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3-n-Butylphthalide (NBP)

Well Researched

Chinese-approved multi-target neuroprotectant derived from celery seed; A-tier evidence in China for acute ischemic stroke (BAST 2023,…

Aliases (12)
DL-3-n-butylphthalide · dl-NBP · 3-n-Butylphthalide · NBP · Butylphthalide · Enbipu · Enbipu-l · Apium graveolens phthalide · 丁苯酞 · CAS 6066-49-5 (DL form) · CAS 3413-15-8 (L form) · CSPC NBP soft capsule
TYPICAL DOSE
200 mg
BID
ROUTE
Oral (tablet)
Oral
CYCLE
60-90 days on, 30-60 days off
As prescribed
STORAGE
Room temp; original container
Room temp

Overview

What is 3-n-Butylphthalide (NBP)?

3-n-Butylphthalide (NBP, brand name Butylphthalide / Enbipo) is a phthalide compound originally isolated from celery seed oil (Apium graveolens). It is approved in China for the treatment of acute ischemic stroke and post-stroke cognitive impairment. Used investigationally for vascular cognitive decline and neuroprotection.

Key Benefits

Improves microcirculation and collateral blood flow in ischemic brain tissue, reduces infarct volume after stroke, attenuates oxidative stress and mitochondrial dysfunction, and shows benefit in vascular dementia and post-stroke cognitive recovery.

Mechanism of Action

Multi-target neuroprotectant: restores microvascular blood flow, inhibits platelet aggregation, scavenges free radicals, stabilizes mitochondrial membranes, and attenuates apoptosis in penumbral neurons. Modulates eNOS and reduces post-ischemic inflammatory cascade.

Pharmacokinetics

—·—
PeakHalf-life
Approximate curve — visual aid only, not data-precise PK
▸Brand options7 known
DL-3-n-butylphthalideNBPButylphthalideEnbipuEnbipu-lApium graveolens phthalideCSPC NBP soft capsule

StatusRx in China (since 2002 SFDA approval); not FDA-approved in US (orphan-drug designation for ALS, IND/Phase trials ongoing); not on WADA Prohibited List as of 2026

Research Protocols

Disclaimer: These are commonly discussed research protocols and not medical advice.

Goal:High-dose alcohol concurrent use
Dose:—
Frequency:—
Solo:—
Cycle:—

Peptide Interactions

cerebrolysin
Synergistic

Different mechanisms, both neuroprotective; cerebrolysin = peptide-mimetic neurotrophic surge (BDNF/NGF/GDNF axis, IM cycled), NBP = small-molecule mitochond…

NAC
Synergistic

(already in V4 at 1200 mg/d) — Hepatoprotective via glutathione replenishment. This is the single most important co-administration: NBP's hepatotoxicity is G…

curcumin / curcumin phytosome
Synergistic

(already in V4) — Anti-neuroinflammatory + anti-oxidative + Nrf2 activator; layered with NBP's Nrf2 activation; phytosome formulation has hepatoprotective si…

astaxanthin
Synergistic

(V5 add) — Lipid-soluble Nrf2 activator + mitochondrial membrane stabilizer; layered antioxidant coverage with NBP. Synergistic.

idebenone
Synergistic

BBB-crossing CoQ10 analog; shores up the electron-transport-chain side while NBP supports mitochondrial biogenesis (PGC-1α) and dynamics (Mfn1, Drp1). Combin…

citicoline
Synergistic

(already in V4) — Membrane phospholipid substrate + cholinergic support; complements NBP's neuroprotection-of-existing-cells with materials for membrane repair.

omega-3 / DHA
Synergistic

(already in V4 at 2 g) — Anti-inflammatory + neuronal membrane fluidity; standard neuroprotection foundation.

semax / n-acetyl-semax-amidate
Synergistic

Russian peptides hitting BDNF / neurotrophic axis intranasally; mechanism-complementary to NBP's mitochondrial/anti-inflammatory.

PS (phosphatidylserine)
Synergistic

(already in V4) — Membrane substrate + cortisol modulator; neutral-to-synergistic.

Strong CYP3A4 inducers — rifampicin, St. John's wort, carbamazepine, phenytoin.
Avoid

Amplify hepatotoxic metabolite burden (rifampicin co-administration in vitro confirmed increased toxicity). None are in this archetype's typical stack.

Heavy alcohol load
Avoid

additive hepatic stress + ADH metabolism overlap. a user in this archetype is alcohol-zero, non-issue.

Other hepatotoxic drugs
Avoid

acetaminophen at high doses (not relevant for users in this archetype), isoniazid, statins (case-by-case; not a hard contraindication but more frequent LFT m…

Quality Indicators

✓

Pharmacy-dispensed, intact packaging

Prescription tablets in original sealed packaging from a licensed pharmacy.

!

Generic vs branded

Generics are usually fine but bioavailability can vary slightly; track if you switch.

✗

Unbranded blister or counterfeit risk

Counterfeit pharmaceuticals are a known issue; verify pharmacy and lot if buying internationally.

What to Expect

  • Day 1
    PK-driven acute peak per administration. Verify dose tolerated.
  • Week 1
    Steady-state reached for most daily-dosed pharma.
  • Week 2-4
    Therapeutic effect established; titration window if needed.
  • Long-term
    Periodic monitoring per drug class (labs, BP, ECG as applicable).

Side Effects & Safety 6

Side Effects

  1. 1Elevated ALT (transaminase elevation). Reported incidence range across trials: 1.4-17.5% depending on dose, duration, baseline liver health, and assay sensitivity. Usually asymptomatic, mild-to-moderate, reversible on discontinuation. The dominant safety signal for NBP.
  2. 2Mild GI symptoms (nausea, abdominal discomfort, occasional diarrhea): 1.7-8% of patients
  3. 3Elevated AST: 1.9-8.82%
  4. 4Skin rash (allergic-pattern; usually mild, resolves on discontinuation)
  5. 5Mild headache (often reported in healthy-control arms too — placebo-equivalent in BAST)
  6. 6Mild dizziness

When to Stop

  • Severe hepatotoxicity / drug-induced liver injury. Documented in Chinese pharmacovigilance literature; rare but not zero. The mechanism is well-understood: NBP → CYP3A4-mediated 3-OH-NBP → sulfotransferase 1A1 (SULT1A1) → 3-OH-NBP sulfate → spontaneous cleavage to electrophilic cation → covalent protein adducts in hepatocytes. Glutathione depletion is the necessary co-factor for toxicity. Risk amplifiers: high CYP3A4 inducer co-medication (rifampicin), alcohol load, baseline glutathione depletion. NAC is mechanistically protective.
  • Bleeding risk (theoretical, mild — antiplatelet activity). No major bleeding events reported in BAST. Watch if combined with strong antiplatelets/anticoagulants.
  • Allergic reactions to celery family proteins are possible but the synthesized DL-form should not contain meaningful celery protein; Apium graveolens whole-seed extracts (different product) carry more allergen burden.
  • First 4-8 weeks of any cycle: Most ALT elevations occur in this window. Check ALT/AST at baseline, week 2-4, week 8. Stop if ALT >3× ULN.
  • Whenever any new CYP3A4 inducer or substrate is added to the stack (modafinil is a mild CYP3A4 inducer — see drug interactions).
  • If symptoms of liver dysfunction develop (right upper quadrant pain, dark urine, jaundice, severe fatigue) — discontinue immediately, recheck LFTs, consult physician.
  • Severe hepatic impairment (Child-Pugh B or C)
  • Known celery / *Apium* family allergy (theoretical for synthetic NBP, real for whole-seed extracts)
  • Active GI bleeding (theoretical, antiplatelet activity)
  • Pregnancy / lactation (insufficient data)

References

BAST trial — Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke (JAMA Neurology, 2023)

jamanetwork.com · 2023

n=1,216, OR 1.70 favorable mRS, 90-day course IV→capsule, NCT03539445. Anchor evidence.

View Study

BAST trial PMC version (PMC10294018)

pmc.ncbi.nlm.nih.gov

open-access mirror.

View Study

BAST trial protocol (BMJ Open 2021, PMC8154958)

pmc.ncbi.nlm.nih.gov · 2021

pre-trial protocol.

View Study

EBMCI — Efficacy and safety of butylphthalide in MCI: multicentre RCT (PMC11253773)

pmc.ncbi.nlm.nih.gov

12-month, n=270, ADAS-cog −2.04 vs placebo; first positive RCT in non-stroke MCI.

View Study

EBMCI Alzheimer's & Dementia (Wang 2024)

alz-journals.onlinelibrary.wiley.com · 2024

A&D report.

View Study
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