Regulation of mitophagy and mitochondrial function: Natural compounds as potential therapeutic strategies for Parkinson's disease.

Mitochondrial damage is associated with the development of Parkinson's disease (PD), indicating that mitochondrial-targeted treatments could hold promise as disease-modifying approaches for PD. Notably, natural compounds have demonstrated the ability to modulate mitochondrial-related processes. In this review article, we discussed the possible neuroprotective mechanisms of natural compounds against PD in modulating mitophagy and mitochondrial function. A comprehensive literature search on natural compounds related to the treatment of PD by regulating mitophagy and mitochondrial function was conducted from PubMed, Web of Science and Chinese National Knowledge Infrastructure databases from their inception until April 2023. We summarize recent advancements in mitophagy's molecular mechanisms, including upstream and downstream processes, and its relationship with PD-related genes or proteins. Importantly, we highlight how natural compounds can therapeutically regulate various mitochondrial processes through multiple targets and pathways to alleviate oxidative stress, neuroinflammation, Lewy's body aggregation and apoptosis, which are key contributors to PD pathogenesis. Unlike the single-target strategy of modern medicine, natural compounds provide neuroprotection against PD by modulating various mitochondrial-related processes, including ameliorating mitophagy by targeting the PINK1/parkin pathway, the NIX/BNIP3 pathway, and autophagosome formation (i.e., LC3 and p62). Given the prevalence of mitochondrial damage in various neurodegenerative diseases, exploring the exact mechanism of natural compounds on mitophagy and mitochondrial dysfunction could shed light on the development of highly effective disease-modifying or adjuvant therapies targeting PD and other neurodegenerative disorders.

Demyelinating diseases of the central nervous system registry for patients with traditional Chinese medicine: Rationale and design of a prospective, multicenter, observational study.

Background: Traditional Chinese medicine (TCM), a main form of complementary and alternative medicine provides a potential possibility for demyelinating disease of the central nervous system (DDC) management and has been applied in considerable amounts of patients with this disorder. Nevertheless, powerful real-world evidences regarding the epidemiological and clinical characteristics, safety, and outcomes of TCM in DDC are lacking. The primary objective of the Demyelinating Diseases of the Central Nervous System Registry for Patients with Traditional Chinese Medicine (DATE-TCM) is to create an organized multicenter data collection structure to define integrative characteristics of DDC patients treated with TCM in an endeavor to fill these knowledge gaps to better inform clinical care and health policy. Method: This study provides a prospective and voluntary registry by using a web-based system. Baseline data will be recorded and subsequently regular follow-up visits will be implemented every 3-6 months for a total of 5 years. The primary outcome is Annualized Aggregate Relapse Rate at 5-year follow-up. Results: DATE-TCM is currently designed to capture the multidimensional (epidemiologic, demographic, clinical, etc.) features of DDC patients receiving TCM treatment, the type and long-term safety and efficacy of TCM intervenes in the DDC populations, as well as the interaction of TCM treatments and disease modifying therapies in the management of DDC, aiming to include 2000 eligible adult DDC patients with TCM intervenes from 35 participating centers, covering 77.4% of provincial administrative regions of mainland China. Conclusion: DATE-TCM is the first, largest, most geographically extensive, and standard registry-based observational study that systematically document the real-world data regarding the TCM application in the DDC populations, which will be extraordinarily important for clarifying the comprehensive characteristics and outcomes of TCM in DDC, further shed light on standardizing and optimizing the TCM measures for DDC management and establishing evidence-based clinical practice guidelines for TCM application in DDC.

China amyotrophic lateral sclerosis registry of patients with Traditional Chinese Medicine (CARE-TCM): Rationale and design.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has become popular interventional treatment for amyotrophic lateral sclerosis (ALS). However, lack of knowledge about the general characteristics and long-term clinical outcomes hampers the development of herbal drugs for ALS. AIM OF THE STUDY: The China Amyotrophic Lateral Sclerosis Registry of Patients with Traditional Chinese Medicine (CARE-TCM) provides an opportunity to better understand which TCM interventions patients with ALS are receiving, what the characteristics of patients with ALS are, and how these interventions impact clinical measures. MATERIALS AND METHODS: This study includes a voluntary nationwide registry, and data will be collected prospectively using an electronic data system. Detailed data collection will be performed every 3 months for 5 years. Baseline characteristics and 5-year survival will be collected. This registry was initiated in March 2021. The number of participating medical centers will be about 30 hospitals, and the target procedure number will be 2000. We will also compare the results with those of other registries in China and other countries. DISCUSSION: The CARE-TCM registry will first provide real-world data regarding TCM and ALS in China, focusing on the clinical characteristics of ALS patients with TCM, disease phenotypes that respond best to TCM, and correlating clinical response with other parameters. The CARE-TCM can be very helpful to improve the efficiency and quality of TCM clinical trial design. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04885374 (registered on May 8, 2021).

Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, in the pathogenesis of which oxidative stress (OS) was believed to play a key role. Shenqi Fuzheng Injection (SFI) concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis and Radix Astragali, was proven to be eligible to reduce the OS injury and increase the activity of the nuclear factor-erythroid-2-related factor 2 (Nrf2) pathway, an antioxidant enzymes inducer. Objective: We aim to investigate the effects and potential mechanisms underlying the action of SFI on a well-established transgenic mouse model of ALS. Methods: Transgenic SOD1-G93A mice were intraperitoneally injected with SFI (40 ml/kg) three times a week from 87 days of age. Motor function, survival, pathological manifestations in the brain, and Nrf2 pathway-related assessments of the mice were performed. Results: SFI treatment efficiently postponed the disease onset (p = 0.022) and extended the overall survival (p = 0.038) of the SOD1-G93A mice. Moreover, SFI significantly reduced motor neuron loss (p < 0.001) and astrocytic activation (p < 0.05) in the motor cortex of the brain of SOD1-G93A mice at 130 days of age. The protective effects of SFI in the SOD1-G93A mice were associated with decreasing the level of malondialdehyde (p < 0.05) and increasing the levels of superoxide dismutase (p < 0.05), Nrf2 (p < 0.05), heme oxygenase-1 (p < 0.05), and glutathione S-transferase (p < 0.05) in the SOD1-G93A mice. Conclusion: The SFI treatment efficiently extended the overall survival and improved the pathological manifestations of the brain via alleviating the OS injury and activating the Nrf2 pathway in the animal model of ALS, which made SFI a potentially promising candidate for ALS treatment.

Biomedical Teleacupuncture between China and Austria Using Heart Rate Variability, Part 1: Poststroke Patients.

Background. Acupuncture has been reported to affect the human autonomic system. Within this pilot study, teleacupuncture between China and Austria is used for the first time for quantifying the effects of heart rate variability (HRV) in poststroke rehabilitation. Methods. In 29 Chinese post-stroke patients (15 f, 14 m; mean age ± SD 64.7 ± 11.3 years; range 40-80 years) electrocardiographic signals before, during, and after acupuncture at the acupoint Tongli (HT 5) were recorded in Harbin and analyzed in Graz using teleacupuncture via internet. HRV data were analyzed in the time and frequency domain, and a protocol from Austria was sent to the team in China immediately after the treatment and recording session. Results. Acupuncture does not change heart rate in the post-stroke patients; however, total HRV increased significantly (P < .05) during and 5-10 minutes after acupuncture. In addition, balance between sympathetic and parasympathetic activity (low frequency/high frequency HRV ratio) changes markedly during treatment. Conclusions. Based on innovative HRV analysis, it could be demonstrated that teleacupuncture between China/Harbin and Austria/Graz over a distance of about 8,500 km is no longer a future vision; it has become reality.