Other Names
4',7-Dihydroxy-8-C-glucosylisoflavone8-(β-D-Glucopyranosyl)-4',7-dihydroxyisoflavone8-(β-D-Glucopyranosyl)-7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-oneDaidzein-8-C-glucosideKakoneinNPI 031GPuerarin
Kakkonein is one of the accepted common names for puerarin, a naturally occurring isoflavone C-glucoside. Puerarin is an isoflavone glycoside derived from Pueraria lobata (Willd.) Ohwi and has been identified as a pharmacologically active component with diverse benefits. The name "Kakkonein" appears in the peer-reviewed literature as a direct synonym: a systematic review and meta-analysis of diabetic peripheral neuropathy trials explicitly used "Puerarin injection" and "Kakkonein injection" as interchangeable search terms, connected with "OR," confirming that the two names refer to the same substance.
Chemical identity: Puerarin (C21H20O9) is an isoflavone glycoside and the major bioactive ingredient of Gegen. Its CAS registry number is 3681-99-0 and its molecular weight is 416.38 g/mol. Puerarin is a C-glucoside of the isoflavone daidzein extracted from Pueraria. The attachment of a glucose unit at the C-8 position of the daidzein aglycone via a C–C bond (rather than the more common O-glycoside bond) defines puerarin's structural class as an isoflavone C-glycoside and distinguishes its pharmacokinetic behavior from many other plant isoflavones.
Botanical source: Pueraria lobata (Willd.) (Family: Fabaceae), a wild leguminous creeper, possesses a high content of flavonoids, coumarins, and isoflavones such as daidzein, puerarin, and daidzin-4′,7-diglucoside. Puerarin can also be isolated from several leguminous plants of the genus Pueraria, such as Pueraria tuberosa (Willd.) and Pueraria thomsonii Benth. Depending on growing conditions, the total isoflavone content of kudzu root varies from 1.77–12.0%, with puerarin in the highest concentration, followed by daidzin and daidzein.
Plant description and distribution: The huge root, which can grow to the size of a human, is the source of medicinal preparations used in Traditional Chinese Medicine and modern herbal products. Kudzu grows in most shaded areas in mountains, fields, along roadsides, thickets, and thin forests throughout most of China and the southeastern United States.
Parts used and co-occurring compounds: The flower of P. lobata (Puerariae Flos) contains various bioactive substances such as triterpenoidal saponins and isoflavonoids. Isoflavones are the major active compounds contained in the crude Pueraria lobata drug and its preparations; nine isoflavones have been isolated and purified, including 3'-hydroxypuerarin, puerarin, 3'-methoxypuerarin, and daidzin. Additional compound classes from Pueraria include flavonols, coumestrols, triterpenoid saponins, xanthones, puerariafurans, lignans, and sterols.
Common dosage forms: Due to the poor water-solubility and liposolubility of puerarin, its applications are limited; so far, only puerarin injections and eye drops are approved on the market in China. In China, the injection form of puerarin, including Puerarin Injection, Puerarin and Glucose Injection, as well as Puerarin and Sodium Chloride Injection, has been approved as a vasodilator for clinical treatment of coronary heart disease, angina, myocardial infarction (MI), retinal vein occlusion, and sudden deafness. Outside formal pharmaceutical channels, puerarin/kakkonein is available as an oral dietary supplement in capsule or tablet form, and as a standardized root powder or extract.
Kudzu root has been known for centuries in Traditional Chinese Medicine as ge-gen. The first written mention of the plant as a medicine is in the ancient herbal text of Shen Nong (circa A.D. 100). For over two thousand years, Chinese herbalists have known of the medicinal value of Ge Gen (Japanese kudzu, English Pueraria lobata). In the Handbook of Prescriptions for Emergency Treatments of 340 AD, the plant including the flower was prescribed as a treatment for alcohol intoxication. A number of herbal remedies containing Pueraria lobata are still commonly used in China to dispel drunkenness.
In Traditional Chinese Medicine, kudzu root is used in prescriptions for the treatment of wei, or "superficial," syndrome (a disease that manifests just under the surface—mild, but with fever), thirst, headache, and stiff neck with pain due to high blood pressure. It is also recommended for allergies, migraine headaches, and diarrhea. The historical application for drunkenness has become a major focal point of modern research on kudzu. It is also used in modern Chinese medicine as a treatment for angina pectoris.
The root of Pueraria lobata (Willd.) Ohwi is an important Chinese herb used in China as an herbal medicine, named "Ge-Gen," to treat hypertension and angina pectoris. The high medicinal and nutritional value of the root of P. lobata (Puerariae Radix) has proven to be responsible for its traditional use as an ingredient in soups and Chinese cuisines. Puerariae lobata is widely used as a soup ingredient in the southern part of China. It is also a major pharmaceutical resource for clinical applications. In 2002, Puerariae lobata was approved for use in food and drugs by the Ministry of Health in China.
The plant's use in Japan is documented through the traditional Kampo system, where the formula kakkonto (Ge-gen-tang in Chinese) was derived from classical Chinese medicine. Kakkonto (Ge-gen-tang in Chinese), one of the most frequently prescribed traditional Japanese (Kampo) medicines, is used for treating common cold, shoulder stiffness, or inflammatory diseases of the upper body.
Although the botanical source (Pueraria lobata) contains numerous phytochemicals, puerarin/kakkonein itself is a discrete, isolatable molecule and is understood to be the principal pharmacologically active constituent responsible for many of the plant's documented effects.
Puerarin, an isoflavone, is a chemotaxonomic marker of the genus Pueraria. Many of the bioactivities of the genus Pueraria are attributed to isoflavone glycosides, mainly puerarin. Puerariae Radix contains isoflavonoids and triterpenoidal saponins, which show estrogenic, antidipsotropic, antioxidant, antimutagenic, and antihepatotoxic activities.
Additional isoflavones co-occurring in the root include daidzein, daidzin, and 3'-methoxypuerarin. The major active ingredients in Puerariae lobata are isoflavone compounds, such as puerarin, 3′-methoxypuerarin, daidzin, and daidzein. They are widely present in soybean foods and traditional herbs including Puerariae lobata. While daidzin is structurally related, its mechanism of action in modulating alcohol metabolism differs from that of puerarin: daidzin is recognized as a selective inhibitor of mitochondrial aldehyde dehydrogenase, whereas puerarin's anti-alcohol effects are thought to involve serotonergic and other pathways.
Puerarin (kakkonein) has been shown across preclinical studies to operate through multiple molecular targets and signaling pathways. Major established and proposed mechanisms include:
A systematic analysis of the preclinical investigations of puerarin in CVDs covers atherosclerosis, cardiac hypertrophy, heart failure, diabetic cardiovascular complications, myocardial infarction, stroke, and hypertension. The potential molecular targets of puerarin are also discussed. Clinical trials of puerarin in the treatment of CVDs have been summarized.
In China, puerarin injections carry regulatory approval for several cardiovascular indications. In China and other Asian countries, puerarin is commonly used to prevent and treat cardiovascular and cerebrovascular diseases, including arteriosclerosis, hypertension, heart failure, and myocardial ischemia. It has also been reported to have protective effects on inflammation, hyperlipidemia, and oxidative stress, and was even reported to improve vascular insulin resistance.
A 2025 systematic review and meta-analysis evaluated the efficacy and safety of puerarin injection as adjunctive therapy for chronic heart failure. Subgroup analysis on the total effective rate revealed that puerarin injection doses of 300 mg/day, 400 mg/day, or 500 mg/day all effectively improved total efficacy; however, the 400 mg/day dose exhibited higher homogeneity. However, the quality of the included RCTs was poor, and the quality evaluation of the meta-analysis was rated as LOW.
Evidence strength (cardiovascular): Substantial preclinical (animal and in vitro) evidence exists. Clinical trial data are largely from Chinese RCTs with known methodological limitations including poor blinding and reporting. Regulatory approval in China for intravenous use reflects a clinical evidence base within that jurisdiction, but independent high-quality RCTs meeting Western regulatory standards are lacking. Evidence should be characterized as promising but of low-to-moderate quality overall.
This is one of the most extensively studied clinical applications of puerarin injection. A systematic literature search was performed in seven medical databases from their inception until June 2017. Fifty-three studies with RCTs, totaling 3,284 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager 5.3 software.
The result showed that puerarin injection for the treatment of DPN significantly improved the probability effect of total effective rate by 48% compared with control groups. Analyses of SNCV showed that puerarin injection for the treatment of DPN can significantly increase the conduction velocity of the median nerve and peroneal nerve by 3 m/s.
This meta-analysis demonstrated that puerarin injection may be more effective and safe for the treatment of DPN. However, further and higher quality RCTs are required to prove its efficacy and provide meaningful evidence for clinical treatment due to the poor methodological quality.
A subgroup analysis on patients with DPN treated with puerarin injection combined with epalrestat (in the treatment group) versus epalrestat alone (in the control group) showed that puerarin injection combined with epalrestat therapy could significantly improve the total effective rate by 38% and increase the SNCV of the median nerve and peroneal nerve, compared with the control group.
Evidence strength (DPN): Multiple meta-analyses aggregate a large number of RCTs and report statistically significant improvements in nerve conduction velocity and clinical symptom scores. However, all meta-analyses conclude that included trials are of poor methodological quality, limiting the strength of conclusions. Evidence is suggestive but not definitive by current standards.
Experimental and clinical investigations have reported that puerarin is widely used in the treatment of CVDs, diabetes and its complications, Alzheimer's disease, Parkinson's disease, osteonecrosis, endometriosis, and cancer.
For Parkinson's disease, clinical data consist of small studies examining puerarin as an adjunct to levodopa therapy. The serum levels of antioxidant enzymes (including GSH-PX and SOD) in the experimental group increased markedly and the serum content of MDA strongly decreased after treatment. Given that both edaravone and puerarin have antioxidant effects, it is speculated that they may have additive or synergistic effects in the treatment of PD. These compounds may prevent cell apoptosis, delay the progression of PD, improve clinical symptoms, and alleviate adverse reactions of levodopa by protecting substantia nigra neurons from oxidative stress damage. In terms of UPDRS score and adverse reactions, the therapeutic effect of levodopa combined with edaravone and puerarin was reported as better than that of levodopa alone. However, these clinical studies may not be rigorous.
Evidence strength (neurology): Predominantly preclinical (in vitro and rodent model) evidence for Alzheimer's and Parkinson's disease. Small, methodologically limited clinical studies for Parkinson's disease as adjunct therapy. Evidence is preliminary and insufficient for clinical conclusions without further high-quality human trials.
Historical texts indicate that extracts of the kudzu root (Pueraria lobata) have been used in traditional Chinese herbal medicines to treat drunkenness and alcohol intoxication.
A landmark published pilot study investigated puerarin alone as an intervention in human drinkers. Ten physically and mentally healthy adult volunteers (average age of 25.8 years ± 3.2) who drank on average 17.6 ± 9.7 drinks per week completed the study. Eight were men and two were women. This pilot study indicated that puerarin given alone suppresses alcohol consumption in humans. Given the historic herbal medicine literature of kudzu root extracts and the more recent animal and human studies, the evidence suggests that isoflavones found in the kudzu root can reduce alcohol consumption and do so without adverse effects. This study is the first demonstration that a single isoflavone found in the kudzu root can alter alcohol drinking in humans. These results suggest that alcohol consumption patterns are influenced by puerarin administration and this botanical medication may be a useful adjunct in the treatment of excessive alcohol intake.
The subject population was restricted to moderate to heavy drinkers who did not meet diagnostic criteria for alcohol dependence. Thus the generalizability of the results to a dependent population remains an area for additional research. This study concentrated on drinking behavior in a laboratory setting and did not assess a full range of alcohol's effects.
The safety profile in this setting was notably favorable: the safety and efficacy of puerarin have already been established in humans, especially in China where it is approved for intravenous injection as a vasodilator to treat coronary heart disease, myocardial infarction, and angina. While it is the most prevalent isoflavone in kudzu, its overall potency is lower, so its side effect profile is likely to be less.
Evidence strength (alcohol reduction): Animal studies are supportive. Human evidence is limited to a single small crossover pilot study (n=10). Results are promising but sample sizes are far too small for clinical recommendations. This area requires larger, adequately powered, double-blind RCTs.
Puerarin is a compound from the group of isoflavones, naturally occurring in plants of the genus Pueraria, whose representatives include, among others, Pueraria lobata and Pueraria mirifica. Relatively many scientific studies on the biological activity of puerarin have been conducted so far. It seems that most attention has been paid to the effect of puerarin on bone health.
A 2026 systematic review and meta-analysis specifically evaluated anti-osteoporotic effects in rodent models. Twenty-eight studies involving 570 animals were included. The meta-analysis demonstrated that puerarin significantly increased femoral bone mineral density (BMD) (SMD = 2.95, 95% CI: 2.32 to 3.58, p < 0.00001) and improved the bone microarchitecture by increasing BV/TV, Tb.Th, and Tb.N, and decreasing Tb.Sp. Subgroup analysis revealed that the most pronounced BMD improvement occurred at doses ≥50 mg/kg/day administered for ≥8 weeks.
Consumption of puerarin may be associated with the prevention of bone mass loss and thus can reduce the risk of developing osteoporosis. However, it is necessary to conduct human intervention studies to confirm the effectiveness of such action.
Evidence strength (bone): Consistent and robust preclinical evidence in animal models. No high-quality human clinical trials have been published as of the most recent literature. Evidence is currently animal/in vitro only and cannot be extrapolated directly to humans.
Puerarin has been demonstrated to enhance lipid metabolism by modulating multiple signaling cascades. It has found extensive application in the pharmaceutical, food, and nutraceutical industries. Preclinical studies have shown modulation of AMPK, PPAR-alpha, and SREBP-1c pathways relevant to hepatic lipid accumulation and dyslipidemia.
Experimental and clinical studies have reported that puerarin has been widely used in the treatment of nonalcoholic fatty liver. Evidence in this area remains predominantly from cell-based and rodent studies, with limited human data.
Evidence strength (NAFLD/lipid): Preclinical evidence is mechanistically plausible and consistent. Human clinical evidence is sparse. This area requires well-designed RCTs before conclusions can be drawn about efficacy in humans.
Puerarin/kakkonein is administered in several distinct dosage forms, and the clinically studied doses differ substantially between routes:
Puerarin's pharmacokinetics in rats after oral administration is characterized by rapid absorption, quick elimination, and minimal accumulation. Puerarin has shown no significant toxicity or adverse effects when administered orally, but caution should be exercised during pregnancy. When administered orally, puerarin has shown no significant toxicity or adverse effects. In a study conducted on Sprague-Dawley rats, oral administration of 250 mg/kg puerarin daily for 28 days did not cause any significant alterations in histological, biochemical, and hematological parameters.
In general, the occurrence of puerarin toxicity in animals and humans is low. The most common adverse reactions caused by puerarin are fever, followed by drug-induced dermatitis and hemolytic reactions.
The safety profile differs markedly between oral and intravenous routes. Intravascular administration of puerarin can cause adverse reactions including drug fever, rash, nausea, vomiting, diarrhea, hepatic/renal damage, palpitations, anaphylactic shock, and hemolysis.
Hemolysis: This is the most clinically significant safety concern for intravenous puerarin. Hemolysis and shock are extremely rare but may be the most serious and fatal adverse effects. Puerarin injection causes fever, mainly because puerarin easily passes through the blood-brain barrier and stimulates the hypothalamic thermoregulatory center, leading to fever.
The results showed that adverse drug reactions of puerarin injection occurred mostly in patients aged 50–79 years and the immune/blood system accounted for the majority. Puerarin also induced some relatively uncommon diseases (drug-induced immune hemolytic anemia). Hemolysis largely limited the clinical use of puerarin injections. High concentrations of puerarin-induced hemolysis were linked to changes in membrane lipids and erythrocyte membrane proteins. Different preparations will significantly improve the adverse drug reactions of puerarin.
Due to the short elimination half-life of puerarin in the human body, frequent and high-dose intravenous administration may be required, which may lead to acute side effects such as hemolysis, acute renal failure, and anaphylactic shock.
To improve solubility of puerarin, cosolvents such as propylene glycol, ethylene glycol, and polyvinylpyrrolidone had been added to the clinical injection formulation. However, adverse drug reactions caused by cosolvents after intravenous administration such as vascular stimulation, fever, allergy, and erythrolysis increased year by year. Due to the short elimination half-life, frequent or high doses of injection are needed.
Newer delivery systems have been developed to address this. Different preparations will significantly improve the adverse drug reactions of puerarin. A submicron emulsion of puerarin prepared by a novel complex-phase inversion-high pressure homogenization technology has been shown to reduce hemolysis compared to conventional cosolvent-based injections.
Caution should be exercised when using puerarin during pregnancy. Studies have demonstrated that puerarin can cross the placental barrier, leading to high concentrations in the plasma of fetal rats. This has been associated with decreased embryonic development and viability. Therefore, pregnant women are advised to use puerarin with caution. Chen and Chan studied the reproductive toxicity effect of puerarin and found that puerarin induced apoptosis in the inner cell mass cells in mouse blastocysts, leading to decreased embryo development and viability.
Daidzein and glucuronides are the main metabolites of puerarin and are excreted in the urine and feces. As active substrates of P-glycoprotein, multidrug resistance-associated protein, and multiple metabolic enzymes, the pharmacokinetics of puerarin can be influenced by different pathological conditions and drug-drug interactions. This suggests that puerarin may interact with other substrates or inhibitors of these transporters and enzymes, though specific well-characterized clinical drug interaction data are limited.
Ge-gen contains compounds with potent antioxidant activity, which impair CYP-catalyzed drug metabolism. This cytochrome P450 interaction potential should be considered in patients taking medications metabolized by CYP enzymes, though definitive clinical pharmacokinetic interaction studies are not yet widely published in the literature.
In China, puerarin injection is a licensed pharmaceutical product for cardiovascular and retinal indications. Due to the frequent occurrence of side effects of TCM injection, China has restricted the use of TCM injection in recent years. In most Western markets, puerarin/kakkonein is available as an unregulated dietary supplement under regulations analogous to those applied to botanical extracts.
Health conditions that Kakkonein may help support.
Body systems that Kakkonein may help support.