Acetylcholinesterase inhibition and antioxidant activity of the water extracts of several Hypericum species
Introduction
Hypericum perforatum, also known as St. John’s wort, has been used in the treatment of mild depression (Eggelkraut-Gottanka et al., 2002, Kasper et al., 2008, Pilkington et al., 2006, Wurglics and Schubert-Zsilavecz, 2006) all over the world. Portugal is no exception (Cunha, Silva, & Roque, 2003). Several studies refer to hypericin (Eggelkraut-Gottanka et al., 2002, Sauviat et al., 2007) and hyperforin (Eggelkraut-Gottanka et al., 2002, Leuner et al., 2007, Menegazzi et al., 2008, Zhou et al., 2004) as the compounds in Hypericum perforatum that may explain its biological activity. Most of the studies carried out with this plant refer to polar organic extracts (Brolis et al., 1998, Gioti et al., 2005, Liu et al., 2005, Silva et al., 2008, Tatsis et al., 2007, Williams et al., 2006). Very few studies deal with the water extracts, e.g. infusions or decoctions.
Depression is also a condition found in people suffering from Alzheimer disease (AD) and one of the processes to alleviate the symptoms is to inhibit acetylcholinesterase (AChE) (Heinrich & Teoh, 2004), the enzyme that catalyses the hydrolysis of the neurotransmitter, acetylcholine. This way to tackle the problem involves the use of drugs that have been the objective of much research. One of the active compounds in use, for instance galantamine, was isolated from the plant genus Galanthus (Latvala et al., 1995). If H. perforatum could show this double action, alleviate depression and simultaneously inhibit AChE, it might be interesting for AD treatment.
The action of Hypericum, on the central nervous system, was previously attributed to the presence hypericin and hyperforin (Verotta, 2003). Although the amounts of hypericin and hyperforin depend on the plant analysed, and also on the extraction procedure, they are usually not the main components of H. perforatum. They are found in smaller concentrations than the flavonoids rutin, hyperoside, isoquercitrin, quercetin and the caffeic acid derivative, cholorogenic acid (Brolis et al., 1998, Williams et al., 2006). These molecules may also participate in the biological activity of H. perforatum (Paulke, Noldner, Scubert-Zsilavecz, & Wurglics, 2008).
The antioxidant activity is also relevant in the treatment of Alzheimer’s disease (Frank and Gupta, 2005, Resende et al., 2008). It was demonstrated that the absence of the natural antioxidant, vitamin E, enhanced AD in a mouse model (Nishida et al., 2006). The endogenous formation of free radicals can contribute to the inflammatory processes (Gomes, Fernandes, Lima, Mira, & Corvo, 2008). It is known that inflammation can also contribute to the development of the disease (Cunningham et al., 2008, Teeling and Perry, 2008).
With the objective of finding whether the Hypericum species, commercially available, drunk as a hot beverage, could contribute to the inhibition of acetylcholinesterase, water extracts of this plant were analysed for their AChE inhibition and antioxidant activity. H. androsaemum and H. perforatum, from different suppliers, and H. undulatum, collected in the east of Portugal, Beira Baixa, were the targets of this study. The main compounds responsible for the enzyme inhibition were determined by HPLC–DAD, comparatively to standards.
Section snippets
Chemicals
All chemicals were of analytical grade. Acetylcholinesterase (AChE) type VI-S, from electric eel, 349 U/mg of solid, 411 U/mg of protein, 5,5′-dithiobis[2-nitrobenzoic acid] (DTNB), acetylthiocholine iodide (AChI), tris[hydroxymethyl]aminomethane (tris buffer), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,6-di-tert-butyl-4-hydroxytoluene (BHT), pyrogallol, chlorogenic acid, rutin, hyperoside, isoquercitrin, quercitrin, quercetin and Folin–Ciocalteau reagent were obtained from Sigma.
Plant material
H. androsaemum and
Results
Previous results have demonstrated that, among several plants analysed, H. undulatum was the one giving the highest inhibition activity towards AChE (Ferreira, Proença, Serralheiro, & Araújo, 2006). This provoked a more detailed study on the effect of different Hypericum species on this enzyme activity, together with the identification of the main compounds responsible for this inhibitory activity. As the origin of the plant is also thought to be responsible for different activities in the
Conclusions
Most literature reports concern the chemical and bio-activity investigation of polar organic extracts, e.g. methanol, ethanol or hydro–alcoholic mixtures. The present work describes the results carried out with decoctions that are usually consumed as herbal tea of Hypericum species. These decoctions contain mainly chlorogenic acid, rutin, hyperoside, isoquercitrin and quercitrin, in different percentages. The samples did not contain either hypericin or hyperforin. Decoctions have antioxidant
References (33)
- et al.
Identification by high-performance liquid chromatography–diode array detection–mass spectrometry and quantification by high-performance liquid chromatography-UV absorbance detection of active constituents of Hypericum perforatum
Journal of Chromatography A
(1998) - et al.
Rosmarinic acid, scutellarein 4′-methyl ether 7-O-glucoronide and (16S)-coleon E are the main compounds responsible for the antiacetylcholinesterase and antioxidant activity in herbal tea of Plectranthus barbatus (“falso boldo”)
Food Chemistry
(2009) - et al.
The in vitro screening for acetylcholinesterase inhibition and antioxidant activity of medicinal plants from Portugal
Journal of Ethnopharmacology
(2006) - et al.
Single-drop liquid-phase microextraction for the determination of hypericin, pseudohypericin and hyperforin in biological fluids by high performance liquid chromatography
Journal of Chromatography A
(2005) - et al.
Galanthamine from snowdrop – The development of a modern drug against Alzheimer’s disease from local Caucasian knowledge
Journal of Ethopharmacology
(2004) - et al.
Inflammation and Alzheimer’s disease: Possible role of periodontal disease
Alzheimer’s and Dementia
(2008) - et al.
Alkaloids of Galanthus elwesii
Phytochemistry
(1995) - et al.
Liquid chromatography–mass spectrometry studies of St. John’s wort methanol extraction: Active constituents and their transformation
Journal of Phramaceutical and Biomedical Analysis
(2005) - et al.
Antioxidant and antiacetylcholinesterase activities of five plants used as Portuguese food spices
Food Chemistry
(2007) - et al.
Protective effects of St. Johns’s wort extract and its component hyperforin against cytokine-induced cytotoxicity in a pancreatic β-cell line
The International Journal of Biochemistry and Cell Biology
(2008)
Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse
Biochemical and Biophysical Research Communications
St John´s wort for depression: Time for a different perspective
Complementary Therapies in Medicine
Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease
Free Radical Biology and Medicine
St. John’s wort (Hypericum perforatum) extracts and isolated phenolic compounds are effective antioxidants in several in vitro models of oxidative stress
Food Chemistry
Phenolic constituents of 17 Hypericum species from Turkey
Biochemical Systematics and Ecology
Identification of the major constituents of Hypericum perforatum by LC/SPE/NMR and/or LC/MS
Phytochemistry
Cited by (76)
Bioactivities of iridoids and flavonoids present in decoctions from aerial parts of Verbascum betonicifolium
2020, European Journal of Integrative MedicineCitation Excerpt :The UV–vis analysis (Fig. 2) indicates the presence of several caffeic acid derivatives, probably chlorogenic acid and verbascoside, usually described in Verbascum genus. The UV–vis spectrum of compounds eluted at retention time 14.72 and 16.93 min show resemblance with the derivatives of caffeic acid [36], Fig. 2a–c and with flavonoid UV–vis spectrum Fig. 2d [36]. The compounds present in V. betonicifolium mucilage-free extract were identified by using an LC–MS/MS. The extract without mucilages was analyzed in positive and negative mode, but the identification was carried out only in negative mode where a higher number of compounds was found, also with higher intensity.
Phenolic profile and biological activities of decoctions from Santolina impressa, a Portuguese endemic species
2020, Journal of Herbal MedicineCitation Excerpt :These EC50 values are similar to those determined in extracts from other Asteraceae (Barroso et al., 2014) or even in extracts from other Santolina species (Chibani et al., 2012), however closer to that shown by the standard BHT, commonly used in the food industry, which presented an EC50 value of 12 ± 0.7 μg/mL (Mata et al., 2007). This strong antiradical activity of S. impressa extracts is probably due to their phenolic components, especially to the dominant constituents, chlorogenic acid and cynarin, two compounds well-known for their antioxidant activity (Hernandez et al., 2010; Fratianni et al., 2014; Pistón et al., 2014; Raudonėa et al., 2015). As decoctions from S. impressa capitula presented the best AChE inhibitory activity and antioxidant capacity, only the toxicity of these extracts was tested in Caco-2 and HepG2 cells, using several concentrations of plant extract to calculate the cell viability by the MTT assay.