====== Natural product ======

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In a [[review]] article (mechanistic overview on mitochondrial regulation by natural products)  
Qin et al.  
from the Qingdao Medical College & Qingdao University, Pharmaceutical University, Nanjing  
published in the [[Neural Regeneration Research]] journal 
to summarize how natural products modulate mitochondrial dysfunction (biogenesis, dynamics, transport, mitophagy, apoptosis, oxidative stress) for [[stroke treatment]], and identify barriers to [[clinical translation]].  
Natural products act via multi-target mechanisms on mitochondrial processes to exert [[neuroprotection]] in both ischemic and [[hemorrhagic stroke]] models, but [[clinical translation]] is impeded by product complexity, [[lack of standardization]], insufficient multicenter data, and unclear long-term safety. Future directions include advanced technologies (single-cell sequencing, organoid models) and multicenter trials
((Qin N, Liu R, Deng R, Shi L, Wang L, Zhu T. Modulation of [[mitochondrial dysfunction]]: Mechanisms and strategies for the use of [[natural product]]s to treat [[stroke]]. Neural Regen Res. 2025 Jul 5. doi: 10.4103/NRR.NRR-D-25-00016. Epub ahead of print. PMID: 40618255.)).

===== Critical review =====

*✅ Strengths*  
  * Comprehensive mechanistic mapping: the article clearly organizes effects into six mitochondrial regulatory domains and links specific natural compounds (e.g., Cordyceps, ginsenosides, Gypenoside XVII, Ginkgolide K, Scutellarin, Chrysophanol) to distinct pathways of protection.  
  * Provides molecular insights: for instance, Cordyceps activates PGC‑1α/NRF‑1 to enhance biogenesis; Gypenoside XVII activates PINK1/Parkin mitophagy to protect the BBB.  
  * Identifies translational challenges—standardization issues, safety gaps, and absent systemic trials are analyzed realistically, demonstrating awareness of clinical hurdles.

*❌ Weaknesses*  
  * Lacks summary of methodological rigor: no discussion of dosage, sample sizes, or statistical quality of cited in‑vivo/in‑vitro studies.  
  * Minimal critical evaluation: the review treats molecular mechanisms as established without weighing conflicting data or study bias.  
  * Omits pharmacokinetic/toxicology details: crucial for natural products, but not addressed.

===== Rating =====

**Score: 7/10** – Strong mechanistic organization and translational awareness, but limited methodological critique and insufficient attention to pharmacokinetics and evidence quality.

===== Takeaway for practicing neurosurgeon =====

Natural compounds show multi-faceted neuroprotection via mitochondrial modulation in animal/stem cell stroke models. However, they are not yet ready for clinical use due to regulatory, safety, and reproducibility gaps. Neurosurgeons should await human data before considering these agents.

===== Bottom line =====

A well-structured mechanistic review that identifies promising mitochondrial-targeting natural products, but lacks [[rigorous evaluation]] of experimental quality and clinical feasibility—future translational efforts are needed.