Exploring the mechanism of action of Bidens pilosa L. in combating hepatic fibrosis through network pharmacology and molecular docking: An observational study.

Based on network pharmacology and molecular docking methods, to explore the possible targets and mechanisms of Bidens pilosa L. in treatment of liver fibrosis. The TCMSP, GeneCard, OMIM, TTD and DrugBank databases were used to obtain the targets of Bidens pilosa L and liver fibrosis, than the intersection targets were screened out by Venny 2.1.0, the protein-protein interaction (PPI) network and the core targets were obtained by the STRING database. Use Cytoscape3.7.2 software to draw the "traditional Chinese medicine-component-target-disease" network. The DAVID database platform was explored to analyze the biological process and pathway, and predict the anti-liver fibrosis mechanism of Bidens pilosa L. AutoDock and PyMol were used to verify the molecular docking between the active ingredients of Bidens pilosa L. and the core targets. Six active components of Bidens pilosa L. and 106 intersection targets were screened. PIK3R1, HSP90AA1, SRC, TP53, AKT1, RELA and other core targets were screened by PPI network analysis. The results of GO and KEGG enrichment analysis showed that the anti-liver fibrosis of Bidens pilosa L mainly involved in the regulation and negative regulation of apoptosis process, positive regulation of protein kinase B signal transduction, positive regulation of cell migration and other biological processes. Pathways acting on cancer, fluid shear stress and atherosclerosis, lipids and atherosclerosis, PI3K-AKT signaling pathway, MAPK signaling pathway and other signaling pathways. Molecular docking showed that the active components of Bidens pilosa L. displayed good binding activity with core target proteins, and the average binding energy was -7.47 kcal/mol. The possible mechanism of the active components against liver fibrosis is to regulate the PI3K-AKT, MAPK, and other signaling pathways by acting on core targets such as PIK3R1, HSP90AA1, SRC, TP53, AKT1, RELA, and induce the apoptosis of activated HSC cells to reverse and improve liver fibrosis.

Oral mucositis management with photobiomodulation, Bidens pilosa L. (Asteraceae) and Curcuma longa L. (Zingiberaceae), the FITOPROT herbal medicine, and its influence on inflammatory cytokine levels: a randomized clinical trial.

PURPOSE: This randomized clinical trial aimed to compare the effects of a mucoadhesive formula, containing curcuminoids from Curcuma longa L. and glycerinated extract of Bidens pilosa L. (FITOPROT), associated with photobiomodulation (PBM), and of PBM exclusively, on the incidence of oral mucositis (OM)-induced by radiotherapy (RT) in the head and neck region, and the salivary expression of inflammatory cytokines, in patients with head neck cancer. METHODS: Patients were randomly assigned into two intervention groups-FITOPROT + PBM (n = 25) or PBM (n = 27). PBM protocol comprised a wavelength of 660 nm, 25 mW, 0.25 J/point, and daily irradiation from the first until the last day of RT. FITOPROT was gargled twice a day. All patients underwent a preventive oral care program throughout the study. OM degree, salivary concentration of nitrite, and inflammatory (IL-1, TNFα, IL-6, IL-8, and IL-12p70), and anti-inflammatory (IL-10) cytokines were assessed at baseline, and at the 7th, 14th, 21st, and 30th RT sessions. RESULTS: There were no differences in the OM degree between groups, but the RT dose significantly affected the OM. The RT significantly affected the salivary nitrite, TNFα, IL-1ß, and IL-10 concentrations. CONCLUSION: FITOPROT associated with PBM showed limited effects on preventing the incidence of severe OM compared to PBM alone. However, FITOPROT + PBM may be associated with nitrite and cytokine balance, which may contribute to the occurrence of fewer cases of severe OM. TRIAL REGISTRATION: Brazilian Clinical Trials database (ReBEC; RBR-9vddmr), registered UTN code: U1111-1193-2066, registered in August 8th, 2017.

Potentials of invasive Bidens pilosa, Conyza bonariensis and Parthenium hysterophorus species based on germination patterns and growth traits.

Invasive alien species drive extensive ecological changes and cause unexpected risks worldwide. Perceptive germination requirements and the growth function of invasive species are crucial for understanding their invasion and subsequent dissemination in various environmental conditions. Therefore, the germination response of invasive Conyza bonariensis, Parthenium hysterophorus, and Bidens pilosa of Asteraceae family were examined under alternating temperature regimes and some environmental factors. The prevailing germination ability occurs highest at moderate-temperature regimes at 20/30°C attained by 94.83% (C. bonariensis) and at 20/25 SS by 96.28% (P. hysterophorus) and high-temperature regimes at 25/30°C reached 92.94% (B. pilosa) respectively. The half germination percentage (G50) was -0.406 MPa and 2878.35 ppm (B. pilosa), -0.579 MPa and 2490.9 ppm (C. bonariensis), and-0.32 MPa and 2490.8 ppm (P. hysterophorus) affected by osmotic pressure and salt stress (NaCl) respectively. The highest growth plasticity characteristics were identified in total dry mass attained at 0.968 (C. bonariensis), 0.985 (B. pilosa) and 0.957 (P. hysterophorus) respectively. The relative growth, net assimilation and plasticity index appeared higher in both B. pilosa, and C. bonariensis than P. hysterophorus in the invaded area. In conclusion, germination and growth traits are precisely functional factors that correlate to invasion success under stressed conditions, and zones, and also lead to successful control plans for invasive species and ecological protection.

Synthesis, characterization of chitosan/tripolyphosphate nanoparticles loaded with 4-chloro-2-methylphenoxyacetate sodium salt and its herbicidal activity against Bidens pilosa L.

Herbicides are widely used to control weeds in agriculture filed, however, the excessive use of the conventional formulation causes harmful side effects on the environment. To relieve this problem, natural polymer nanoparticles as herbicide carrier were rapidly developed and applied in recent years. In the present study, chitosan/tripolyphosphate (CS/TPP) nanoparticles were synthesized as nanocarrier to load herbicide 4-chloro-2-methylphenoxyacetate sodium salt (MCPA-Na). The encapsulation efficiency (EE) of 51.32% was obtained through measuring indirectly by high performance liquid chromatography (HPLC). The free and MCPA-Na-loaded CS/TPP nanoparticles were characterized by using dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The encapsulation of MCPA-Na in CS/TPP nanoparticles resulted in the change of MCPA-Na release profile in different pH media and displayed effective sustained-release under neutral condition. The evaluation of herbicidal activity against Bidens pilosa L. showed that the efficacy enhancement of MCPA-Na was realized after encapsulation in CS/TPP nanoparticles. The proposed herbicide nanoformulation presented a good potential as a sustainable alternative for weed control in agriculture.

Transcriptomics and gut microbiome analysis of the edible herb Bidens pilosa as a functional feed additive to promote growth and metabolism in tilapia (Oreochromis spp.).

To reduce the use of antibiotics and chemicals in aquaculture, an edible herb, Bidens pilosa, has been selected as a multifunctional feed additive. Although there has been considerable research into the effects of B. pilosa on poultry, the wider effects of B. pilosa, particularly on the growth and gut microbiota of fish, remain largely unexplored. We aimed to investigate the interactive effects between the host on growth and the gut microbiota using transcriptomics and the gut microbiota in B. pilosa-fed tilapia. In this study, we added 0.5% and 1% B. pilosa to the diet and observed that the growth performance of tilapia significantly increased over 8 weeks of feeding. Comparative transcriptome analysis was performed on RNA sequence profiles obtained from liver and muscle tissues. Functional enrichment analysis revealed that B. pilosa regulates several pathways and genes involved in amino acid metabolism, lipid metabolism, carbohydrate metabolism, endocrine system, signal transduction, and metabolism of other amino acids. The expression of the selected growth-associated genes was validated by qRT-PCR. The qRT-PCR results indicated that B. pilosa may enhance growth performance by activating the expression of the liver igf1 and muscle igf1rb genes and inhibiting the expression of the muscle negative regulator mstnb. Both the enhancement of liver endocrine IGF1/IGF1Rb signaling and the suppression of muscle autocrine/paracrine MSTN signaling induced the expression of myogenic regulatory factors (MRFs), myod1, myog and mrf4 in muscle to promote muscle growth in tilapia. The predicted function of the gut microbiota showed several significantly different pathways that overlapped with the KEGG enrichment results of differentially expressed genes in the liver transcriptomes. This finding suggested that the gut microbiota may influence liver metabolism through the gut-liver axis in B. pilosa-fed tilapia. In conclusion, dietary B. pilosa can regulate endocrine IGF1 signaling and autocrine/paracrine MSTN signaling to activate the expression of MRFs to promote muscle growth and alter the composition of gut bacteria, which can then affect liver amino acid metabolism, carbohydrate metabolism, endocrine system, lipid metabolism, metabolism of other amino acids, and signal transduction in the host, ultimately enhancing growth performance. Our results suggest that B. pilosa has the potential to be a functional additive that can be used as an alternative to reduce antibiotic use as a growth promoter in aquaculture.

Inhibition of DNA Topoisomerase Ι by Flavonoids and Polyacetylenes Isolated from Bidens pilosa L.

Human DNA topoisomerase I (Topo I) is an essential enzyme in regulating DNA supercoiling during transcription and replication, and it is an important therapeutic target for anti-tumor agents. Bidens pilosa L. is a medicinal herb that is used as a folk medicine for cancers in China. A new flavonoid (1) and a new polyacetylene (20), along with eighteen flavonoids (2-19) and nine polyacetylenes (21-29), were isolated and identified from the methanol extract of the whole plant of B. pilosa, and some of the compounds (4, 5, 6 and 7) exhibited potent cytotoxicity against a panel of five human cancer cell lines. The DNA relaxation assay revealed that some flavonoids and polyacetylenes exerted inhibitory activities on human DNA Topo I, among them compounds 1, 2, 5, 6, 7, 8, 15, 19, 20, 22, and 24 were the most active ones, with IC50 values of 393.5, 328.98, 145.57, 239.27, 224.38, 189.84, 89.91, 47.5, 301.32, 178.03, and 218.27 µM, respectively. The structure-activity analysis of flavonoids was performed according to the results from the Topo I inhibition assay. The DNA content analysis revealed that 5, 6, and 7 potently arrested cell cycle at the G1/S and G2/M phases in human colon cancer cell DLD-1 depending on the concentration of the inhibitors. The levels of protein expression related to the G1/S and G2/M cell cycle checkpoints were in accordance with the results from the DNA content analysis. These findings suggest that flavonoids are one of the key active ingredients accounting for the anti-tumor effect of B. pilosa.

Antifungal Synergy: Mechanistic Insights into the R-1-R Peptide and Bidens pilosa Extract as Potent Therapeutics against Candida spp. through Proteomics.

Previous reports have demonstrated that the peptide derived from LfcinB, R-1-R, exhibits anti-Candida activity, which is enhanced when combined with an extract from the Bidens pilosa plant. However, the mechanism of action remains unexplored. In this research, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both the SC5314 strain and a fluconazole-resistant isolate of Candida albicans after incubation with R-1-R. The proteomic data revealed that treatment with R-1-R led to the up-regulation of most differentially expressed proteins compared to the controls in both strains. These proteins are primarily involved in membrane and cell wall biosynthesis, membrane transport, oxidative stress response, the mitochondrial respiratory chain, and DNA damage response. Additionally, proteomic analysis of the C. albicans parental strain SC5314 treated with R-1-R combined with an ethanolic extract of B. pilosa was performed. The differentially expressed proteins following this combined treatment were involved in similar functional processes as those treated with the R-1-R peptide alone but were mostly down-regulated (data are available through ProteomeXchange with identifier PXD053558). Biological assays validated the proteomic results, evidencing cell surface damage, reactive oxygen species generation, and decreased mitochondrial membrane potential. These findings provide insights into the complex antifungal mechanisms of the R-1-R peptide and its combination with the B. pilosa extract, potentially informing future studies on natural product derivatives.

Role of arbuscular mycorrhizal fungi in lead translocation from Bidens pilosa L. plants to soil.

Bidens pilosa frequently forms a symbiotic association with arbuscular mycorrhizal fungi (AMF). This plant species can grow in Pb-polluted soils, accumulating Pb in its tissues. The aims of the study were to determine whether Pb accumulated in the tissues of B. pilosa can be transferred to the soil through AMF and to compare the role of AMF communities that have a history of exposure to the contaminant with those that have never been exposed. The experiment combined plants with and without Pb accumulated in their tissues, and inoculated with AMF collected from the rhizosphere of B. pilosa in soils contaminated and not contaminated with Pb. The results showed that AMF participate in the removal of Pb that had entered the plant and release it into the soil, as evidenced by the presence of Pb in the AMF spores and in the glomalin produced by AMF. We propose that Pb accumulation in AMF spores would be a protection mechanism that interrupts Pb uptake by the plant; however, that mechanism would not be fully exploited in detoxification, whereas the production of Pb-enriched glomalin could be an important detoxification mechanism to eliminate Pb already taken up by plants. AMF with a history of Pb exposure achieved only higher rates of root colonization, while AMF without previous exposure showed higher Pb concentration in the spores and higher glomalin production, and successfully removed Pb from both the roots and aboveground parts of the plant. The use of AMF communities not adapted to Pb may be a more effective option for microbe-mediated phytoremediation methods in which detoxification mechanisms are desirable.

The genomes of Dahlia pinnata, Cosmos bipinnatus, and Bidens alba in tribe Coreopsideae provide insights into polyploid evolution and inulin biosynthesis.

BACKGROUND: The Coreopsideae tribe, a subset of the Asteraceae family, encompasses economically vital genera like Dahlia, Cosmos, and Bidens, which are widely employed in medicine, horticulture, ecology, and food applications. Nevertheless, the lack of reference genomes hinders evolutionary and biological investigations in this tribe. RESULTS: Here, we present 3 haplotype-resolved chromosome-level reference genomes of the tribe Coreopsideae, including 2 popular flowering plants (Dahlia pinnata and Cosmos bipinnatus) and 1 invasive weed plant (Bidens alba), with assembled genome sizes 3.93 G, 1.02 G, and 1.87 G, respectively. We found that Gypsy transposable elements contribute mostly to the larger genome size of D. pinnata, and multiple chromosome rearrangements have occurred in tribe Coreopsideae. Besides the shared whole-genome duplication (WGD-2) in the Heliantheae alliance, our analyses showed that D. pinnata and B. alba each underwent an independent recent WGD-3 event: in D. pinnata, it is more likely to be a self-WGD, while in B. alba, it is from the hybridization of 2 ancestor species. Further, we identified key genes in the inulin metabolic pathway and found that the pseudogenization of 1-FEH1 and 1-FEH2 genes in D. pinnata and the deletion of 3 key residues of 1-FFT proteins in C. bipinnatus and B. alba may probably explain why D. pinnata produces much more inulin than the other 2 plants. CONCLUSIONS: Collectively, the genomic resources for the Coreopsideae tribe will promote phylogenomics in Asteraceae plants, facilitate ornamental molecular breeding improvements and inulin production, and help prevent invasive weeds.

Unveiling allelopathic dynamics and impacts of invasive Erigeron bonariensis and Bidens pilosa on plant communities and soil parameters.

Invasive alien species are becoming more and more prevalent worldwide, Erigeron bonariensis and Bidens pilosa are two invasive species of Asteraceae in Egypt. To mitigate their detrimental effects and understand their differences in invasiveness, we compared the allelopathic potentials of E. bonariensis and B. pilosa using leachates, decaying residues, and volatilization processes. Notably, the allelopathic variances in leachates were significant, influenced by plant types, concentrations, and response patterns of target plant traits, as indicated by EC50. The relative phytotoxicity of the invasive species decayed residues peaked between 20 and 25 days in the soil, with a positive correlation with concentrations and soil properties. The highest quantities of phenolic acids were chlorogenic acid and caffeic acid reaching (5.41 and 4.39 µg g-1) E. bonariensis and (4.53 and 4.46 µg g-1) B. pilosa, in leachates extracts respectively, while in the soil extract of decayed residues were coumaric acid and ferulic acid measuring (1.66 and 1.67 µg g-1) E. bonariensis and (1.47 and 1.57 µg g-1) B. pilosa, respectively. Using GC/MS analysis, the main volatile components in E. bonariensis were 1, 8 cineole (5.62%), and α-terpinene (5.43%) and iso-Caryophyllene (5.2%) which showed the greatest inhibitory effects. While B. pilosa main constituents were trans-sabinene (5.39%) and Camphene (5.11%), respectively. Finally, the high invasion level displayed from E. bonariensis (0.221) compared with B. pilosa (0.094) which correlated with the stronger allelopathic activities against plant species, and soil properties. Therefore, the allelopathic potentialities of these species are critically relevant to their invasion success.

Synthesis of magnetic MFe2O4 (M = Ni, Co, Zn, Fe) supported on porous carbons derived from Bidens pilosa weed and their adsorptive comparison of toxic dyes.

Bidens pilosa is classified as an invasive plant and has become a problematic weed to many agricultural crops. This species strongly germinates, grows and reproduces and competing for nutrients with local plants. To lessen the influence of Bidens pilosa, therefore, converting this harmful species into carbon materials as adsorbents in harm-to-wealth and valorization strategies is required. Here, we synthesized a series of magnetic composites based on MFe2O4 (M = Ni, Co, Zn, Fe) supported on porous carbon (MFOAC) derived from Bidens pilosa by a facile hydrothermal method. The Bidens pilosa carbon was initially activated by condensed H3PO4 to increase the surface chemistry. We observed that porous carbon loaded NiFe2O4 (NFOAC) reached the highest surface area (795.7 m2 g-1), followed by CoFe2O4/AC (449.1 m2 g-1), Fe3O4/AC (426.1 m2 g-1), ZnFe2O4/AC (409.5 m2 g-1). Morphological results showed nanoparticles were well-dispersed on the surface of carbon. RhB, MO, and MR dyes were used as adsorbate to test the adsorption by MFOAC. Effect of time (0-360 min), concentration (5-50 mg L-1), dosage (0.05-0.2 g L-1), and pH (3-9) on dyes adsorption onto MFOAC was investigated. It was found that NFOAC obtained the highest maximum adsorption capacity against dyes, RhB (107.96 mg g-1) < MO (148.05 mg g-1) < MR (153.1 mg g-1). Several mechanisms such as H bonding, π-π stacking, cation-π interaction, and electrostatic interaction were suggested. With sufficient stability and capacity, NFOAC can be used as potential adsorbent for real water treatment systems.

In vitro anti-Trypanosoma cruzi activity of methanolic extract of Bidens pilosa and identification of active compounds by gas chromatography-mass spectrometry analysis.

Chagas disease, caused by Trypanosoma cruzi parasite, is a significant but neglected tropical public health issue in Latin America due to the diversity of its genotypes and pathogenic profiles. This complexity is compounded by the adverse effects of current treatments, underscoring the need for new therapeutic options that employ medicinal plant extracts without negative side effects. Our research aimed to evaluate the trypanocidal activity of Bidens pilosa fractions against epimastigote and trypomastigote stages of T. cruzi, specifically targeting the Brener and Nuevo León strains-the latter isolated from Triatoma gerstaeckeri in General Terán, Nuevo León, México. We processed the plant's aerial parts (stems, leaves, and flowers) to obtain a methanolic extract (Bp-mOH) and fractions with varying solvent polarities. These preparations inhibited more than 90% of growth at concentrations as low as 800 µg/ml for both parasite stages. The median lethal concentration (LC50) values for the Bp-mOH extract and its fractions were below 500 µg/ml. Tests for cytotoxicity using Artemia salina and Vero cells and hemolytic activity assays for the extract and its fractions yielded negative results. The methanol fraction (BPFC3MOH1) exhibited superior inhibitory activity. Its functional groups, identified as phenols, enols, alkaloids, carbohydrates, and proteins, include compounds such as 2-hydroxy-3-methylbenzaldehyde (50.9%), pentadecyl prop-2-enoate (22.1%), and linalool (15.4%). Eight compounds were identified, with a match confirmed by the National Institute of Standards and Technology (NIST-MS) software through mass spectrometry analysis.

The co-phytotoxicity of two Asteraceae invasive plants Solidago canadensis L. and Bidens pilosa L. with different invasion degrees.

The phytotoxicity of invasive plants (IPS) has been identified as one of the main factors influencing their invasion success. The invasion of IPS can occur to varying degrees in the habitats. Two IPS can invade one habitat. This study aimed to evaluate the mono- and co-phytotoxicity of two Asteraceae IPS Solidago canadensis L. and Bidens pilosa L. with different invasion degrees (including light invasion (relative abundance <50%) and heavy invasion (relative abundance ≥50%)) on the horticultural Asteraceae species Lactuca sativa L., through a hydroponic experiment conducted on 9 cm Petri dishes. Leaf extracts of the two IPS can cause significant mono- and co-phytotoxicity. The mono- and co-phytotoxicity of the two IPS were concentration-dependent. The mono-phytotoxicity of S. canadensis was significantly increased with increasing invasion degree, but the opposite was true for the mono-phytotoxicity of B. pilosa. Leaf extracts of B. pilosa with light invasion caused stronger phytotoxicity than those of S. canadensis with light invasion. There may be an antagonistic effect for the co-phytotoxicity caused by mixed leaf extracts of the two IPS compared with those of either S. canadensis or B. pilosa. The phytotoxicity of the two IPS on the growth performance of neighboring plants may play a more important role in their mono-invasion than in their co-invasion. The phytotoxicity appeared to affect the growth performance of S. canadensis individuals more significantly when the invasion was heavy, while the growth performance of B. pilosa individuals seemed to be more influenced by phytotoxicity when the invasion was light. Consequently, the concentration of leaf extracts of IPS, the invasion degree of IPS, the species identity of IPS, and the species number of IPS modulated the mono- and co-phytotoxicity of the two IPS.

A Bidens pilosa L. Non-Polar Extract Modulates the Polarization of Human Macrophages and Dendritic Cells into an Anti-Inflammatory Phenotype.

Different communities around the world traditionally use Bidens pilosa L. for medicinal purposes, mainly for its anti-inflammatory, antinociceptive, and antioxidant properties; it is used as an ingredient in teas or herbal medicines for the treatment of pain, inflammation, and immunological disorders. Several studies have been conducted that prove the immunomodulatory properties of this plant; however, it is not known whether the immunomodulatory properties of B. pilosa are mediated by its ability to modulate antigen-presenting cells (APCs) such as macrophages (MØs) and dendritic cells (DCs) (through polarization or the maturation state, respectively). Different polar and non-polar extracts and fractions were prepared from the aerial part of B. pilosa. Their cytotoxic and immunomodulatory effects were first tested on human peripheral blood mononuclear cells (PBMCs) and phytohemagglutinin (PHA)-stimulated PBMCs, respectively, via an MTT assay. Then, the non-cytotoxic plant extracts and fractions that showed the highest immunomodulatory activity were selected to evaluate their effects on human MØ polarization and DC maturation (cell surface phenotype and cytokine secretion) through multiparametric flow cytometry. Finally, the chemical compounds of the B. pilosa extract that showed the most significant immunomodulatory effects on human APCs were identified using gas chromatography coupled with mass spectrometry. The petroleum ether extract and the ethyl acetate and hydroalcoholic fractions obtained from B. pilosa showed low cytotoxicity and modulated the PHA-stimulated proliferation of PBMCs. Furthermore, the B. pilosa petroleum ether extract induced M2 polarization or a hybrid M1/M2 phenotype in MØs and a semi-mature status in DCs, regardless of exposure to a maturation stimulus. The immunomodulatory activity of the non-polar (petroleum ether) extract of B. pilosa on human PBMC proliferation, M2 polarization of MØs, and semi-mature status in DCs might be attributed to the low-medium polarity components in the extract, such as phytosterol terpenes and fatty acid esters.

[Effects of Exogenous Plant Hormone Spraying on the Phytoremediation by Bidens pilosa L. in Cadmium-contaminated Soil].

To explore the effect of exogenous plant hormone spraying on the absorption of heavy metals by hyperaccumulated plants, Bidens pilosa L. was selected as the tested plant owing to the large biomass, short growth cycle, and high accumulation efficiency. Here, the effect of foliar spraying 6-benzylaminopurine (6-BA), salicylic acid (SA), and 24-epi-brassinosteroid (24-EBR) on the remediation of cadmium (Cd)-contaminated soil by B. pilosa L. was examined. The results showed:① the efficiency of the remediation in Cd-contaminated soil by B. pilosa L. was effectively enhanced after the spraying of all three kinds of exogenous plant hormones with appropriate concentrations. The spraying of the three exogenous plant hormones could promote the cadmium concentration in the leaves of B. pilosa L. to increase by 4.21%, 31.79%, and 14.89%; promote the translocation factor (TF) to increase by 9.67%, 18.83%, and 17.85%; promote the phytoextraction rates (PR) to increase by 15.36%, 32.33%, and 64.38%, respectively. ② The growth of B. pilosa L. was significantly promoted after the spraying of the three kinds of exogenous plant hormones with appropriate concentrations. The spraying of the three exogenous plant hormones could promote plant growth under cadmium stress, and the dry weight of the plant root, stem, and leaf was increased by 37.53%, 74.50%, and 104.02%, respectively. ③ The photosynthesis of B. pilosa L. was significantly enhanced after the spraying of the three kinds of exogenous plant hormones with appropriate concentrations. The chlorophyll concentration of the plant was significantly increased after foliar spraying with plant hormones, and the concentration of chlorophyll a was increased by 79.31%, 92.27%, and 51.12%; the photochemical quenching coefficient (qP) was increased by 11.32%, 89.16%, and 78.43%; and the non-photochemical quenching coefficient (NPQ) was increased by 51.71%, 241.12%, and 27.85%, respectively, after foliar spraying with appropriate concentrations of 6-BA, SA, and 24-EBR. ④ The antioxidant capacity of B. pilosa L. was significantly strengthened after the spraying of the three kinds of exogenous plant hormones with appropriate concentrations. The malondialdehyde (MDA) concentration of the plant was reduced by 62.41%, 68.67%, and 46.76% after the application of 6-BA, SA, and 24-EBR, respectively. Meanwhile, superoxide dismutase (SOD) was increased by 68.33%, 10.28%, and 6.17%, and catalase (CAT) was increased by 31.43%, 37.87%, and 37.31%, respectively. Generally, the spraying of exogenous 6-BA, SA, and 24-EBR with the appropriate concentration under Cd stress could significantly increase the biomass of B. pilosa L. and promote the accumulation of heavy metals in the plant, improve the photosynthetic ability of the plant, reduce the oxidative damage of the plant under heavy metal stress, enhance the antioxidant capacity, and improve the absorption and tolerance of plants to Cd. It also could promote the transfer of Cd from roots to shoots, improve the phytoextraction rates of Cd from the plant, and effectively strengthen the phytoremediation efficiency. Among them, 30 mg·L-1 SA foliar spraying had the best effect.

Anti-Inflammatory Effects of Miyako Bidens pilosa in a Mouse Model of Amyotrophic Lateral Sclerosis and Lipopolysaccharide-Stimulated BV-2 Microglia.

Neuroinflammation is a fundamental feature in the pathogenesis of amyotrophic lateral sclerosis (ALS) and arises from the activation of astrocytes and microglial cells. Previously, we reported that Miyako Bidens pilosa extract (MBP) inhibited microglial activation and prolonged the life span in a human ALS-linked mutant superoxide dismutase-1 (SOD1G93A) transgenic mouse model of ALS (G93A mice). Herein, we evaluated the effect of MBP on microglial activation in the spinal cord of G93A mice and lipopolysaccharide-stimulated BV-2 microglial cells. The administration of MBP inhibited the upregulation of the M1-microglia/macrophage marker (interferon-γ receptor (IFN-γR)) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6) in G93A mice. However, MBP did not affect the increase in the M2-microglia/macrophage marker (IL-13R) and anti-inflammatory cytokines (transforming growth factor (TGF)-ß and IL-10) in G93A mice. BV-2 cell exposure to MBP resulted in a decrease in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) reduction activity and bromodeoxyuridine incorporation, without an increase in the number of ethidium homodimer-1-stained dead cells. Moreover, MBP suppressed the production of lipopolysaccharide-induced pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in BV-2 cells. These results suggest that the selective suppression of M1-related pro-inflammatory cytokines is involved in the therapeutic potential of MBP in ALS model mice.

Effects of a mucoadhesive phytomedicine (Curcuma longa L. and Bidens pilosa L.) on radiotherapy-induced oral mucositis and quality of life of patients undergoing head and neck cancer treatment: randomized clinical trial.

PURPOSE: To assess the effect of a mucoadhesive herbal medicine containing curcuminoids and a glycerinated extract of Bidens pilosa L. (FITOPROT) in association with photobiomodulation (PBM) therapy and a Preventive Oral Care Program (POCP) compared to PBM and POCP in the treatment of radiotherapy (RT)-induced oral mucositis (ROM) and in the quality of life of these patients. METHODS: A double-blind clinical trial was performed with head and neck cancer patients undergoing RT or chemoradiotherapy. Participants were randomized into two groups: Group 1 (n=27): PBM and POCP; and Group 2 (n=25): PBM, POCP and FITOPROT. The PBM protocol was daily irradiation, 660 nm, 25mW, 0.25 J/point from the first until the last day of RT. The FITOPROT was used as mouthwash twice a day. ROM was evaluated based on the scales of the World Health Organization and National Cancer Institute. The quality of life was evaluated using the University of Washington Questionnaire, OHIP-14 and Patient-Reported Oral Mucositis Symptom Scale. The MMAS-8 questionnaire was used to evaluated the adherence to POCP and FITOPROT. Data were collected at baseline, 7th, 14th, 21st, and 30th RT sessions. RESULTS: No statistical differences were found between the groups for the ROM evaluation. Both groups experienced worsening of the quality of life during the RT. No statistically significant differences between groups were observed for any of the instruments evaluated. CONCLUSION: The results suggest that PBM associated with FITOPROT and POCP control the severity of ROM and stabilize the QoL of patients with head and neck cancer. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC-RBR-9vddmr; UTN code: U1111-1193-2066), registered in August 8th, 2017.

Metagenomics combined with metabolomics reveals the effect of Enterobacter sp. inoculation on the rhizosphere microenvironment of Bidens pilosa L. in heavy metal contaminated soil.

Metagenomics analysis was performed to determine the effects of Enterobacter sp. FM-1 (FM-1) on key genera as well as functional genes in the rhizosphere of Bidens pilosa L. (B. pilosa L.). Moreover, metabolomics was used to reveal the differences among rhizosphere metabolites after FM-1 inoculation. FM-1 inoculation significantly increased the activity of enzymes associated with the carbon cycle in soil; among them, invertase activity increased by 5.52 units compared to a control. Specifically, the relative abundance of beneficial genera increased significantly, such as Lysobacter (0.45-2.58 unit increase) in low-contamination soils (LC) and Pseudomonas (31.17-45.99 unit increase) in high-contamination soils (HC). Comparison of different transformation processes of the C cycle revealed that inoculation of FM-1 increased the abundance of functional genes related to the carbon cycle in LC soil. In contrast, the nitrogen cycling pathway was significantly elevated in both the LC and HC soils. FM-1 inoculation reduced HM resistance gene abundance in the rhizosphere soil of B. pilosa L. in the LC soil. Moreover, FM-1 and B. pilosa L. interactions promoted the secretion of rhizosphere metabolites, in which lipids and amino acids played important roles in the phytoremediation process. Overall, we explored the rhizosphere effects induced by plantmicrobe interactions, providing new insights into the functional microbes and rhizosphere metabolites involved in phytoremediation.

Gut microbiome helps honeybee (Apis mellifera) resist the stress of toxic nectar plant (Bidens pilosa) exposure: Evidence for survival and immunity.

Honeybee (Apis mellifera) ingestion of toxic nectar plants can threaten their health and survival. However, little is known about how to help honeybees mitigate the effects of toxic nectar plant poisoning. We exposed honeybees to different concentrations of Bidens pilosa flower extracts and found that B. pilosa exposure significantly reduced honeybee survival in a dose-dependent manner. By measuring changes in detoxification and antioxidant enzymes and the gut microbiome, we found that superoxide dismutase, glutathione-S-transferase and carboxylesterase activities were significantly activated with increasing concentrations of B. pilosa and that different concentrations of B. pilosa exposure changed the structure of the honeybee gut microbiome, causing a significant reduction in the abundance of Bartonella (p < 0.001) and an increase in Lactobacillus. Importantly, by using Germ-Free bees, we found that colonization by the gut microbes Bartonella apis and Apilactobacillus kunkeei (original classification as Lactobacillus kunkeei) significantly increased the resistance of honeybees to B. pilosa and significantly upregulated bee-associated immune genes. These results suggest that honeybee detoxification systems possess a level of resistance to the toxic nectar plant B. pilosa and that the gut microbes B. apis and A. kunkeei may augment resistance to B. pilosa stress by improving host immunity.

(E)-7-phenyl-2-heptene-4,6-diyn-1-ol from Bidens pilosa as a repellent against isopods.

The development of repellents as alternatives to insecticides has expanded in recent years. However, their use in isopod pest control is limited. To develop an isopod repellent, a plant extract library from wild plants native to the Kochi Prefecture was screened for repellent activity against pillbugs, and 82 samples (87%) exhibited repellent activity. Among them, (E)-7-phenyl-2-heptene-4,6-diyn-1-ol was isolated and identified as a repellent from the root of Bidens pilosa. It had a half-maximal effective concentration of 0.20 µm, with a strong repellency. A study of the structure-activity relationship to (E)-7-phenyl-2-heptene-4,6-diyn-1-ol revealed that the presence of a hydroxyl group and an aromatic at both ends of the length of the seven-carbon chain is important for the expression of repellency. These results can potentially lead to a new repellent of phenylalkyl alcohol.