Zishen pingchan granules combined with pramipexole in the improvement of depressive symptoms in Parkinson's disease: a prospective, multicenter, randomized, double-blind, controlled clinical study.

BACKGROUND AND OBJECTIVE: Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson's disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). METHODS: A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. RESULTS: After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (- 1.43 scores [- 2.50, - 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (- 3.56 scores [- 5.77, - 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. CONCLUSION: ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432.

Methodological Considerations in N-of-1 Trials of Traditional Chinese Medicine.

More and more scholars choose N-of-1 trials for TCM clinical research. However, the quality of the experimental designs was uneven. Accumulating more than eight years of experience in exploring the N-of-1 trials of TCM, the authors and their team searched the related literature in main Chinese and English databases, referenced to relevant Chinese and international guidelines. The design, implementation, and data analysis of N-of-1 trials of TCM are still in in-depth exploration and practice. "Carryover effect" may affect the design and quality of the trials. Individualized treatment should be guided by the classic theories of TCM. It is expected to formulate reasonable observation periods and pairs and closely integrate individual and group statistical analysis.

A Series of N-of-1 Trials for Traditional Chinese Medicine Using a Bayesian Method: Study Rationale and Protocol.

Background. Our previous studies showed that N-of-1 trials could reflect the individualized characteristics of traditional Chinese medicine (TCM) syndrome differentiation with good feasibility, but the sensitivity was low. Therefore, this study will use hierarchical Bayesian statistical method to improve the sensitivity and applicability of N-of-1 trials of TCM. Methods/Design. This is a randomized, double-blind, placebo-controlled, three-pair crossover trial for a single subject, including 4-8 weeks of run-in period and 24 weeks of formal trial. In this study, we will recruit a total of 30 participants who are in the stable stage of bronchiectasis. The trial will be divided into three pairs (cycles), and one cycle contains two observation periods. The medications will be taken for three weeks and stopped for one week in the last week of each observation period. The order of syndrome differentiation decoction and placebo will be randomly determined. Patient self-reported symptom score (on a 7-point Likert scale) is the primary outcome. Discussion. Some confounding variables (such as TCM syndrome type and potential carryover effect of TCM) will be introduced into hierarchical Bayesian statistical method to improve the sensitivity and applicability of N-of-1 trials of TCM, and the use of prior available information (e.g., "borrowing from strength" of previous trial results) within the analysis may improve the sensitivity of the results of a series of N-of-1 trials, from both the individual and population level to study the efficacy of TCM syndrome differentiation. It is the exploration of improving the objective evaluation method of the clinical efficacy of TCM and may provide reference value for clinical trials of TCM in other chronic diseases. This trial is registered with ClinicalTrials.gov (ID: NCT04601792).

Antidepressant-like effects of auraptenol in mice.

Depression is a major psychiatric disorder affecting nearly 21% of the world population and imposes a substantial health burden on society. Current available antidepressants are not adequate to meet the clinical needs. Here we report that auraptenol, an active component of the traditional Chinese medicine, angelicae dahuricae radix, had antidepressant-like effects in mice models of depression. In mouse forced swimming test and tail suspension test, two validated models of depression, auraptenol dose-dependently decreased the immobility duration within the dose range of 0.05-0.4 mg/kg. In addition, the antidepressant-like effects of auraptenol was significantly averted by a selective serotonin 5-HT1A receptor antagonist WAY100635 (1 mg/kg). These doses that affected the immobile response did not affect locomotor activity. In summary, this study for the first time identified an active component from the herbal medicine angelicae dahuricae radix that possesses robust antidepressant-like efficacy in mice. These data support further exploration for the possibility of developing auraptenol as a novel antidepressant agent in the treatment of major depression disorders.

[Characteristics of soil microbial community under different vegetation types in Wuyishan National Nature Reserve, East China].

By using Biolog Ecoplate system, this paper studied the structure and functional diversity of soil microbial community under different vegetation types in Wuyishan National Nature Reserve, aimed to probe into the effects of vegetation type on the diversity of soil microbial community. The results showed that the soil chemical properties, soil enzyme activities, and average well color development (AWCD) were higher in natural forest than in planted forest, and were the lowest in abandoned field. The AWCD reflecting soil microbial activity and functional diversity was increased with increasing incubation time, but there existed significant differences among different vegetation types. The carbon sources mostly used by soil microbes were carbohydrates and carboxylic acids, followed by amino acids, phenolic acids and polymers, and amines had the lowest utilization rate. The Simpson index, Shannon index, Richness index and McIntosh index in natural forest were holistically higher than those in planted forest. Principal component analysis (PCA) identified 2 principal component factors in relation to carbon sources, explaining 56.3% and 30.2% of the variation, respectively. The carbon sources used by soil microbial community differed with vegetation types. Amino acids and amides were the two main carbon sources separating the 2 principal component factors. The results of this study could provide basis for further approaching the relationships between vegetation diversity and soil microbial community diversity.

Tyrosine and tyramine increase endogenous ganglionic morphine and dopamine levels in vitro and in vivo: cyp2d6 and tyrosine hydroxylase modulation demonstrates a dopamine coupling.

BACKGROUND: The ability of animals to make morphine has been in question for the last 30 years. Studies have demonstrated that animals do contain morphine precursors and metabolites, as well as the ability to use some morphine precursors to make morphine. MATERIAL/METHODS: The present study uses excised ganglia from the marine invertebrate Mytilus edulis as well as whole animals. Morphine and dopamine levels were determined by high performance liquid chromatography coupled to electrochemical detection and radioimmunoassay. Tissues and whole animals were also exposed to morphine precursors and exposed to the CYP2D6 inhibitor quinidine and the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). Additionally, via RT-PCR, a cDNA fragment of the CYP2D6 enzyme in the ganglia of M. edulis was identified. RESULTS: Pedal ganglia incubated with either tyramine or tyrosine, or whole animals receiving injections, exhibited a statistically significant concentration- and time-dependent increase in their endogenous morphine and dopamine levels (2.51 +/- 0.76 ng/g for tyrosine and 2.39 +/- 0.64 ng/g for tyramine compared to approximately 1.0 ng/g morphine wet weight). Incubation with quinidine and/or AMPT diminished ganglionic morphine and dopamine synthesis at various steps in the synthesis process. We also demonstrated that CYP2D6 mediates the tyramine to dopamine step in this process, as did tyrosine hydroxylase in the step from tyrosine to L-DOPA. Furthermore, via RT-PCR, we identified a cDNA fragment of the CYP2D6 enzyme in the ganglia, which exhibits 94% sequence identity with its human counterpart. Evidence that tyrosine and tyramine were, in part, being converted to dopamine then morphine, and that this process can be inhibited by altering either or both CYP2D6 or tyrosine hydroxylase, is also provided. CONCLUSIONS: It appears that animals have the ability to make morphine. This process also appears to be dynamic in that the inhibition of one pathway allows the other to continue with morphine synthesis. Moreover, dopamine and morphine synthesis were coupled.

[Terpenoids in root exudates of different allelopathic rice varieties].

In this paper, a strong allelopathic rice variety PI312777 and a weak allelopathic rice variety Lemont were used as test materials, and the root exudates of two rice varieties grown in the media of sand and soil were respectively collected by using circulation system approach. The terpenoids in ether-extracts were detected by GC-MS, and characterized by spectrum database. The results showed that some terpenoids such as limonene oxide, limonene dioxide, carvone oxide, carveol, and cedrol were detected in the ether-extracts. Different rice varieties had the similar kinds of terpenoids, but their existing modes and quantities were different. The differences between different various cultural methods and between rice varieties were further discussed.

[Chemical components of root exudates from allelopathic rice accession PI312777 seedlings].

In this study, allelopathic rice accession PI312777 seedlings were grown on a paddy soil under near natural condition, and their root exudates were collected by using circulation method, with the solution collected from no seedlings- planted soil as the control. The ether extracts of the root exudates and soil solution were detected by GC-MS, and identified with the mass spectral database of NIST and WILEY Library. The results showed that there were 36 compounds in the rice root exudates, including 9 terpenoids (peak area 10.97%), 8 phenols or quinones (5.87%), 6 esters (10.68%), 3 aldehydes or ketones (1.44%), 4 heterocycles (68.04%), 2 alcohols (1.23%), 2 ethers (0.57%), and 2 others (1.20%). A distinctly similar structure was observed among the terpenoids and among the phenols or quinones. In the soil solution, 39 compounds were detected, and 7 of them were the same of the root exudates. The difference of the compounds in rice root exudates and soil solution, and the possible allelopathic mechanisms of these compounds were discussed in this paper.