Structure and cytotoxic activity of sesquiterpene glycoside esters from Calendula officinalis L.: Studies on the conformation of viridiflorol

Abstract

Topic applications of Calendula officinalis L. lipophilic extracts are used in phytotherapy to relieve skin inflammatory conditions whereas infusions are used as a remedy for gastric complaints. Such a different usage might be explained by some cytotoxicity of lipophilic extracts at gastric level but little is known about this. Therefore, we screened the CH2Cl2 extract from the flowers of C. officinalis by MTT and LDH assays in human epithelial gastric cells AGS. This bioassay-oriented approach led to the isolation of several sesquiterpene glycosides which were structurally characterized by spectroscopic measurements, chemical reactions and MM calculations. The conformational preferences of viridiflorol fucoside were established and a previously assigned stereochemistry was revised. The compounds 1a, 2a and 3f showed comparably high cytotoxicity in the MTT assays, whereas the effect on LDH release was lower. Our study provides new insights on the composition of C. officinalis extracts of medium polarity and identifies the main compounds that could be responsible for cytotoxic effects at gastric level.

A Bio-Guided Fractionation to Assess the Inhibitory Activity ofCalendula officinalisL. on the NF-κB Driven Transcription in Human Gastric Epithelial Cells

“…However, internal use of lipophilic preparations from marigold flowers is not recommended for their renowned toxicity. In fact, our group has recently succeeded in identifying fractions and pure compounds which occur in the lipophilic extract from Calendula officinalis flowers and are toxic at the gastric level [ 28 ]. In the same work we demonstrated that the composition of lipophilic extract was not altered by gastric digestion.…”

“…Dry flowers of Calendula officinalis L. (variety Calypso Orange Florensis) were obtained and extracted as previously described [ 27 , 28 ]. A voucher specimen (number 20040929) is deposited at the Laboratory of Bioorganic Chemistry (Trento, Italy).…”

“…After 48 h, medium was replaced with FBS-free medium and cells were exposed for 24 h to the compounds or fractions under study in the presence of TNF- α (10 ng/mL) as proinflammatory stimulus. To study the NF- κ B nuclear translocation, cells were plated in 10 mm dishes (3 × 10 6 cells/dish) with fresh complete medium for 48 h. Then, medium was replaced with FBS-free medium containing increasing concentrations of fractions in the presence of TNF- α (10 ng/mL) for 1 h. We previously found that the fractions H and I are highly cytotoxic to AGS cells [ 28 ], so these fractions were excluded from the biological assays.…”

Testicular Caspase-3 and β-Catenin Regulators Predicted via Comparative Metabolomics and Docking Studies

“…The four Lipinski's properties molecular weight (MW), log P, hydrogen bond acceptor (HBA), and hydrogen bond donor (HBD) as well as two additional descriptors topological polar surface area (tPSA) and numbers of rotation bonds of compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were calculated by Instant JChem version 17.10.0 from ChemAxon Ltd (Budapest, Hungary) of the molecules and projected onto a drug-like cut-off threshold of Lipinski's rules and Veber's oral bioavailability rule (Figure 8). Lipinski's rule of five, which considers orally active compounds and defines four simple physicochemical parameter ranges (MW ≤ 500, logP ≤ 5, HBD ≤ 5, and HBA ≤ 10) was combined with Veber's oral bioavailability rule, which includes two additional parameter ranges (tPSA ≤ 140 Å, number of rotatable bonds ≤10) [105,106].…”

“…Recently, researchers have given priority to the use of medicinal plants for their contraceptive properties, with a majority of them being used as female contraceptive agents, while some affect the male reproductive system [2,3]. Albizzia lebbeck L. Benth (Mimosoidae), Anagallis arvensis L. (primulaceae), and Calendula officinalis L. (Astraceae) are annual plants containing oleanane saponins which have been linked to various biological activites affecting sperm [4][5][6]. A. lebbeck extracts have exhibited anti-inflammatory, antiallergic, and antidiabetic activities [7][8][9].…”