Morinda officinalis oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin (5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan; meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation, and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide, as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.

OBJECTIVE: To construct the RNA interference(RNAi) lentiviral vector of suppressor of variegation 3-9 homolog 1(Suv39 h1) and verify its interfering efficiency by transfecting it to the bone marrow-derived mesenchymal stem cells(BMSCs). METHODS: The oligonucleotides of RNA plasmid were designed and synthesized according to the gene sequence of Suv39 h1 and short hairpin RNA design principles. Three kinds of LV-Suv39 h1-RNAi recombinant plasmids with different lentivirus knockdown targets(KD1, KD2 and KD3) were constructed. After identification by restriction analysis and sequencing, the packaged lentivirus vectors with the three kinds of Suv39 h1 gene were transfected into rat BMSCs at logarithmic growth stage, and were named KD1, KD2 and KD3 transfection groups. The control group was transfected with the negative control virus. After 72 hours transfection, the transfection efficiency was evaluated, and the relative mRNA levels of Suv39 h1 were determined by quantitative real-time polymerase chain reaction(qPCR). RESULTS: Sequencing analysis demonstrated that three kinds of LV-Suv39 h1-RNAi recombinant plasmids were constructed correctly. The results of transfection efficiency evaluation showed that more than 80.00% green fluorescence was expressed in the BMSCs transfected with the three lentiviral vectors with a multiplicity of infection of 20. These results indicated that lentivirus was successfully constructed and transfection efficiency was high. The results of qPCR showed that the relative expression of Suv39 h1 mRNA in BMSCs of KD1, KD2 and KD3 transfection groups was lower than that in the control group(all P<0.05), and the relative expression of Suv39 h1 mRNA in KD1 and KD3 transfection groups was lower than that in KD2 transfection group(both P<0.05). However, there was no significant difference in the relative expression of Suv39 h1 mRNA between KD1 and KD3 transfection groups(P>0.05). CONCLUSION: The constructed lentiviral vector with low expression of Suv39 h1 was constructed successfully. This vector can be expressed in rat BMSCs, which lays a foundation to study the effect of Suv39 h1 gene in acute myeloid leukemia.

Objective:To study the effect of Shenshuai Xiezhuo decoction and its deficiency tonifying and pathogen eliminating components on renal interstitial fibrosis in UUO rats. Method:A rat model of unilateral ureteral obstruction (UUO) was established through ligation of a unilateral ureter. The rats were divided into six groups: sham operation group, model group, benazepril group, Shenshuai Xiezhuo decoction group, Buxufang group, and phlegm group, with 24 rats in each group. On the third day after operation, the rats in the Shenshuai Xiezhuo decoction group, Buxufang group, and phlegm group were given Shenshuai Xiezhuo decoction concentrating agent at a dose of 8.0 g·kg^-1·d^-1, the rats in the benazepril group were given benazepril 1.5 mg·kg^-1·d^-1, and the rats in the sham operation group and the model group were given the same volume of saline. On the 7^th, 14^th and 21^st days after operation, the expressions of peripheral cells and relevant signal pathway markers in renal tissue were detected by Western blot and Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) respectively. Result:The stromal damage score and the interstitial collagen accumulation on the 14^th and 21^st days after UUO were significantly lower in the Shenshuai Xiezhuo decoction group, Buxu prescription group and Qixie prescription group than those in the model group (P<0.05). Except for the sham operation group, the protein expressions of α smooth muscle actin (α-SMA), platelet derived growth factor A (PDGFA), nerve/glial type 2 chondroitin sulfate glycoprotein (NG-2), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 1 (VEGFR1), platelet-derived growth factor -β (PDGF-β) and platelet-derived growth factor receptor-β (PDGFR-β) in the kidney tissues of the 14^th and 21^st days were significantly increased compared with those on the 7^th day (P<0.05). On the 21^st day after surgery, the expressions of NG-2, VEGFA, VEGFR1 and PDGFR-β in renal tissue of Shenshuai Xiezhuo decoction group were significantly lower than those in the model group (P<0.05). Compared with the model group, relevant expressions of α-SMA, PDGFA, NG-2, VEGFA, VEGFR1, PDGF-β, and PDGFR-β in kidney tissue of Shenshuai Xiezhuo decoction group decreased significantly on the 21^st day after operation (P<0.05), and relative expressions of α-SMA, NG-2, VEGFA, VEGFR1 and PDGFR-β in the Shenshuai Xiezhuo decoction group were significantly lower than those in the benazepril group on the 21^st day after surgery (P<0.05). Conclusion:Shenshuai Xiezhuo decoction and its deficiency tonifying and pathogen eliminating components have an antagonistic effect on renal interstitial fibrosis in UUO rats. Its mechanism is related to the inhibition of activation of peripheral cells and relevant cell signaling pathways.