Ethanolic extract from leaves of tithonia diversifolia induces apoptosis in HCT-116 cells through oxidative stress.

Tithonia diversifolia is a perennial bushy plant found in South America with significant ethnopharmacological importance as an antimalarial, antidiabetic, antibacterial, and anticancer agent. The aim of the present study was to determine the cytotoxicity of the ethanolic extract from leaves of T. diversifolia (TdE) on human cancer cell lines (HCT-116, SNB-19, NCIH-460 and MCF-7), as well as the mechanism of action involved in cell death and cellular modulation of oxidative stress. The TdE exhibited significant activity with IC50 values ranging from 7.12 to 38.41 µg/ml, with HCT-116 being the most sensitive cell line. Subsequent experiments were conducted with HCT-116 cell line. TdE decreased the number of viable cells, followed by induction of apoptotic events, increase in mitochondrial membrane permeabilization, and enhanced G2/M phase of the cell cycle. Pro-oxidative effects including elevated acidic vesicular organelle formation, lipid peroxidation, and nitric oxide by-products, as well as reduced levels of intracellular glutathione and reactive oxygen species production were also observed following incubation with TdE, which may lead to DNA damage followed by apoptotic cell death. These results demonstrate the potential of TdE ethanolic leaf extraction for biological activity and enhance the importance of continuing to study natural sources of plants for the development of anticancer agents.

Sesquiterpenoids from Tithonia diversifolia (Hemsl.) A. Gray induce apoptosis and inhibit the cell cycle progression of acute myeloid leukemia cells.

Three sesquiterpene lactones (1-3) were isolated from the aerial part of Tithonia diversifolia (Hemsl.) A. Gray grown in the Hoa Binh province in Viet Nam. The structures of these three sesquiterpene lactones were identified as tagitinin A (1), 1ß-hydroxytirotundin 3-O-methyl ether (2), and tagitinin C (3) by analyzing spectroscopic data. For the first time, compound 2 was isolated from T. diversifolia growing in Viet Nam. Furthermore, contrary to existing literature, we determined that compound 1 was the major isolate. Compounds 1 and 3 significantly decreased numbers of acute myeloid leukemia OCI-AML3 cells by promoting apoptosis and causing cell cycle arrest at G0/G1 phase at concentrations as low as 2.5 µg/mL (compound 1) and 0.25 µg/mL (compound 3). Additionally, all three compounds showed cytotoxic activity against five human cancer cell lines (A549, T24, Huh-7, 8505, and SNU-1), with IC50 values ranging from 1.32 ± 0.14 to 46.34 ± 2.74 µM. Overall, our findings suggest that compounds 1 and 3 may be potential anti-cancer therapeutics and thus warrant further study.

Use of Tithonia diversifolia (hemsl) A. Gray in the diet of growing lambs / [Uso de tithonia diversifolia (hemsl) A. Gray na dieta de cordeiros em crescimento]

Two assays were conducted to study the Tithonia diversifolia (Td) plant: (1) chemical analysis and in vitro dry matter digestibility (IVDMD) of plant parts and (2) productive performance of lambs fed a traditional diet or a Td diet (30% of Td plus 70% of the traditional diet). The plant parts studied were leaves (L), leaves and petioles (LP); and leaves, petioles and stems (LPS). Feed intake, weight gain and feed conversion were registered weekly during five weeks of experimentation. The L showed higher (P<0.05) crude protein content (26.7%) than LP and LPS (25.5 and 19.7%, respectively). Crude fiber (11.2%), neutral detergent fiber (45.4%), cellulose (16.9%) and hemicellulose (33.5%) were lower in L than in LP (12.5, 46.7, 18.0 and 35.7%, respectively) and LPS (22.6, 59.2, 27.0 and 43.5%, respectively). The L and LP showed the highest IVDMD (89.2 and 88.2%, respectively vs. 77.2% of LPS). The Td diet resulted in greater feed intake and weight gain and lower feed conversion than the traditional diet. Therefore, Tithonia diversifolia is a forage plant of good quality for lambs which does not affect the productive performance.(AU)

Dois ensaios foram realizados para estudar a planta de Tithonia diversifolia (Td): (1) análise química e digestibilidade in vitro da matéria seca (DIVMS) de partes de plantas e (2) desempenho produtivo de cordeiros alimentados com dieta tradicional ou dieta Td (30% de Td mais 70% da dieta tradicional). As partes vegetais estudadas foram folhas (L), folhas e pecíolos (LP); folhas, pecíolos e caules (LPS). O consumo de ração, o ganho de peso e a conversão alimentar foram registrados semanalmente, durante cinco semanas de experimentação. O L apresentou maior (P<0,05) conteúdo de proteína bruta (26,7%) que o LP e o LPS (25,5 e 19,7%, respectivamente). Fibra bruta (11,2%), fibra em detergente neutro (45,4%), celulose (16,9%) e hemicelulose (33,5%) foram menores em L do que em LP (12,5, 46,7, 18,0 e 35,7%, respectivamente) e LPS (22,6, 59,2, 27,0 e 43,5%, respectivamente). O L e o LP apresentaram o maior DIVMS (89,2 e 88,2%, respectivamente vs. 77,2% do LPS). A dieta Td resultou em maior consumo de ração e maior ganho de peso e menor conversão alimentar que a dieta tradicional. Portanto, Tithonia diversifolia é uma planta forrageira de boa qualidade para cordeiros que não afeta o desempenho produtivo.(AU)

Tithonia diversifolia-derived orizabin suppresses cell adhesion, differentiation, and oxidized LDL accumulation by Akt signaling suppression via PTEN promotion in THP-1 cells.

As a Japanese folk medicine, Tithonia diversifolia is used for cardiovascular disease prevention and health maintenance. We isolated T. diversifolia-derived orizabin based on the nitric oxide production inhibitory effect. This study aimed to consider orizabin as a novel functional compound with anti-atherosclerotic activity. Orizabin significantly inhibited the adhesion of THP-1 cells to human umbilical vein endothelial cells (HUVECs) and suppressed the mRNA expression of adhesion molecules in HUVECs. In Phorbol 12-myristate 13-acetate stimulated THP-1 cells, orizabin suppressed macrophage differentiation, CD36 expression (1% at 10 µM), and NFκB transcriptional activity. Furthermore, orizabin suppressed oxidized low-density lipoprotein (oxLDL) uptake in macrophages and the Akt phosphorylation. On the contrary, we revealed that phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN) mRNA and protein expression were promoted significantly by orizabin (mRNA, 270-fold at 10 µM). Our study presented the possibility that T. diversifolia-derived orizabin is novel anti-atherosclerotic compound via the suppression of Akt phosphorylation, and T. diversifolia may be effective as a new crop for vascular health maintenance. PRACTICAL APPLICATIONS: In this study, the differentiation of monocytes was suppressed without any toxicity, it was obvious in the image, and the oxLDL uptake in monocytes was clearly suppressed by orizabin. Our findings presented that T. diversifolia-derived compound orizabin specifically contributes to the promotion of PTEN expression and suppression of Akt signal in cells, and acts to suppress inflammation by suppression of NFκB transcriptional activity. As a component derived from food, it has a strong function and can be used to maintain the health for blood vessels. It is also a finding that deserves to expand production currently being carried out on a small scale. Furthermore, the promoting effect of PTEN known as a cancer suppressor in orizabin may result in further use for pharmaceuticals research. Orizabin can be safely used as a food-derived compound for maintaining human health.