Polygala tenuifolia

Polygala tenuifolia (family Polygalaceae) is a perennial herb native to East Asia, especially China, Korea, and Japan. Its dried root (commonly called “Yuán Zǐ”) has been used for centuries in traditional Chinese medicine as a “brain‑tonic” that supports mental function, mood, and overall vitality. Modern research focuses on its neuro‑protective and anti‑inflammatory properties, which underpin its use in contemporary nutraceuticals.

• Cognitive support: Randomized‑controlled trials (RCTs) in healthy adults and in mild cognitive impairment show improvements in learning, memory, and attention after 4–12 weeks of standardized Polygala extracts (10–30 mg saponin equivalent).
• Neuro‑protection: In vivo rodent studies demonstrate reduced neuronal loss in models of ischemic stroke and Alzheimer‑type pathology, linked to reduced oxidative stress and inflammation.
• Mood and stress: Clinical pilot studies report reduced depressive‑like scores and lower cortisol after 8 weeks of 300 mg/day of Polygala extract, suggesting anxiolytic activity.
• Anti‑fatigue & physical performance: Animal studies show increased endurance and reduced lactate accumulation during exercise, likely via enhanced mitochondrial function.
• Metabolic modulation: Preliminary human data suggest modest improvements in fasting glucose and lipid profiles, possibly through modulation of the AMPK pathway.

Polygala tenuifolia contains bioactive saponins (e.g., polygalasaponins), flavonoids (e.g., quercetin‑3‑O‑glucoside), and oligosaccharide‑based polysaccharides.

• Key actions:
  • The key saponin “tenuifolin” binds to the N‑methyl‑D‑aspartate (NMDA) receptor as a partial agonist, enhancing synaptic plasticity and long‑term potentiation.
  • Polygalasaponin M also up‑regulates brain‑derived neurotrophic factor (BDNF) via the ERK/CREB pathway, promoting neuronal survival.
  • Antioxidant flavonoids scavenge reactive oxygen species and inhibit NF‑κB, reducing neuroinflammation.
  • Polysaccharides activate AMP‑activated protein kinase (AMPK), improving mitochondrial biogenesis and glucose uptake.
• Overall effect: These actions improve synaptic transmission, reduce oxidative damage, and support energy metabolism, underlying the observed cognitive, mood‑, and metabolic benefits.

• Principal bioactive component: polygalasaponin M (C₃₈H₆₀O₁₁, M ≈ 620 g·mol⁻¹).
  • IUPAC name: (25R)-3β,25-dihydroxy-5β-furost-22-ene-3‑O‑β‑D‑glucopyranoside.
• Other components: Polygala tenuifolia also contains polygala‑tensii‑saponin‑A (C₄₀H₆₈O₁₄) and flavonoids such as quercetin‑3‑O‑glucoside (C₂₁H₂₀O₁₁).
• Saponin properties: The saponins possess a triterpenoid aglycone (furostanol) skeleton with a glycosidic side chain that confers amphiphilic properties, enabling interaction with cell membranes and receptors.
• Bioavailability: The high‑polarity glycosidic moiety contributes to poor oral bio‑availability; however, intestinal microbiota can convert the glycoside to more absorbable aglycones.

Polygala tenuifolia is cultivated primarily in the Hebei, Shanxi, and Inner Mongolia provinces of China, where the root is harvested after 2–3 years of growth.

• Extraction process:
  • Standardized extracts are obtained via 80 % ethanol extraction, followed by liquid‑liquid partitioning to enrich saponins (30–50 % polygalasaponins).
  • High‑performance liquid chromatography (HPLC) is used for quantitative standardization.
• Quality control:
  • Quality‑controlled supplements require GMP‑certified factories.
  • Third‑party testing for heavy metals (< 5 ppm lead), microbial limits (< 10⁴ CFU/g), and verification of the marker saponin content.
• Considerations: Wild‑harvested material may contain higher levels of polygalacic acid, a compound associated with mild hepatotoxicity; thus, cultivated, standardized sources are recommended for consistent safety and efficacy.