Olivier Potterat

Root extracts of Cryptolepis decidua are used in the traditional medicine of South-West Africa to treat various conditions. Here, we report the potent cytotoxic activity of a methanol root extract against a human adenocarcinomic cell line, which prompted us to establish a comprehensive metabolite profile. Overall, six previously undescribed compounds were isolated from this extract by a combination of open-column chromatography (CC), centrifugal partition chromatography (CPC), and preparative HPLC. They include two sarmentogenin-type cardenolides (2 and 3), an androstane lactone (5), two dinormonoterpenoid diglucosides, dinosides A and B (9 and 10), and a quinic acid derivative (12). In addition, six previously reported constituents were identified (1, 4, 6–8, 11). The structures of the isolates were elucidated using HPLC-MS^2/3, HRESIMS, and NMR spectroscopy. Feature-based molecular networking was used to map a comprehensive metabolite profile. The cytotoxic activity of the methanol extract was evaluated by WST-1 cell-viability assays, apoptosis/necrosis tests, and cell-cycle analyses. Cardenolides 1–3 were identified as the primary cytotoxic agents, exhibiting IC₅₀ values of 0.25 μM (1), 2.20 μM (2), and 0.28 μM (3) in A549 human lung epithelial cancer cells, and 0.41 μM (1), 2.31 μM (2), and 0.39 μM (3) against peripheral blood mononuclear cells (PBMCs).

Pre-clinical studies suggest that extracts prepared from the fruits of Vitex agnus castus (VAC) interact with dopamine D2 receptors, leading to reduced prolactin secretion. In previous experiments, dopaminergic activity was mostly evaluated using radioligand binding assays or via the inhibition of prolactin release from rat pituitary cells. Diterpenes featuring a clerodadienol scaffold were identified as major active compounds, but no conclusive data regarding their potency and intrinsic activity are available. Utilising advances in chromatography, we re-examined this topic using HPLC-based tracking of bioactivity via microfractionation of the VAC extract Ze 440. Using a cAMP-based assay, we measured dopaminergic activity in CHO-K1 cells that overexpress the human D2 receptor. Six diterpenes were isolated from two active HPLC microfractions. Viteagnusin I emerged as the most potent diterpene (EC₅₀: 6.6 µM), followed by rotundifuran (EC₅₀: 12.8 µM), whereas vitexilactone was inactive (EC₅₀: >50 µM). Interestingly, triterpenes were also identified as active, with 3-epi-maslinic acid being the most active compound (EC₅₀: 5.1 µM). To better understand these interactions at the molecular level, selected diterpenes and triterpenes were analysed through molecular docking against D2 receptor structures. Our data show that the dopaminergic activity of VAC diterpenes seems to depend on the configuration and on ring substitution in the side chain. This study also highlights for the first time the dopaminergic contribution of triterpenes such as 3-epi-maslinic acid.

Ribwort plantain (Plantago lanceolata L.) is expected to open up new crop cultivation perspectives in arable farming in order to significantly reduce nitrogen losses through leaching, N₂O emissions and to increase resilience under drought conditions. Therefore, this study investigated the properties of the roots as an alternative to grasses for forage production under drought conditions. Ten genotypes of ribwort plantain were compared under field conditions in northern Switzerland, focusing on the characteristics of the root system and the aucubin content in the leaves and roots. Aucubin, known for inhibiting the nitrification process in the soil, varied according to genotype and season. All tested genotypes showed higher aucubin content in leaves than in roots, which may indicate the greater importance of leaves in reducing soil nitrification. Dry matter yield and for the first time root characteristics, such as root length density (RLD) and specific root length (SRL), were evaluated at two different soil depths, and at different distances from the plants. The results showed that ribwort is well adapted to acquire water and nutrients in terms of rooting in topsoil. In addition, a second field experiment conducted in eastern Germany (Saxony) confirmed the plant’s ability to root deeply after one year of cultivation, reaching depths of up to even 1.88 m. The obtained results indicate the high capacity of ribwort plantain to take up water and nutrients also from deeper soil layers. To reduce N₂O emissions through the cultivation of ribwort plantain, the choice of genotype seems to be of great importance due to varying aucubin contents.

The aims of the present study were (i) to characterize the dichloromethane extract of the fresh aerial parts of S. somalensis, cultivated in Liguria (Italy), (ii) to quantify carnosic acid production and (iii) to find an eco-friendly alternative approach to control diseases caused by phytopathogenic fungi. The phytochemical investigation yielded several known terpenoids, as well as a diterpene, 4α,9α-epoxy-2H-dibenzo[a,d]cyclohepten-7(5H)-one, not previously described as a plant metabolite before. The results showed a noteworthy quantity of carnosic acid (113.90 µg/mg of dried extract). The potential antifungal activity of the plant surface extract and carnosic acid against five phytopathogenic fungi (Colletotrichum coccodes, Fusarium oxysporum, Sclerotinia sclerotiorum, Botrytis cinerea and Rhizoctonia solani) was considered. A complete inhibition of C. coccodes, S. sclerotiorum and R. solani mycelium growth was observed by carnosic acid at 500 µg/mL. High inhibition values were observed against B. cinerea and F. oxysporum compared to reference active ingredients. Four different B. cinerea strains exhibited a pronounced sensitivity to carnosic acid, as well as those originating from agricultural crop scenarios where a high load of active ingredient for gray mold control was historically adopted. Additionally, the formation and development of the germinative tube in B. cinerea were greatly slowed down.

The medicinal plant Bryophyllum pinnatum was previously shown to block oxytocin (OT)-induced signals in myometrial cells, consistent with its tocolytic effect observed in patients. OT activates not only OT receptors but also V_1A receptors, two receptors with high receptor homology that are both expressed in the myometrium and play a crucial role in myometrial contraction signaling. We aimed to study the molecular pharmacology of B. pinnatum herbal preparations using specific receptor ligands, the human myometrial cell line hTERT-C3, and cell lines expressing recombinant human OT and V_1A receptors. We found that press juice from B. pinnatum (BPJ) inhibits both OT- and vasopressin (AVP)-induced intracellular calcium increases in hTERT-C3 myometrial cells. In additional assays performed with cells expressing recombinant receptors, BPJ also inhibited OT and V_1A receptor-mediated signals with a similar potency (IC₅₀ about 0.5 mg/mL). We further studied endogenous OT- and AVP-sensitive receptors in hTERT-C3 cells and found that OT and AVP stimulated those receptors with similar potency (EC₅₀ of ~ 1 nM), suggesting expression of both receptor subtypes. This interpretation was corroborated by the antagonist potencies of atosiban and relcovaptan that we found. However, using qPCR, we almost exclusively found expression of OT receptors suggesting a pharmacological difference between recombinant OT receptors and native receptors expressed in hTERT-C3 cells. In conclusion, we show that B. pinnatum inhibits both OT and AVP signaling, which may point beyond its tocolytic effects to other indications involving a disbalance in the vasopressinergic system. Received: 11 February 2024 Accepted after revision: 10 April 2024 Accepted Manuscript online: 10 April 2024 Article published online: 08 May 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany