Backgrounds Gut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to explore the relationships between gut microbiota and host’s metabolism in depression. Methods Chronic social defeat stress (CSDS) model of depression was established using C57BL/6 male mice. Fecal samples were collected from CSDS group and control group to measure gut microbiota and microbial metabolites. Meanwhile, tryptophan metabolism-related metabolites in hippocampus were also analyzed. Results CSDS successfully induced depressive-like behaviors in CSDS group. The 24 differential bacterial taxa between the two groups were identified, and 14 (60.87%) differential bacterial taxa belonged to phylum Firmicutes. Functional analysis showed that tryptophan metabolism was significantly affected in CSDS mice. Meanwhile, 120 differential microbial metabolites were identified, and two key tryptophan metabolism-related metabolites (tryptophan and 5-hydroxytryptophan (5-HTP)) were significantly decreased in feces of CSDS mice. The correlation analysis found the significant relationships between tryptophan and differential bacterial taxa under Firmicutes, especially genus Lactobacillus (r=0.801, p=0.0002). In addition, the significantly decreased 5-hydroxytryptamine (5-HT) in hippocampus of depressed mice was also observed. Conclusions Our results showed that tryptophan metabolism might have an important role in the crosstalk between gut microbioa and brain in depression, and phylum Firmicutes, especially genus Lactobacillus, might be involved in the onset of depression through regulating tryptophan metabolism.

/pdf/tryptophan-metabolism-as-bridge-between-gut-microbiota-and-6t8lumy2.pdf

Tryptophan metabolism as bridge between gut microbiota and brain in chronic social defeat stress-induced depression mice

Abstract Major diseases cause a double blow to patients' physical and mental health and family life and pose a great challenge to the healthcare system. The high incidence of major diseases compels us to constantly improve the medical prevention and treatment system to reduce disability and death rates as much as possible. Traditional Chinese medicine (TCM) has been widely used in the treatment of malignancies and cardiovascular and cerebrovascular diseases such as myocardial infarction and stroke, in the rehabilitation of patients with these diseases, as well as in the prevention and treatment of new outbreaks of infectious diseases and other major illnesses. After the coronavirus disease 2019 outbreak, the clinical application of “three prescriptions and three drugs” has greatly increased the cure rate, reduced the mortality rate, and provided a “Chinese solution” for global epidemic prevention and control. This article reviewed the clinical evidence and mechanisms of action of TCM in the prevention and treatment of major diseases, summarized the advances, and proposed future research directions to provide scientific evidence to expand the clinical application of TCM and improve its efficacy for the benefit of all humankind. 

Clinical evidence and mechanisms of traditional Chinese medicine in major diseases

Parkinson’s disease (PD) is a progressive, age-related neurodegenerative disease. The disease is characterized by the loss of dopaminergic neurons in the substantia nigra, pars compacta of the midbrain. Pramipexole (PPX) is a novel drug used for the treatment of PD. It has a high affinity for the dopamine (DA) D2 receptor subfamily and acts as a targeted mitochondrial antioxidant. It is less effective in the treatment of PD due to its short half-life, highly inconvenient dosing schedule, and long-term side effects. In recent years, PPX-loaded nanoformulations have been actively reported to overcome these limitations. In the current study, we focused on increasing the effectiveness of PPX by minimizing the dosing frequency and improving the treatment strategy for PD. Herein, we report the synthesis of biodegradable polyvinylpyrrolidone (PVP)-capped copper oxide nanoparticles (PVP–CuO NPs), followed by PPX anchoring on the surface of the PVP–CuO NPs (PPX–PVP–CuO NC), in a simple and inexpensive method. The newly formulated PPX–PVP–CuO NC complex was analyzed for its chemical and physical properties. The PPX–PVP–CuO NC was tested to protect against rotenone (RT)-induced toxicity in the Drosophila PD model. The in vivo studies using the RT-induced Drosophila PD model showed significant changes in negative geotaxis behavior and the level of DA and acetylcholinesterase. In addition, oxidative stress markers such as glutathione-S-transferase, total glutathione, thiobarbituric acid reactive species, and protein carbonyl content showed significant amelioration. The positive changes of PPX–PVP–CuO NC treatment in behavior, neurotransmitter level, and antioxidant level suggest its potential role in mitigating the PD phenotype. The formulation can be used for treatment or pharmacological intervention against PD.

Polyvinylpyrrolidone-Capped Copper Oxide Nanoparticles-Anchored Pramipexole Attenuates the Rotenone-Induced Phenotypes in a Drosophila Parkinson’s Disease Model

Background: Parkinson disease (PD) is the second most common neurodegenerative disease, which has impacts on the patient’s quality of life due to non-motor symptoms such as sleep disorders, anxiety, and depression. Traditional Chinese medicine (TCM) has gained increasing attention in the diagnosis and treatment of PD with the concept of “overall concepts and dialectical treatment.” Therefore, exploring the characteristics of TCM in the treatment of PD can improve the level of diagnosis and treatment of PD. Methods: A comprehensive literature search was conducted using the following electronic databases: PubMed, Web of Science, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure. The inclusion criteria were randomized controlled trials (RCTs) that compared TCM intervention with conventional treatments or placebo for non-motor symptoms in PD. The quality of the included RCTs was assessed using the Cochrane risk of bias tool. Results: A total of 9 RCTs involving 1714 participants with PD were included in this systematic review and meta-analysis. The meta-analysis showed that TCM was effective in improving non-motor symptoms, including depression (Hamilton depression rating scale [HAMD], weighted mean difference [WMD] = 4.24, 95% CI = 2.84–5.65, P < .0001), anxiety (HAMA, WMD = 4.03, 95% CI = 2.64–5.41, P < .0001), autonomic dysfunction (Scales for Outcomes in Parkinson’s disease–Autonomic, WMD = 4.57, 95% CI = 1.69–7.45, P = .002), non-motor symptoms (Movement Disorder Society-Unified Parkinson’s Disease Rating Scale-part 1, WMD = 0.66, 95% CI = 0.20–1011, P = .004), and quality of life (PDQ-39, WMD = 6.72, 95% CI = 0.87–12.58, P < .05), compared with baseline. Zishen Pingchan granules was particularly effective for depression (HAMD, WMD = −1.94, 95% CI = −3.07 to −0.81, P < .001, compared to placebo; HAMD, WMD = 3.40, 95% CI = 0.52–6.28, P < .05, after treatment). Pingchan granules was particularly effective for quality of life after treatment (PDQ-39, WMD = 10.20, 95% CI = 1.87−18.53, P < .05). Conclusions: TCM is effective and safety for improvement of depression, anxiety, autonomic dysfunctions, and quality of life in PD. Zishen Pingchan granules was particularly effective for depression; and Pingchan granules was particularly effective for quality of life.

Traditional Chinese Medicine for non-motor symptoms in Parkinson disease: A systematic review and meta-analysis of RCTs

Parkinson's Disease and the Microbiota-Gut-Brain Axis: Metabolites, Mechanisms, and Innovative Therapeutic Strategies Targeting the Gut Microbiota

Abstract 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 

/pdf/zishen-pingchan-granules-combined-with-pramipexole-in-the-34job7mj.pdf

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

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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