovery by analysing select examples from the literature and publicly-available datasets. We also examine and comment on technologies used to experimentally identify these potentially problematic entities. We focus on evidencebased computational filters and machine learning algorithms that may be swiftly deployed to flag chemical matter and mitigate the impact of aggregates in discovery programs, and highlight the tools that can be used to scrutinize libraries, identify, and eliminate these problematic compounds.

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“…In another anti-HAase screening study, Tomohara et al [73] evaluated the decoction extracts of 98 plant species for HAase inhibitory activity in an in vitro HAase assay. They observed 17 extracts exhibited moderate to high inhibitory activity (>50% inhibition at 500 μg/mL) and also noted correlation between the total phenol present in the extract and their cumulative effect as anti-HAase activity was varying.…”

Section: Anti-hyaluronidase Medicinal Plant Extractsmentioning

confidence: 99%

Plant Natural Products: A Promising Source of Hyaluronidase Enzyme Inhibitors

Bhatti¹,

Karim²

2021

Biochemistry

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Hyaluronidase enzyme degrades hyaluronan, the primary component of the extracellular matrix found in connective tissues animals and on the surface of certain pathogenic bacteria. The degradation of hyaluronan is linked to a wide range of physiological and pathological process. Inhibiting the hyaluronidase enzyme is thus significant as an approach to treat a variety of diseases and health conditions such as anti-fertility, anti-tumor, antimicrobial, and anti-venom/toxin agents. HAase inhibitors of different chemical types have been identified include both synthetic compounds and constituents obtained from naturally sources. Plant natural products as HAase inhibitors are unique due to their structural features and diversity. Medicinal plants have historically been used as contraceptives, antidote for snakebites and to promote wound healing. In recent years, small molecules, particularly plant natural products (alkaloids, flavonoids, polyphenol and flavonoids, triterpenes and steroids) possessing potent HAase have been discovered. A number of plant species from various families, which have folk medicinal claims for these ailments (related to hyaluronan disturbances) were scientifically proven for their potential to block HAase enzymes.

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Discovery of hyaluronidase inhibitors from natural products and their mechanistic characterization under DMSO-perturbed assay conditions

Cited by 15 publications

References 41 publications

Water-Based Extraction of Bioactive Principles from Blackcurrant Leaves and Chrysanthellum americanum: A Comparative Study

Water-Based Extraction of Bioactive Principles from Blackcurrant Leaves and Chrysanthellum americanum: A Comparative Study

Computational advances in combating colloidal aggregation in drug discovery

Plant Natural Products: A Promising Source of Hyaluronidase Enzyme Inhibitors

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