Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

4-methylumbelliferone (4-MU) enhances drought tolerance of apple by regulating rhizosphere microbial diversity and root architecture

The dwarfing rootstocks-mediated high-density apple orchard is becoming the main practice management.Currently,dwarfing rootstocks are widely used worldwide,but their shallow root system and drought sensitivity necessitate high irrigation requirements.Here,the root transcriptome and metabolome of dwarfing(M9-T337,a drought-sensitive rootstock)and vigorous rootstocks(Malus sieversii,a drought-tolerant species,is commonly used as a rootstock)showed that a coumarin derivative,4-Methylumbelliferon(4-MU),was found to accumulate significantly in the roots of vigorous rootstock under drought condition.When exogenous 4-MU was applied to the roots of dwarfing rootstock under drought treatment,the plants displayed increased root biomass,higher root-to-shoot ratio,greater photosynthesis,and elevated water use efficiency.In addition,diversity and structure analysis of the rhizosphere soil microbial community demonstrated that 4-MU treatment increased the relative abundance of putatively beneficial bacteria and fungi.Of these,Pseudomonas,Bacillus,Streptomyces,and Chryseolinea bacterial strains and Acremonium,Trichoderma,and Phoma fungal strains known for root growth,or systemic resistance against drought stress,were significantly accumulated in the roots of dwarfing rootstock after 4-MU treatment under drought stress condition.Taken together,we identified a promising compound—4-MU,as a useful tool,to strengthen the drought tolerance of apple dwarfing rootstock.