Extracts From Hypericum hircinum subsp. majus Exert Antifungal Activity Against a Panel of Sensitive and Drug-Resistant Clinical Strains.

Abstract

During the last two decades incidences of fungal infections dramatically increased and the often accompanying failure of available antifungal therapies represents a substantial clinical problem. The urgent need for novel antimycotics called particular attention to the study of natural products. The genus Hypericum includes many species that are used in the traditional medicine to treat pathological states like inflammations and infections caused by fungi. However, despite the diffused use of Hypericum-based products the antifungal potential of the genus is still poorly investigated. In this study five Hypericum species autochthonous of Central and Eastern Europe were evaluated regarding their polyphenolic content, their toxicological safety and their antifungal potential against a broad panel of clinical fungal isolates. LC-MS analysis led to the identification and quantification of 52 compounds, revealing that Hypericum extracts are rich sources of flavonols, benzoates and cinnamates, and of flavan-3-ols. An in-depth screen of the biological activity of crude extracts clearly unveiled H. hircinum subsp. majus as a promising candidate species for the search of novel antifungals. H. hircinum is diffused in the Mediterranean basin from Spain to Turkey where it is traditionally used to prepare a herbal tea indicated for the treatment of respiratory tract disorders, several of which are caused by fungi. Noteworthy, the infusion of H. hircinum subsp. majus excreted broad antifungal activity against Penicillium, Aspergillus and non-albicans Candida isolates comprising strains both sensitive and resistant to fluconazole. Additionally, it showed no cytotoxicity on human cells and the chemical characterization of the H. hircinum subsp. majus infusion revealed high amounts of the metabolite hyperoside. These results scientifically support the traditional use of H. hircinum extracts for the treatment of respiratory tract infections and suggest the presence of exploitable antifungal principles for further investigations aimed at developing novel antifungal therapies.

Hypericum triquetrifolium and H. neurocalycinum as Sources of Antioxidants and Multi-Target Bioactive Compounds: A Comprehensive Characterization Combining In Vitro Bioassays and Integrated NMR and LC-MS Characterization by Using a Multivariate Approach

“…Although, to the best of our knowledge, previous studies reporting procyanidins in H. triquetifolium and H. neurocalycinum have not been published, catechin and several oligomeric procyanidins (such as A2, B2, and B3) have been identified and isolated from H. perforatum ( Ploss et al, 2001 ; Hellenbrand et al, 2015 ) and H. hircinum subsp. Majus ( Tocci et al, 2018 ).…”

Potent Antifungal Properties of Dimeric Acylphloroglucinols from Hypericum mexicanum and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin B

“…The cytotoxicity was evaluated on two normal cell lines, namely PBMC and human foreskin fibroblast Hs27 (ATCC ® CRL-1634™, Manassas, VA, USA). PBMCs were obtained from buffy coat of healthy donors (as approved by the ethical committee of the local health center, Azienda Provinciale per i Servizi Sanitari, Provincia Autonoma di Trento) within 4 h from sample collection and isolated as previously described [ 9 ]. Cells were seeded in 96-well culture plates at concentration of 5000 cells/well and incubated for 24 h before treatment with H. mexicanum extracts and isolated compounds.…”

“…Overall, the outcomes of the available antifungal therapy are not satisfactory, and therefore the discovery of new active compounds is a priority considering this alarming gap in the anti-fungal pipeline [ 7 ]. The search for novel antifungal agents from medicinal plant sources [ 8 , 9 ] offers a promising path to addressing this gap.…”

“…The plant genus Hypericum, including many medicinal species, is considered as a prolific source of phloroglucinols. Despite the genus being mainly known for the extensively investigated H. perforatum , an increasing number of publications is calling attention towards less distributed or neglected species as well for the discovery of new antifungal formulations and compounds [ 8 , 9 , 10 ]. Here, in particular, lipophilic extracts obtained from Hypericum species in South America have shown inhibitory activity on the growth of human fungal pathogens [ 8 , 9 , 10 ] and their properties have been suggested to be related to the presence of a class of dimeric phloroglucinols: the dimeric acylphloglucinols (DAPs) [ 11 ] consisting of filicinic acid and phloroglucinol moieties [ 12 ] Despite available studies documenting a great potential for this class of compounds as antimicrobial, antidepressant and cytotoxic drug leads, DAPs are poorly investigated, maybe due to difficulties in isolation, low yield, and instability [ 13 ].…”

A Systematic Study of Mechanism of Sargentodoxa cuneata and Patrinia scabiosifolia Against Pelvic Inflammatory Disease With Dampness-Heat Stasis Syndrome via Network Pharmacology Approach

“…Recently, UPLC-QTOF-MS/MS or GC/MS studies have shown that both SC and PS contains a variety of active components such as phenols, flavonoids, phenylpropenoids and triterpenoids, which exerts anti-oxidant, anti-bacteria, anti-inflammatory and anti-virus effects ( Lee et al, 2012 ; Hwang et al, 2019 ; Yang et al, 2019 ). A large number of experimental data showed that herbal extracts and natural products were effective in preventing and treating several disease such as Non-alcoholic fatty liver disease, fungal infection ( Tocci et al, 2018 ; Zhang et al, 2018b ). However, due to the complexity of the composition of the herbs, the underlying molecular mechanism of this two herbs in treatment of pelvic inflammatory disease is not clear.…”