Casearia coriacea Vent., an endemic plant from the Mascarene Islands, was investigated following its antiplasmodial potentialities highlighted during a previous screening. Three clerodane diterpene compounds were isolated and identified as being responsible for the antiplasmodial activity of the leaves of the plant: caseamembrin T (1), corybulosin I (2), and isocaseamembrin E (3), which exhibited half maximal inhibitory concentrations (IC₅₀) of 0.25 to 0.51 µg/mL. These compounds were tested on two other parasites, Leishmania mexicana mexicana and Trypanosoma brucei brucei, to identify possible selectivity in one of them. Although these products possess both antileishmanial and antitrypanosomal properties, they displayed selectivity for the malaria parasite, with a selectivity index between 6 and 12 regarding antitrypanosomal activity and between 25 and 100 regarding antileishmanial activity. These compounds were tested on three cell lines, breast cancer cells MDA-MB-231, pulmonary adenocarcinoma cells A549, and pancreatic carcinoma cells PANC-1, to evaluate their selectivity towards Plasmodium. This has not enabled us to establish selectivity for Plasmodium, but has revealed the promising activity of compounds 1–3 (IC₅₀ < 2 µg/mL), particularly against pancreatic carcinoma cells (IC₅₀ < 1 µg/mL). The toxicity of the main compound, caseamembrin T (1), was then evaluated on zebrafish embryos to extend our cytotoxicity study to normal, non-cancerous cells. This highlighted the non-negligible toxicity of caseamembrin T (1).

Background: Triple-negative breast cancer (TNBC) presents significant therapeutic limitations due to its aggressive heterogeneity and the rapid emergence of adaptive resistance to apoptosis-based regimens. Addressing these challenges requires polypharmacological strategies capable of modulating multiple signalling networks simultaneously. While the Cannabis sativa phytocomplex offers a vast chemical space for multi-target intervention, the quantitative pharmacological basis of its synergistic interactions remains largely uncharacterised. Purpose: This study aimed to deconstruct the synergistic landscape of high-purity phytocannabinoids (CBD, CBG, CBD-A) in combination with the sesquiterpene β-caryophyllene (BCP) against TNBC, using MDA-MB-231 as a primary model and Hs578T as a validation line. Methods: Growth Rate (GR) inhibition metrics and the SynergyFinder+ framework were used to map pharmacological interactions across four reference models. Subcellular dynamics and phenotypic transitions were characterised by high-resolution label-free holotomographic microscopy combined with live-cell kinetic imaging and single-cell fate mapping. Results: Two highly potent synergistic clusters were identified for CBD-CBG-BCP combinations, with ZIP, HSA, and Bliss synergy scores exceeding 65. CBD-A exhibited minimal interaction potential and was excluded from ternary studies. GR-based quantification further revealed that these combinations produced net cytotoxicity (GR < 0) at sub-IC₅₀ concentrations of each component. Single-cell fate mapping by holotomographic microscopy identified a temporally ordered death programme: an initial phase of extensive cytoplasmic vacuolisation associated with focal perinuclear space swelling and progressive nuclear compression, morphological hallmarks of autosis, which is followed by a transition to apoptotic execution. The autotic nature of the primary death phase was confirmed by pharmacological rescue with digoxin, a selective inhibitor of the Na⁺,K⁺-ATPase. To the best of our knowledge, this sequential engagement of autosis followed by apoptotic execution represents the first documented instance of such a two-stage death programme in any cellular model. Conclusion: These findings provide robust evidence that specific phytocannabinoid-terpene ratios engage a Na⁺,K⁺-ATPase-regulated autotic programme as an upstream commitment step, followed by apoptotic execution, effectively circumventing the caspase-independent resistance mechanisms characteristic of TNBC. This study establishes a rational, quantitatively validated framework for transitioning from empirical botanical use to evidence-based, multi-target cannabinoid polypharmacology in aggressive breast cancer.

The development of new anticancer agents from natural sources is a promising approach due to limitations of existing chemotherapies. This study assesses the cytotoxic potential of two plants, Uvaria brevistipitata (UB) and Harungana madagascariensis (HM), used in traditional Congolese medicine. Ethanolic extracts were fractionated and analyzed using HPLC and GC-MS. The in vitro anticancer activity was tested on MDA-MB-231 (triple-negative breast cancer) and A2058 (invasive skin melanoma) cell lines. The Uvaria fractions, especially UB-2, UB-3, and UB-4, showed strong cytotoxicity with IC50 values of 11.15 µg/mL, 6.5 µg/mL, and 9.1 µg/mL, respectively. In comparison, the HM-3 fraction from Harungana exhibited moderate activity (IC50 = 21.24 µg/mL). The UB-4 subfractions demonstrated significant cytotoxicity against both cell lines, indicating larger anticancer potential than the original extract utilized in folk medicine.As a result, Uvaria sp. has been identified as a potentially useful source of naturally occurring anticancer chemicals. The findings provide justification for our research, that aimed at isolating and structurally characterizing the active chemical entities by supporting the ethnopharmacological use of the plant. This is especially important because it has been found that the refined sub-fractions have more cytotoxic activity than the crude extracts.

Valorizing the full phytochemical profile of hemp (Cannabis sativa L.), including the synergistic activity often referred to as the “entourage effect,” requires efficient recovery of both its cannabinoid and terpene fractions. However, initiating cannabinoid decarboxylation through high drying temperatures leads to substantial loss of the terpene profile, making the two objectives thermally incompatible in conventional workflows. This study first investigated the influence of post-harvest conditions on cannabinoid content and decarboxylation using a Design of Experiments approach, and then developed a process bypassing the drying step, based on freezing and hydrodistillation, to formulate a broad-spectrum product combining high cannabinoid and terpene content. Two hemp chemotypes (Felina 32, CBD-dominant; Santhica 27, CBG-dominant) were characterized, and drying temperature was identified as the critical parameter governing decarboxylation. Freezing before hydrodistillation preserved monoterpenes and improved essential oil yield relative to oven-drying, while the heat of hydrodistillation itself drove in situ cannabinoid decarboxylation, enabling near-complete recovery in a subsequent pressurized liquid extraction step. This integrated process achieved near-quantitative recovery of cannabinoids and monoterpenes across independent production batches, with encouraging recovery of sesquiterpenes, supporting the standardized and reproducible valorization of hemp, especially for pharmaceutical applications.