 Etymology
- Ashitaba derives from the Japanese words ashita (tomorrow) and ba (leaf), which relates to the plant's ability to regenerate new leaves after taking cuttings.
- Angelica derives from Latin for angel. Keiskei derives from Ito Keisuke, the 19th century Japanese botanist, also referred to as the father of modern Japanese botany.
Botany
Ashitaba is a herbaceous, perennial plant growing to a height of 50 to 120 centimeters. Roots are stout, conic, or cylindric. Flowers are hermaphrodite (having both male and female organs). Plant is self-fertile and regenerative. Harvesting a leaf at the break of day often results in a new sprout growing overnight.
Note: Archangelica keiskei Miq. is a plant often confused with Angelica keiskei. It is often considered synonymous with Angelica keiskei. The name Archangelical keiskei Miq. is unresolved.
Distribution
- Endemic to Japan; especially in the Seven Islands of Izu.
- Of recent interest and cultivation in the Philippines for its herbal medicinal benefits.
 Constituents
- Substantial in vitamin B12 and chalconoids.
- All genus members contain furocoumarins.
- Roots have yielded psoralen, bergapten, xanthotoxin, and angelicin.
- Study isolated seven compounds: 1-cerotol (1), daucosterol (2), stigmasterol (3), quercetin-3-O-β-D-glucopyranside (4), luteolin-7-rhamno-glucoside (5), luteolin-7-O-α-D-glucpyranoside (6) and steviol-l3-O-β-glucopyranoside 19-β-glucopyranosyl ester octaacetate (7). (5)
- Study of leave isolated six chalcone compounds, 2′,4′,4-trihydroxy-3′-[2-hydroxy-7-methyl-3-methylene-6-octaenyl]chalcone (1), 2′,4′,4-trihydroxy-3′-geranylchalcone (2), 2′,4′,4-trihydroxy-3′-[6-hydroxy-3,7-dimethyl-2,7-octadienyl]chalcone (3), 2′,4-dihydroxy-4′-methoxy-3′-[2-hydroperoxy-3-methyl-3-butenyl]chalcone (4), 2′,4-dihydroxy-4′-methoxy-3′-geranylchalcone (5), and 2′,4-dihydroxy-4′-methoxy-3′-[3-methyl-3-butenyl]chalcone (6). (see study below) (28)
- Roots yielded a prenyl chalcone, xanthoangelol, together with known compound 4-hydroxydericin. (39)
Properties
- Considered tonic, diuretic, appetite stimulant, wound healing and anti-infective.
- Fumocourmarin increases sensitivity to sunlight and may cause photodermatitis.
- Studies have suggest anti-cancer, antibacterial, antiviral, hepatoprotective, antioxidant, antiproliferative, chemopreventive, antidiabetic activities.
 Parts used
Roots, leaves, stems.
Uses
Edibility / Nutrition
- Consumed as vegetable and medicine for hundreds of years.
-
Leaves, roots and stems are edible.
- Leaves are eaten raw or cooked.
- Roots are cooked or pickled.
- In Japan, used in the preparation of soba, tempura, socho, tea, ice cream, etc.
- Rich in vitamins, minerals, and dietary fiber.
Folkloric
- In Japan, the yellow sap from stems and stalks once used for external treatment of smallpox.
- Roots traditionally used as diuretic, laxative, analeptic, and galactagogue.
- Used as remedy for bowel disturbances, dysuria, arthritis, and immune diseases.
- In Chinese medicine, believed to activate Qi and Xue. Use in the treatment of menstrual problems. Also believed to increase kidney yin and yang qi.
- Used as lactagogue, to increase mother's milk.
 Studies
• Cosmetic Toxicity Study / Leaf Extract: Study evaluated aqueous and ethanol fractions of leaf extract for toxicity when used for cosmetic purposes using the acute eye irritancy test. No changes or damage was seen in terms of ocular or corneal lesions, corneal turbidity, eyelid swelling or discharge. The extracts showed promise as cosmetic ingredients. (2)
• Xanthoangelols / Inhibition of Inflammatory-Induced Plasminogen Activator Inhibitor: Ashitaba exudates yielded xanthoangelol and xanthoangelols B and D which significantly inhibited TNFα-induced PAI-1 production. Results suggest Ashitaba can decrease elevated PAI-1 production, and daily consumption might maintain anticoagulant status by inhibition of elevation of PAI-1 under inflammatory conditions. (3)
• Chemopreventive / Chalcones, Coumarins and Flavanones / Exudate: Study of an ethyl acetate fraction of stem exudates yielded 17 compounds, viz., five chalcones, seven coumarins, and three flavanones. All compounds, except for 10, 16, ad 17, exhibited potent inhibitory effects on EBV-EA (Epstein-Barr virus early antigen) induction in Raji cells, known to be a primary screening test for antitumor-promoters. Results suggest the chalcones, coumarins, and flavanones from the stem exudates may be useful as a chemopreventive in chemical carcinogenesis, and may also be valuable as food ingredients. (6)
• Chalcones / Adiponectin / Anti-Metabolic Syndrome: Study of an ethanol extract yielded xanthoangelol, 4-hydroxyderricin and six chalcones. The chalcones markedly increased the expression of the adiponectin gene and production of adiponectin in 3T3-L1 adipocytes. Results suggest potential benefit in preventing the metabolic syndrome. (7)
• Antitumor / Leaves: Study evaluated a leaf extract of A. archangelica on growth of Crl mouse breast cancer cells in vitro and in vivo. Results showed antiproliferative activity in vitro and antitumor activity in vivo. The antiproliferative activity could not be attributed to xanthotoxin or furanocoumarins alone. Flavanoids and polysaccharides present in the leaves might have contributed to the antitumor activity. (8)
• Anti-Inflammatory / Leaves: Study of an n-hexane fraction of A. keiskei showed an anti-inflammatory effect, probably mediated through down-modulation of iNOS and COX-2 gene products by blocking the signaling pathways of MAPKs and NF-kB. (9)
• Antiproliferative / Hepatocarcinoma Cells: Study showed Angelica keiskei chalcone can increase the expression of Caspase-3 and Bax protein in mice, and inhibit the proliferative activity of mice hepatocarcinoma cells. (10)
• Angiotensin 1-Converting Enzyme Inhibitor / Antihypertensive: An ACE inhibitor was extracted from an 80% ethanol extract of leaves. The antihypertensive effects on spontaneously hypertensive rats were observed by long-term administration and by single intravenous administration. (11)
• Antitumor / Antimetastatic / Xanthoangelol / Roots: Study evaluated the antitumor and antimetastatic effects of various fractions from a 50% ethanol extract of roots. Study isolated xanthoangelol which showed inhibition of tumor growth in LLC-bearing mice as well as lung metastases, and prolonged survival time in carcinectomized mice. The effects may be due to inhibition of DNA synthesis in LLC cells and tumor-induced neovascularization through inhibition of capillary-like tubes by vascular endothelial cells, and inhibition of binding of VEGF to vascular endothelial cells. (12)
• CCl4 Toxicity Exacerbation / Hepatoprotective on D-Galactosamine-Induced Hepatotoxicity: Study evaluated the hepatoprotective effects of a methanol extract of AK in rats with D-galactosamine and carbon tetrachloride hepatotoxicity. Results showed AK exerted protective effects on D-galactosamine induced hepatotoxicity. However, it exacerbated toxicity induced by CCl4, possibly through increase in activity of aniline hydroxylase, a cytochrome P450 isoenzyme responsible for the metabolic activation of CCl4. (13)
• Antioxidant Enzymes / Lipid Effects / Luteolin: Study on the feeding effects of AL and its processed products in rats fed on a high fat diet showed an increase in expression of antioxidant enzymes, reduced hepatic cholesterol content, and increased effective absorption of luteolin. (14)
• Effects on Metabolic Syndrome: Ingestion of Ashitaba green juice for 8 weeks significantly decreased visceral fat are, body weight, BMI and body fat. No adverse effects were observed. Results suggest a safe foodstuff or supplement for the prevention of metabolic syndrome. (15) This review summarizes current information derived from studies on effects of ashitaba on various pathological disorders associated with metabolic syndrome and discusses effects on blood glucose, obesity, lipid metabolism, and thrombotic tendencies of MetS. Despite numerous convincing studies on biologic activities on how ashitaba chalcones could positively impact human health, chalcones have not yet been developed as pharmaceuticals. Study suggests larger cohort studies of humans and to confirm possible medical applications from a clinical standpoint. (24)
• Inhibition of SARS-Cov Cysteine Proteases / Chalcone 6 : Two viral proteases of severe acute respiratory syndrome corona virus (SARS-CoV), a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro) are attractive targets of anti-SAR drugs. Study isolated nine alkylated chalcones and four coumarins from A. keiskei. One of the chalcones, chalcone 6, showed potent inhibitory activity against the two viral proteases with competitive inhibition of 3CLpro and non-competitive inhibition with PLpro. (16)
• Antidiabetic / Chalcone : Ethanol extract of A. keiskei yielded two major chalcones, 4-hydroxyderricin (4HD) and xanthoangelol, that showed strong insulin-like activities via an independent pathway of peroxisome proliferator-activated-y activation. 4-HD specially showed preventive effects on diabetic progression in genetically diabetic KK-Ay mice. (17)
• Chalcones / Apoptosis in Stomach Cancer Cells / Stems: Study of stems identified two chalcones: xanthoangelol and 4-hydroxyderricin. The chalcones showed anticancer activity as evidenced by growth inhibition of human stomach cancer KATO III cells via induction of apoptosis. (19)
• Inhibition of PAI-1 Release from Human Endothelial Cells: Ashitaba exudate suppresses lipopolysaccharide (LPS)-induced plasma plasminogen activator inhibitor 1 (PAI-1), a risk factor for thrombotic disease in mice. Study evaluated the effects of ashitaba chalcones on PAI-1 levels in medium of stimulated human endothelial cells. Xanthoangelol inhibited PAI-1 production by 77.1%. Study suggests further research towards understanding the antithrombotic mechanism of ashitaba. (20)
• Antioxidant: Study evaluated three medicinal plants viz. Neem (Azadirachta indica), Ashitaba (Angelica keiskei) and Lemon grass (Cymbopogon citratus) for antioxidant activity and trace elements. Angelica keiskei yielded carotenoids (120), tocotrienols (11), tocopherols (3.7), Mg (167), Mn (1.6), Cu (1.2), Se (6.5) and Zn (7.7) in mg/kg. Of the three, ashitaba showed the highest antioxidant activity. (21)
• Effect on Body Weight and Visceral Fat / Double Blind Pilot Study / Chalcone: A two-part randomized, placebo controlled double blind pilot study evaluated the effect of ashitaba chalcone powder on body weight and visceral fat in slightly obese adults. There was no significant differences in primary endpoints or safety measures. There was a significant reduction of visceral fat and body weight in the treatment group at 8 weeks compared to baseline. Study sowed evidence of safety of ashitaba chalcones at dose of 200 mg/day for 56 days in humans. (22)
• Antihyperglycemic / No Cholesterol Effect / 7-Day Study: Study evaluated the effect of ashitaba in patients with elevated blood glucose and blood cholesterol levels . Ashitaba leaves and stems, where chalcones are most prominent, were separated from the plant, dried, and powdered. Results showed a seven-day consumption of Ashitaba reduced blood glucose level but not the cholesterol level. (24)
• Possible Antithrombotic Effects / Chalcones: Studies have shown that A. keiskei exerts activity that lead to prevention of thrombosis. Chalcones, xanthoangelol (XA) and 4-hydroxydelicin (4-HD), account for >90% of all chalcones identified in Ashitaba. Chalones are found in leaves, stems, and roots, and are particularly abundant in yellow exudats from cut ends of stems. Whether or no specific amounts of Ashitaba chalcones are actually effective for preventing thrombotic disease in humans remains to be elucidated. (26)
• Improvement of Liver Function in Heavy Drinkers/ Clinical Trial: Alcohol induced oxidative stress and inflammatory response which can lead to hepatitis and cirrhosis. Previous studies have suggested antioxidant and anti-inflammatory properties, and that AKE could improve abnormalities associated with alcoholic liver disease. A randomized double-blind clinical trial for 12 weeks using heaving drinkers consuming more than 35 units weekly. AJE treatment showed significant decrease in GGT levels, with no significant difference in AST and ALT levels between AKE- and placebo-treated groups. Results suggest AKE supplementation might improve liver function in heavy drinkers. (27)
• Chalcones / Inhibition of IL-6 Production in TNF-a-Stimulated MG-63 Cell / Leaves: Study isolated six chalcone compounds from the leaves of A. keiskei. Among the isolates, compounds 1-3 showed potent inhibitory activity of IL-6 production in TNF-a-stimulated MG063 cell. The inhibitory activity may be affected by the presence of C-4' hydroxyl group in the chalcone moiety. (see constituents above) (28)
• Effect on Lipid Metabolism in Stroke-Prone Spontaneously Hypertensive Rats: Study evaluated the effect of dietary A. keiskei on lipid metabolism in stroke-prone spontaneously hypertensive rats. Results showed an elevation of serum HDL levels and a reduction of liver triglycerides. (29)
• Extraction Efficiency of Phytonutrients / Antioxidant: LC-ESI-MS/MS analysis identified chlorogenic acid, chalcones, and glucosides of luteolin and quercetin as major components. A. keiskei grown in three different conditions showed range in lutein content of 205-265 mg/kg dw, trans-ß-carotene 103-130 mg/kg dw, and total phenols 8.6-9.7 g/kg. Study indicates phytonutrients rich in AK can be extracted partially using ethanol/water and substantial loss of ß-carotene can occur during storage at 4ºC within 2 months and lutein at room temperature within 12 months. (30)
•
Chalcone / Effect on Microvessel Density and VEGF Expression of Hepatocarcinoma Cells: Study evaluated the effect of AK chalcone on microvessel density and vascular endothelial growth factor (VEGF) expression on mice hepatocarcinoma cells. Result showed AC could inhibit tumor angiogenesis effectively. Inhibition mechanism may be associated with the down-regulation of VEGF. (31)
• Nanoethosomal gel from leaves for burn treatment: The WHO reports 265,000 deaths a year worldwide due to burn wounds (direct contact with heat or radiation, radioactivity, electricity, friction or chemicals). A collaborative research invented a transdermal delivery therapy with ashitaba leave in the form of a "nanoethosomal gel" for healing burns, The new vesicular carrier improved delivery through the skin. The size of the nanoethosomal vesicles can be modulated from microns to 10 nano microns,increasing bioavailability, penetrating the intercellular space, while also improving the target specificity of the drug. The trial was performed on burns induced on Wistar rats and showed significant results. (33)
• DMC / Natural Compound with Anti-Ageing Properties: Study reports on the identification of the flavonoid 4,4'-dimethoxychalcone (DMC) in the plant Angelica keiskei, as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischemia. DMC also induced autophagy, which is essential to its cytoprotective effects from yeast to mice. In Asian traditional medicine, the plant has been ascribed longevity and health-promoting effects. (34)
• Attenuation of Hyperlipidemia and Hepatic Steatosis Caused by Western Diet in C57FK/6J Mice: Study evaluated the protective effects of A. keiskei juice against hyperlipidemia and hepatic steatosis in WD-fed mice. AK significantly attenuated WD-induced increase in plasma triglyceride and VLDL (p<0.001) and hepatic triglyceride (pM0.001). Results suggested daily consumption of AK juice may have potential to prevent WD-induced NAFLD development through mitigation of intestinal barrier damage, intestinal lid absorption, and hepatic ER oxidative stress. (35)
• Prevention of Adiposity in High-Fat Diet Fed Mice: Two main chalcones, 4-hydroxyderricin and xanthoangelol, from Ashitaba have been demonstrated to modulate lipid metabolism in 3T4-L1 and HepG2 cells. This study investigated the effects of Ashitaba extract on adiposity in mice fed a high-fat diet. Ashitaba extract suppressed HF diet induced body weight gain and fat deposition, reduced plasma cholesterol. Ashitaba extract can possibly prevent adiposity through modulation of lipid metabolism through phosphorylation of AMPK in adipose tissue and liver. (36)
• Chalcones / Suppression of Melanogenesis by Targeting BRAF and PI3-K: In melanoma, both BRAF/MEK/ERK and PI3-K/AKT signaling pathways are activated through multiple mechanisms, which results in cell cycle progression and prevention of apoptosis. Study found Ashitaba chalcones, 4-hydroxyderricin (4HD) and xanthoangelol (XAG), suppressed melanoma development by directly targeting both BRAFV600E and P13-K, which blocked activation of downstream signaling. which led to induction of G1 phase cell cycle arrest and induction of apoptosis in melanoma cells. Findings suggest 4HD and XAG are promising chemopreventive or potential therapeutic agents against melanogenesis that act by targeting both BRAF and P13-K. (38)
• Improvement of Immune Response in Mice Vaccinated with Rabies Vaccine. Study determined effect of ethanol extract of leaves on immune response on IL-2, IFN-? Ba;b/C mice vaccinated with rabies vaccine. Results showed Ashitaba significantly increased levels of IL-2 (p<0.05). Study used a simple randomized design. The extract can improved the immune response of IL2 and IFM-? mice vaccinated with rabies vaccine.(41)
In the news
• Secret of longevity in plant that appears to slow aging: News item reports on a Japanese plant that may contain a compound which could slow aging. The compound is found in Angelica keiskei Koidzumi plant. Researchers identified it as flavonoid 4,4'-dimethoxychalcone, a natural compound with anti-aging properties. (32)
Buyer beware !
• Ashitaba has been getting a lot of press, being touted as the new "miracle" herb. However, a lot of potted "ashitaba" being sold locally from roadside herbal gardens and mall stalls, intentionally or unintentionally, is actually Sabungai (Gynura procumbens) rather than ashitaba (Angelica keiskei). (See Sabungai)
Availability
- Cultivation.
- Seeds, plants, leaf powder, and tea products in the cybermarket.
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