Search Results (6)

“Vomiting disease” in ruminants is one of the most economically significant phytotoxicities in South Africa and is caused by chronic ingestion of sesquiterpene lactone compounds present in plants of the Geigeria genus. Affected livestock demonstrate mortality due to actin and myosin damage in the striated musculature; however, a validated parental-exposure laboratory animal model would be useful for further study of the toxicodynamics. We exposed Sprague–Dawley rats to ivalin in a sequential dosing procedure and evaluated clinical signs, mortality, histopathology and muscle ultrastructure. Three of the five exposed rats died acutely, and a maximum likelihood estimate method was used to calculate a Median Lethality (LD₅₀) of 135.4 mg/kg Body Weight (BW). Striated muscle in exposed rats showed only minimal and inconsistent histopathological and ultrastructural changes. Subcutaneous ivalin exposure causes acute mortality with minimal muscle pathology, contrasting with the more protracted muscular disease seen in ruminants after plant ingestion. This suggests toxicity by parenteral exposure is due to another mechanism, most likely mitochondrial energy pathway disturbances. Whilst subcutaneously exposed rats do not appear to provide a suitable model for oral sesquiterpene lactone exposure in ruminants, this study provides a starting dose for further investigation of plant extracts in both species. Full article

Fungi from the genus Candida are very important human and animal pathogens. Many strains can produce biofilms, which inhibit the activity of antifungal drugs and increase the tolerance or resistance to them as well. Clinically, this process leads to persistent infections and increased mortality. Today, many Candida species are resistant to drugs, including C. auris, which is a multiresistant pathogen. Natural compounds may potentially be used to combat multiresistant and biofilm-forming strains. The aim of this review was to present plant-derived preparations and compounds that inhibit Candida biofilm formation by at least 50%. A total of 29 essential oils and 16 plant extracts demonstrate activity against Candida biofilms, with the following families predominating: Lamiaceae, Myrtaceae, Asteraceae, Fabaceae, and Apiacae. Lavandula dentata (0.045–0.07 mg/L), Satureja macrosiphon (0.06–8 mg/L), and Ziziphora tenuior (2.5 mg/L) have the best antifungal activity. High efficacy has also been observed with Artemisia judaica, Lawsonia inermis, and Thymus vulgaris. Moreover, 69 plant compounds demonstrate activity against Candida biofilms. Activity in concentrations below 16 mg/L was observed with phenolic compounds (thymol, pterostilbene, and eugenol), sesquiterpene derivatives (warburganal, polygodial, and ivalin), chalconoid (lichochalcone A), steroidal saponin (dioscin), flavonoid (baicalein), alkaloids (waltheriones), macrocyclic bisbibenzyl (riccardin D), and cannabinoid (cannabidiol). The above compounds act on biofilm formation and/or mature biofilms. In summary, plant preparations and compounds exhibit anti-biofilm activity against Candida. Given this, they may be a promising alternative to antifungal drugs. Full article

Marine aquaculture development is recently impeded by parasitic leech Zeylanicobdellaarugamensis (Hirudinea, Piscicolidae) in Sabah, Malaysia. The parasitic leech infests a variety of cultured fishes in aquaculture facilities. In this study, we evaluated the antiparasitic activity of the chromatographic fractions of the medicinal plant Nephrolepis biserrata methanol extract against Z.arugamensis and highlighted the potential metabolites responsible for the antiparasitic properties through liquid chromatography (LC)–quadrupole time-of-flight (QTOF)–mass spectrometry (MS) analysis. Out of seven fractions obtained through flash column chromatography techniques, three fractions demonstrated antiparasitic properties. Significant parasitic mortality was indicated by fraction 3 at a concentration of 2.50 mg/mL, all the leeches were killed in a time limit of 1.92 ± 0.59 min. followed by fraction 4 (14 mg/mL) in 34.57 ± 3.39 and fraction 5 (15.3 mg/mL) in 36.82 ± 4.53 min. LC-QTOF-MS analysis indicated the presence of secondary metabolites including phytosphingosine (6), pyrethrosin (1), haplophytine (9), ivalin (2), warburganal (3), isodomedin (4) and pheophorbide a (16), representing sphingoid, alkaloid, terpenoid, phenolic and flavonoid groups. Thus, our study indicated that the chromatographic fractions of N. biserrata demonstrated significant antiparasitic activity against the marine parasitic leeches due to the presence of potent antiparasitic bioactive compounds. Full article

Vermeersiekte or “vomiting disease” is an economically important disease of ruminants following ingestion of Geigeria (G.) species in South Africa. Sheep are more susceptible, and poisoning is characterized by stiffness, regurgitation, bloat, paresis, and paralysis. Various sesquiterpene lactones have been implicated as the cause of poisoning. The in vitro cytotoxicity of two sesquiterpene lactones, namely, ivalin (purified from Geigeria aspera) and parthenolide (a commercially available sesquiterpene lactone), were compared using mouse skeletal myoblast (C2C12) and rat embryonic cardiac myocyte (H9c2) cell lines, representing the oesophageal, skeletal and cardiac muscles, which are affected in sheep. For 24, 48, and 72 h, both cell lines were exposed. A colorimetric viability assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), was used to assess cytotoxicity. A concentration-dependent cytotoxic response was observed in both cell lines, however, the C2C12 cells were more sensitive, with the half-maximal effective concentrations (EC₅₀s) ranging between 2.7 and 3.3 µM. In addition, the effect that ivalin and parthenolide has on desmin, an important cytoskeletal intermediate filament in myocytes, was evaluated using the C2C12 myoblasts. Disorganization and aggregation of desmin were caused by both sesquiterpene lactones, which could clarify some of the ultrastructural lesions described in vermeersiekte. Full article

Ivalin, a natural compound isolated from Carpesium divaricatum, showed excellent microtubule depolymerization activities among human hepatocellular carcinoma in our previous work. Here, we investigated its functions on mitochondria-mediated apoptosis in hepatocellular carcinoma SMMC-7721 cells. DAPI (4′,6-diamidino-2-phenylindole) staining, annexin V-fluorexcein isothiocyanate (FITC) apoptosis detection, and western blotting were applied to explore the apoptotic effect of Ivalin. Next, the induction effect of Ivalin on the mitochondrial pathway was also confirmed via a series of phenomena including the damage of mitochondria membrane potential, mitochondria cytochrome c escape, cleaved caspase-3 induction, and the reactive oxygen species generation. In this connection, we understood that Ivalin induced apoptosis through the mitochondrial pathway and the overload of reactive oxygen species. Furthermore, we found that the activation of nuclear factor-κB (NF-κB) and subsequent p53 induction were associated with the apoptotic effect of Ivalin. These data confirmed that Ivalin might be a promising pro-apoptotic compound that can be utilized as a potential drug for clinical treatment. Full article

Background and Objectives: Microtubules are an attractive target for cancer chemotherapy. Previously, we reported that Ivalin exhibited excellent anti-migration and anti-invasion activities in human breast cancer cells. Here, we examined the microtubule inhibition effect of Ivalin in human hepatocellular carcinoma SMMC-7721 cells. Materials and Methods: We used the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate the cell proliferation effect of Ivalin and flow cytometry analysis to detect the apoptotic and cell cycle arrest effects of Ivalin. Immunofluorescence staining was used to measure the effect of Ivalin on the cytoskeleton network, and Western blotting was used to detect the expression levels of Bax, Bcl-2, Cdc2, phosphor-Cdc2, Cdc25A, Cyclin B1, and tubulin. Results: Ivalin induced cell cycle G2/M arrest and subsequent triggered apoptosis in human hepatocellular carcinoma SMMC-7721 cells. Furthermore, microtubules were shown to be involved in Ivalin-meditated apoptosis. In this connection, Ivalin treatment suppressed cellular microtubule network formation by regulating microtubule depolymerization. Moreover, Western blotting revealed Cdc25A and Cyclin B1 were upregulated in Ivalin-meditated cell cycle arrest. Subsequently, the induction of Bax (a proapoptotic protein) and reduction of Bcl-2 (an anti-apoptotic protein) expression were observed in Ivalin-treated SMMC-7721 cells. Conclusion: Ivalin induced microtubule depolymerization, then blocked cells in mitotic phase, and eventually resulted in apoptosis in SMMC-7721 cells. Collectively, these data indicate that Ivalin, acting as a novel inhibitor of microtubules, could be considered as a promising lead in anticancer drug development. Full article