Real-world Chinese herbal medicine for Parkinson's disease: a hospital-based retrospective analysis of electronic medical records.

Background: Parkinson's disease (PD) is a progressive neurodegenerative condition. Chinese medicine therapies have demonstrated effectiveness for PD in controlled settings. However, the utilization of Chinese medicine therapies for PD in real-world clinical practice and the characteristics of patients seeking these therapies have not been thoroughly summarized. Method: The study retrospectively analyzed initial patient encounters (PEs) with a first-listed diagnosis of PD, based on electronic medical records from Guangdong Provincial Hospital of Chinese Medicine between July 2018 and July 2023. Results: A total of 3,206 PEs, each corresponding to an individual patient, were eligible for analyses. Approximately 60% of patients made initial visits to the Chinese medicine hospital after receiving a PD diagnosis, around 4.59 years after the onset of motor symptoms. Over 75% of the patients visited the Internal Medicine Outpatient Clinic at their initial visits, while a mere 13.85% visited PD Chronic Care Clinic. Rest tremor (61.98%) and bradykinesia (52.34%) are the most commonly reported motor symptoms, followed by rigidity (40.70%). The most commonly recorded non-motor symptoms included constipation (31.88%) and sleep disturbance (25.27%). Integration of Chinese medicine and conventional medicine therapies was the most common treatment method (39.15%), followed by single use of Chinese herbal medicine (27.14%). The most frequently prescribed herbs for PD included Glycyrrhiza uralensis Fisch. (gan cao), Astragalus mongholicus Bunge (huang qi), Atractylodes macrocephala Koidz. (bai zhu), Angelica sinensis (Oliv.) Diels (dang gui), Rehmannia glutinosa (Gaertn.) DC. (di huang), Paeonia lactiflora Pall. (bai shao), Bupleurum chinense DC. (chai hu), Citrus aurantium L. (zhi qiao/zhi shi/chen pi), Panax ginseng C. A. Mey. (ren shen), and Poria cocos (Schw.) Wolf (fu ling). These herbs contribute to formulation of Bu zhong yi qi tang (BZYQT). Conclusion: Patients typically initiated Chinese medical care after the establishment of PD diagnosis, ~4.59 years post-onset of motor symptoms. The prevalent utilization of CHM decoctions and patented Chinese herbal medicine products, underscores its potential in addressing both motor and non-motor symptoms. Despite available evidence, rigorous clinical trials are needed to validate and optimize the integration of CHM, particularly BZYQT, into therapeutic strategies for PD.

Real-world observations and impacts of Chinese herbal medicine for migraine: results of a registry-based cohort study.

Background: Migraine is a prevalent, recurrent condition with substantial disease burden. Chinese herbal medicine (CHM) has been used frequently for migraine in controlled clinical settings. This study is to summarise the characteristics of patients who seek clinical care in a tertiary Chinese medicine hospital in China; to gather their preferences and values of using CHM; to explore the effect of CHM for migraine and its comorbidities in a real-world setting, and to collect first-hand expertise of clinicians' practice pattern in prescribing CHM for migraine. Methods: This registry-based cohort study was prospectively conducted at Guangdong Provincial Hospital of Chinese Medicine from December 2020 to May 2022. Adult migraine patients seeking their initial anti-migraine clinical care at the hospital were consecutively recruited and followed up for 12 weeks. Practitioners specialised in headache management prescribed individualised treatments without research interference. Standardised case report forms were employed to gather information on patients' preferences and perspective of seeking clinical care, as well as to assess participants' migraine severity, comorbidities, and quality of life, at 4-weeks intervals. Various analytical methods were utilised based on the computed data. Results: In this study, we observed 248 participants. Of these, 73 received CHM treatment for 28 days or longer. Notably, these participants exhibited a greater disease severity, compared to those treated with CHM for less than 28 days. Of the 248 participants, 83.47% of them expected CHM would effectively reduce the severity of their migraine, around 50% expected effects for migraine-associated comorbidities, while 51.61% expressing concerns about potential side effects. CHM appeared to be effective in reducing monthly migraine days and pain intensity, improving patients' quality of life, and potentially reducing comorbid anxiety, with a minimum of 28 days CHM treatment. Herbs such as gan cao, gui zhi, chuan xiong, fu ling, bai zhu, yan hu suo, etc. were frequently prescribed for migraine, based on patients' specific symptoms. Conclusion: CHM appeared to be beneficial for migraine and comorbid anxiety in real-world clinical practice when used continuously for 28 days or more. Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR2000041003.

Prokinetic effects of Citrus reticulata and Citrus aurantium extract with/without Bupleurum chinense using multistress-induced delayed gastric emptying models.

CONTEXT: Citrus aurantium L (Rutaceae) (Au) and Citrus reticulata Blanco (Rutaceae) (Ci) are commonly used as couplet prokinetics and Bupleurum chinense DC. (Umbelliferae) (Bup) is an herbal antidepressant in traditional Chinese medicine. OBJECTIVE: This study evaluates the synergistic prokinetic effects of Bup with Au and Ci in mice suffering from multistress-induced delayed gastric emptying (DGE). MATERIALS AND METHODS: Kunming mice were divided into four groups: control, DGE, AuCi and AuCiBup. Mice were gavaged with AuCi (14.25 g/kg) or AuCiBup (22.13 g/kg) extract for 12 days. Gastric reminder rate, intestinal driving ratio, sucrose preference and open field test were examined, and serotonin (5-HT), motilin (MTL), substance P (SP), 5-HT4R and c-kit were assayed. Intracellular Ca2+ levels in primary cultured gastric smooth muscle cells (GSMCs) were determined. RESULTS: Both AuCi and AuCiBup treatment significantly reduced gastric residual rate (39.5% and 67.7%, p < 0.01). Higher serum levels of 5-HT, MTL and SP were observed in treatment groups (AuCi: 0.060 mg/L, AuCiBup: 0.089 mg/L, DGE: 0.025 mg/L, p < 0.01). The expression of 5-HT4R and c-kit in the antrum and duodenum was upregulated after treatment (AuCi and AuCiBup, 4.3-times, 2.8-times to DGE, p < 0.01). Medicated serums of AuCi and AuCiBup effectively increased the influx of Ca2+ into GSMCs in vitro (1.8-times, p < 0.01). In terms of 5-HT4R expression, circulatory contents of 5-HT and SP and Ca2+ influx, AuCiBup demonstrated better prokinetic effects than AuCi. CONCLUSIONS: These findings indicate the potential for developing combination therapy with antidepressants and prokinetics in gastrointestinal dysmotility management.

Gut bacterial profiles in Parkinson's disease: A systematic review.

INTRODUCTION: Recent advances have highlighted the relationships between gut dysbiosis and Parkinson's disease (PD). Microbiota transplantation from PD patients to mice can induce increased alpha-synuclein-mediated motor deficits. Human studies have identified differences in the gut microbiota of PD patients compared to healthy controls. We undertook a systematic review to evaluate the available evidence for the involvement of gut bacteria in the etiology of PD. METHODS: The PubMed databank, the China National Knowledge Infrastructure databank, and Wanfang Data were searched from inception until June 2021 to identify human case-control studies that investigated relationships between PD and microbiota quantified from feces. We evaluated the resulting studies focusing on bacterial taxa that were different between PD patients and healthy controls. RESULTS: Twenty-six studies were found in which 53 microbial families and 98 genera exhibited differences between patients with PD and healthy controls. The genera identified by more than two studies as increased in PD were Bifidobacterium, Alistipes, Christensenella, Enterococcus, Oscillospira, Bilophila, Desulfovibrio, Escherichia/Shigella, and Akkermansia, while Prevotella, Blautia, Faecalibacterium, Fusicatenibacter, and Haemophilus had three or more reports of being lower in PD patients. More than one report demonstrated that Bacteroides, Odoribacter, Parabacteroides, Butyricicoccus, Butyrivibrio, Clostridium, Coprococcus, Lachnospira, Lactobacillus, Megasphaera, Phascolarctobacterium, Roseburia, Ruminococcus, Streptococcus, and Klebsiella were altered in both directions. CONCLUSION: Our review shows that the involvement of the gut microbiome in the etiology of PD may involve alterations of short-chain fatty acids (SCFAs)-producing bacteria and an increase in putative gut pathobionts. SCFAs-producing bacteria may vary above or below an "optimal range," causing imbalances. Considering that Bifidobacterium, Lactobacillus, and Akkermansia are beneficial for human health, increased Bifidobacterium and Lactobacillus in the PD gut microbiome may be associated with PD medications, especially COMT inhibitors, while a high level of Akkermansia may be associated with aging.

Oral, Nasal, and Gut Microbiota in Parkinson's Disease.

Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease. The purpose of this study was to investigate the link between microbiota composition in important mucosal interfaces (oral, nasal, and intestinal) and PD. Sequencing was undertaken of the V4-V5 region of the 16S ribosomal RNA (rRNA) gene of the microbiome from the oral cavity, nasal cavity, and gut of 91 PD patients and 91 healthy controls. Significant differences were found in microbiota composition in the oral cavity and gut, but not the nasal cavity, between PD patients and healthy controls after adjusting for age, gender, and body mass index (BMI). More genera in the oral cavity were significantly positively correlated with clinical characteristics, such as the HAMA and HAMD rating scales. The taxa c_Clostridia, o_Clostridiales, and f_Ruminococcaceae in the gut microbiota were associated with weight and MMSE score. Furthermore, as a result of dysbiosis, there was an enrichment of ion channel-, oxidative phosphorylation-, and carbohydrate metabolism-related pathways in the oral cavity and glycolysis/gluconeogenesis- and propanoate metabolism-related pathways in the intestine. Changes in these pathways can influence metabolism and inflammation, thereby contributing to PD pathogenesis. In addition, several subnetworks containing differentially abundant microbiota in the oral cavity and gut samples from PD patients may regulate microbial composition and function in PD. Overall, our results indicate that oral and gut dysbiosis may affect PD progression and provide a basis for understanding the pathogenesis of PD and identifying potential therapeutic targets for the treatment of this disease.

Altered Actinobacteria and Firmicutes Phylum Associated Epitopes in Patients With Parkinson's Disease.

Recent evidence suggests that inflammation was participated in the pathogenesis of PD, thus, to understand the potential mechanism of gut microbiota in the pathogenesis of Parkinson's disease (PD), we performed a metagenomic analysis of fecal samples from PD patient and controls. Using a two-stage metagenome-wide association strategy, fecal DNA samples from 69 PD patients and 244 controls in three groups (comprising 66 spouses, 97 age-matched, and 81 normal samples, respectively) were analyzed, and differences between candidate gut microbiota and microbiota-associated epitopes (MEs) were compared. In the study, 27 candidate bacterial biomarkers and twenty-eight candidate epitope peptides were significantly different between the PD patients and control groups. Further, enriched 4 and 13 MEs in PD were positively associated with abnormal inflammatory indicators [neutrophil percentage (NEUT.1), monocyte count/percentage (MONO/MONO.1), white blood cell count (WBC)] and five candidate bacterial biomarkers (c_Actinobacteria, f_Bifidobacteriaceae, g_Bifidobacterium, o_Bifidobacteriales, p_Actinobacteria) from Actinobacteria phylum, and they were also positively associated with histidine degradation and proline biosynthesis pathways, respectively. Additionally, enriched 2 MEs and 1 ME in PD were positively associated with above inflammatory indicators and two bacteria (f_Lactobacillaceae, g_Lactobacillus) from Firmicutes phylum, and they were also positively associated with pyruvate fermentation to propanoate I and negatively associated with isopropanol biosynthesis, respectively. Of these MEs, two MEs from GROEL2, RPSC were derived from Mycobacterium tuberculosis, triggered the T cell immune response, as previously reported. Additionally, other candidate epitope peptides derived from Mycobacterium tuberculosis and Mycobacterium leprae may also have potential immune effects in PD. In all, the altered MEs in PD may relate to abnormalities in immunity and glutamate and propionate metabolism, which furthers our understanding of the pathogenesis of PD.

Rules of Meridians and Acupoints Selection in Treatment of Parkinson's Disease Based on Data Mining Techniques.

OBJECTIVE: To help selecting appropriate meridians and acupoints in clinical practice and experimental study for Parkinson's disease (PD), the rules of meridians and acupoints selection of acupuncture and moxibustion were analyzed in domestic and foreign clinical treatment for PD based on data mining techniques. METHODS: Literature about PD treated by acupuncture and moxibustion in China and abroad was searched and selected from China National Knowledge Infrastructure and MEDLINE. Then the data from all eligible articles were extracted to establish the database of acupuncture-moxibustion for PD. The association rules of data mining techniques were used to analyze the rules of meridians and acupoints selection. RESULTS: Totally, 168 eligible articles were included and 184 acupoints were applied. The total frequency of acupoints application was 1,090 times. Those acupoints were mainly distributed in head and neck and extremities. Among all, Taichong (LR 3), Baihui (DU 20), Fengchi (GB 20), Hegu (LI 4) and Chorea-tremor Controlled Zone were the top five acupoints that had been used. Superior-inferior acupoints matching was utilized the most. As to involved meridians, Du Meridian, Dan (Gallbladder) Meridian, Dachang (Large Intestine) Meridian, and Gan (Liver) Meridian were the most popular meridians. CONCLUSIONS: The application of meridians and acupoints for PD treatment lay emphasis on the acupoints on the head, attach importance to extinguishing Gan wind, tonifying qi and blood, and nourishing sinews, and make good use of superior-inferior acupoints matching.

YY1 promotes IL-6 expression in LPS-stimulated BV2 microglial cells by interacting with p65 to promote transcriptional activation of IL-6.

Neuroinflammation plays a critical role in the process of neurodegenerative disorders, during which microglia, the principal resident immune cells in the central nervous system, are activated and produce proinflammatory mediators. Yin-Yang 1 (YY1), a multi-functional transcription factor, is widely expressed in cells of the immune system and participate in various cellular processes. However, whether YY1 is involved in the process of neuroinflammation is still unknown. In the present study, we found that YY1 was progressively up-regulated in BV2 microglial cells stimulated with lipopolysaccharide (LPS), which was dependent on the transactivation function of nuclear factor kappa B (NF-κB). Furthermore, YY1 knockdown notably inhibited LPS-induced the activation of NF-κB signaling and interleukin-6 (IL-6) expression in BV-2 cells, but not mitogen-activated protein kinase (MAPK) signaling. Moreover, YY1 strengthened p65 binding to IL-6 promoter by interacting with p65 but decreased H3K27ac modification on IL-6 promoter, eventually increasing IL-6 transcription. Taken together, these results for the first time uncover the regulatory mechanism of YY1 on IL-6 expression during neuroinflammation responses and provide new lights into neuroinflammation.

Mitochondria-Associated Apoptosis in Human Melanoma Cells Induced by Cardanol Monoene from Cashew Nut Shell Liquid.

Cardanol monoene (CM) is the major phenolic component extracted from cashew nut shell liquid (CNSL), which has been relevant to wide range of biological effects. In this study, we found that CM could inhibit the M14 human melanoma cells proliferation in a dose dependent and time dependent manner, and the IC50 values were determined to be 23.15 ± 2.42 µM and 12.30 ± 1.67 µM after 24 and 48 h treatment, respectively. The flow cytometric analysis demonstrated that CM induced M14 cell cycle arrest at the S phase, along with the collapse of mitochondrial membrane potential (ΔΨm) and the accumulation of reactive oxygen species (ROS) level in cells, but the apoptotic cells reduced when treated with Z-VAD-FMK (pan-caspase inhibitor). Western blotting showed that the expressions of p53, cytosol cytochrome C, cleaved-caspase-3, and cleaved-PARP were up-regulated, and the expression level of Bax/Bcl-2 ratio increased significantly. The 2527 significant differentially expressed genes were obtained by RNA-seq, which were assigned to 270 KEGG pathways. These results indicated that CM induced M14 cells apoptosis via the ROS triggered mitochondrial-associated pathways, which supports the potential application of CM for the therapy of melanoma cancer.

[Pathogenesis of Parkinson's Disease Viewing from Modern Chinese Medicine].

Modern pathological studies of Parkinson's disease. (PD) reveal that 70% -80% sub- stantia nigra striatum nerve endings degenerate before -motor symptoms occur. But till now, Chinese medicine (CM) infers its pathogeneses still at the theoretical level. Braak H, et al. raised six pathological stages of PD. They also beleived that symptoms of PD occurred one by one acocrding to staging sequence. All these indicated important evidence for the developing process of PD's pathogenesis. Authors expounded modern CM pathogenesis of PD.

Honokiol suppresses renal cancer cells' metastasis via dual-blocking epithelial-mesenchymal transition and cancer stem cell properties through modulating miR-141/ZEB2 signaling.

Renal cell carcinoma (RCC) is associated with a high frequency of metastasis and only few therapies substantially prolong survival. Honokiol, isolated from Magnolia spp. bark, has been shown to exhibit pleiotropic anticancer effects in many cancer types. However, whether honokiol could suppress RCC metastasis has not been fully elucidated. In the present study, we found that honokiol suppressed renal cancer cells' metastasis via dual-blocking epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties. In addition, honokiol inhibited tumor growth in vivo. It was found that honokiol could upregulate miR-141, which targeted ZEB2 and modulated ZEB2 expression. Honokiol reversed EMT and suppressed CSC properties partly through the miR-141/ZEB2 axis. Our study suggested that honokiol may be a suitable therapeutic strategy for RCC treatment.