The production of hypericins and hyperforin by in vitro cultures of St. John's wort (Hypericum perforatum)

Abstract

St. John's wort ( Hypericum perforatum L.) is a herbaceous perennial distributed throughout the World that has been widely used in traditional medicine. H. perforatum produces several types of biologically active compound, including the hypericins--a family of light-activated anthraquinones, localized within specialized glands found predominantly on flowers and leaves--and the hyperforins--a family of prenylated acylphloroglucinols localized in the reproductive structures of the plant. Hypericins are known to be toxic to mammals and display antiviral and anticancer activity, but the role of these compounds within the plant is unknown. Hyperforins display potent antimicrobial activity and are thought to be the primary bioactive ingredient for anti-depressive effects of the herb. The introduction of H. perforatum from Europe into the U.S.A. occurred in the 17th Century. Since the plant is considered a noxious weed, few efforts have been carried out to analyse populations in the context of secondary-metabolite concentrations. But in terms of secondary-metabolite studies, H. perforatum is an ideal model system to study the biosyntheses of aromatic polyketides and regulation of those pathways by environmental and genetic influences. This is due, in part, to the ease of conducting these studies in plant tissue culture. This review describes the progress of secondary-metabolite studies currently underway using H. perforatum. Specifically, this Review focuses on the production and regulation of the hypericins and the hyperforin in wild populations, field cultivation, greenhouse studies and plant tissue culture. Additionally, factors optimizing compound production--particularly in in vitro cultures--are presented and reviewed.

Cold stress affects antioxidative response and accumulation of medicinally important withanolides in Withania somnifera (L.) Dunal

“…Increase in withanolide contents might be due to the increased regulation of large number of transcripts including withanolide metabolic pathway genes. Previous studies have also reported positive correlation between biotic/abiotic stress and secondary metabolite accumulation (Kirakosyan et al, 2004;Wahid and Ghazanfar 2006;Cheng et al, 2007Ghorpade et al, 2011Abrol et al, 2012. Recently, Ahire et al (2014) also reported enhanced accumulation of bacoside A in Bacopa monnieri exposed to salt stress under controlled environmental conditions.…”

Arbuscular mycorrhizal fungi altered the hypericin, pseudohypericin, and hyperforin content in flowers of Hypericum perforatum grown under contrasting P availability in a highly organic substrate

“…For example, the application of either a living or autoclaved cell suspension of the fungus Nomuraea rileyi to H. polyanthemum reduced the content of uliginosin B, a phloroglucinol derivative. Furthermore, hyperforin has an antimicrobial function in the plant (Kirakosyan et al 2004), and thus its reduced accumulation in mycorrhizal compared to nonmycorrhizal plants could be related to the ability of the AM partner to suppress some of the plant's defense mechanisms (Garcia-Garrido 2002). Finally, the unclear relationship between available sugars and hyperforin content in H. perforatum, as assessed in a bioreactor (Zobayed et al 2003), and the demand for sugars by the AM fungi could be related to the reduced hyperforin content of the mycorrhizal plants.…”

“…Besides having been extensively studied for their medicinal applications, such compounds are recognized to possess antimicrobial and antifeedant properties and are involved in interaction mechanisms between plants and other organisms (Kirakosyan et al 2004). However, scarce information is available about the effects of AM fungi and nutrient availability on plant biomass accumulation and flower content of hypericin, pseudohypericin, and hyperforin for H. perforatum.…”

Interações medicamentosas de fitoterápicos e fármacos: Hypericum perforatum e Piper methysticum

“…Bahls (2001) e Ratz et al (2001) sugerem que as hipericinas sejam responsáveis pela atividade antidepressiva, segundo pesquisas realizadas na Alemanha e na Áustria. Já Kirakosyan et al (2004) atribuem essa atividade ao grupo das hiperforinas, porém o mecanismo de ação ainda não é totalmente conhecido.…”