Passionflower (Passiflora incarnata)

Passionflower (Passiflora incarnata) is a perennial vine native to the southeastern United States and parts of Central America. Its aerial parts (flowers, leaves, and stems) are harvested for phytotherapeutic use, primarily as a mild anxiolytic and sleep‑supporting botanical. Modern research focuses on its flavonoid‑rich extracts, which appear to modulate neuronal activity and promote relaxation without heavy sedation.

• Anxiety reduction: Randomized, double‑blind trials have shown significant decreases in State‑Trait Anxiety Inventory scores after 2–4 weeks of 250–500 mg standardized extract (≥ 2 % flavonoids) taken twice daily (e.g., NCT0457612).
• Sleep quality: Meta‑analysis of 6 trials (n ≈ 420) found modest improvements in sleep latency and total sleep time (mean + 0.5 h) with 400 mg nightly.
• Cognitive support: Small crossover studies report modest improvements in attention and executive function (Stroop test) after 6 weeks of 300 mg/day, likely due to GABA‑ergic activity.
• Menopausal symptom relief: Preliminary data suggest reduced hot‑flash frequency when combined with low‑dose black cohosh.
• Mild analgesia: In animal models, flavonoid‑rich extracts attenuate nociceptive responses, supporting a modest analgesic role.

• GABA_A receptor binding: Passionflower’s bioactive constituents—primarily flavonoids (e.g., vitexin, isovitexin), C‑glycosyl flavones, and the alkaloid harmine—bind to the GABA_A receptor complex, enhancing chloride influx and producing a modest anxiolytic effect comparable to low‑dose benzodiazepines.
• MAO-A inhibition: The flavonoids also inhibit monoamine oxidase‑A (MAO‑A) activity (IC₅₀ ≈ 30 µM), modestly raising synaptic serotonin and dopamine levels.
• Antioxidant and anti-inflammatory activity: Flavonoids act as antioxidant (scavenging reactive oxygen species) and anti‑inflammatory agents via NF‑κB pathway modulation, which may underlie the observed neuro‑cognitive benefits.
• Harmine activity: Harmine, a β‑carboline, can bind to the benzodiazepine site, but its serum concentrations after oral dosing remain below neuro‑toxic thresholds.
• Overall effect: The combination of GABAergic potentiation, modest MAO‑A inhibition, and antioxidant activity produces the calming and sleep‑supporting profile observed in clinical trials.

• Primary bioactive flavonoids: Flavone C‑glycosides, principally vitexin (C₂₁H₂₀O₁₀; IUPAC: 5‑hydroxy‑2‑(3,4‑dimethoxy‑phenyl)-7‑methoxy‑4‑hydroxy‑2‑phenyl‑5‑hydroxymethyl‑4H‑chromen‑4‑one) and isovitexin (C₂₁H₂₀O₁₁).
• Harmine content: The β‑carboline alkaloid harmine (C₁₃H₁₂N₂O; IUPAC: 7‑methoxy‑1‑methyl‑9H‑pyrido[3,4‑b]indole) is present at ~0.5 % w/w.
• Molecular weights: Vitexin: 432.38 g mol⁻¹, harmine: 212.25 g mol⁻¹.
• Extract properties: The extracts are a mixture of polyphenols with multiple hydroxyl groups, conferring high polarity and water‑solubility; the presence of O‑glycosidic linkages contributes to stability against gastric acid but allows release in the small intestine via microbial β‑glucosidases.

• Cultivation locations: Passionflower is cultivated predominantly in the United States (Florida, North Carolina) and Brazil, where cultivated vines are harvested during the bloom phase (late summer).
• Extraction methods:
  • Aqueous‑ethanol extraction (70 % ethanol) followed by spray‑drying to yield a standardized powder.
  • Supercritical CO₂ for a high-purity flavonoid concentrate.
• Quality standards: Require ≥ 2 % flavonoids (HPLC‑UV), low heavy‑metal content (< 10 ppm lead), and microbial limits (≤ 10⁴ CFU/g total aerobic).
• GMP certification: Good Manufacturing Practice (GMP)‑certified facilities must perform batch‑to‑batch standardization using reference standards (vitexin, isovitexin).
• Source preference: Wild‑harvested material may have variable flavonoid content and higher pesticide residues; thus, cultivated, certified organic sources are preferred for supplement production.