3α-Angeloyloxy-ent-kaur-16-en-19-oic Acid Isolated from Wedelia trilobata L. Alleviates Xylene-Induced Mouse Ear Edema and Inhibits NF-κB and MAPK Pathway in LPS-Stimulated Macrophages.

Uncontrolled inflammation is associated with many major diseases, and there is still an urgent need to develop new anti-inflammatory drugs. 3α-Angeloyloxy-ent-kaur-16-en-19-oic acid (WT-25) is an ent-kaurane dieterpenoid extracted from Wedelia trilobata, a medicinal plant with potential anti-inflammatory activity. The anti-inflammatory activity of WT-25 is better than that of its analog kaurenoic acid, but the underlying mechanism is still unknown. In this study, our aim was to study the anti-inflammatory effect of WT-25. In xylene-induced edema in mice, WT-25 produced 51% inhibition. WT-25 suppressed nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-stimulated RAW264.7 cells by downregulating the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). WT-25 reduced expression and secretion of TNF-α and IL-6. Moreover, WT-25 inhibited NF-κB activation and its upstream signaling, decreasing phosphorylation IKK and p65 levels. WT-25 also inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs) family. Additionally, it reduced LPS-induced excessive release of reactive oxygen species (ROS) and maintained mitochondrial integrity in RAW264.7 cells. All these results indicate that WT-25 is a bioactive molecule with the potential to be developed as a novel structured anti-inflammatory drug.

Anti-proliferative and anti-neuroinflammatory eudesmanolides from Wedelia (Sphagneticola trilobata (L.) Pruski).

Wedelia (Sphagneticola trilobata, Syn. Wedelia trilobata), a notoriously invasive agricultural weed, can inhibit the growth and development of crops in the field. Eight new eudesmanolides (1-8), along with twelve known congeners (9-20), were isolated and identified from the flowers of Wedelia. Their chemical structures were elucidated through various spectroscopic techniques. The isolates were tested for anti-proliferative activities against HeLa, HepG2, and SGC-7901 tumor cell lines. Most eudesmanolides exhibited significant anti-proliferative activities with good selectivity. Meanwhile, the cells morphology and clonogenic survival assays were observed for compounds 1-3. Moreover, compound 6 displayed obvious anti-neuroinflammatory effect by inhibition of NO production in LPS-induced microglia BV-2 cells with the IC50 value of 11.77 ± 0.83 µM. Hence, this study demonstrated that the eudesmanolides from Wedelia possessed significant antitumor and anti-inflammatory activity, which provided some guides for the further development and a new thinking for its control.

Wedtrilosides A and B, two new diterpenoid glycosides from the leaves of Wedelia trilobata (L.) Hitchc. with α-amylase and α-glucosidase inhibitory activities.

In the ongoing research to find new diabetes constituents from the genus Wedelia, the chemical constituent of Wedelia trilobata leaves, a Vietnamese medicinal plant species used to treat type 2 diabetes mellitus, was selected for detailed investigation. From a methanolic extract, two new ent-kaurane diterpenoids, wedtrilosides A and B (1 and 2), along with five known metabolites (3-7), were isolated from W. trilobata. The chemical structures of (1-7) were assigned via spectroscopic techniques (IR, 1D, 2D NMR and HR-QTOF-MS data) and chemical methods. The isolates were evaluated for α-amylase and α-glucosidase inhibitory activities compared to the clinical drug acarbose. Among them, compounds 4, 6, and 7 showed the most potent against α-glucosidase enzyme with IC50 values of 27.54 ±â€¯1.12, 173.78 ±â€¯2.37, and 190.40 ±â€¯2.01 µg/mL. While moderate inhibitory effect against α-amylase was observed with compounds 6 and 7 (with IC50 = 181.97 ±â€¯2.62 and 52.08 ±â€¯0.56 µg/mL, respectively). The results suggested that the antidiabetic properties from the leaves of W. trilobata are not simply a result of each isolated compound, but are due to other factors such as the accessibility of polyphenolic groups to α-amylase and α-glucosidase activities.

Chemical composition and antimicrobial activities of essential oil from Wedelia urticifolia growing wild in Hunan Province, China.

The essential oil obtained from Wedelia urticifolia growing in Hunan Province, China, was analyzed for the first time by capillary GC and GC-MS. A total of 67 constituents, representing 98.68% in essential oil were identified. The major constituents of the oil were: α-pinene (8.85%), limonene (6.38%), carvacrol (6.15%), caryophyllene (6.08%), spathulenol (5.49%), sabinene (5.36%), camphor (4.34%). Antimicrobial potential of oil against bacterial strains (Pseudomonas aeruginosa, Escherichia coli and Bacillus subtilis, and Staphylococcus aureus), yeast strains (Hansenula anomala and Saccharomy cescerevisiae) and molds (Aspergillus niger, Chaetomium globosum, Mucor racemosus, and Monascus anka) was determined by disc diffusion method and broth micro dilution method, respectively. The oil exhibited promising antimicrobial effect as a diameter of zones of inhibition (16.8-24.9 mm). Minimum inhibitory concentration values of oil were ranged 62.5-1000 µg/mL.

Transcriptomic analysis reveals a controlling mechanism for NLRP3 and IL-17A in dextran sulfate sodium (DSS)-induced colitis.

The incidence of inflammatory bowel disease (IBD) has markedly increased. Our research findings during the past showed that medicinal plant extracts and the derived phytochemical components from Wedelia chinensis (WC) can have strong anti-colitis activities. Here, we further identified the key component phytochemicals from active fractions of different WC preparations (WCHA) that are responsible for the protective effect of WCHA in colitis mice. Of the 3 major compounds (wedelolactone, luteolin and apigenin) in this fraction, luteolin had the highest anti-inflammatory effect in vivo. Using a next-generation sequencing (NGS) (e.g., RNA-seq) system to analyze the transcriptome of colorectal cells/tissues in mice with dextran sulfate sodium (DSS)-induced colitis with/without phytochemicals treatment, luteolin was found to strongly suppress the DSS-activated IL-17 pathway in colon tissue. In addition, co-treatment with wedelolactone and luteolin had a synergistic effect on the expression level of some IL-17 pathway-related genes. Interestingly, our NGS analyses also indicated that luteolin and wedelolactone can specifically suppress the expression of NLRP3 and NLRP1. Using a 3-dimensional cell co-culture system, we further demonstrated that luteolin could efficiently suppress NLRP3 expression via disruption of IL-17A signaling in inflamed colon tissue, which also indicates the pharmacological potential of luteolin and wedelolactone in treating IBD.

Exploration of Wedelia chinensis leaf-assisted silver nanoparticles for antioxidant, antibacterial and in vitro cytotoxic applications.

Green synthetic route of silver nanoparticles (AgNPs) has already been proved to be an advantageous over other physico-chemical approaches due to its simplicity, cost effectiveness, ecofriendly and nontoxicity. In this finding, aqueous Wedelia chinensis leaf extract (WLE) mediated synthesis of AgNPs was approached. Surface plasmon resonance (SPR) band at 408 nm preliminary indicated the formation of AgNPs, while TEM and XRD characterization confirmed the formation of spherically shaped and crystalline AgNPs with an average size of 31.68 nm, respectively. The plausible biomolecules in the aqueous leaf extract responsible for the reduction and stabilization of AgNPs were identified by FTIR analysis and found to be polyphenolic groups in flavonoid. Further, synthesized AgNPs was explored for different biological applications. Biosynthesized AgNPs showed significant free radical scavenging activity as compared to Wedelia leaf extract and antibacterial activity against clinically isolated test pathogens where Gram-negative bacteria were found more susceptible to AgNPs than Gram-positive one. In addition, in vitro cytotoxic response was also evaluated on hepatocellular carcinoma Hep G2 cell lines and showed a dose-dependent cytotoxic response with an IC50 value of 25 µg/mL.

Eudesmanolides and Other Constituents from the Flowers of Wedelia trilobata.

Two eudesmane sesquiterpene lactones, wedetrilides B (1) and C (2), along with five known analogues (3 - 8), an ent-kaurane diterpenoid (9), a steroid (10), as well as cinnamic acid derivatives (11 - 13), were isolated from the flowers of Wedelia trilobata. Their structures were elucidated on the basis of extensive spectroscopic analyses and by comparison of their NMR data with those of related compounds. Furthermore, the structures of 1 and 3 - 5 were confirmed by X-ray single-crystal diffraction analyses. Compounds 4 and 5 exhibited weak cytotoxic activities against the MCF-7, HeLa, and A549 cell lines. Compounds 3 - 5 were also evaluated for their inhibitory effects against HIV lytic replication.

Triterpenoids principle of Wedelia calendulacea attenuated diethynitrosamine-induced hepatocellular carcinoma via down-regulating oxidative stress, inflammation and pathology via NF-kB pathway.

The aerial part of Wedelia calendulacea have been used in Ayurveda, Unani, Tibetan, Siddha and other folk medicine systems to protect the liver and renal tissue. Liver is considered as primary metabolizing site of body, which is prone to damage by endogenous and exogenous toxicants. A reason for liver toxicity, and major causes of the hepatocellular carcinoma (HCC). 19-α-Hydroxyurs-12(13)-ene-28 oic acid-3-O-ß-D-glucopyranoside (HEG), a triterpenoids found in the higher plants, has been known to possess protective effect against various toxicants. The aim of the current study was to scrutinize the hepatoprotective mechanism of HEG against DEN-induced oxidative stress, hyperproliferation, inflammation and apoptosis tissue injury in Wistar rats. Invitro cell lines study of HEG scrutinized against the Hep-G2 and HuH-7 cells. A single dose of DEN (200 mg/kg) and double dose of phenobarbitol were administered to induce the liver damage in rats; the dose treatment of HEG was terminated at the end of 22 weeks. Macroscopical study was performed for the confirmation of hepatic nodules. The serum and hepatic samples were collected for further biochemical and histopathological analysis. Hepatic; non-hepatic; Phase I and II antioxidant enzymes were also examined. Additionally, we also scrutinized the inflammatory cytokines viz., tumor necrosis factor-α, interlukin-6, interlukin-1ß, and Nuclear factor kappa beta (NF-kB), respectively. Histopathological study was also performed for analyzing the changes during the HCC. HEG confirmed the reduction of growth and deoxyribonucleic acid synthesis of both cell lines. DEN successfully induced the HCC in all group, which was significantly (p < 0.001) altered by the HEG in a dose-dependent manner. The decreased level of pro-inflammatory cytokines and altered membrane-bound enzyme activity were also observed. HEG inhibits the phase I, II and antioxidant enzymes at the effective dose-dependent manner, which were considered as the precursor of the HCC. The alteration of phase I, II and antioxidant enzymes confirmed the inhibition of inflammatory reaction and oxidative stress, which directly or indirectly inhibited the NF-kB expression. Collectively, we can conclude that the HEG inhibited the growth of Hepatocellular carcinoma via attenuating the NF-kB pathway.

A standardized herbal extract mitigates tumor inflammation and augments chemotherapy effect of docetaxel in prostate cancer.

Activation of the NFκB pathway is often associated with advanced cancer and has thus been regarded as a rational therapeutic target. Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Interestingly, our evaluation of a standardized Wedelia chinensis herbal extract (WCE) concluded its efficacy on hormone-refractory prostate cancer through systemic mechanisms. Oral administration of WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 and DU145 xenografts. Genome-wide transcriptome analysis of these tumors revealed that WCE suppressed the expression of IKKα/ß phosphorylation and downstream cytokines/chemokines, e.g., IL6, CXCL1, and CXCL8. Through restraining the cytokines expression, WCE reduced tumor-elicited infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and endothelial cells into the tumors, therefore inhibiting angiogenesis, tumor growth, and metastasis. In MDSCs, WCE also reduced STAT3 activation, downregulated S100A8 expression and prevented their expansion. Use of WCE in combination with docetaxel significantly suppressed docetaxel-induced NFκB activation, boosted the therapeutic effect and reduced the systemic toxicity caused by docetaxel monotherapy. These data suggest that a standardized preparation of Wedelia chinensis extract improved prostate cancer therapy through immunomodulation and has potential application as an adjuvant agent for castration-resistant prostate cancer.

PURIFICATION AND FRACTIONAL ANALYSIS OF METHANOLIC EXTRACT OF WEDELIA TRILOBATA POSSESSING APOPTOTIC AND ANTI-LEUKEMIC ACTIVITY.

BACKGROUND: Wedelia trilobata (L.) Hitch (WT), commonly known as yellow dots or creeping daisy, is a shrub possessing potent biological activities, and is traditionally used a medicinal plant in Ayurveda, Siddha and Unani systems of medicines, and it has also been tried against leukemia cell line MEG- 01. In the present study, purification and screening of the plant was done for bioactive compounds in methanolic extract of WT for apoptotic and anti-leukemia activity. MATERIALS AND METHODS: The methanolic extract of WT was initially purified through thin layer chromatography (TLC) and screened for the apoptotic and anti-leukemia activities. The positive band of TLC was subjected to silica gel column chromatography for further purification and the fractions obtained from it were screened again for anti-leukemia activity through thymidine uptake assay and apoptotic activity by DNA fragmentation, nuclear staining and flow cytometry assays. The fraction with positive result was subjected to HPLC for analysis of bioactive components. RESULTS: Out of many combinations of solvents, the methanol and dichloromethane combination in the ratio 6:4 has revealed two bands in TLC, among which the second band showed positive results for apoptotic and anti-leukemic activities. Further purification of second band through silica gel chromatography gave five fractions in which the 3rd fraction gave positive results and it shows single peak during compositional analysis through HPLC. CONCLUSION: The single peak revealed through HPLC indicates the presence of pure compound with apoptotic and anti-leukemia activities encouraging for further structural analysis.

Two new kaurane-type diterpenoids from Wedelia chinensis (Osbeck.) Merr.

Two new kaurane-type diterpenoids, 3α-(angeloyloxy)-17-hydroxy-ent-kaur-15-en-19-oic acid (1) and 3α-(tigloyloxy)-17-hydroxy-ent-kaur-15-en-19-oic acid (2), along with 10 known compounds (3-12) were isolated from the whole plant of Wedelia chinensis (Osbeck.) Merr. Their structures were elucidated on the basis of extensive spectroscopic analyses (UV, IR, MS and NMR) and comparison with literature data. Compounds 3 and 4 showed moderate inhibitory activity against the Staphylococcus aureus subsp. aureus ATCC29213 with MIC50 19.35 and 18.31 µg/mL, respectively.

Three new ent-kaurane diterpenes from the herbs of Wedelia prostrata.

Three new ent-kaurane diterpenes, 3α-angeloyloxy-17-hydroxy-ent-kaur-15-en-19-oic acid (1), 3α-tigloyloxy-17-hydroxy-ent-kaur-15-en-19-oic acid (2) and 3α-cinnamoyloxykaur-9(11),16-dien-19-oic acid (3), along with five known compounds (4-8), were isolated from the herbs of Wedelia prostrata (Asteraceae). The structures were determined by extensive analysis of their spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolated compounds were evaluated for their cytotoxic activity on human hepatocellular carcinoma HepG2 cells. Among them, all isolates exhibited cytotoxic activities with IC50 values ranging from 9.55 ± 0.45 to 53.92 ± 1.22 µM.

Antimicrobial Diterpenoids of Wedelia trilobata (L.) Hitchc.

Continued interest in the metabolites of Wedelia trilobata (L.) Hitchc, a notoriously invasive weed in South China, led to the isolation of twenty-six ent-kaurane diterpenoids, including seven new ones 1-7. Their structures and relative configuration were elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR experiments. The antimicrobial activities of all isolated diterpenoids were evaluated against a panel of bacteria and fungi.

Anti-angiogenic activity and mechanism of kaurane diterpenoids from Wedelia chinensis.

BACKGROUND: Wedelia chinensis is a traditional medicinal herb used in Asia and it has been reported to possess various bioactivities including anti-inflammatory and anticancer effects. However, its anti-angiogenic activity has never been reported. PURPOSE: To determine the most potent anti-angiogenic component in W. chinensis and its molecular mechanism of action. STUDY DESIGN: Initially, the active fraction of the plant was studied. Then, we determined the active components of the fraction and explored the mechanism of the most active compound. METHODS: The ethanol extract of W. chinensis and its four fractions with different polarities were evaluated for their anti-angiogenic activity in the Zebrafish model using quantitative endogenous alkaline phosphatase (EAP) assay. The molecular mechanism of the most active compound from the active fraction was studied using the real-time polymerase chain reaction (PCR) assay on Zebrafish embryos. The inhibitory effect of the most active compound on the proliferation, invasion and tube formation steps of angiogenesis was evaluated using the vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs) model, and the influences of the active compound on tyrosine phosphorylation of VEGF receptor (VEGFR-2) and its downstream signal pathway were evaluated by western blotting assay. Moreover, its anti-angiogenic effect was further evaluated by the VEGF-induced sprouts formation on aortic ring assay and the VEGF-induced vessel formation of mice on matrigel plug assay, respectively. RESULTS: Petroleum ether (PE) fraction of the plant displayed potent anti-angiogenic activity. Twelve kaurane diterpenoids (1-12) isolated from this fraction showed quite different effects. Compounds 9-12 could dose-dependently inhibit vessel formation in the Zebrafish embryos while the others showed little inhibitory effect. Among the active diterpenoids, compound 10, 3α-cinnamoyloxy-9ß-hydroxy-ent-kaura-16-en-19-oic acid (CHKA), possessed the strongest effect, and it affected multiple molecular targets related to angiogenesis including VEGF and angiopoietin in Zerbrafish. Moreover, CHKA significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, invasion, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR-2 tyrosine kinase activity and its downstream signaling pathways in HUVECs. CHKA also obviously inhibited sprouts formation of aortic ring, and block vessel formation in mice. CONCLUSION: Our findings demonstrate that kaurane diterpenoids is one of anti-angiogenic components in W. chinensis, and CHKA may become a promising candidate for the development of anti-angiogenic agent.

Integrative approach to analyze biodiversity and anti-inflammatory bioactivity of Wedelia medicinal plants.

For the development of "medical foods" and/or botanical drugs as defined USA FDA, clear and systemic characterizations of the taxonomy, index phytochemical components, and the functional or medicinal bioactivities of the reputed or candidate medicinal plant are needed. In this study, we used an integrative approach, including macroscopic and microscopic examination, marker gene analysis, and chemical fingerprinting, to authenticate and validate various species/varieties of Wedelia, a reputed medicinal plant that grows naturally and commonly used in Asian countries. The anti-inflammatory bioactivities of Wedelia extracts were then evaluated in a DSS-induced murine colitis model. Different species/varieties of Wedelia exhibited distinguishable morphology and histological structures. Analysis of the ribosomal DNA internal transcribed spacer (ITS) region revealed significant differences among these plants. Chemical profiling of test Wedelia species demonstrated candidate index compounds and distinguishable secondary metabolites, such as caffeic acid derivatives, which may serve as phytochemical markers or index for quality control and identification of specific Wedelia species. In assessing their effect on treating DSS induced-murine colitis, we observed that only the phytoextract from W. chinensis species exhibited significant anti-inflammatory bioactivity on DSS-induced murine colitis among the various Wedelia species commonly found in Taiwan. Our results provide a translational research approach that may serve as a useful reference platform for biotechnological applications of traditional phytomedicines. Our findings indicate that specific Wedelia species warrant further investigation for potential treatment of human inflammatory bowel disease.

Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca²âº-ATPase PfATP6.

Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisinin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosa were tested in silico against the Plasmodium falciparum Ca2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.

Development of a standardized and effect-optimized herbal extract of Wedelia chinensis for prostate cancer.

Herbal medicine is a popular complementary or alternative treatment for prostate cancer. Wedelia chinensis has at least three active compounds, wedelolactone, luteolin, and apigenin synergistically inhibiting prostate cancer cell growth in vitro. Here, we report a systematic study to develop a standardized and effect-optimized herbal extract, designated as W. chinensis extract (WCE) to facilitate its future scientific validation and clinical use. Ethanolic extract of dried W. chinensis plant was further condensed, acid hydrolyzed, and enriched with preparative chromatography. The chemical compositions of multiple batches of the standardized preparation WCE were quantified by LC/MS/MS, and biological activities were analyzed by in vitro and in vivo assays. Furthermore, the pharmacokinetics of the holistic WCE were compared with the combination of the equivalent principal active compounds through oral administration. The results indicated that quantitative chemical assay and PSA (prostate-specific antigen)-reporter assay together are suitable to measure the quality and efficacy of a standardized Wedelia extract on a xenograft tumor model. The presence of minor concomitant compounds in WCE prolonged the systemic exposure to the active compounds, thus augmented the anti-tumor efficacy of WCE. In conclusion, a combination of LC/MS/MS and PSA reporter assay is suitable to qualify a standardized preparation of WCE. Furthermore, the pharmacokinetics and oral bioavailability of active compounds demonstrate that holistic WCE exerted additional pharmacological synergy beyond the multi-targeted therapeutic effects caused by more than one active compound. WCE merits a higher priority to be studied for use in prostate cancer treatment.

Ethyl acetate extract of Wedelia chinensis inhibits tert-butyl hydroperoxide-induced damage in PC12 cells and D-galactose-induced neuronal cell loss in mice.

BACKGROUND: Wedelia chinensis is traditionally used as a hepatoprotective herb in Taiwan. The aim of this study was to evaluate the neuroprotective potential of W. chinensis. METHODS: An ethyl acetate extract of W. chinensis (EAW) was prepared and analyzed by HPLC. The neuroprotective potential of EAW was assessed by tert-butylhydroperoxide (t-BHP)-induced damage in PC12 cells and D-galactose-induced damage in mouse cortex. RESULTS: EAW exhibited potent radical scavenging property and highly contained luteolin and wedelolactone. EAW decreased t-BHP-induced reactive oxygen species (ROS) accumulation, cytotoxicity and apoptosis in PC12 cells. EAW and its major constituents blocked t-BHP-induced cytochrome C release and Bcl-2 family protein ratio change. EAW and its major constituents increased the endogenous antioxidant capacity evaluated by the binding activity assay of nuclear factor E2-related factor 2 (Nrf2) to antioxidant response element (ARE) and nuclear translocation of Nrf2 respectively in PC12 cells. Finally, EAW inhibited D-galactose-induced lipid peroxidation, apoptosis and neuron loss in the cerebral cortex of mice. CONCLUSION: These results demonstrate that W. chinensis has neuroprotective potential through blocking oxidative stress-induced damage and that luteolin and wedelolactone contribute to the protective action.

Dietary uptake of Wedelia chinensis extract attenuates dextran sulfate sodium-induced colitis in mice.

SCOPE: Traditional medicinal herbs are increasingly used as alternative therapies in patients with inflammatory diseases. Here we evaluated the effect of Wedelia chinensis, a medicinal herb commonly used in Asia, on the prevention of dextran sulfate sodium (DSS)-induced acute colitis in mice. General safety and the effect of different extraction methods on the bioactivity of W. chinensis were also explored. METHODS AND RESULTS: C57BL/6 mice were administrated hot water extract of fresh W. chinensis (WCHF) orally for one week followed by drinking water containing 2% DSS for nine days. WCHF significantly attenuated the symptoms of colitis including diarrhea, rectal bleeding and loss of body weight; it also reduced the shortening of colon length and histopathological damage caused by colonic inflammation. Among four W. chinensis extracts prepared using different extraction techniques, WCHF showed the highest anti-colitis efficacy. Analyses of specific T-cell regulatory cytokines (TNF-α, IL-4, IFN-γ, IL-17, TGF-ß, IL-12) revealed that WCHF treatment can suppress the Th1 and Th17, but not Th2, responses in colon tissues and dendritic cells of DSS-induced colitis mice. A 28-day subacute toxicity study showed that daily oral administration of WCHF (100, 500, 1000 mg/kg body weight) was not toxic to mice. CONCLUSION: Together, our findings suggest that specific extracts of W. chinensis have nutritional potential for future development into nutraceuticals or dietary supplements for treatment of inflammatory bowel disease.

Six new phenolic glycosides and a new ceramide from the flowers of Wedelia biflora and their cytotoxicity against some cancer cell lines.

The plant Wedelia biflora has been used in traditional medicine in India and Vietnam to treat various symptoms. However, the chemical composition of its flowers remains mostly unknown. Therefore, we now report the isolation and structural elucidation of six new phenolic glycosides {wedebicoside A - F (1-6)} and one new ceramide [wedebiceramide (9)], together with six known compounds, 1-O-(2',4'-diangeloyloxy-beta-D-fucopyranosyl)-6-hydroxythymol (7), 1-O-[2',4'-diangeloyloxy-3'-(3"-angeloyloxy-beta-D-fucopyranosyl)-beta-D-fucopyransyl]-6-hydroxythymol (8), anhydrosecoisolariciresinol (10), friedeline (11), epifriedelanol (12) and stigmasterol (13) from the flowers of Wedelia biflora. Their structures were established by 1D and 2D NMR spectroscopy, as well as by high resolution ESI-MS analysis and comparison with literature data. The cytotoxic activities against HeLa, MCF-7 and NCI-H460 were evaluated on some purified compounds at the concentration of 100 microg/mL. Compounds 1, 2, 3 and 5 showed strong cytotoxic activities against three surveyed cancer cell lines. Consequently, this study elucidated the phytochemical composition of W. biflora, as well as the potential use of some of the new compounds against some cancers.