Search

Eclipta prostrata L. has been used in traditional medicine and known for its liver-protective properties for centuries. Wedelolactone (WEL) and demethylwedelolactone (DWEL) are the major coumarins found in E. prostrata L. However, the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease (NAFLD) still remains to be explored. Utilizing a well-established zebrafish model of thioacetamide (TAA)-induced liver injury, the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis. Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver. The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped, and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized. Based on spatial metabolomics and transcriptomics, we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL. Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD, and presents a “multi-omics” platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Eclipta prostrata L. has been used in traditional medicine and known for its liver-protective properties for centuries. Wedelolactone (WEL) and demethylwedelolactone (DWEL) are the major coumarins found in E. prostrata L. However, the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease (NAFLD) still remains to be explored. Utilizing a well-established zebrafish model of thioacetamide (TAA)-induced liver injury, the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis. Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver. The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped, and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized. Based on spatial metabolomics and transcriptomics, we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL. Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD, and presents a "multi-omics" platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy. [Display omitted] • Wedelolactone and demethylwedelolactone ameliorated TAA-induced non-alcoholic fatty liver disease (NAFLD). • Spatial metabolomics mapped the biodistributions and metabolism of wedelolactone and demethylwedelolactone in zebrafish. • The metabolic modulation by wedelolactone and demethylwedelolactone on NAFLD were imaged. • Liver-specific transcriptomics revealed distinct gene expression patterns between wedelolactone and demethylwedelolactone. • Wedelolactone suppressed steroid biosynthesis and fatty acid elongation by regulating related genes, like ebp and dgat2. [ABSTRACT FROM AUTHOR]

Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals. A methanolic extract of E. prostrata (MEEP), the major components of which are wedelolactone (WED) and demethylwedelolactone (DMW), exhibited anti-inflammatory activity in acute asthma models but the effects on lung inflammation and the mechanisms of action of MEEP in a chronic asthma model are not known. To study the effects of MEEP in vivo using a chronic ovalbumin (OVA)-induced allergic asthma model in mice. The identities of WED and DMW in MEEP were confirmed and the concentrations determined by liquid chromatography and tandem mass spectrometry. Male Balb/c mice were sensitized and challenged with OVA and experimental animals were treated with MEEP (100, 250 or 500 mg/kg) while control animals were treated with dexamethasone (2 mg/kg) or normal saline. Bronchial hyperresponsiveness, total and differential cell counts in bronchoalveolar lavage (BAL), and the production of Th2 cytokines in lung homogenates were assessed. Lung inflammation and mucus production were evaluated by histological analysis while nuclear factor kappa -B (NF-κB) activation was assessed immunohistochemically. Concentrations of WED and DMW in MEEP were 5.12% and 1.04%, respectively. Treatments with MEEP (250 or 500 mg/kg) significantly decreased bronchial hyperresponsiveness, reduced total cell and eosinophil counts in BAL and IL-4 concentrations in lung homogenate, and inhibited NF-κB activation. Treatment with MEEP at 500 mg/kg reduced the level of IL-5 in lung homogenates but did not decrease IL-13 concentration or mucus production. MEEP attenuated bronchial hyperresponsiveness and decreased lung and airway inflammation in a chronic asthma model in mice. The mechanism of action involves inhibition of NF-κB activation, most likely associated with the presence of the coumestans WED and DMW. These results support the ethnopharmacological evidence for the use of E. prostrata against asthma and other respiratory inflammatory diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Phosphodiesterase PDEs are the only pathways that catalyze the hydrolysis of second messenger cAMP and cGMP in cells. Phosphodiesterase(PDE)inhibitors can regulate learning and cognitive dysfunction(AD)by altering the concentrations of cAMP and cGMP. Demethylwedelolactone(DWEL)is one of the main components of Eclipta prostrata L. Alpha kit test confirmed the inhibition effect of Demethylwedelolactone on PDE2A with IC50 value 9.17 μmol·L-1. However, no obvious inhibition effect was found on PDE4D and PDE10A which indicate Demethylwedelolactone can inhibit PDE2A selectively. HT-22 cell model induced by cortisone showed that Demethylwedelolactone could increase the survival rate of HT-22 cell cells. When the concentration reached 20 μmol·L-1, the cell viability was 76.98%(P<0.05). These results suggested that DWEL could protect HT-22 cell indured by cortisone. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Eclipta prostrata (L.) L. (Asteraceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory illnesses. Aims of the study To investigate the effects of different doses of a standardized extract of E. prostrata using a murine model of allergen induced asthma. Materials and methods Balb/c mice were sensitized twice with ovalbumin (OVA) administered intraperitoneally and challenged over four alternate days with nasal instillations of OVA solution. The standardized methanol extract of E. prostrata was administered in doses of 100, 250 and 500 mg kg − 1 concomitantly with nasal instillation over seven consecutive days. Control animals were treated with dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, allergen sensitization, airway and lung inflammation, mucous secretion and airway remodeling were assessed. Results The concentrations of chemical markers in the standardized methanol extract were 0.02% oroboside, 1.69% demethylwedelolactone and 1.71% wedelolactone. Treatment with 250 mg kg −1 of extract, which provided 0.745, 4.22 and 4.30 mg kg − 1 day −1 of oroboside, demethylwedelolactone and wedelolactone, respectively, significantly reduced ( P <0.05) respiratory resistance and elastance. Such effects were comparable with those produced by dexamethasone. The total number of inflammatory cells and eosinophils in the bronchoalveolar lavage and the concentrations of interleukin (IL)-4, IL-5 and IL-13 in lung homogenate were significantly reduced ( P <0.05) by the methanol extract of E. prostrata. Conclusion The results presented herein demonstrate for the first time the anti-inflammatory activity of E. prostrata in a murine model of asthma, thereby supporting the ethnopharmacological uses of the plant. [ABSTRACT FROM AUTHOR]

Wedelia chinensis is a medicinal herb, traditionally used to treat variety of immunological disorders. The herb and its coumestans, wedelolactone (WL) and demethylwedelolactone (DWL) were demonstrated to possess several biological actions . This work was aimed to evaluate the in vitro immunomodulatory effect of DWL as well as the standardized Wedelia chinensis extract (WCE). In vitro immunomodulatory potential was evaluated by assessing the effects on Compound 48/80 (C 48/80)-induced de-granulation of mast cell and LPS-stimulated production of NO, pro-inflammatory cytokines and the expression of costimulatory molecules in macrophages. RP-HPLC analysis of WCE indicated the abundance of WL (1.96 ± 0.03 %, w/w) and DWL (0.61 ± 0.005 %, w/w). Results of the present investigation showed that WCE and DWL dose dependently inhibited the de-granulation of mast cells induced by C 48/80. Additionally, WCE and DWL were also inhibited the production of NO, pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 and the expression of costimulatory molecules such as CD40, CD80 and CD86 in LPS-stimulated macrophages. These findings suggest that WCE has modulatory effect on various immune-inflammatory mediators mainly due to the presence of WL along with the lesser amount of DWL. Therefore, this plant as well as its coumestans, WL and DWL can be exploited as alternative new therapeutics for various inflammatory diseases. [ABSTRACT FROM AUTHOR]

Abstract: The anticancer properties of demethylwedelolactone (DWEL) and wedelolactone (WEL), which are naturally occurring coumestans, have not been well characterized. In this study, we investigated the anti-invasive effects of synthetic WEL and DWEL on human MDA-MB-231 breast cancer cells. We found that WEL and DWEL inhibited the anchorage-independent growth and also suppressed cell motility and cell invasion of MDA-MB-231 cells. In addition, WEL and DWEL reduced the activity and expression of matrix metalloproteinases (MMPs) involved in blocking the IκB-α/NFκB and MEK/ERK signaling pathways in MDA-MB-231 cells. Furthermore, DWEL suppressed the metastasis and lung colonization of the tumor cells in the nude mice. Altogether, these data suggest that DWEL derivatives exert anti-invasive growth effect on breast cancer cells. [Copyright &y& Elsevier]

Abstract: Hedysarimcoumestan B, which can be isolated from Chinese herbal medicine, is achieved, in which the longest linear sequence is only eight steps, in 50% overall yield from commercially available phloroglucinol. The key transformations in the synthesis are Cu-mediated/Pd(0)-catalysis and I2/pyridine oxidative-cyclization reactions. This synthetic strategy can be applied to give access to the demethylwedelolactone (4) and wedelolactone (5), which were afforded from commercially available phloroglucinol in high 38 and 33% yields, respectively. [Copyright &y& Elsevier]

The butanolic and purified butanolic extracts (PBEs) of Eclipta prostrata were evaluated for their anti-venom potential. Inhibition of lethal, hemorrhagic, proteolytic, and phospholipase A2 activities of Calloselasma rhodostoma (Malayan pit viper (MPV)) venom by these extracts were determined. Demethylwedelolactone was identified as their major constituent. The butanolic extract, at 2.5 mg per mouse, was able to completely neutralize the lethal activity of 2LD50 of MPV venom, but increasing the dose diminished the effect. The PBE, at 1.5–4.5 mg per mouse, was able to neutralize the lethality of the venom at around 50–58%. Both extracts partially inhibited the hemorrhagic activity but displayed very low anti-phospholipase A2 activity and did not inhibit proteolytic activity of MPV venom. [Copyright &y& Elsevier]

Aims and Objective: Wedelolactone and demethylwedelolactone are the two major coumarin constituents of Herba Ecliptae. The objective of this work was to develop and validate a sensitive, rapid, and robust UPLC-MS/MS method for the simultaneous quantification of wedelolactone and demethylwedelolactone in rat plasma., Materials and Methods: Wedelolactone and demethylwedelolactone were extracted from rat plasma by protein precipitation with acetonitrile. Electrospray ionization in negative mode and selected reaction monitoring (SRM) were used for wedelolactone and demethylwedelolactone at the transitions m/z 312.8→298.0 and m/z 299.1→270.6, respectively. Chromatographic separation was conducted on a Venusil C 18 column (50 mm × 2.1 mm, 5 μm) with isocratic elution of acetonitrile-0.1% formic acid in water (55:45, v/v) at a flow rate of 0.3 mL/min. A linear range was observed over the concentration range of 0.25-100 ng/mL for wedelolactone and demethylwedelolactone., Results: They reached their maximum plasma concentrations (C max , 74.9±13.4 ng/mL for wedelolactone and 41.3±9.57 ng/mL for demethylwedelolactone) at the peak time (T max ) of 0.633 h and 0.800 h, respectively. The AUC 0-t value of wedelolactone (260.8±141.8 ng h/mL) was higher than that of demethylwedelolactone (127.4±52.7 ng h/mL) by approximately 2-fold, whereas the terminal elimination half-life (t 1/2 ) of wedelolactone (2.20±0.59 h) showed the approximately same as that of demethylwedelolactone (2.08±0.69 h)., Conclusion: Based on full validation according to US FDA guidelines, this UPLC-MS/MS method was successfully applied to a pharmacokinetic study in rats., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Changcs in the growth and secondary metabolite production were investigated in Eclipta alba, a medicinal plant with antihepatotoxic activity in extracts, under different soil pH. Leaf and stem development were not affected by the soil pH, although some effect of pH was noted on root elongation. Plants growing in acidic soil accumulated lower levels of wedelolactone (a coumestan) in the roots. The yield of wedelolactone in the vegetative tissue of field grown plants was approximately twice the content in roots. Yield of demethylwedelolactone was greater in roots than in vegetative tissue. [ABSTRACT FROM PUBLISHER]