Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain.Iin this process,tyrosine hydroxylase(TH)isthe rate-limiting enzyme that hydroxylates tyrosine and generates levodopa(L-dopa)with tetranydrobiopterin(BH_(4))as a coenzyme.Here,we show that oral berberine(BBR)might supply H^(·) through dihydroberberine(reduced BBR produced by bacterial nitroreductase)and promote the production of BHl from dihydrobiopterin;the increased BH,enhances TH activity,which accelerates the production of L-dopa by the gut bacteria.Oral BBR acts in a way similar to vitamins.The L-dopa produced by theintestinal bacteria enters the brain through the circulation and is transformed to dopamine.To verify the gut-brain dialog activatedby BBR's effect,Enterococcus foecalis or Enterococcus faecium was transplanted into Parkinson's disease(PD)mice.The bacteriasignificantly increased brain dopamine and ameliorated PD manifestation in mice;additionally,combination of BBR with bacteriashowed better therapeutic effect than that with bacteria alone.Moreover,2,4,6-trimethy-pyranylium tetrafluoroborate(TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry(MALDI-MS)imaging of dopamine identihed elevated striataldopamine levels in mouse brains with oral Enterococcus,and BBR strengthened the imaging intensity of brain dopamine.Theseresults demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut.Furthermore,a study of 28 patients with hyperlipidemia conhrmed that oral BBR increased bloodfecal L-dopa by the intestinalbacteria.Hence,BBR might improve the brain function by upregulating the biosynthesis of-dopa in the gut microbiota through avitamin-like effect.

Manipulating the light-matter interactions in plasmonic nanocavities at 1 nm spatial resolution

The light-matter interaction between plasmonic nanocavity and exciton at the sub-diffraction limit is a central research field in nanophotonics.Here,we demonstrated the vertical distribution of the light-matter interactions at~1 nm spatial resolution by coupling A excitons of MoS2 and gap-mode plasmonic nanocavities.Moreover,we observed the significant photoluminescence(PL)enhancement factor reaching up to 2800 times,which is attributed to the Purcell effect and large local density of states in gap-mode plasmonic nanocavities.Meanwhile,the theoretical calculations are well reproduced and support the experimental results.