Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease

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.

Wedelolactone from Eclipta prostrata(L)L.suppresses inflammation and improves insulin resistance

Objective:To evaluate the effects of wedelolactone,a major flavonoid from Vietnamese Eclipta prostrata(L)L.,on inflammation and insulin resistance.Methods:Wedelolactone was extracted from the leaves of Vietnamese Eclipta prostrata(L.)L.with methanol by Soxhlet.The effects of wedelolactone on lipopolysaccharide(LPS)-induced cytokine production,reactive oxygen species(ROS)generation,and nicotinamide adenine dinucleotide phosphate(NADPH)oxidase activities in Raw 264.7 cells were measured by enzyme-linked immunosorbent assay(ELISA),specific immunofluorescent dyes and luminometric analysis,respectively.In addition,its effects on glucose uptake and the protein expression of insulin receptor substrate 1(IRS1)and glucose transporter 4(GLUT4)were examined in 3T3-L1 cells by immunofluorescent dyes and Western blot.Results:Wedelolactone at 30μg/mL significantly inhibited LPS-induced production of tumor necrosis factor-α,interleukin(IL)-6,and IL-8(P<0.01)with no noticeable effects on IL-10 level.It also reduced ROS generation and NADPH oxidase activities in LPS-stimulated Raw 264.7 cells(P<0.01).Furthermore,wedelolactone showed anti-insulin resistance activity,as evidenced by improved glucose uptake and the upregulated expression of IRS1 and GLUT4 in 3T3-L1 cells(P<0.01).Conclusions:Wedelolactone exhibits anti-inflammation and anti-insulin resistance effects,which may be used for the treatment of diabetes and inflammation-associated diseases.

Biological and Functional Properties of Wedelolactone in Human Chronic Diseases

Medicinal herbs are well known and studied over the past millennia in most of the developing countries as a rational means of treatment against various diseases and disorders.Wedelolactone(WDL),a major bioactive compound in Eclipta prostrata L(Eclipta alba L),has been reported with potential benefits in human health against chronic diseases.However,a comprehensive study on WDL pharmacological benefits in various ailments,to the best of our knowledge,is not yet reported.Thereof,the present review provides the recent therapeutic applications in reference to biological and functional activities against major human chronic diseases,including cardiovascular,cancer,diabetes mellitus,liver disease,Alzheimer’s disease,and androgenetic alopecia.In this study,we collected all the relevant experimental information on WDL from Scientific databases such as PubMed,Web of Science,Science Direct,and Google Scholar.Conclusively,WDL is recognized as a key anti-oxidant with both specific regulator and inhibitor of major drug targetable proteins in human chronic diseases and disorders.Hence,WDL as a novel therapeutic bioactive molecule is advised to explore further for relevant pharmacological activities.

A New and Efficient Synthesis of Wedelolactone Derivatives

A new and facile method based on an intermolecular cycloaddition was described for the synthesis of wedel-olactone derivatives.

Optimization of microwave-assisted extraction of wedelolactone from Eclipta alba using response surface methodology

An efficient microwave-assisted extraction tech- nique was used to extract wedelolactone from Eclipta alba. To optimize the effects of the microwave-assisted extraction （MAE） processing parameters on the yield ofwedelolactone, a response surface methodology with a central composite rotatable design was employed. Four independent variables were investigated： microwave power, ethanol concentration, extraction time and the solvent-to-solid ratio. The optimum conditions were： microwave power, 208 W; ethanol con- centration, 90%; extraction time, 26.5 min; and solvent-to- solid ratio, 33 mL.g-~. Under the optimal conditions, the extraction yield of wedelolactone was （82.67±0.16）%, which is in close agreement with the value predicted by the statistical model. MAE was also compared to other conventional methods, including ultrasonic assisted extrac- tion, extraction at room temperature and heat reflux extraction. MAE has distinct advantages for the extraction of wedelolactone in terms of both time and efficiency. Therefore, MAE is a reliable method for the extraction of wedelolactone from Eclipta alba.