Bioactivity in Rhododendron: A Systemic Analysis of Antimicrobial and Cytotoxic Activities and Their Phylogenetic and Phytochemical Origins

Abstract

The exceptional diversity of the genus Rhododendron has a strong potential for identification, characterization, and production of bioactive lead compounds for health purposes. A particularly relevant field of application is the search for new antibiotics. Here, we present a comparative analysis of nearly 90 Rhododendron species targeted toward the search for such candidate substances. Through a combination of phytochemical profiles with antimicrobial susceptibility and cytotoxicity, complemented by phylogenetic analyses, we identify seven potentially antimicrobial active but non-cytotoxic compounds in terms of mass-to-charge ratios and retention times. Exemplary bioactivity-guided fractionation for a promising Rhododendron species experimentally supports in fact one of these candidate lead compounds. By combining categorical correlation analysis with Boolean operations, we have been able to investigate the origin of bioactive effects in further detail. Intriguingly, we discovered clear indications of systems effects (synergistic interactions and functional redundancies of compounds) in the manifestation of antimicrobial activities in this plant genus.

Incongruent phylogenies and its implications for the study of diversification, taxonomy and genome size evolution ofRhododendron(Ericaceae)

“…Rhododendron and some as sister to R. albrechtii in his combined analysis of plastid and nuclear DNA, which suggests that missing data in their dataset causes different accessions of species from this group to end up in different positions. In Grimbs et al (2017) the plastid DNA signal apparently overruled the nuclear signal.…”

“…However, ITS and the plastid DNA markers retrieve it in different positions (Fig. 1-2 and S1-6; Kurashige et al, 2001;Grimbs et al, 2017). The former genus Menziesia has been found to be nested in Rhododendron since the studies of Kron (1997) and Kurashige et al (2001).…”

“…For example, R. albrechtii, which takes only a distant relationship with R. schlippenbachii in the plastid DNA-based analyses (Fig. 1 and S1 -3;Kurashige et al, 2001;Grimbs et al, 2017).…”

“…However, these studies mostly focused on some specific subgenera and/or sections. Only few studies considered the phylogeny of the whole genus Rhododendron and mostly using a single DNA region, e.g., plastid matK -51 species (Kurashige et al, 2001); nuclear ITS -21 species (Gao et al, 2002); nuclear rpb2 -88 species (Goetsch et al, 2005) or trnK, trnL-F & ITS -87 species (Grimbs et al, 2017). Shrestha et al (2018) investigated the global distribution and molecular phylogeny of Rhododendron in a biogeographical context, using 423 species with a concatenated dataset of nine plastid genes, nuclear ribosomal ITS data and six introns of one nuclear gene (RPB).…”

Which Plants Used in Ethnomedicine Are Characterized? Phylogenetic Patterns in Traditional Use Related to Research Effort

“…If lineages rich in species with ethnomedicinal use are those that have metabolites of interest, phylogenetic methods predict bioprospecting potential ( Saslis-Lagoudakis et al, 2011 ; Ernst et al, 2016 ). Direct tests of phylogenetic structuring of phytochemistry for groups of ethnomedicinal and bioprospecting interest show that some (e.g., Rønsted et al, 2008 ) but not all (e.g., Grimbs et al, 2017 ) reveal phylogenetic signal. Nevertheless, it seems probable that close relatives of species of interest might yield larger quantities, or interesting variants, of valuable compounds.…”