| Objective:To observe the clinical effect of Wenshen Yanggan(Wsyg)decoction in the treatment of Parkinson's disease and to explore its mechanism of action in treating Parkinson's disease from the correlation between brain and intestine.By exploring the differences in intestinal flora between Parkinson's patients and healthy people,and comparing the changes in the intestinal flora structure of patients before and after treatment with decoction,we want to study the mechanism of Wsyg decoction on intestinal flora.To investigate the effect of Wsyg decoction on the improvement of rotenone-induced symptoms and intestinal flora in mice with chronic Parkinson's diseaseMethod:Study 1:A randomized,placebo-controlled clinical trial was conducted to evaluate the effectiveness of Wsyg decoction in treating 41 patients with Parkinson's disease,20 in the treatment group while 21 in the control group.In the treatment group,Wsyg decoction was added to the original anti-Parkinson's drug,while in the control group,placebo granules were added.Observation of efficacy indicators after 8 weeks of treatment:Unified Parkinson's disease rating scale(UPDRS score),assessment of non-motor symptoms,gastrointestinal symptoms(NMSS score),39 items of quality of life questionnaire for PD patients(PDQ-39,L-dopa equivalent dose(LDE),TCM syndrome score and constipation score.The plasma levels of intestinal peptide including cholecystokinin and vasoactive were observed.Study 2:We collected 35 subjects from Nanjing Hospital of Chinese Medicine and adopted a randomized,controlled clinical trial method,of which 20 were in the PD group and 15 were in the healthy population.We collected fecal samples,extracted bacterial DNA,amplified the V3-V4 sequence of bacterial to compare the intestinal flora differences between PD and healthy people.The PD group was randomly divided into the treatment group(basic treatment plus Wsyg decoction)and the control group(basic treatment plus placebo)with 10 people.After 8 weeks of treatment,the difference in intestinal flora between the two groups was compared.Study 3:Thirty healthy 10-month-old C57BL/6 mice were selected and randomly divided into the blank group(Saline),Model group(Model),kidney warming nourishing the liver square-high(Wsyg-H),medium(Wsyg-M),low(Wsyg-L)dose group and positive drug control group(Sinemet),with 5 mice in each group.By in vivo experiments,rotenone chronic PD model was established,and Sinemet was used as a positive drug reference to study the neuroprotective effect of Wsyg-H,Wsyg-M and Wsyg-L on PD model mice.After the treatment of Wsyg decoction,the bacterial 16SrRNA V3-V4 region in faecal specimens from ileocecal mice was qualitatively analyzed,we compared the characteristics of intestinal flora of PD model mice and the changes of intestinal flora after drug intervention.Result:1.The total clinical effective rate of Wsyg decoction for Parkinson's disease is 75.00%,and the curative effect is better than that of the control group.The UPDRS score,PDQ-39 score,NMSS score,and non-motor symptoms-gastrointestinal tract score of the treatment group were lower than those of the control group(P<0.05,P<0.01,P<0.01,P<0.01).TCM syndrome scores,score of constipation symptoms was lower than that of the control group(P<0.01,P<0.01),and the levels of CCK and VIP of brain and gut peptides in the treatment group were lower than those of the control group(P<0.01,P<0.01).2.There are differences in the intestinal flora of Parkinson's patients and healthy people:Fecal cocci,Rumen cocci,Lactobacillus,Bifidobacteria,and Trichinella are significantly less than healthy people;Bacillus,Enterococcus,Proteus,and Klebsiella Genus is more abundant in PD patients.After treatment with Wsyg decoction,the abundance of Lactococcus lactis?Lachnospiraceae and Prevotella in PD patients increased,and the abundance of Chloroflexi decreased.3.Wenshen Yanggan decoction in high,medium and low dosages could reduce the turning time of chronic PD model mice(P<0.01,P<0.01,P<0.05),and the high and medium dosages of the decoction shortened the total climbing time of PD mice in pole test(P<0.01,P<0.05).The high,medium and low dosages of this decoction could increase the rod-standing time of PD mice in rotarod test(P<0.01,P<0.05,P<0.05).Besides,the decoction reversed the decrease of TH-positive neurons induced by rotenone,upregulated the expression of TH protein and downregulated of ?-syn expression in the PD model.Meanwhile,the decoction in high dosage significantly inhibited the expression of p-JNK,Cleaved caspase-3 and NF-?B in midbrain of PD mice(P<0.05,P<0.05,P<0.01),upregulated the expression of Bcl-2(P<0.05),decreased the content of TNF-?,IFN-y,NF-?B and IL-1? in serum(all P<0.001).Wsyg decoction mainly affects Proteobacteria?Lachnospiraceae and Prevotella of PD mice.Conclusion:1.The clinical efficacy of Wsyg decoction is better than placebo in the treatment of Parkinson's disease,which can reduce the dosage of anti-Parkinson medication.Short-term treatment can relieve non-exercise symptoms,especially gastrointestinal symptoms in PD patients.Wsyg decoction treats Parkinson's disease with intestinal tract as a target,which can improve the symptoms of constipation in Parkinson's disease and regulate the level of brain and intestinal peptide in the blood of patients.2.There are some differences in the flora between healthy people and patients with Parkinson's disease.The intestinal flora changes after Wsyg decoction treatment.3.Wsyg decoction has significant neuroprotective effects,and its mechanism may be through regulating the JNK signaling pathway,thereby inhibiting inflammation and apoptosis.The decoction may treat Parkinson's disease by regulating the intestinal flora,increase the abundance of beneficial bacteria,and reduce the proliferation of harmful bacteria. |
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