New Cytotoxic Sesquiterpene Lactones from the Leaves of Tithonia diversifolia and their Apoptosis Effect Evaluation in KB Cancer Cells.

From the leaves of Tithonia diversifolia,  nine sesquiterpenoids (1-9), including two new ones (1, 2) were isolated and structurally determined. Their chemical structures were elucidated by extensive analyses of HRESIMS and NMR spectral data, as well as comparison with the literature. All of the isolated compounds (except compounds 7, 8, 9) significantly exhibited cytotoxic activity against four human cancer cell lines (KB, HepG2, A549 and MCF7), with IC50 values ranging from 0.29-17.0 µM,  which was in the same range as the positive control ellipticine or even lower. Further, the apoptosis induction of two new compounds 1 and 2 were also investigated and reported. While compound 2 did not induce cell apoptosis in KB cells at test concentrations, compound 1 was found to possess anti-proliferative activity through concentration-dependently inducing cell cycle arrest at S phase, morphological changes, activation of caspase 3, and an increase in the early-stage apoptosis of KB cells at a concentration of 7.26 µM.

Sesquiterpene lactones from Tithonia diversifolia with ferroptosis-inducing activities.

Eight previously undescribed sesquiterpene lactones (1-8), together with six known ones (9-14) were isolated from the aerial parts of Tithonia diversifolia (Hemsl.) A. Gray. The absolute configurations of these compounds were elucidated using HRMS, NMR spectroscopy, optical rotation measurements, X-ray crystallography, and ECD. Among them, sesquiterpene lactones 2-4 share a unique carbon skeleton with a rare C-3/C-4 ring-opened structure. Compounds 1 and 8 showed moderate inhibitory effects toward CT26 murine colon carcinoma cells by promoting lipid ROS production, highlighting their potential as ferroptosis inducers.

Photosynthetic response dynamics in the invasive species Tithonia diversifolia and two co-occurring native shrub species under fluctuating light conditions.

To determine the invasiveness of invasive plants, many studies have compared photosynthetic traits or strategies between invasive and native species. However, few studies have compared the photosynthetic dynamics between invasive and native species during light fluctuations. We compared photosynthetic induction, relaxation dynamics and leaf traits between the invasive species, Tithonia diversifolia and two native species, Clerodendrum bungei and Blumea balsamifera, in full-sun and shady habitats. The photosynthetic dynamics and leaf traits differed among species. T. diversifolia showed a slower induction speed and stomatal opening response but had higher average intrinsic water-use efficiency than the two native species in full-sun habitats. Thus, the slow induction response may be attributed to the longer stomatal length in T. diversifolia. Habitat had a significant effect on photosynthetic dynamics in T. diversifolia and B. balsamifera but not in C. bungei. In shady habitat, T. diversifolia had a faster photosynthetic induction response than in full-sun habitat, leading to a higher average stomatal conductance during photosynthetic induction in T. diversifolia than in the two native species. In contrast, B. balsamifera had a larger stomatal length and slower photosynthetic induction and relaxation response in shady habitat than in full-sun habitat, resulting in higher carbon gain during photosynthetic relaxation. Nevertheless, in both habitats, T. diversifolia had an overall higher carbon gain during light fluctuations than the two native species. Our results indicated that T. diversifolia can adopt more effective response strategies under fluctuating light environments to maximize carbon gain, which may contribute to its successful invasion.

Identification of phytase producing bacteria from acidifying Tithonia diversifolia: Potential for ruminant feed development.

Phytate content in feed ingredients can negatively impact digestibility and palatability. To address this issue, it is necessary to study microbes capable of breaking down phytate content. This study aimed to isolate and characterize phytase-producing bacteria from decaying materials rich in phytic acid. The research was conducted in several stages. The first stage involved isolating phytase-producing bacteria from the acidification of Tithonia diversifolia using growth media containing Na-phytate. Bacterial isolates that produced clear zones were then tested for their activity and ability to produce several enzymes, specifically phytase, cellulase, and protease. The next step was to test the morphological characteristics of the bacterial isolate. The final stage of bacterial identification consisted of DNA isolation, followed by PCR amplification of the 16S rRNA gene, DNA sequence homology analysis, and construction of a phylogenetic tree. Based on research, three isolates were found to produce clear phytase zones: isolates R5 (20.3 mm), R7 (16.1 mm) and R8 (31.7 mm). All isolates were able to produce the enzymes phytase (5.45-6.54 U/ml), cellulase (2.60-2.92 U/ml), and protease (22.2-23.4 U/ml). Metagenomic testing identified isolate R7 and R8 as Alcaligenes faecalis and isolate R5 as Achromobacter xylosoxidans. The isolation and characterization of phytase-producing bacteria from Tithonia diversifolia acidification resulted in the identification of two promising candidates that can be applied as sources of phytase producers. Phytase-producing bacteria can be utilized to improve digestibility and palatability in animal feed.

Nutrition profile and rumen fermentation of Tithonia diversifolia fermented with Lactobacillus bulgaricus at different times and doses.

Objective: This study aims to investigate the nutritional composition and rumen fermentation attributes of the tithonia plant (Tithonia diversifolia) treated with Lactobacillus bulgaricus bacteria at different fermentation durations and doses. Materials and Methods: In this research, an experimental approach employed a factorial pattern with two factors as treatments with three replications using a complete randomized design. The primary factor was the dose of L. bulgaricus inoculum, with concentrations at 2% and 3%. The secondary factor examined during the study revolved around the duration of fermentation, offering three time frames of 1 day, 3 days, and 5 days for analysis. The inoculum of L. bulgaricus contained 65 × 1015 CFU/ml. Results: The use of L. bulgaricus bacteria on tithonia plants (T. diversifolia) with different inoculum doses and fermentation times demonstrated a highly significant effect and significant disparities (p < 0.05). In phytic acid content, nutrient content (crude protein (CP), crude fiber, crude fat, and dry matter (DM)), and in vitro digestibility, which includes DM, organic matter (OM), CP, volatile fatty acids (VFA), NH3, and gas production. However, it did not show any significant interaction between pH and OM content. Conclusion: The optimal results of nutrient profiling and in vitro digestibility, including DM, OM, CP, rumen pH, VFA, NH3 (ammonia), and gas production, were observed when the tithonia plant (T. diversifolia) was fermented using L. bulgaricus with 3% inoculum doses and a fermentation time of 5 days.

Effects of Host Plants on Development and Immunity of a Generalist Insect Herbivore.

Secondary plant chemistry mediates a variety of communication signals among species, playing a fundamental role in the evolutionary diversification of communities and ecosystems. Herein, we explored diet-mediated host plant effects on development and immune response of a generalist insect herbivore. Vanessa cardui (Nymphalidae) caterpillars were reared on leaves of three host plants that vary in secondary metabolites, Plantago lanceolata (Plantaginaceae), Taraxacum officinale (Asteraceae) and Tithonia diversifolia (Asteraceae). Insect development was evaluated by larval and pupal viabilities, survivorship, and development rate. Immune response was measured as phenoloxidase (PO) activity. Additionally, chemical profiles of the host plants were obtained by liquid chromatograph-mass spectrometry (LC-MS) and the discriminant metabolites were determined using a metabolomic approach. Caterpillars reared on P. lanceolata exhibited the highest larval and pupal viabilities, as well as PO activity, and P. lanceolata leaves were chemically characterized by the presence of iridoid glycosides, phenylpropanoids and flavonoids. Taraxacum officinale leaves were characterized mainly by the presence of phenylpropanoids, flavones O-glycoside and germacranolide-type sesquiterpene lactones; caterpillars reared on this host plant fully developed to the adult stage, however they exhibited lower larval and pupal viabilities compared to individuals reared on P. lanceolata. Conversely, caterpillars reared on T. diversifolia leaves, which contain phenylpropanoids, flavones and diverse furanoheliangolide-type sesquiterpene lactones, were not able to complete larval development and exhibited the lowest PO activity. These findings suggested that V. cardui have adapted to tolerate potentially toxic metabolites occurring in P. lanceolata (iridoid glycosides), however caterpillars were not able to cope with potentially detrimental metabolites occurring in T. diversifolia (furanoheliangolides). Therefore, we suggest that furanoheliangolide-type sesquiterpene lactones were responsible for the poor development and immune response observed for caterpillars reared on T. diversifolia.

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.

Acute and sub-acute toxicity evaluation of dihydro-p-coumaric acid isolated from leaves of Tithonia diversifolia Hemsl. A. Gray in BALB/c mice.

In present study, the acute and sub-acute toxicities of Dihydro-p-coumaric acid isolated from the leaves of Tithonia diversifolia (Hemsl.) A. Gray was studied for safety issues in mammals. For acute toxicity tests, isolated compound was administered orally in both male and female BALB/c mice at the doses of 200, 800, and 1,600 mg/kg body weight for 7 days. In sub-acute toxicity study 50 and 500 mg/kg bw of the compound was orally administered for 14 days. Toxicity induced behavioural changes, haematological parameters, biochemical markers and histopathological sections were studied after Dihydro-p-coumaric acid administration. The vital organs like heart, kidney, uterus and testis revealed no adverse effects at doses of upto 1,600 mg/kg bw and 500 mg/kg bw. Slight hepatotoxicity was however demonstrated by ALT and AST assay but histopathological section did not concur as much. The study demonstrated insignificant difference in the percentage of feed intake, water intake, weight gain, haematological parameters and histopathological changes, with no toxicity signs and mortality. Dihydro-p-coumaric acid can be regarded as safe in both acute and sub-acute toxicity assay in both sexes. This indicates Dihydro-p-coumaric acid as a viable alternative to synthetic pesticides.

A novel biofumigant from Tithonia diversifolia (Hemsl.) A. Gray for control of stored grain insect pests.

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 LC50 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.

Improving soil physical properties and cassava productivity through organic manures management in the southern Cameroon.

Cassava cultivation causes serious soil fertility depletion in Cameroon. Organic manures can contribute to maintaining the productivity and sustainability of cassava production systems due to their availability and cheapness. This study was conducted during two successive cropping seasons (2016/2017 and 2017/2018) in the Southern Cameroon, to determine the effects of organic manures on soil physical properties, and cassava growth and yield. Tithonia diversifolia fresh biomass (TB) and poultry manure (PM) were used as organic manures. Different treatments were used, namely: (i) control (no amendment), (ii) mineral fertilizer (MF (450 kg ha-1 13-13-23 NPK + 100 kg ha-1 Urea)), (iii) two rates of TB (applied at 10 and 20 t ha-1), (iv) two rates of PM (applied at 10 and 20 t ha-1) and (v) two rates of the mixture of TB and PM (applied at 5 and 10 t ha-1 each). The experimental designed was randomized complete block with three replicates per treatment. The application of TB, PM and TB + PM (mixture) lowered bulk density by 14-22.6%, 21.5-26.2% and 18.2-25%, respectively. While total porosity and water holding capacity were increased with manure application by 9.8-15.1% and 13.3-30.3%, respectively. The mineral fertilizer had no significant effect on these soil physical parameters. Application of TB and PM either solely or mixed significantly improved growth of cassava. Stem height, stem diameter and canopy diameter increased by 34.3-60%, 17.4-30.4% and 19.7-32.7%, respectively. Organic manures performed better than the mineral fertilizer. Aboveground dry biomass and fresh tubers yield increased by 21.7-59.6 and 76.6-112.2% with organic manures, and by 23.2 and 68.5% with mineral fertilizer, respectively. The best performance of cassava in terms of fresh tubers yield (51.78 t ha-1) occurred with the mixture of TB and PM applied at 10 t ha-1 each. The study revealed that fresh biomass of Tithonia diversifolia and poultry manure can be used to improve cassava production and sustain soil productivity in the humid forest zone of Southern Cameroon.

Effect of Tithonia diversifolia Leaf Extract on Leptin, Adiponectin, and Insulin Receptor Levels in Diabetic Rats.

This study aimed to evaluate the effect of Tithonia diversifolia extract (TDE) on leptin, adiponectin, and insulin receptor (IR) concentrations in diabetic rats. Twenty-four Wistar rats were divided into a control and treatment groups (n=6 per group). The control group received normal saline, and the treatment groups received 0.25% sodium carboxymethyl cellulose, TDE at 100 mg/kg body weight (bw), and catechin at 10 mg/kg bw for 7 days. On day 8, the rats were sacrificed, blood samples were obtained, and leptin, adiponectin, and insulin concentrations were measured using avidinhorseradish peroxidase sandwich-enzyme-linked immunosorbent assay. A calorimetric method was used to measure blood glucose (BG) and total serum cholesterol concentrations. The pancreas and kidneys were collected for the measurement of renal IR and macrophage cluster of differentiation (CD)14 levels using immunohistochemical staining. Acute type 2 diabetes mellitus (T2DM) with elevated BG and total serum cholesterol concentrations was observed in the treatment groups administered streptozotocin. The administration of TDE at 100 mg/kg bw significantly decreased leptin and increased adiponectin concentrations (P≤0.05). Furthermore, TDE treatment significantly increased renal IR and decreased macrophage CD14 levels (P<0.05). Therefore, TDE decreased leptin and BG concentrations by increasing IR levels. TDE also suppressed the necrosis of pancreatic tissues by inhibiting macrophage CD14 expression in diabetic rats. However, further research is necessary to determine the effect of TDE on interleukin and IR levels in the related tissues of patients with T2DM.

Agronomic and financial benefits of direct Minjingu phosphate rock use in acidic humic nitisols of Upper Eastern Kenya.

A major constraint to crop production in Sub-Saharan Africa is nutrient deficiency, especially phosphorus (P) deficiency. Phosphorus plays a crucial role in photosynthesis but is usually deficient in acidic soils since it is converted to less available forms, affecting crop yields. There is a need to improve phosphorus availability to crops for maximum production. This study assessed Minjingu phosphate rock fertilizer's impact on maize yields, soil chemical composition, and cost-effectiveness in acidic humic nitisols of Tharaka Nithi County, Upper Eastern Kenya. A field experiment in a randomized complete block design (RCBD) was set during long rains (SR2017) and Short rains (LR2018) seasons. The treatments were Minjingu phosphate rock, manure, Tithonia diversifolia, Minjingu phosphate rock + manure, Tithonia diversifolia + Minjingu phosphate rock, Calcium Ammonium Nitrate (CAN) + Triple Superphosphate (TSP), and a control. Soil samples were collected at a depth of 0-20 cm before and at the end of the experiment for pH, P-sorption, and other soil nutrient determinations. Other auxiliary data collected included labor and input costs besides output prices. The CAN+TSP treatment had significantly higher grain yields (6.86 Mg ha-1), while Minjingu phosphate rock on its own had the second-lowest than the control treatment (3.0 Mg ha-1). Also, a similar trend in the stover yields was observed. Minjingu phosphate rock combined with either manure or Tithonia diversifolia led to a significant increase (over 100%) in the phosphorous levels. Sole application of Minjingu phosphate rock increased soil iron levels while magnesium, copper, and zinc levels decreased significantly. Other than the control, all treatments significantly lowered the P-sorption levels. However, CAN+TSP had the highest P-sorption (913 mg kg-1)while Tithonia diversifolia had the lowest (744 mg kg-1). During the LR2018 season, all treatments reached a break-even point, and the net benefit was significantly higher at P < 0.05. Conclusively, the use of phosphate rock, either solely or in combination with organic elements, improved yields, soil chemical composition, P-sorption and was very cost-effective.

Zai pits for heightened sorghum production in drier parts of Upper Eastern Kenya.

Water harvesting technologies and soil conservation measures promote water-nutrient synergy and increase agricultural production in the dryland zones of sub-Saharan Africa. To alleviate water stress, soil fertility decline and reduce runoff, soil and water conservation measures are promising options whose impact on agricultural productivity has not been fully explored. The objective of the study was to assess the effect of using zai pits in combination with selected soil fertility ammendments. An experiment was conducted in Tharaka Nithi County, Kenya to assess effects of using Zai pits in combination with selected amendments on sorghum production. The experiment was set up in a Randomized Complete Block Design (RCBD) involving 12 soil and water conservation treatments with three replications per block. Experimental data were subjected to analysis of variance and mean separation done using least significant difference (LSD) at p < 0.05. Zai pit in combination with tithonia amendment had the highest yields of 4.30 Mg ha-1 during short rains season of 2013 while Zai pit in combination with cattle manure had the highest yield of 4.18 Mg ha-1 during short rains season of 2014. Conventional planting with full rate NPK had the highest benefit-cost ratio (BCR) of 3.58 while Zai pit without input had the least BCR of 0.99. The experiment showed that Zai pit technology contributed to increments of yields in comparison to conventional planting although its BCR was lower than conventional planting with similar amendments. However, both Zai pit and conventional practices should be used in combination with organic and inorganic amendments to enhance yields in sorghum production.

Phosphorus availability and exchangeable aluminum response to phosphate rock and organic inputs in the Central Highlands of Kenya.

Soil acidity and phosphorus deficiency are some of the constraints hampering agricultural production in tropical regions. The prevalence of soil acidity is associated with phosphorus (P) insufficiency and aluminum saturation. We conducted a two-seasons experiment to evaluate soil phosphorus availability and exchangeable aluminum in response to phosphate rock and organic inputs in acidic humic nitisols. The field experiment was installed in Tharaka Nithi County in the Central Highlands of Kenya. The experimental design was a randomized complete block design with treatments replicated thrice. The treatments were: Green manure (Tithonia diversifolia Hemsl.) (60 kg P ha-1), phosphate rock (60 kg P ha-1), goat manure (60 kg P ha-1), Tithonia diversifolia (20 kg P ha-1) combined with phosphate rock (40 kg P ha-1), manure (20 kg P ha-1) combined with phosphate rock (40 kg P ha-1), Triple Super Phosphate combined with Calcium Ammonium Nitrate (TSP + CAN) (60 kg P ha-1) and a control (no input). During the long rains of the 2018 season (LR2018), Tithonia diversifolia + phosphate rock had a significantly higher reduction (67%) of exchangeable aluminum than the sole use of Tithonia diversifolia. Grain yield under TSP + CAN was the highest, followed by the sole organics during the LR2018. Tithonia diversifolia + phosphate rock resulted in a 99% and a 90% increase in NaHCO3-Pi compared to sole phosphate rock and sole Tithonia diversifolia, respectively. Tithonia diversifolia led to 14% and 62% higher resin-Pi and NaOH-Pi, respectively, compared to manure in the short rains of 2017 (SR2017). The increase in NaOH-Po after the two seasons was statistically significant in sole TSP + CAN. Based on the observed reduced exchangeable aluminum and additional nutrients like Ca, Mg, and K in the soil, sole organic inputs or in combination with phosphate rock treatments are feasible alternatives for sustaining soil phosphorus. Our findings underscore an integrated approach utilizing organic amendments combined with phosphate rock in acidic humic nitisols' phosphorus nutrient management.

Soil productivity improvement under different fallow types on Alfisol of a derived savanna ecology of Nigeria.

Fallowing is considered an important management strategy for the restoration of soil productivity. Therefore, a three-year fallow of pigeon pea (Cajanus cajan), mexican sunflower (Tithonia diversifolia) and elephant grass (Pennisetum purpureum) was established at Landmark University, Nigeria between 2016 - 2019. Leaf nutrient concentrations of maize (Zea mays) planted with soils taken from each fallowed plots after three years were also determined. The experimental design was a randomized complete block design with three replications. Soil samples were collected from each fallow plots for physical and chemical analysis (bulk density, porosity, moisture content, particle size, dispersion ratio, soil erosion loss, soil organic matter (SOM), total N, available P, exchangeables K, Ca, Mg, CEC and pH.) before and at the end of the experiment. Means of data collected were separated using Tukey's HSD test at p = 0.05. Tithonia fallow improved soil properties and leaf nutrient concentration of maize compared with Pennisetum and Cajanus fallows. The order was Tithonia > Pennisetum > Cajanus. This was adduced to the regular return of plant residues to the soil in Tithonia fallow which resulted in high SOM (Tithonia increased SOM by about 23%, 7.5%, and 20%, respectively, compared with the initial soil, Pennisetum and Cajanus fallows) and increases soil N, P, K, Ca, Mg, CEC and pH and also stabilized soil structure by increasing porosity, moisture content and reducing bulk density, dispersion ratio, and soil loss. Therefore, plant species of high nutrient contents and high return of biomass to the soil are necessary for quick restoration of soil productivity in a derived savanna ecology.

Plant Metabolites Involved in the Differential Development of a Heliantheae-Specialist Insect.

Balanced nutritional intake is essential to ensure that insects undergo adequate larval development and metamorphosis. Integrative multidisciplinary approaches have contributed valuable insights regarding the ecological and evolutionary outcomes of plant-insect interactions. To address the plant metabolites involved in the larval development of a specialist insect, we investigated the development of Chlosyne lacinia caterpillars fed on Heliantheae species (Tithonia diversifolia, Tridax procumbens and Aldama robusta) leaves and determined the chemical profile of plants and insects using a metabolomic approach. By means of LC-MS and GC-MS combined analyses, 51 metabolites were putatively identified in Heliantheae species and C. lacinia caterpillars and frass; these metabolites included flavonoids, sesquiterpene lactones, monoterpenoids, sesquiterpenoids, diterpenes, triterpenes, oxygenated terpene derivatives, steroids and lipid derivatives. The leading discriminant metabolites were diterpenes, which were detected only in A. robusta leaves and insects that were fed on this plant-based diet. Additionally, caterpillars fed on A. robusta leaves took longer to complete their development to the adult phase and exhibited a greater diapause rate. Hence, we hypothesized that diterpenes may be involved in the differential larval development. Our findings shed light on the plant metabolites that play roles in insect development and metabolism, opening new research avenues for integrative studies of insect nutritional ecology.

Curative effects of the aqueous extract of Tithonia diversifolia (Hemsl.) A. gray (Asteraceae) against ethanol induced-hepatotoxicity in rats.

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.

Involvement of Allelopathy in the Invasive Potential of Tithonia diversifolia.

Tithonia diversifolia (Hemsl.) A. Gray (Asteraceae) is native to Mexico and Central America. The species is spreading quickly and has naturalized in more than 70 countries. It has often been recorded as a harmful invasive plant that disturbs native plant communities. Phytotoxic chemical interactions such as allelopathy between invasive plants and native plants have been reported to play an important role in the invasion. Evidence for allelopathy of T. diversifolia has accumulated in the literature over 30 years. Thus, the objective of this review was to discuss the possible involvement of allelopathy in the invasive potential of T. diversifolia. The extracts, root exudates, and plant residues of T. diversifolia inhibited the germination and growth of other plant species. The soil water and soil collected from T. diversifolia fields also showed inhibitory growth effects. The decomposition rate of T. diversifolia residues in soil was reported to be high. Phytotoxic substances such as sesquiterpene lactones were isolated and identified in the extracts of T. diversifolia. Some phytotoxic substances in T. diversifolia may be released into the soil through the decomposition of the plant residues and the exudation from living tissues of T. diversifolia, including its root exudates, which act as allelopathic substances. Those allelopathic substances can inhibit the germination and growth of neighboring plants and may enhance the competitive ability of the plants, make them invasive.

Antitubercular compounds isolated and characterized in Tithonia diversifolia and Couroupita guianensis.

Background: Tuberculosis (TB) has become a public health challenge in the current scenario with a single causative agent, Mycobacterium tuberculosis (MTB) causing the highest morbidity and mortality affecting almost 1.7 million of the population. Furthermore, there has been no novel drug discovery for the past five decades, and the emergence of latent, multiple drug-resistant, and extensively drug-resistant species has given rise to an alarming necessity for a novel compound/s for treating this highly untamable microbe. In developing countries, plant-based drugs have shown promising results in combating TB or its symptoms; naturally occurring secondary metabolites can act as lead-drug molecules or can be co-administered with conventional drugs. Therefore, the present study was focused to identify and characterize potential antimycobacterial compounds found in the screened ethnobotanical plants, Tithonia diversifolia (TD) and Couroupita guianensis (CG). These plants are used for treating respiratory disorders and allergies in the traditional medicinal systems. Methods: These plant leaf extracts were detected and purified using chromatographic techniques for potent antitubercular phytochemicals, and the purified eluents were tested on Mycobacterium smegmatis (MSM) as a surrogate for MTB; further, the fractions inhibiting growth of MSM were characterized through gas chromatography-mass spectrometry. A toxicity test of the purified samples was also assessed by an in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and hemolytic assays. Results: The analyzed plant extracts showed the presence of a C-15 sesquiterpene, zingiberene in TD, and a phthalate ester, bis (2-ethylhexyl) phthalate, in CG leaf extracts. The toxicity assessment proved the purified fractions to be moderately toxic at higher concentrations (≥100 µg/mL). Conclusion: Therefore, the identified compounds can be promising antitubercular agents; however, further in vivo investigations will add substantial value to the compounds being pharmacologically useful.

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.