Akebia: A Comprehensive Reference Article
1. Identity and Botanical Description
Akebia is a genus of woody climbing vines belonging to the family Lardizabalaceae. The two species of greatest medicinal and dietary significance are Akebia quinata (Houtt.) Decne. and Akebia trifoliata (Thunb.) Koidz., along with the latter's subspecies A. trifoliata var. australis (Diels) Rehd. Akebia quinata is a woody climber from the Lardizabalaceae family, commonly known as a "chocolate vine," and is widespread in East Asia, including Korea, China, and Japan. Akebia trifoliata is a climbing vine with leaves composed of three ovate, slightly lobed leaflets, often bronze-tinted when young. It grows up to 9.1 m long, loses its leaves in cold climates, and produces deep purple flowers in short racemes followed by light purple fruits.
A. quinata is a creeping woody vine distributed in East Asia, including Korea, China, and Japan. It belongs to the Lardizabalaceae family of plants and is commonly known as "wild banana" in China and "chocolate vine" in the United States. A. trifoliata, commonly known as "Bayuezha" in China, is a deciduous woody liana mainly distributed in East Asia, especially in China, Korea, and Japan. Its ripe fruit has a sweet and juicy pulp containing multiple saccharides, crude proteins, amino acids, minerals, and vitamins. The nearly ripe, dry fruit of A. trifoliata is an important traditional Chinese medicine and is described as Akebiae Fructus in the Pharmacopoeia of China.
In pharmacognosy and official compendia, the dried stem of Akebia species is known as Akebiae Caulis (Chinese: Mutong; Mu tong, 木通), while the dried ripe fruit is known as Akebiae Fructus (Chinese: Bayuezha). According to the Pharmacopoeia of the People's Republic of China, Akebiae Caulis is derived from the dried stems of A. quinata (Thunb.) Decne., A. trifoliata (Thunb.) Koidz, and A. trifoliata (Thunb.) Koidz. var. australis (Diels) Rehd. Textual research revealed that A. quinata of Lardizabalaceae is the authentic Akebiae Caulis in TCM.
"Akebia stem" (Akebiae caulis) is one of the newest raw materials officially introduced into therapeutic practice from traditional Chinese medicine. A monograph on this material appeared for the first time in 2018 in Supplement 9.6 to the 9th edition of the European Pharmacopoeia. In the latest 10th edition of the European Pharmacopoeia, the monograph remained unchanged. The "Akebia stem" monograph allows the use, as a raw material, of Akebia quinata (Houtt.) Decne., A. trifoliata (Thunb.) Koidz, or a mixture of the two species. The monograph is listed under pharmacopoeia number 2472.
Common Names and Synonyms
- Chocolate vine (English, most widely used in Europe and North America)
- Five-leaf akebia (English, referring to A. quinata)
- Three-leaf akebia / Three leaf chocolate vine (English, referring to A. trifoliata)
- Mu tong (木通) — stem drug in TCM
- Bayuezha (八月炸) — fruit drug name in TCM
- Mokutsu — Japanese Kampo name for the dried stem
- Wild banana (Chinese colloquial, referring to the large purplish fruit)
Botanical Description and Fruit
A. trifoliata is grown for its ornamental appeal but also for the edible oblong purplish fruits. The fruit itself has a mild flavor reminiscent of coconut or tapioca and is considered quite sweet. It is a multipurpose plant used in traditional medicine as an edible oil plant and as a fruit crop. Akebia quinata (Houtt.) Decne., also known as five-leaf akebia, is a versatile plant known for its dual role in both medicine and food.
2. Traditional and Historical Use
Traditional Chinese Medicine (TCM)
Akebiae Caulis has been used in Traditional Chinese Medicine (TCM) since ancient times. Akebiae Caulis, previously known as Tongcao (通草 in Chinese), was first recorded in Shennong's Herbal Classic of Materia Medica, in which it is reported that Akebiae Caulis could "dredge nine orifices, veins, and joints." The earliest recorded use of A. trifoliata as a traditional Chinese medicine was in "Shen Nong's Herbal Classic" (around 100 BC), where it was mainly used for soothing the liver and promoting blood circulation.
Traditionally, Akebiae Caulis has been used to treat conditions such as gonorrhea, edema, and tongue sores. The stems are described ethnobotanically as analgesic, antibacterial, antifungal, anti-inflammatory, antitumor, blood tonic, cardiotonic, diuretic, emmenagogue, and galactogogue. Taken internally, they were used to control gram-positive bacterial and fungal infections and in the treatment of urinary tract infections, lack of menstruation, and to improve lactation. Other reported ethnobotanical uses include the treatment of amenorrhea, poor circulation, dysuria, edema, gonorrhea, jaundice, rheumatoid arthritis, and as a nervine.
In traditional medicines, different plant parts and preparations of A. quinata are exploited. Aqueous and alcoholic extracts, which have antioxidant and free radical scavenging properties, were mainly used to treat edema, hypothermia, and rheumatic pain. Dry ripe fruit and stem extracts were used as anti-inflammatory, sedative, and diuretic agents.
Mu-tong (Akebiae Caulis) is a common traditional Chinese medicine used as a diuretic and antiphlogistic. It is used in traditional Chinese medicine to help with urinary tract infections and "quickening blood flow."
Traditional Korean Medicine
Akebia quinata fruit extract has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. Furthermore, A. quinata is used as a crude drug material for treating obesity in traditional Korean medicine. The dried fruits, leaves, and stem of the plant are also ingredients of a traditional Korean weight-loss tea used as a folk remedy. The fruits, leaves, and stems of A. quinata were reported as ingredients of a slimming tea used to treat obesity in traditional Korean medicine.
Kampo (Japanese Traditional Medicine)
Akebia species have been used for centuries in the traditional medicinal practices of China and Japan. The dried stems of A. trifoliata are known as mutong in the Chinese Pharmacopoeia and mokutsu in Kampo, the traditional herbal medicine of Japan. Plants in the Akebia genus were the primary source of the medicinal mu tong in ancient times, but today the total production of the three official species of Akebia used as mu tong is insufficient to meet the entire global demand. As only Akebia species are listed in the Japanese Pharmacopoeia for use as mu tong, Japan purchases most of the global supply of the Akebia species (Akebia quinata, A. trifoliata, and A. trifoliata var. australis).
Food and Culinary Traditions
Akebia plants are grown as ornamental crops in China or garden plants in Europe and the United States. Akebia plants have historically been eaten as wild fruit in East Asia. A. quinata is used as a diuretic and tranquilizer to treat hypothermia and rheumatic pain, while the fruit, including the seeds, is used as an antitumor agent, analgesic, antiphlogistic, and diuretic. Its fruits and leaves are registered as raw food materials in a database hosted by the Korean Ministry of Food and Drug Safety, suggesting that they can be used as raw materials for functional food development.
3. Key Constituents and Active Compounds
Overview of Phytochemistry
This critical review of phytochemical studies demonstrates that triterpenoid saponins are dominant secondary metabolites of these species. A comparative analysis of phytochemical studies on A. quinata and A. trifoliata stems, roots, fruits, and seeds showed differences in metabolites based on the plant parts and species. Various phytochemical components, such as polyphenols, steroids, triterpenoids, triterpenoid saponins, coumarins, pentacyclic alkaloids, essential oils, and polysaccharides, have been isolated and reported from various parts of A. quinata.
Among the 1,429 metabolites detected and putatively identified in Akebia pulp using UPLC-MS/MS and GC-MS techniques, terpenoids, amino acids, flavonoids, and phenolics were predominant. The diversity of Akebiae Caulis's biological and pharmacological activities is associated with the presence of a large number of chemical substances, among which terpenoids are predominant.
Triterpenoid Saponins
Triterpenoid saponins are the most thoroughly studied and pharmacologically significant class of compounds in Akebia. The stems of Akebia quinata have been analyzed for their triterpene glycoside constituents, resulting in the isolation of six new triterpene glycosides, along with 19 known ones. Key saponins identified across species and plant parts include:
- Akebia saponin D (ASD) — the most pharmacologically studied, isolated from fruits and stems
- Akebia saponin PA — isolated from the fruits of A. quinata
- Hederacoside C (kalopanax-saponin B) — isolated from the fruits of A. quinata
- Hederacolchiside F — identified in fruits and seeds
- α-Hederin — identified in leaves and seeds
- Mutongsaponin C and Saponin Pj1 — found exclusively in A. trifoliata
A phytosterol glucoside stigmasterol-3-O-β-D-glucoside, three triterpenoids (maslinic acid, scutellaric acid, and hederagenin), and three triterpenoidal saponins (akebia saponin PA, hederacoside C, and hederacolchiside F) were isolated from a 70% EtOH extract of the fruits of A. quinata. The triterpenoid saponins mutongsaponin C and saponin Pj1 have been found only in A. trifoliata, whereas the phenolic glycoside 2-(3,4-dihydroxyphenyl)-ethyl-O-β-D-glucopyranoside has been found only in A. quinata.
Phenolic Acids and Chlorogenic Acid Derivatives
Akebia quinata extract has been reported to contain chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C, in addition to triterpenoid saponins. Key marker compounds for quality assessment of A. quinata seeds include chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, hederacolchiside F, hederacoside C, dipsacoside B, akebia saponin D, and α-hederin. Analysis of A. quinata seeds confirmed that these eight components were found in concentrations of 0.42–9.07 mg/g.
Lignans and Phenylpropanoids
Previous phytochemical investigations resulted in the isolation of triterpenoid saponins, triterpenoids, phenylethanoid glycosides, essential oil, alkaloids, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C from various parts of A. quinata. A specific megastigmane glycoside, named akequintoside D, along with six known compounds including roseoside II, 3-O-caffeoylquinic acid, and related phenylpropanoids, was isolated from the stem of Akebia quinata.
Alkaloids
Flower buds of A. trifoliata were enriched with defense-related alkaloids, including dhurrin. Pentacyclic alkaloids have also been identified among the major compound classes of A. quinata as part of the broad phytochemical diversity of the genus.
Flavonoids and Anthocyanins
Fully open flowers of A. trifoliata were found to be rich in cyanidin-based anthocyanins, notably cyanidin-3-O-glucoside, identifying this flowering stage as optimal for natural colorants. Previous studies on Akebia have primarily focused on isolated bioactive compounds such as flavonoids, saponins, and alkaloids, which are known for their anti-inflammatory, antioxidant, and anticancer properties.
Other Notable Compounds
From selected bioactive zones in effect-directed profiling of A. quinata, syringin, vanilloloside, salidroside, α-hederin, cuneataside E, betulin, and oleanolic acid were tentatively assigned in the leaf extract, while salidroside and quinatic acid were tentatively identified in the fruit extract. Akebia quinata has been reported to contain chlorogenic acid and triterpenoid saponins such as oleanolic acid and hederagenin.
4. Established Mechanisms of Action
Anti-Inflammatory Mechanisms
The anti-inflammatory activity of Akebia extracts and isolated compounds, particularly akebia saponin D, is among the most studied areas of the plant's pharmacology. Studies have aimed to explore the anti-inflammatory effect of akebia saponin D (ASD) and its underlying mechanisms from the perspective of DNA methylation and inflammation-related pathways. ASD was found to significantly reduce the production of multiple inflammatory mediators, including nitric oxide (NO) and prostaglandin E₂ (PGE₂), in LPS-induced RAW264.7 cells. The expression of DNA methyltransferase (DNMT) 3b and inducible nitric oxide synthase (iNOS) was also obviously inhibited by ASD treatment. The protein and mRNA levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were also significantly inhibited by ASD.
In the context of diabetic nephropathy, ASD prevented kidney damage, improved renal function and inflammatory reaction, ameliorated oxidative stress, and inhibited apoptosis of renal tubular cells in diabetic nephropathy mice via activation of the NRF2/HO-1 pathway and inhibition of the NF-κB pathway.
In analgesic and anti-nociceptive models, Akebia saponin D dose-dependently decreased the licking time in the formalin test, delayed the reaction time of mice to the hot plate, and inhibited acetic acid-induced writhing. Treatment with Akebia saponin D attenuated carrageenan-induced paw edema in rats, inhibited mouse ear swelling, and decreased Evans blue concentration in acetic acid-induced vascular permeability test. Akebia saponin D significantly decreased NO production and iNOS expression.
Anti-Obesity and Lipid-Regulating Mechanisms
AQE (Akebia quinata extract) treatment ameliorated HFD-induced hyperlipidemia and hyperleptinemia, reduced excessive gains in body and adipose tissue weight, and improved serum lipid profiles in mice consuming a high-fat diet. Changes in gene expression and AMPK phosphorylation accompanied the AQE-induced physiological improvements, suggesting that AQE exerts anti-obesity and hypolipidemic effects by activating AMPK in white adipose tissue. Furthermore, AQE treatment increased AMPK phosphorylation and reduced differentiation of 3T3-L1 adipocytes in vitro. AQE supplementation also reduced expression of genes related to adipogenesis and increased expression of PPARα, acetyl-CoA oxidase, and adiponectin in epididymal adipose tissue.
Antidiabetic Mechanisms
Chemical analysis of A. quinata fruit extract led to the isolation of stigmasterol-3-O-β-D-glucoside, maslinic acid, scutellaric acid, hederagenin, akebia saponin PA, hederacoside C, and hederacolchiside F. Hederacoside C and hederacolchiside F weakly increased glucose-stimulated insulin secretion (GSIS) without inducing cytotoxicity. Stigmasterol-3-O-D-glucoside, maslinic acid, scutellaric acid, hederagenin, and akebia saponin PA increased the glucose stimulation index by more than a threshold amount. Although further studies are necessary, findings highlighted the potential of stigmasterol-3-O-β-D-glucoside, isolated from A. quinata, as an attractive drug candidate for the treatment and prevention of type 2 diabetes mellitus.
Antioxidant and Antiglycation Mechanisms
Akebia quinata fruit extract (AQFE) was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs) from oxidative stress and inhibits cellular senescence induced by oxidative stress. Akebia quinata has been reported to contain chlorogenic acid and triterpenoid saponins such as oleanolic acid and hederagenin. Chlorogenic acid and triterpenoid saponins were reported to contribute antioxidant and antiglycation activity.
Neuroprotective Mechanisms
A. quinata significantly increased the expression of serotonin, adrenaline, and noradrenaline in the brain and reduced brain atrophy, due to the presence of chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C. The triterpene glucoside of A. quinata stems, Akequintoside F, was reported to have an inhibitory effect on Aβ42 fibrillogenesis, and it was suggested that A. quinata could be considered a non-toxic source for treating Alzheimer's disease.
Anticancer Mechanisms
The pentacyclic triterpene saponins of Lardizabalaceae, such as akebia saponin E, inhibited the proliferation of carcinoma cells. More recently, the anticancer properties of A. quinata seed extract (AQSE) were investigated, focusing on its role in inducing apoptosis and immunogenic cell death (ICD) in non-small cell lung cancer (NSCLC). In human NSCLC cell lines (A549 and H460), AQSE exhibited potent cytotoxic effects in a dose-dependent manner. AQSE triggered hallmark features of ICD, characterized by surface exposure of calreticulin and the release of extracellular HMGB1 and ATP. An in vivo vaccination assay using a syngeneic mouse model demonstrated that immunization with AQSE-treated dying cells significantly suppressed tumor growth upon rechallenge, confirming the establishment of antitumor immunological memory.
Antibacterial Mechanisms
The antibacterial activity of A. trifoliata against Staphylococcus aureus, Bacillus thuringiensis, Escherichia coli, Salmonella enterica, and Shigella dysenteriae has been extensively studied in vitro, which pointed to the presence of triterpenoids 2α,3β-dihydroxy-23-oxo-olean-12-en-28-oic acid, maslinic acid, arjunolic acid, oleanolic acid, 3-epi-oleanolic acid, and 2α,3β-dihydroxyolean-13(18)-en-28-oic acid.
Enzyme Inhibition
A. quinata extracts showed antioxidant, antibacterial (against B. subtilis and A. fischeri), and enzyme (AChE, BChE, tyrosinase, β-glucuronidase, and α-amylase) inhibition properties. α-Amylase participates in carbohydrate metabolism in the human body; inhibitors of α-amylase limit the digestion and absorption of carbohydrates and therefore may prevent diabetes, obesity, hyperglycemia, and hyperlipemia.
5. Scientific Evidence by Area of Use
5.1 Anti-Inflammatory and Analgesic Effects
The anti-inflammatory and analgesic evidence for Akebia is primarily preclinical. Research results indicate that Akebia saponin D has anti-nociceptive and anti-inflammatory effects. Akebia saponin D, which originates from Dipsacus asper Wall, has been used as a tonic, an analgesic, and an anti-inflammatory agent for the therapy of low back pain, rheumatic arthritis, traumatic hematoma, habitual abortion, and bone fractures in traditional Chinese medicine.
Evidence strength: Preclinical only (in vitro cell culture and animal models). Standard analgesic testing methods including the formalin test, acetic acid-induced abdominal writhing, and hot plate test were used in rodent models. Pharmacological studies have demonstrated the anti-inflammatory, antitumor, antihypertensive, antibacterial, and analgesic properties of Akebiae Caulis. No randomized controlled clinical trials in human subjects have been reported in the published literature as of the sources reviewed.
5.2 Diuretic Effects
Extracts of the fruits have been shown to have diuretic properties (reduction of water-weight), hepato-regenerative, neuroprotective, analgesic, anti-inflammatory, and anti-obesity effects. An evaluation of the diuretic and hemodynamic effects of extract from Akebia quinata in dogs was reported in the veterinary literature, showing diuretic potential. Studies on the biological activity of A. quinata have demonstrated the diuretic and neuroprotective effects of the stem extract.
Evidence strength: Animal and in vitro only. No human clinical trials specifically assessing diuretic endpoints have been identified in the peer-reviewed sources consulted.
5.3 Anti-Obesity and Hypolipidemic Effects
Mice fed a high-fat diet (HFD) supplemented with AQE showed ameliorated HFD-induced hyperlipidemia, hyperleptinemia, excessive gains in body and adipose tissue weight, and improved serum lipid profiles. The dose used in this mouse study was AQE at 400 mg/kg/day for 6.5 weeks.
In a study using bioconverted extract, treatment with bioconverted fruit extract of A. quinata (BFE) at concentrations of 20 and 40 μg reduced intracellular lipids by 74.8% (p < 0.05) and 54.9% (p < 0.01), respectively, without inducing cytotoxicity in preadipocytes. Moreover, oral administration of BFE at the concentration of 300 mg/kg/day significantly reduced body and adipose tissue weights (p < 0.01) in HFD-induced obese rats.
Evidence strength: Animal (rodent models) and in vitro (3T3-L1 adipocyte cell line). No published human clinical trials. All anti-obesity evidence is preclinical.
5.4 Antidiabetic Effects
The anti-inflammatory and antidiabetic effects of compounds, mainly akebia saponin D and stigmasterol-3-O-β-D-glucoside, isolated from the stem and fruit of A. quinata, have been reported. Mechanistic studies in the INS-1 rat pancreatic β-cell line showed that multiple isolated compounds from A. quinata fruits enhanced glucose-stimulated insulin secretion, with the value of glucose stimulation index following treatment with stigmasterol-3-O-D-glucoside being similar to that after treatment with the same concentration of gliclazide.
Evidence strength: In vitro (cell lines) and preclinical animal models. No human clinical evidence is available. Results are considered preliminary and hypothesis-generating.
5.5 Hepatoprotective Effects
The hepatoprotective, anti-skin-aging, anti-obesity, and hypolipidemic effects of the fruit extract of A. quinata have been demonstrated in biological activity studies. An in vivo study pointed to the potential reduction of the ethanol concentration in blood in mice with alcohol-induced hepatotoxicity. This suggests that A. quinata extracts can be used as a competitive hangover beverage with a beneficial function on hangover relief.
Evidence strength: Animal studies only. No clinical human trial data are available in the sources reviewed.
5.6 Neuroprotective Effects
Neuroprotective evidence is largely preclinical. A. quinata significantly increased the expression of serotonin, adrenaline, and noradrenaline in the brain and reduced brain atrophy, attributed to the presence of chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C. The identification of Akequintoside F as an inhibitor of Aβ42 fibrillogenesis, a hallmark of Alzheimer's disease pathology, suggests a potential but currently unvalidated neuroprotective role.
Evidence strength: Preclinical (in vitro and animal). No human clinical trial data.
5.7 Anticancer and Cytotoxic Effects
Studies have proven the antibacterial and anticancer (liver and stomach) effects of Akebia species. Bioassay-guided fractionation revealed that the anticancer activity of A. quinata seed extract was primarily concentrated in the ethyl acetate fraction. These findings suggest that AQSE exerts anticancer effects via the induction of apoptosis and ICD, highlighting its potential as a promising natural candidate for the development of novel therapeutic strategies against NSCLC.
Akebia quinata is a saponin-rich medicinal plant that exhibits diverse pharmacological properties; however, studies on its seeds are limited, and their immunomodulatory activity in cancer remains largely unexplored.
Evidence strength: In vitro (human cancer cell lines) and one syngeneic mouse model study. All cancer-related evidence is preclinical. No human data.
5.8 Skin Aging and Cosmetic Applications
Findings demonstrated that AQFE protects against glucose-mediated glycation in vitro. Additionally, AQFE clearly prevented glycation in human skin explants. AQFE has the potential to inhibit cellular senescence by oxidative stress in HDF cells with no skin primary irritation in humans. The efficacy of AQFE as an anti-skin aging agent was clinically validated.
This represents one of the few areas where Akebia research has been extended to an ex vivo human tissue model and preliminary clinical validation. However, this study was limited in scope and scale and was not a large randomized controlled trial. The strong antioxidant activity makes Akebia stems widely used in cosmetics, health care products, and food.
Evidence strength: Mixed in vitro / ex vivo (human skin explants) with limited clinical component. Cosmetic applications appear more advanced than internal medicine claims, but large-scale clinical trial data are lacking.
5.9 Antifatigue Effects
An animal-based study (referenced in the literature) investigated A. quinata aqueous extract as a novel anti-fatigue agent in mice exposed to chronic restraint stress. This area of research remains preclinical, with results restricted to rodent models of stress-induced fatigue.
Evidence strength: Animal models only. No human trials identified.
6. Body Systems and Health Areas
Based on the published phytochemical and preclinical literature, Akebia species have been associated with the following body systems and health domains:
- Urinary system: Diuretic effects; historically used for urinary tract infections, dysuria, and edema. This is the most historically documented traditional indication across TCM, Kampo, and Korean medicine.
- Musculoskeletal and pain: Analgesic and anti-inflammatory use for rheumatic pain, low back pain, and edema. Aqueous and alcoholic extracts were mainly used to treat edema, hypothermia, and rheumatic pain.
- Metabolic system: Preclinical evidence for anti-obesity, hypolipidemic, and antidiabetic effects via AMPK activation and GSIS enhancement.
- Hepatic system: Hepatoprotective and hepato-regenerative effects demonstrated in preclinical studies.
- Nervous system: Neuroprotective effects including upregulation of monoamine neurotransmitters and inhibition of Aβ42 fibrillogenesis observed preclinically.
- Reproductive system: Traditional emmenagogue and galactogogue use (stimulating menstruation and promoting lactation) documented in ethnobotanical literature.
- Integumentary system: Antioxidant and antiglycation effects on skin; anti-aging applications in cosmetics.
- Oncology: Preclinical cytotoxicity against hepatic, gastric, and non-small cell lung cancer cell lines.
- Cardiovascular system: Antihypertensive and cardiotonic effects noted in traditional use and preclinical pharmacology.
It must be emphasized that biological activity studies of A. quinata stem, leaf and/or fruit extracts have confirmed diuretic, hepatoregenerative, neuroprotective, analgesic, anti-inflammatory, and anti-obesity effects and an influence on ethanol metabolism — but nearly all such evidence derives from preclinical (in vitro and animal) research. Human clinical evidence remains very limited across all areas.
7. Dosage Forms and Dosages Reported in Studies
There is no established human clinical dose for Akebia-based products, as no large clinical trials have been completed. The following dosages appear in the preclinical literature and should not be interpreted as recommended human doses:
- AQE (total extract) — mice: 400 mg/kg/day for 6.5 weeks in high-fat diet-fed mice, assessing anti-obesity and hypolipidemic endpoints.
- Bioconverted fruit extract (BFE) — rats: Oral administration of BFE at 300 mg/kg/day significantly reduced body and adipose tissue weights in HFD-induced obese rats.
- BFE — cell culture (3T3-L1 adipocytes): BFE at concentrations of 20 μg and 40 μg reduced intracellular lipids by 74.8% and 54.9%, respectively, without inducing cytotoxicity in preadipocytes.
- Quality marker concentrations in seeds: Analysis of A. quinata seeds confirmed that eight marker components were found in concentrations of 0.42–9.07 mg/g.
Dosage Forms
The primary dosage forms described in the ethnopharmacological and scientific literature include:
- Dried crude drug (stem): The dried and sliced stem (Akebiae Caulis / Mu tong) used as a decoction. This is the traditional preparation form in TCM and Kampo.
- Dried ripe fruit (Akebiae Fructus / Bayuezha): Used in decoctions and as food.
- Aqueous extract (decoction): The traditional preparation, used for diuretic and anti-inflammatory purposes.
- Ethanolic extract: Used widely in modern research studies (typically 70% ethanol extraction).
- Herbal tea: The dried fruits, leaves, and stem are ingredients of a traditional Korean weight-loss tea used as a folk remedy.
- Cosmetic preparations: The strong antioxidant activity makes Akebia stems widely used in cosmetics, health care products, and food.
8. Safety Considerations and Drug Interactions
8.1 The Critical Adulteration and Substitution Risk: Aristolochic Acid
The most serious safety issue associated with Akebia products is not inherent to the plant itself, but relates to the historical substitution of genuine Akebia stems with the highly toxic and carcinogenic herb Aristolochia manshuriensis. This is a well-documented, fatal substitution error with regulatory consequences worldwide.
Mu-tong (Akebiae Caulis) may be adulterated by an aristolochic acid-containing herb, Guan-mu-tong (Aristolochiae Manshuriensis Caulis), derived from the stem of Aristolochia manshuriensis Komarov (Aristolochiaceae). Guan-mu-tong contains nephrotoxic and carcinogenic aristolochic acids (AAs), which cause aristolochic acid nephropathy (AAN) and upper tract urothelial carcinomas (UTUC), with the inadvertent use of adulterated Guan-mu-tong by consumers leading to possible renal failure.
Research has directly compared the nephrotoxic potential of the adulterant versus genuine Akebia: Although Aristolochia manshuriensis, which was incriminated in the Japanese variety of Chinese herbs nephropathy, has been recently shown to be nephrotoxic in rats, Akebia quinata (AQ) has similar components to AM but is free of aristolochic acids. Nephrotoxicity caused by Aristolochiae Manshuriensis Caulis can be attributed to the use of this species instead of Akebiae Caulis, as the toxicity and chemical compositions of the two are obviously different. The latter exerts negligible saponin toxicity, whereas the former contains highly toxic aristolochic acid and its lactam.
Cases have been reported of Chinese herbal medicine in which Aristolochia manshuriensis had been substituted for Akebia quinata. Following reports of Aristolochia-related nephrotoxicity in Belgian patients, most EU Member States have taken regulatory action to protect the public from unlicensed medicines containing toxic Aristolochia species. In many Member States, Stephania species have also been restricted because of the risk of substitution. Unless appropriate quality control procedures are in place, the prohibition of species at risk of being confused with Aristolochia species needs to be considered. These include: Akebia quinata, Akebia trifoliata, Clematis armandii, Clematis montana, Cocculus orbiculatus, Cocculus laurifolius, Cocculus trilobus, and Stephania tetrandra.
Among the plants that the FDA considers to have a possibility of adulteration with Aristolochia are species of Akebia, Clematis, Cocculus, Diploclisia, Menispermum, Sinomenium, and Stephania. Nephrotoxicity has been reported in association with aristolochic acids. The American Herbal Products Association currently has trade recommendations in place that advise companies using Stephania tetrandra root, Clematis armandii stem, or Akebia stem to test for Aristolochia adulteration.
8.2 Regulatory Status Regarding Aristolochic Acid
The biological origin of Akebiae Caulis is diverse. This diversity has contributed historically to substitution errors. Aristolochiae Manshuriensis Caulis (Aristolochiaceae) contains aristolochic acid that has raised concerns globally because of its nephrotoxicity. Clarifying the biological origin of traditional herbal medicines is critical for their safe and effective use.
8.3 Genotoxic Potential of Akebia Extracts
Effect-directed profiling of A. quinata extracts surprisingly revealed up to four genotoxins. The multiplex bioautograms pointed to up to four antagonistic compounds concerning estrogenic and androgenic activity in two leaf and one fruit extracts, whereas no androgens were detected. The identity and clinical significance of these genotoxic fractions require further investigation and represent an area of safety concern meriting attention in any development of Akebia-based products.
8.4 Saponin-Related Considerations
Like many saponin-rich herbs, Akebia products may carry dose-dependent risks related to their saponin content. Genuine Akebiae Caulis exerts negligible saponin toxicity at customary doses. However, the dose-response profile of individual saponins at high concentrations has not been fully characterized in human studies.
8.5 Resource Scarcity and Adulteration Risk
The resource reserve of Akebia plants has dramatically declined due to habitat destruction, which has seriously affected their adequate supply and sustainable utilization. This scarcity increases the practical risk that commercial supplies may incorporate lower-quality or misidentified material, underscoring the need for rigorous botanical authentication and quality control testing in any commercial product.
8.6 Pregnancy and Lactation
Akebia has been traditionally classified as an emmenagogue (stimulating menstrual flow). Given this traditional classification and the lack of safety data in pregnancy, its use during pregnancy should be approached with caution. No controlled human safety studies in pregnant or lactating women are available in the reviewed literature.
9. Summary of Evidence Quality
Across all investigated health applications, the current evidence base for Akebia consists predominantly of in vitro cell culture studies and animal model experiments. The aim of peer-reviewed reviews has been a detailed assessment of the scientific literature on the genus Akebia, with particular emphasis on A. quinata and A. trifoliata, providing information on botanical, ecological, and chemical characteristics. Professional research on biological activity, phytochemistry, and cosmetological potential has been reviewed and assessed. Despite a rich traditional history and promising preclinical findings across multiple mechanistic pathways, the transition to human clinical trials has not yet been substantiated in the published literature. Well-designed, randomized, placebo-controlled clinical trials are needed before any efficacy claims in human health can be established with confidence.
References
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