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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 IC 50 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 G 2 /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.

The present study aims to evaluate the nutritional value of different tree and shrub leaves in Brazilian ruminant production systems. Eight potentially edible trees and shrubs were identified from interviews with 30 ruminant producers: Aroeira (ARO; Lithraea molleoides ), Black Mulberry (BMU; Morus nigra ), Candeia (CAN; Eremanthus erythropappus ), Jatobá (JAT; Hymenaea courbaril ), Gliricídia (GLI; Gliricidia sepium ), Santa Bárbara tree (SBT; Mélia azedarach ), Tithonia (TIT; Tithonia diversifolia ), and White Mulberry (WMU; Morus alba ). Four leaf samples of each edible tree were sampled, and chemical analyses and in vitro assays were performed. Edible trees (except CAN and JAT) had lower neutral detergent fiber content than Mombasa grass. In addition, SBT, BMU, WMU, and TIT had lower fiber content than the other evaluated edible trees. Consequently, SBT, TIT, BMU, and WMU had improved dry matter degradation. Among the edible trees and shrubs, SMW and WMU increased the potential for gas production (a parameter). On the other hand, CAN decreased the estimated gas production 48 h after incubation. Furthermore, TIT decreased methane production up to 24 h after in vitro fermentation. Thus, except ARO, CAN, and JAT, the edible trees evaluated in the present study are potential feeds in moderate- to high-producing animals. Additionally, TIT fermentation reduces in vitro methane production.

Tithonia diversifolia is widely used in African traditional medicine for the treatment of a large number of ailments and disorders, including malaria. In the present study, we evaluated the repellent activity of essential oils (EO) of this plant against Anopheles coluzzii, a major vector of malaria in Africa. Fresh leaves of T. diversifolia were used to extract EO, which were used to perform repellency assays in the laboratory and in the field using commercially available N,N-Diethyl-meta-toluamide (DEET) and Cymbopogon (C.) citratus EO as positive controls and vaseline as negative control. The repellency rates and durations of protection of the human volunteers involved were used as measures of repellent activity. Chemical composition of the T. diversifolia EO was established further by gas chromatography coupled with mass spectrometry. The moisture content and oil yield were 81% and 0.02% respectively. A total of 29 compounds in the T. diversifolia EO was identified, with D-limonene (20.1%), α-Copaene (10.3%) and o-Cymene (10.0%) as the most represented. In field studies, the mean time of protection against mosquito bites was significantly lower in T. diversifolia EO-treated volunteers compared to treatments with C. citratus EO (71 min versus 125 min, p = 0.04), but significantly higher when compared with the non-treated volunteers (71 min vs 0.5 min, p = 0.03). The same pattern was found in laboratory repellency assays against A. coluzzii. In contrast, repulsion rates were statistically similar between T. diversifolia EO and positive controls. In conclusion, the study suggests promising repellent potential of leaves of T. diversifolia EO against A. coluzzii., (© 2023. The Author(s).)

Background: Thermophilic composting is a promising method of sanitizing pathogens in manure and a source of agriculturally important thermostable enzymes and microorganisms from organic wastes. Despite the extensive studies on compost prokaryotes, shifts in microbial profiles under the influence of various green materials and composting days are still not well understood, considering the complexity of the green material sources. Here, the effect of regimens of green composting material on the diversity, abundance, and metabolic capacity of prokaryotic communities in a thermophilic compost environment was examined., Methods: Total community 16S rRNA was recovered from triplicate compost samples of Lantana-based, Tithonia-based, Grass-based, and mixed (Lantana + Tithonia + Grass)- based at 21, 42, 63, and 84 days of composting. The 16S rRNA was sequenced using the Illumina Miseq platform. Bioinformatics analysis was done using Divisive Amplicon Denoising Algorithm version 2 (DADA2) R version 4.1 and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States version 2 (PICRUSt2) pipelines for community structure and metabolic profiles, respectively. In DADA2, prokaryotic classification was done using the Refseq-ribosomal database project (RDP) and SILVA version 138 databases., Results: Our results showed apparent differences in prokaryotic community structure for total diversity and abundance within the four compost regimens and composting days. The study showed that the most prevalent phyla during composting included Acidobacteriota, Actinobacteriota, Bacteroidota, Chloroflexi, and Proteobacteria. Additionally, there were differences in the overall diversity of metabolic pathways but no significant differences among the various compost treatments on major metabolic pathways like carbohydrate biosynthesis, carbohydrate degradation, and nitrogen biosynthesis., Conclusion: Various sources of green material affect the succession of compost nutrients and prokaryotic communities. The similarity of amounts of nutrients, such as total Nitrogen, at the end of the composting process, despite differences in feedstock material, indicates a significant influence of composting days on the stability of nutrients during composting., (© 2023. The Author(s).)

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 ), 1 β -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 IC 50 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., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

For the well-being of human health as well as ecological concerns and the development of insect resistance to conventional chemical insecticides, efforts have increased worldwide, to find eco-friendly, effective and safer insect control agents which are of natural origin. A bioactive biofumigant molecule named dihydro-p-coumaric acid was isolated and characterized from the leaves of Tithonia diversifolia Hemsl. A. Gray following laboratory bioassays against the rice weevil, Sitophilus oryzae L (Coleoptera: Curculionidae); the lesser grain borer, Rhyzopertha dominica F (Coleoptera: Bostrichidae) and the rust-red flour beetle, Tribolium castaneum Herbst (Coleoptera: Tenebrionidae). The isolated compound acted as a fumigant, toxic to adults of stored grain insect pests with LC 50 values of 17.86, and 11.49 μg/L (S. oryzae), 19.80 and 10.29 μg/L (R. dominica) and 24.41 and 17.80 μg/L air (T. casatneum) respectively. Further, in vivo data reveal that the percentage of inhibition of acetyl cholinesterase (AChE) was dose-dependent and in vitro results showed potent AChE inhibitor. The isolated compound acts as an efficient biofumigant against the stored grain insect pests and has no adverse effect on seed germination. From this study, we assume that the isolated biofumigant molecule has the ability for used in IPM programs for stored-grain pests because of its biofumigant activity., (Copyright © 2022. Published by Elsevier Inc.)

Background: In this study, we examined the anti-diabetic activity of standardised extracts of Tithonia diversifolia (Hemsley) A Gray ( T. diversifolia ) leaves for their effects on insulin resistance and mitochondrial DNA (mtDNA) copy number., Methods: T. diversifolia leaves were extracted using an ultrasound-assisted method and standardised using Tagitinin C. There were six groups: i) normal control; ii) diabetic group; iii) metformin group (300 mg/kg) and iv) groups treated with three different doses of extract (50 mg/kg, 100 mg/kg and 150 mg/kg). Blood samples were taken before and after 28 days of treatment for fasting plasma glucose (FPG) and insulin analysis, which were used for a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) calculation. The soleus and gastrocnemius muscles were harvested after 28 days of treatment for the measurement of mtDNA copy number., Results: The results showed an improvement in blood glucose levels and HOMA-IR scores in all treatment groups. The results of mtDNA copy number analysis also revealed significant improvement with the highest number observed at an extract dose of 100 mg/kg in which the mtDNA copy number increased up to 3 times in the soleus muscles ( P < 0.001)., Conclusion: T. diversifolia extract has the potential to be used as an anti-diabetic agent that improves insulin resistance, possibly by increasing mtDNA content., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2022.)

Acetylcholinesterase (AChE) is an enzyme that catalyzes acetylcholine into choline and acetic acid. Conventional pesticides, including organophosphates and carbamates target and inhibit the activity of AChE. To obtain more pesticide precursors that meet the safety requirements, more than 200 compounds were screened. Tirotundin and parthenolide identified as potential neurotoxins to nematodes were isolated from Tithonia diversifolia and Chrysanthemum parthenium , respectively. Their IC 50 values were 6.89 ± 0.30 and 5.51 ± 0.23 μg/mL, respectively against the AChE isolated from Caenorhabditis elegans . AChE was inhibited in a dose-dependent manner using the two compounds. And the Lineweaver-Burk and Dixon plots indicated that tirotundin and parthenolide were reversible inhibitors against AChE, both inhibiting AChE in a mixed-type competitive manner and demonstrating these compounds may possess dual binding site AChE inhibitors. LC 50 values of tirotundin and parthenolide against C. elegans were 9.16 ± 0.21 and 7.23 ± 0.48 μg/mL, respectively. These results provide a certain theoretical basis for the development and utilization of novel pesticides.

Historical climate changes and interspecific gene flow have played an important role in shaping the distribution and genetic diversity of the biota in the Neotropics. In this study, we explored the role of both the Pleistocene climate changes and hybridization on the contemporary geographic structure of two Neotropical weedy species: Tithonia tubaeformis and T. rotundifolia. Distribution shifts under past and current climate conditions were explored through ecological niche modelling (ENM). We then tested these hypotheses using chloroplast microsatellite (cpSSR) data in T. tubaeformis and compared the patterns deduced with those previously reported for T. rotundifolia using the same cpSSR loci. Lastly, we searched for shared haplotypes between species. Both species exhibited significant downwards altitudinal shifts during the last interglacial (LIG) and the Last Glacial Maximum (LGM). For instance, T. rotundifolia showed large suitable habitat areas since the LIG at xeric conditions in western Mesoamerica. Tithonia tubaeformis showed a ~five-fold range contraction during the LIG compared to current climate conditions, followed by a range expansion in the LGM. Despite the large shared refugial areas predicted through ENM, we found a low number of shared haplotypes, suggesting a minor role of hybridization in shaping the geographic structure of these species. Our results provide additional patterns of the population history of the northern Neotropics during the Quaternary, and we suggest that weedy widespread species are a well-suited group for the study of the effects of historic climatic changes on the biota of this region., (© 2021 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)

The methanolic extract of aerial parts of Tithonia tubaeformis showed significant antioxidant activity in DPPH assay. It was subjected to bioassay guided fractionation affording more active ethyl acetate fraction which on further purification led to the isolation and identification of a series of bioactive phenolic compounds having important biosynthetic relationship. Of these, 4-hydroxyphenethyl henicosanoate (tithonoid) is a new compound. Moreover, in the carrageenan induced paw edema test, significant attenuation of inflammation was also produced by the extract at 50-200 mg/kg. The structures of all the constituents were determined through spectroscopic methods. It is the first systematic biological and chemical investigation on T. tubaeformis , which showed that phenolics may play an important role in the antioxidant and anti-inflammatory activity of the plant, probably through synergism.

The ingestion of organic and mineral materials by earthworms is a prominent functional role that has profound consequences for the decomposition and stabilization of soil organic matter. To investigate the litter consumption of the African nightcrawler earthworm Eudrilus eugeniae under different tropical conditions, we used DNA barcoding to identify specimens of E. eugeniae collected from sites across the Adamawa region in Cameroon, and studied the influence of habitat suitability (soil properties), soil moisture, litter type, and population density on litter consumption. A total of four litter consumption experiments were carried out using soils collected from refuse disposal sites, agricultural lands, and savannahs dominated by the Mexican sunflower Tithonia diversifolia. The results revealed that litter consumption significantly increased in the refuse disposal and agricultural soils as opposed to the Mexican sunflower (T. diversifolia) soil, a cow dung enriched substrate, and a sterile soil horizon from the savannah (P < 0.05). The optimum moistures for litter consumption were between 24% and 50%. Litter type did not affect the consumption rate of the earthworms (P > 0.05). We observed a general positive density-dependent consumption with litter mass loss increasing with increasing density. Our results suggest that E. eugeniae has a strong direct effect on the decomposition of plant materials than expected from previous estimations, and that litter consumption rates are determined by several habitat components and population density., (© 2020 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Objectives: Tithonia diversifolia (Asteraceae) is used in Cameroonian traditional medicine for the treatment of several diseases amongst which are hepatic disorders. Anti-inflammatory, analgesic and anti-diabetic properties have been reported but, there is no scientific information on its hepato-protective effects. The aim of this study was to evaluate the curative effects of the Tithonia diversifolia ( T. diversifolia ) leaves aqueous extract on ethanol induced-hepatotoxicity in rats., Methods: Ethanol 40° (4 g/kg) was administered daily by intragastric gavage for 21 days, and then the extract was administered concomitantly with ethanol for two more weeks. Some biochemical serum and tissue parameters were evaluated. Histopathologic analysis of the liver was carried out., Results: The ingestion of ethanol induced a significant reduction of body weight and a significant increase in some markers of hepatic function (Alanine Amino-transferase, Aspartate Amino-transferase, alkaline phosphatase, gamma glutamyl-transferase, total bilirubin and albumin). These alterations were accompanied by a significant increase in the levels of serum triglycerides (p<0.001). Intoxicated animals were also characterized by a significant decrease of reduced glutathione and nitrites concentrations, catalase and superoxide dismutase activities as well as an increase of malondialdehyde levels. The histopathological examination showed vascular congestion, disorganized parenchyma, liver inflammation and dilation of sinusoid. The extract at the doses of 60 and 120 mg/kg reversed ethanol-induced adverse effects., Conclusion: Our study found that, the aqueous extract of T. diversifolia leaves has hepato-protective activity against ethanol-induced liver damages due partly to its antioxidant effect. This result justifies its empirical use for the treatment of liver problems., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Tomato spotted wilt orthotospovirus (TSWV) causes devastating losses to agronomic and ornamental crops worldwide. Currently, there is no effective strategy to control this disease. Use of biotic inducers to enhance plant resistance to viruses maybe an effective approach. Our previous study indicated that Tagitinin A (Tag A) has a high curative and protective effect against TSWV. However, the underlying molecular mechanism of Tag A-mediated antiviral activity remains unknown. In this study, Tag A reduced the expression of the NSs, NSm genes was very low in untreated leaves following TSWV infection. In addition, the expression of all TSWV genes in the inoculated and systemic leaves was inhibited in the protective assay, and with an inhibition rate of more than 85% in systemic leaves. Tag A increased phenylalanine ammonia-lyase (PAL) activity in the curative and protective assays. The concentrations of jasmonic acid (JA) and jasmonic acid -isoleucine (JA-Ile) and the expression of its key gene NtCOI1 in Tag A-treated and systemic leaves of treated plants were significantly higher than those of the control plant. Furthermore, Tag A-induced resistance to TSWV could be eliminated by VIGS-mediated silencing of the NtCOI1 gene. These indicated that Tag A acts against TSWV by activating the JA defense signaling pathway., (Copyright © 2020. Published by Elsevier Inc.)

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., (© 2020 Wiley Periodicals LLC.)

Ethnopharmacological Relevance: Tithonia diversifolia (Helms.) A. Gray, popularly known in Brazil as "margaridão" or "mão-de-Deus" has been used in the folk medicine as anti-inflammatory and against other illnesses in several countries. Indeed, many studies show de effect of T. diversifolia in the inflammatory process, however, any of them have demonstrated the mechanism of cell migration., Aim of the Study: The aim of this investigation was to show the in vivo and in vitro effects of T. diversifolia leaves ethanol extract on neutrophil trafficking from the blood to the inflamed tissue and on cell-derived secretion of chemical mediators, as well as, the effects on inflammatory resolution and inflammatory pain., Materials and Methods: Anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally treated with the T. diversifolia extract (0.1, 1 or 3 mg/kg). The leukocyte influx (optical microscopy) and the secretion of chemical mediators (TNF, IL-6, IL-1β and CXCL1, by enzyme-linked immunosorbent assay) were quantified in the inflamed exudate. Histological analysis of the pouches was performed. N-Formyl-methionine-leucine-phenylalanine-induced chemotaxis, lipopolysaccharide-induced TNF, IL-6, IL-1β, CXCL1 and NO production, and adhesion molecule expression (CD62L and CD18, flow cytometry) were in vitro quantified using oyster glycogen recruited peritoneal neutrophils previous treated with the extract (1, 10, or 100 μg/mL). The resolution of inflammation was accessed by efferocytosis assay, and the antinociceptive activity was investigated using carrageenan-induced mechanical hypersensitivity., Results: The oral treatment with T. diversifolia promoted reduction in the neutrophil migration as well as the decrease in total protein, TNF, IL-1β and CXCL1 levels in the inflamed exudate. In vitro treatment with T. diversifolia shedding of β2 integrin expressions, without alter CD62L expression. The extract was able to increase the efferocytosis of apoptotic neutrophils, and the increase of the IL-10 and the decrease of TNF secretion. Additionally, the extract reduced the hypersensitivity induced by carrageenan., Conclusions: Together, the data herein obtained showed that T. diversifolia extract presented anti-inflammatory activity by inhibiting the cytokine and NO production, and also the leukocyte migration. The mechanisms involved in the extract anti-inflammatory effects include the impairment in the leukocyte migration to the inflamed tissue, the pro-resolution activity, and consequently the anti-hypersensitivity., (Copyright © 2019 Elsevier B.V. All rights reserved.)