Methanolic Extracts of D. viscosa Specifically Affect the Cytoskeleton and Exert an Antiproliferative Effect on Human Colorectal Cancer Cell Lines, According to Their Proliferation Rate.

Numerous studies have reported the pharmacological effects exhibited by Dittrichia viscosa, (D. viscosa) including antioxidant, cytotoxic, antiproliferative, and anticancer properties. In our research, our primary objective was to validate a prescreening methodology aimed at identifying the fraction that demonstrates the most potent antiproliferative and anticancer effects. Specifically, we investigated the impact of various extract fractions on the cytoskeleton using a screening method involving transgenic plants. Tumors are inherently heterogeneous, and the components of the cytoskeleton, particularly tubulin, are considered a strategic target for antitumor agents. To take heterogeneity into account, we used different lines of colorectal cancer, specifically one of the most common cancers regardless of gender. In patients with metastasis, the effectiveness of chemotherapy has been limited by severe side effects and by the development of resistance. Additional therapies and antiproliferative molecules are therefore needed. In our study, we used colon-like cell lines characterized by the expression of gastrointestinal differentiation markers (such as the HT-29 cell line) and undifferentiated cell lines showing the positive regulation of epithelial-mesenchymal transition and TGFß signatures (such as the DLD-1, SW480, and SW620 cell lines). We showed that all three of the D. viscosa extract fractions have an antiproliferative effect but the pre-screening on transgenic plants anticipated that the methanolic fraction may be the most promising, targeting the cytoskeleton specifically and possibly resulting in fewer side effects. Here, we show that the preliminary use of screening in transgenic plants expressing subcellular markers can significantly reduce costs and focus the advanced characterization only on the most promising therapeutic molecules.

Antioxidant, Antimicrobial, and Insecticidal Properties of a Chemically Characterized Essential Oil from the Leaves of Dittrichia viscosa L.

Since some synthetic insecticides cause damage to human health, compounds in plants can be viable alternatives to conventional synthetic pesticides. Dittrichia viscosa L. is a perennial Mediterranean plant known to possess biological activities, including insecticidal properties. The chemical composition of an essential oil (EOD) from D. viscosa, as well as its antioxidant, antimicrobial, and insecticidal effects on the cowpea weevil (Callosobruchus maculatus) were determined. Forty-one volatile compounds were identified in EOD, which accounted for 97.5% of its constituents. Bornyl acetate (41%) was a major compound, followed by borneol (9.3%), α-amorphene (6.6%), and caryophyllene oxide (5.7%). EOD exhibited significant antioxidant activity in all tests performed, with an IC50 of 1.30 ± 0.05 mg/mL in the DPPH test and an EC50 equal to 36.0 ± 2.5 mg/mL in the FRAP assay. In the phosphor-molybdenum test, EOD results ranged from 39.81 ± 0.7 to 192.1 ± 0.8 mg AAE/g E. EOD was active on E. coli (9.5 ± 0.5 mm), S. aureus (31.0 ± 1.5 mm), C. albicans (20.4 ± 0.5 mm), and S. cerevisiae (28.0 ± 1.0 mm), with MICs ranging from 0.1 mg/mL to 3.3 mg/mL. We found that 1 µL of EOD caused 97.5 ± 5.0% insect mortality after 96 h in the inhalation test and 60.0 ± 8.3% in the ingestion assay. The median lethal concentration (LC50) was 7.8 ± 0.3 µL EO/L, while the effective concentration in the ingestion test (LC50) was 15.0 ± 2.1 µL EO/L. We found that 20 µL of EOD caused a reduction of more than 91% of C. maculatus laid eggs.

Ointment-Based Combination of Dittrichia viscosa L. and Marrubium vulgare L. Accelerate Burn Wound Healing.

Burns constitute a major challenge in medical science, and plants can be part of the solution. Dittrichia viscosa L. (Asteraceae) and Marrubium vulgare L. (Lamiaceae) are widely used in Moroccan traditional medicine to treat several diseases and possess high potency to cure wounds. This study aimed to investigate in vivo the analgesic, anti-inflammatory, and burn-healing effects of both plants and their mixture. The hydro-ethanolic extract of both plants was analyzed using high-performance liquid chromatography with diode-array detection (HPLC-DAD). Burns were conducted on dorsal part of rats, and the wound healing process was evaluated during 21 days. Gallic acid, caffeic acid, ferulic acid, and quercetin were identified in M. vulgare extract. The analysis recorded the presence of caffeic acid, rosmarinic acid, rutin, and quercetin in D. viscosa. The group treated with the mixture showed the lowest abdominal contractions (30.4 ± 7.52) with the highest percentage of inhibition (69.12 ± 7.04%). The inhibition of paw inflammation for M. vulgare was 47.65%, followed by D. viscosa (33.86%) and the mixture (30.41%). The mixture showed the highest wound contraction at day 7 (33.16 ± 14.33%) and day 14 (87.54 ± 3.98%). D. viscosa showed the highest wound contraction on the 21st day (99.28 ± 0.44%). In conclusion, both plants and their combination showed promising results for burn healing.

Dodonaea viscosa var angustifolia derived 5,6,8-trihydroxy-7,4' dimethoxy flavone inhibits ergosterol synthesis and the production of hyphae and biofilm in Candida albicans.

ETHNOPHARMACOLOGICAL RELEVANCE: Candida albicans is developing resistance to existing drugs increasing morbidity and mortality, which elevates an immediate need to explore new antifungal agents. Phytochemicals are an excellent source of therapeutic agents. We previously reported the antifungal activity of the crude extract of Dodonaea viscosa var. angustifolia Jacq. (DVA) from which a beneficial compound flavone: 5,6,8-trihydroxy-7,4' dimethoxy flavone (5,6,8-trihydroxy-7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one) abbreviated as TMMC, was extracted. AIM OF THE STUDY: The present study evaluated the effect of a TMMC subfraction on biofilms, membrane stability, ergosterol biosynthesis and germ tube (GT) formation in Candida albicans. MATERIALS AND METHODS: Extracts were prepared and fractionated to obtain purified TMMC. Minimum inhibitory concentrations of TMMC were obtained and subinhibitory concentrations were selected for further studies. Confocal laser scanning microscopy (CLSM) was performed to assess the effect of TMMC on membrane permeability and sterol deposition using propidium iodide (PI) and filipin stains, respectively. RESULTS: Minimum inhibitory concentrations (MIC) and Minimum Fungicidal concentrations (MFC) of TMMC were 0.39 mg/mL and 1.56 mg/mL, respectively. TMMC inhibited biofilm formation and damaged mature biofilms at 0.39 mg/mL and 1.56 mg/mL, respectively. CLSM further confirmed the disruption and architectural changes in biofilms following treatment with TMMC. TMMC also inhibited GT formation and ergosterol biosynthesis in a concentration dependent manner, which was further confirmed by varying sterol distribution and membrane disruption in treated and untreated cells. CONCLUSIONS: With the multiple targets at different concentrations, TMMC warrants its potential use as antifungal drug against C. albicans. However further studies using animal models and more mechanistic approaches will be required.