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RESEARCH PAPER ANALYSIS

Research progress on employing medicinal plants and their active compounds to target autophagic pathways for Parkinson's disease therapy.

Systematic review of medicinal plants and their active compounds that target autophagy in Parkinson's disease, summarizing preclinical evidence for multi-target neuroprotective effects while noting limited mechanistic validation and a lack of rigorous clinical trials.

PMID41895540
JournalJournal of ethnopharmacology
Publication Date2026-06-28
Ingested2026-04-28 08:58 PM
EXECUTIVE SUMMARY

What the AI sees

Systematic review of medicinal plants and their active compounds that target autophagy in Parkinson's disease, summarizing preclinical evidence for multi-target neuroprotective effects while noting limited mechanistic validation and a lack of rigorous clinical trials.

WHY IT MATTERS

Research significance

Emphasizes autophagy modulation and related anti-inflammatory/antioxidant mechanisms as promising translational avenues and flags specific gaps—target specificity, toxicity, standardization, and need for mechanistic and clinical validation—that are critical for prioritizing plant-derived leads for…

ABSTRACT

Source abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) significantly affects patients' quality of life. Natural plant therapies, characterized by holistic, multi-target regulatory effects, have demonstrated unique value in managing complex diseases, particularly through regulating autophagy, inhibiting neuroinflammation, and reducing oxidative stress. Combined with their favourable safety profile-especially lower hepatotoxicity and nephrotoxicity-they represent an important direction in anti-PD drug development. AIM OF THE REVIEW: This review systematically examines the ethnopharmacological applications of natural plants that regulate autophagy in PD treatment, summarizing current progress and challenges to inform traditional Chinese medicine (TCM) modernization and anti-PD drug development. METHODS: This study investigates natural herbal therapies for PD, focusing on their regulatory mechanisms of autophagy. Primary sources included traditional medical classics and ethnomedicinal literature, supplemented by data from online databases such as PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, and Wanfang. A systematic search was conducted using keywords including "PD," "autophagy," "regulatory mechanisms," "medicinal plants," "TCM compound preparations," "single herbal extracts," and "active compounds" to identify relevant studies published in recent years. Original research articles (in vitro, in vivo, or clinical) and high-quality reviews with mechanistic data involving autophagy in PD were included. Topical-independent literature, thesis, conference abstracts, books, case reports, and commentaries were excluded. Only articles published in English or Chinese were considered. RESULTS: Incorporating medicinal plants into PD management offers significant advantages in multi-target regulation and safety. However, a critical examination reveals several complexities. While modulating multiple autophagy-related pathways provides a theoretical advantage over single-target drugs, this broad-spectrum activity raises concerns about target specificity and off-target effects, which remain poorly characterized. Current evidence largely relies on correlational observations rather than direct mechanistic validation, leaving uncertainty about whether these compounds genuinely engage key autophagy targets under physiological conditions. Regarding safety, although centuries of traditional use of TCM compound preparations imply tolerability, assuming medicinal plants are inherently safer than Western drugs is problematic, as many constituents exhibit dose-dependent toxicity, and the lack of rigorous long-term trials limits generalizability. Furthermore, the prevailing reductionist approach-isolating active components for mechanistic studies-may overlook synergistic interactions inherent in herbal formulations, thus failing to capture their full therapeutic potential. Bridging traditional knowledge and modern evidence-based medicine requires not only advanced target identification techniques but also a holistic framework that respects herbal therapy's foundations while subjecting it to the same scientific scrutiny as conventional treatments. CONCLUSIONS: Although medicinal plants have garnered considerable attention for the treatment of PD, claims of their "significant clinical efficacy" should be approached with caution. Current evidence is primarily derived from basic research or observational studies and lacks validation through rigorous randomized controlled trials. Moreover, while autophagy regulation remains a prominent area of research, the multi-component and multi-target nature of compound formulations means their mechanisms cannot be explained by a single pathway. The transition from traditional use to evidence-based treatment continues to face challenges, including standardization, quality control, and dosage optimization. Therefore, although medicinal plants show potential, their therapeutic value must be confirmed through more rigorous methodologies and large-scale clinical trials.

SUPPORTING PAPER SET

32 more papers to review

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1 The cGAS-STING-Glymphatic-gut Axis in Parkinson's disease: A proposed self-amplifying triad of Neuroinflammation and therapeutic opportunity. International immunopharmacology 91.0 2 Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications. Cells 91.0 3 Flavonoids improve neurotransmitters for Parkinson's treatment: mechanism and therapeutic potential. Frontiers in pharmacology 88.0 4 Alpha-Lipoic Acid and Biotin in Neurodegenerative Diseases: Convergent Mechanistic Insights from Preclinical Models to Clinical Perspectives. Neurology international 78.0 5 The Gut Microbiota in Parkinson's Disease: Mechanistic Insights into Microbial-Host Interactions. Microorganisms 85.0 6 Linking inflammation, metabolic dysfunction, and neurodegeneration: a comprehensive review of TLR2 pathways in type 2 diabetes. 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B, Biointerfaces 86.0 13 Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases. Experimental physiology 84.0 14 Flavonoid Rutin Reduces Intestinal Inflammation in an Experimental Model of Parkinson's Disease. Neurotoxicity research 70.0 15 Nanostructured Lipid Carriers Enhance Brain Delivery and Antioxidant Efficacy of a Small-Molecule MAO B Inhibitor for Neurodegenerative Disease Therapy. Molecular pharmaceutics 78.0 16 Pathophysiological Role of the Gut Brain Axis in Parkinson's Disease: From Microbial Metabolites and Intestinal Permeability to Central Neuroinflammation. Current neurovascular research 86.0 17 Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review. Current issues in molecular biology 86.0 18 Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders. Neuroprotection (Chichester, England) 76.0 19 Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Computers in biology and medicine 65.0 20 Models of neuroprotection in Parkinson's disease: Exploring cellular, molecular, and microenvironmental targets. Experimental neurology 78.0 21 Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy. Frontiers in pharmacology 75.2 22 Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy. Frontiers in pharmacology 75.0 23 Lipid droplets in neurodegenerative diseases: pathological drivers and therapeutic vulnerabilities. Cell death discovery 82.0 24 Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions. Frontiers in microbiology 74.0 25 Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review. Biomolecules & biomedicine 84.0 26 Neurosyphilis and Parkinsonism: Overlapping Pathophysiology and Emerging Therapeutic Insights. Current neurovascular research 76.0 27 Molecular biochemistry of soluble epoxide hydrolase in lipid mediator pathways and neuroinflammatory responses. The Journal of steroid biochemistry and molecular biology 82.0 28 Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential. Cell stress 83.3 29 Neuroprotective Role of Exercise-based Physiotherapy Combined with Pharmacological Agents in Parkinson's Disease. Central nervous system agents in medicinal chemistry 64.0 30 Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder. Signal transduction and targeted therapy 84.0 31 HMGB1-mediated neuroinflammation: molecular mechanisms and emerging therapeutic approaches. Inflammopharmacology 78.0 32 Beyond acid-base dyshomeostasis: Dynamic instability of neuronal lysosomal pH as a pathogenic mechanism and therapeutic target in neurological diseases. Biochemical pharmacology 88.0
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