Ashitaba (Angelica keiskei) | Supplementopedia

Overview

Ashitaba (Angelica keiskei), a perennial herb native to Japan’s mountainous regions, belongs to the Apiaceae family. Its young shoots and leaves have been used for centuries as a culinary and medicinal plant, and modern supplements aim to harness its rich phytochemical profile—particularly chalcones—to support cellular health and metabolic resilience.

Benefits

Research on A. keiskei and its purified chalcones (e.g., “keisin” and “4‑hydroxyderivatives”) suggests several evidence‑based benefits:

Antioxidant & anti‑inflammatory – In vitro and animal studies show robust free‑radical scavenging and suppression of NF‑κB signaling, reducing oxidative stress markers.
Metabolic support – Chalcones activate AMPK and improve insulin sensitivity in rodent models, helping to lower fasting glucose and lipid accumulation.
Bone health – In vitro osteoblast proliferation and inhibition of osteoclast activity have been documented, suggesting potential to support bone density.
Neuroprotection – Animal studies show attenuation of neuro‑inflammation and preservation of hippocampal neurons, implying cognitive‑protective potential.
Skin & wound healing – Topical extracts accelerate fibroblast migration and collagen synthesis, accelerating wound closure in murine models.
Longevity signals – Activation of the Nrf2‑ARE pathway and up‑regulation of phase‑II detoxifying enzymes have been linked to longevity pathways in C. elegans and mice.

How It Works

The primary bioactive constituents are chalcones—a class of open‑chain flavonoids. Upon oral ingestion, chalcones are absorbed via the small intestine and undergo rapid glucuronidation. Their key mechanisms include:

Nrf2 activation – Electrophilic chalcones covalently modify Keap‑1 cysteine residues, releasing Nrf2 which translocates to the nucleus to up‑regulate antioxidant‑response elements (e.g., HO‑1, NQO1).
AMPK stimulation – Direct binding to the γ‑subunit of AMPK enhances phosphorylation of ACC, promoting fatty‑acid oxidation and glucose uptake via GLUT4 translocation.
PI3K/Akt modulation – Chalcones inhibit PTEN, leading to downstream Akt activation that promotes cell survival and protein synthesis (mTORC1).
Anti‑inflammatory effects – Suppression of NF‑κB (via IκBα stabilization) reduces cytokine production (TNF‑α, IL‑6).
Bone remodeling – Up‑regulation of Run‑related transcription factor 2 (Runx2) and down‑regulation of RANKL diminish osteoclastogenesis.

Collectively, these pathways account for the antioxidant, metabolic, and tissue‑protective actions observed.

Dosage

Clinical and animal data converge on a practical range of 300–900 mg of standardized A. keiskei extract (containing 5–15 % total chalcones) per day. Typical regimens:

General health – 300 mg once daily with meals.
Metabolic support – 600 mg split (morning & evening) to sustain AMPK activation.
Bone‑health protocols – 900 mg divided into two doses, combined with calcium/vitamin D.

Capsules or powdered leaf form should be taken with food to improve bioavailability. For acute antioxidant effects (e.g., post‑exercise), a single 300 mg dose 30 min before activity is common. Always start at the lower end and titrate based on tolerance.

Safety & Side Effects

Ashitava is generally well‑tolerated, but safety considerations include:

Mild GI upset (bloating, mild diarrhea) at >1 g/day.
Potential anticoagulant effect – In vitro inhibition of platelet aggregation suggests caution with warfarin, clopidogrel, or NSAIDs.
Hormonal sensitivity – Chalcones exhibit weak phytoestrogenic activity; women with estrogen‑sensitive cancers should avoid use.
Pregnancy & lactation – Human data lacking; precautionary avoidance is advised.
Allergy – Cross‑reactivity with other Apiaceae (celery, carrot) can trigger dermatitis or anaphylaxis.

Renal or hepatic impairment may reduce clearance; a reduced dose (150–300 mg) is advisable. Discontinue if rash, pruritus, or severe GI symptoms occur.

Chemistry

The most studied constituent is keisin (4‑hydroxy‑6‑methoxy‑2‑(3‑hydroxy‑4‑methoxyphenyl)‑1‑phenyl‑but‑1‑en‑3‑one), a chalcone with molecular formula C₁₅H₁₂O₄ (M ≈ 244 g mol⁻¹). Its IUPAC name: 3‑(4‑hydroxy‑3‑methoxyphenyl)‑1‑(4‑hydroxy‑2‑methoxyphenyl)prop‑2‑en‑1‑one. Key features: an α,β‑unsaturated carbonyl (Michael acceptor) and two phenolic rings providing antioxidant capacity. Other phytochemicals include coumarins (e.g., umbelliferone), flavonoids (quercetin, kaempferol), and vitamin C. The chalcone scaffold is planar, enabling interaction with cysteine residues of Keap‑1, while the phenolic hydroxyls confer radical‑scavenging properties. The plant also contains essential oils (e.g., α‑pinene) and mineral content (potassium, calcium).

Sources & Quality

Angelica keiskei is cultivated primarily in Japan’s Nagano and Miyazaki prefectures, where the plant is harvested in spring when young shoots are tender. Commercial supplements typically use either:

Whole‑plant dried powder – harvested, washed, freeze‑dried, and milled to a fine powder.
Standardized extract – ethanol or 70 % ethanol‐water extraction, followed by vacuum‑evaporation and spray‑drying to yield a 5–15 % chalcone‑standardized powder.

Quality measures include: HPLC quantification of keisin, absence of heavy metals (<10 ppm lead, cadmium), microbial limits (<10⁴ CFU/g), and verification of botanical identity via DNA barcoding. Organic cultivation and GMP‑certified processing minimize pesticide residues and preserve the phytochemical profile.