Puerarin

• Cardiovascular protection
• Neuroprotection
• Antioxidant
• Anti-inflammatory

• Hepatoprotective
• Antidiabetic
• Alcohol craving reduction
• Osteoprotective
• Vasodilatory

Puerarin (daidzein-8-C-glucoside) exerts its diverse biological effects through multiple molecular pathways. As a C-glycosylisoflavone, puerarin possesses a unique structural feature where a glucose molecule is directly attached to the C-8 position of the daidzein backbone via a carbon-carbon bond, rather than through an oxygen atom as in O-glycosides. This C-glycosidic bond is resistant to hydrolysis by glycosidases, contributing to puerarin’s distinct pharmacokinetic profile and biological activities. In the cardiovascular system, puerarin demonstrates potent protective effects through multiple mechanisms.

It promotes vasodilation by activating endothelial nitric oxide synthase (eNOS) through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, leading to increased nitric oxide (NO) production. Puerarin also activates large-conductance calcium-activated potassium (BKCa) channels in vascular smooth muscle cells, causing hyperpolarization and relaxation. Additionally, it inhibits voltage-dependent calcium channels, reducing calcium influx and further promoting vasodilation. These combined effects improve blood flow, reduce blood pressure, and enhance tissue perfusion.

Puerarin exhibits significant cardioprotective effects, particularly in the context of ischemia-reperfusion injury. It activates the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which enhances energy metabolism and reduces oxidative stress in cardiomyocytes. Puerarin also inhibits the opening of the mitochondrial permeability transition pore (mPTP), preserving mitochondrial function and preventing apoptosis during ischemia-reperfusion. Furthermore, it upregulates the expression of heat shock proteins (HSPs), particularly HSP70, which protect cardiomyocytes from stress-induced damage.

As an antioxidant, puerarin scavenges reactive oxygen species (ROS) and free radicals through its hydroxyl groups on the isoflavone structure. It neutralizes superoxide anions, hydroxyl radicals, and other reactive species, preventing oxidative damage to cellular components including lipids, proteins, and DNA. Beyond direct scavenging, puerarin enhances endogenous antioxidant defenses by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. By promoting Nrf2 nuclear translocation and binding to antioxidant response elements (AREs), puerarin upregulates the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1).

This dual approach to antioxidant protection—direct scavenging and enhancement of endogenous antioxidant systems—provides comprehensive defense against oxidative stress. As an anti-inflammatory agent, puerarin inhibits the nuclear factor-kappa B (NF-κB) signaling pathway by preventing IκB kinase (IKK) activation and subsequent nuclear translocation of NF-κB, thereby reducing the expression of pro-inflammatory genes. It suppresses the production of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), while inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Puerarin also modulates the mitogen-activated protein kinase (MAPK) signaling pathways, including p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), further contributing to its anti-inflammatory properties.

In the central nervous system, puerarin exhibits neuroprotective effects through multiple mechanisms. It crosses the blood-brain barrier, though to a limited extent due to its hydrophilicity, and protects neurons from oxidative stress and excitotoxicity. Puerarin inhibits glutamate-induced calcium influx, reduces ROS production, and maintains mitochondrial function in neurons. It also enhances the expression of brain-derived neurotrophic factor (BDNF) and activates the PI3K/Akt/glycogen synthase kinase-3β (GSK-3β) pathway, promoting neuronal survival and synaptic plasticity.

Puerarin has demonstrated particular efficacy in cerebral ischemia models, where it improves cerebral blood flow, reduces infarct size, and enhances neurological recovery. Puerarin’s effects on alcohol consumption and craving involve modulation of the dopaminergic system. It inhibits alcohol dehydrogenase and aldehyde dehydrogenase, altering alcohol metabolism and potentially reducing the rewarding effects of alcohol. Puerarin also modulates dopamine release and signaling in the brain’s reward pathways, which may contribute to its ability to reduce alcohol cravings.

Additionally, it has anxiolytic effects through modulation of the gamma-aminobutyric acid (GABA) system, which may help manage anxiety associated with alcohol withdrawal. In metabolic regulation, puerarin improves insulin sensitivity and glucose metabolism through multiple mechanisms. It activates AMPK in skeletal muscle and liver, leading to increased glucose uptake, enhanced glycolysis, and reduced gluconeogenesis. Puerarin also promotes the translocation of glucose transporter 4 (GLUT4) to the cell membrane in muscle and adipose tissue, further enhancing glucose uptake.

Additionally, it protects pancreatic β-cells from oxidative stress and inflammation, preserving insulin secretion capacity. Puerarin exhibits hepatoprotective effects by reducing oxidative stress, inflammation, and lipid accumulation in the liver. It activates AMPK and peroxisome proliferator-activated receptor alpha (PPARα), promoting fatty acid oxidation and reducing lipogenesis. Puerarin also inhibits the activation of hepatic stellate cells and reduces collagen production, suggesting potential anti-fibrotic effects in chronic liver diseases.

As a phytoestrogen, puerarin has weak estrogenic activity due to its structural similarity to estradiol. It binds to estrogen receptors (ERs), particularly ER-β, with much lower affinity than estradiol. This weak estrogenic activity contributes to some of puerarin’s biological effects, including its osteoprotective properties. In bone, puerarin inhibits osteoclast differentiation and activity while promoting osteoblast proliferation and differentiation, leading to increased bone formation and reduced bone resorption.

The C-glycosidic bond in puerarin contributes to its unique pharmacological profile compared to its aglycone daidzein. This structural feature affects its bioavailability, metabolism, and tissue distribution, potentially leading to different biological activities and therapeutic applications. The glucose moiety enhances water solubility while maintaining some of the lipophilicity of the isoflavone backbone, creating a balanced structure that can interact with various molecular targets.

Optimal dosage ranges for puerarin vary depending on the form and intended use. In clinical studies and traditional use, the following dosage ranges have been established: For standardized kudzu root extract (typically containing 30-40% puerarin), the common dosage range is 300-1200 mg daily, corresponding to approximately 90-480 mg of puerarin. For isolated puerarin supplements, typical dosages range from 100-500 mg daily. In China, where puerarin is approved as a pharmaceutical, intravenous dosages typically range from 200-600 mg daily for acute conditions, but this form is not available in most Western countries.

It’s important to note that puerarin’s bioavailability is relatively low when taken orally (approximately 7-15%), so higher oral doses are often required to achieve therapeutic effects compared to intravenous administration. For most health applications, starting with a lower dose (e.g., 100-200 mg of puerarin or 300-500 mg of standardized kudzu extract) and gradually increasing as needed and tolerated is recommended. Divided doses (2-3 times daily) are often preferred due to puerarin’s relatively short half-life (approximately 4-6 hours).

Puerarin has relatively low oral bioavailability, estimated at approximately 7-15% in human studies. This limited bioavailability is primarily due to its C-glycosidic structure and physicochemical properties. Unlike O-glycosides, the C-glycosidic bond in puerarin (where glucose is directly attached to the C-8 position of daidzein via a carbon-carbon bond) is resistant to hydrolysis by intestinal and hepatic glycosidases. This means that puerarin is primarily absorbed intact rather than being converted to its aglycone (daidzein) in the gastrointestinal tract.

Puerarin has moderate water solubility due to its glucose moiety but limited lipid solubility due to its overall structure, creating a balance that affects its passive diffusion across cell membranes. Absorption occurs through a combination of passive diffusion and active transport mechanisms, including sodium-dependent glucose transporters (SGLTs) and possibly other transporters. Once absorbed, puerarin undergoes limited phase II metabolism, primarily glucuronidation and sulfation in the liver. The C-glycosidic bond makes puerarin less susceptible to extensive metabolism compared to many other flavonoids.

Puerarin demonstrates a relatively short half-life of approximately 4-6 hours in humans, necessitating multiple daily doses for sustained therapeutic effects. Puerarin has demonstrated the ability to cross the blood-brain barrier, though to a limited extent due to its hydrophilicity, which is relevant for its neuroprotective effects. In traditional Chinese medicine, puerarin is often administered intravenously for acute conditions, bypassing the limitations of oral bioavailability, though this form is not commonly available outside of China.

Liposomal formulations – can increase bioavailability by 2-4 fold by enhancing cellular uptake and protecting puerarin from degradation, Nanoemulsion formulations – can increase bioavailability by 3-5 fold by improving solubility and enhancing intestinal permeability, Self-emulsifying drug delivery systems (SEDDS) – improve dissolution and absorption in the gastrointestinal tract, Phospholipid complexes – enhance lipid solubility and membrane permeability, Cyclodextrin inclusion complexes – improve aqueous solubility while maintaining stability, Solid dispersion techniques – enhance dissolution rate and solubility, Combination with piperine – inhibits P-glycoprotein efflux and intestinal metabolism, potentially increasing bioavailability by 30-60%, Microemulsions – provide a stable delivery system with enhanced solubility, Co-administration with fatty meals – can increase absorption by stimulating bile secretion and enhancing lymphatic transport, Micronization and nanosizing – reduce particle size to increase surface area and dissolution rate

Puerarin is best absorbed when taken with meals containing some fat, which can enhance solubility and stimulate bile secretion, improving dissolution and absorption. Due to its relatively short half-life (4-6 hours), divided doses (2-3 times daily) are recommended for maintaining consistent blood levels throughout the day. For cardiovascular benefits, consistent daily dosing is important, with some evidence suggesting that morning and evening doses may be particularly beneficial for managing blood pressure fluctuations throughout the day. For neuroprotective effects, consistent daily dosing is important for maintaining protective mechanisms against oxidative stress and neuroinflammation.

For alcohol craving reduction, some studies suggest taking puerarin 2-3 hours before anticipated alcohol consumption, while others support consistent daily dosing for cumulative effects. The timing may depend on individual patterns of alcohol use and response to puerarin. For menopausal symptom relief, consistent daily dosing is recommended, with some women reporting better results when taking puerarin in the morning for hot flashes that occur during the day, or in the evening for night sweats. For diabetes support, taking puerarin with meals may enhance its effects on postprandial glucose levels.

Enhanced delivery formulations like liposomes or nanoemulsions may have different optimal timing recommendations based on their specific pharmacokinetic profiles, but generally follow the same principles of taking with food for optimal absorption. Traditional preparation methods, such as decoctions of kudzu root, may have different absorption characteristics compared to modern extract formulations, but are generally also recommended to be consumed with meals.

• Gastrointestinal discomfort (mild to moderate, common)
• Nausea (uncommon)
• Headache (uncommon)
• Dizziness (uncommon)
• Hypotension (uncommon, primarily with higher doses)
• Allergic reactions (rare)
• Flushing (uncommon)
• Palpitations (rare)
• Menstrual changes in women (uncommon, due to phytoestrogenic effects)
• Increased bleeding time (rare, primarily with high doses)

• Pregnancy and breastfeeding (due to phytoestrogenic effects and insufficient safety data)
• Hormone-sensitive conditions including hormone-dependent cancers (breast, uterine, ovarian) due to phytoestrogenic effects
• Scheduled surgery (discontinue 2 weeks before due to potential effects on blood flow and clotting)
• Individuals with severe hypotension (due to vasodilatory effects)
• Individuals with known allergies to plants in the Fabaceae family (including kudzu, soybeans, peanuts)
• Individuals with severe liver or kidney disease (due to limited data on metabolism and excretion in these populations)
• Individuals taking medications for cardiovascular conditions (due to potential interactions)
• Individuals with bleeding disorders (due to potential antiplatelet effects)

• Anticoagulant and antiplatelet medications (may enhance antiplatelet effects, potentially increasing bleeding risk)
• Antihypertensive medications (may enhance blood pressure-lowering effects)
• Hormone replacement therapy and hormonal contraceptives (may interfere with or enhance effects due to phytoestrogenic activity)
• Cytochrome P450 substrates (may inhibit CYP1A2, CYP2B6, CYP2C9, and CYP3A4, potentially affecting the metabolism of drugs that are substrates for these enzymes)
• Alcohol (may alter alcohol metabolism and effects)
• Antidiabetic medications (may enhance blood glucose-lowering effects)
• Sedatives and CNS depressants (potential for additive effects)
• Drugs requiring active transport for absorption (potential competition for transporters)
• Hepatically metabolized drugs (potential for competition for metabolic enzymes)
• Drugs with narrow therapeutic indices (warfarin, digoxin, etc.) require careful monitoring due to potential interactions

Based on clinical studies and traditional use, the upper limit for puerarin supplementation is generally considered to be 500-600 mg daily for isolated puerarin or 1200-1500 mg daily for standardized kudzu extract (30-40% puerarin). Higher doses have been used in clinical settings, particularly for intravenous administration in China, but these should only be administered under medical supervision. For general supplementation, doses exceeding these levels are not recommended without medical supervision due to potential side effects including hypotension, increased bleeding risk, and hormonal effects. Individuals with pre-existing cardiovascular conditions, bleeding disorders, or hormone-sensitive conditions should use lower doses and consult with healthcare providers before use.

The safety profile of puerarin is generally favorable at recommended doses, with most side effects being mild and transient. However, the phytoestrogenic properties and potential for drug interactions necessitate caution, particularly with long-term use or in vulnerable populations. Acute toxicity studies in animals have shown relatively low toxicity, with LD50 values well above any reasonable supplemental dose. Chronic toxicity studies suggest that long-term use at moderate doses is generally well-tolerated, though hormonal effects may accumulate over time.

In the United States, puerarin is not approved by the FDA as a drug. Kudzu root extracts containing puerarin are regulated as dietary supplements under the Dietary Supplement Health and Education Act (DSHEA) of 1994. Manufacturers cannot make specific disease treatment claims but may make general structure/function claims with appropriate disclaimers. The FDA has not evaluated the safety or efficacy of puerarin specifically.

Kudzu root is generally recognized as safe (GRAS) when used in traditional amounts as an herb or supplement. Puerarin injection, which is used in China for various cardiovascular and cerebrovascular conditions, is not approved for use in the United States.

China: In China, puerarin has been approved as a pharmaceutical drug since the 1990s. Puerarin injection is included in the Chinese Pharmacopoeia and is widely used in clinical practice for treating coronary heart disease, angina pectoris, cerebral infarction, and diabetic complications. It is available by prescription only and is administered in hospital settings. Kudzu root (Ge Gen) is officially listed in the Chinese Pharmacopoeia as a traditional Chinese medicine and is available as various oral preparations including tablets, capsules, and traditional decoctions.

Japan: In Japan, kudzu root (kakkonto) is recognized as a traditional Kampo medicine ingredient and is included in several approved Kampo formulations for treating the common cold, influenza, and headaches. Isolated puerarin is not specifically approved as a pharmaceutical but is available as a component of various dietary supplements.

Korea: In South Korea, kudzu root (galgeun) is recognized as a traditional herbal medicine and is included in the Korean Pharmacopoeia. Puerarin as an isolated compound is primarily used in research rather than as an approved therapeutic agent, though it is available in some dietary supplements.

Eu: In the European Union, puerarin is not approved as a medicinal product. Kudzu root extracts are primarily regulated as food supplements under the Food Supplements Directive (2002/46/EC). The European Food Safety Authority (EFSA) has not issued specific opinions on puerarin or kudzu root. Some EU countries may have specific national regulations regarding kudzu root preparations.

Uk: In the United Kingdom, kudzu root extracts are regulated as food supplements. They are not licensed as medicines and cannot be marketed with medicinal claims. The Medicines and Healthcare products Regulatory Agency (MHRA) has not issued specific guidance on puerarin or kudzu root.

Canada: Health Canada regulates kudzu root extracts as Natural Health Products (NHPs). Several products containing kudzu root have been issued Natural Product Numbers (NPNs), allowing them to be sold with specific health claims, primarily related to its traditional use in herbal medicine. Isolated puerarin is not specifically approved as a standalone ingredient.

Australia: The Therapeutic Goods Administration (TGA) regulates kudzu root extracts as complementary medicines. Several products containing kudzu root are listed on the Australian Register of Therapeutic Goods (ARTG). Traditional use claims are permitted with appropriate evidence of traditional use. Puerarin as an isolated compound is not specifically regulated.

Medium

Isolated puerarin supplements typically cost $0.50-$2.00 per day for effective doses (100-500 mg daily). Standardized kudzu root extracts (30-40% puerarin) typically cost $0.30-$1.50 per day for basic extracts (300-1200 mg daily) and $1.50-$3.00 per day for premium, highly standardized formulations. Pharmaceutical-grade puerarin injection (available in China) costs approximately $5-$15 per day for typical clinical doses (200-600 mg daily), though

this form is not commonly available outside of China. Dried kudzu root for traditional decoctions is the most cost-effective option, typically costing $0.10-$0.30 per day, though

it provides less consistent and potentially lower amounts of puerarin.

For cardiovascular support, puerarin offers moderate to good value compared to many pharmaceutical interventions for conditions like coronary artery disease and hypertension. Clinical studies have demonstrated significant improvements in symptoms, electrocardiogram results, and cardiac function in patients with coronary artery disease, with minimal side effects and at a fraction of the cost of many conventional medications. The long-term benefits for cardiovascular health may justify the moderate cost of high-quality extracts. For neuroprotection, particularly in the context of stroke recovery and prevention, puerarin offers promising value.

Meta-analyses of clinical trials in China have shown significant improvements in neurological function and clinical outcomes in patients with acute ischemic stroke when puerarin is used as an adjunct to conventional therapy. However, most of these studies used injectable forms not widely available outside China, so the value proposition for oral supplements is less clear. For alcohol craving reduction, puerarin offers unique value that may justify its cost for individuals struggling with alcohol use. Clinical studies have demonstrated reduced alcohol consumption and cravings with relatively modest doses of kudzu extract, providing a potentially cost-effective complement to behavioral interventions for alcohol use disorder.

For menopausal symptom relief, there are likely more cost-effective options than puerarin, as many other phytoestrogens and botanical remedies have stronger clinical evidence for this application at similar or lower costs. For diabetes support, puerarin offers moderate value compared to other natural supplements for metabolic health. Preclinical evidence is strong, but clinical evidence in humans is still limited, making it difficult to fully assess the cost-effectiveness for this application. When comparing the cost-effectiveness of puerarin to other supplements with similar indications: For cardiovascular support, puerarin is comparably priced to CoQ10 and fish oil supplements, with potentially stronger evidence for certain cardiovascular conditions like angina and coronary artery disease.

For neuroprotection, puerarin is generally less expensive than specialized neuroprotective supplements like phosphatidylserine or acetyl-L-carnitine, though with variable clinical evidence depending on the specific neurological condition. For alcohol craving reduction, puerarin from kudzu extract appears to offer unique benefits not readily available from other supplements, potentially justifying its cost for this specific application. Enhanced delivery systems such as liposomes, nanoemulsions, or phospholipid complexes offer better bioavailability and potentially superior therapeutic outcomes, which may justify their higher cost for specific health conditions, particularly those affecting the cardiovascular and nervous systems where clinical benefits have been well-documented. The most cost-effective approach for general health maintenance may be traditional kudzu root tea or decoction, which can be prepared from dried root at a fraction of the cost of processed extracts, though standardized extracts provide more consistent dosing for specific therapeutic applications.

Pure puerarin is moderately stable, with a typical shelf life of 2-3 years when properly stored. The C-glycosidic bond (where glucose is directly attached to the C-8 position of daidzein via a carbon-carbon bond) provides better stability compared to O-glycosides, as it is resistant to hydrolysis by acids and enzymes. Standardized kudzu root extracts containing puerarin typically have a shelf life of 1-2 years from the date of manufacture. Dried kudzu root properly stored can maintain acceptable puerarin content for 2-3 years.

Traditional decoctions and liquid extracts have a much shorter shelf life, with optimal potency maintained for only a few days under refrigeration. Pharmaceutical-grade puerarin injection (available in China) typically has a shelf life of 2 years when properly stored, though this form is not commonly available outside of China. Enhanced delivery formulations such as liposomes or nanoemulsions generally have shorter shelf lives of 1-2 years, depending on the specific formulation and preservative system.

Store in a cool, dry place away from direct sunlight in airtight, opaque containers. Refrigeration is recommended for liquid formulations and can extend shelf life of extracts containing puerarin. Protect from moisture, heat, oxygen, and light exposure, which can accelerate degradation. For research-grade pure puerarin, storage under inert gas (nitrogen or argon) at -20°C is recommended for maximum stability.

For dried kudzu root, store in airtight containers away from light and moisture to preserve the puerarin content. The addition of antioxidants such as vitamin E or ascorbic acid to formulations can help prevent oxidation and extend shelf life. Enhanced delivery formulations may have specific storage requirements provided by the manufacturer, which should be followed carefully to maintain stability and potency. Avoid repeated freeze-thaw cycles, particularly for liquid formulations, as this can destabilize the product.

For traditional decoctions, prepare fresh and consume within 24-48 hours, storing any remainder in the refrigerator.

Exposure to UV light and sunlight – causes photodegradation, High temperatures (above 30°C) – accelerates decomposition, Moisture – can promote hydrolysis (though to a lesser extent than with O-glycosides) and microbial growth, particularly in liquid formulations, Oxygen exposure – leads to oxidation, particularly affecting the hydroxyl groups, pH extremes – puerarin is most stable at slightly acidic to neutral pH (5-7), with increased degradation in strongly acidic or alkaline conditions, Metal ions (particularly iron and copper) – can catalyze oxidation reactions, Enzymatic activity – while the C-glycosidic bond is resistant to glycosidases, other enzymes may affect the isoflavone structure, Incompatible excipients in formulations – certain preservatives or other ingredients may interact negatively with puerarin, Repeated freeze-thaw cycles – can destabilize enhanced delivery formulations such as liposomes or nanoemulsions, Microbial contamination – particularly relevant for liquid formulations, can lead to degradation of active compounds

Synthesis Methods

Natural Sources

Quality Considerations

Puerarin itself was not identified or isolated until the modern era, but it is a major bioactive constituent of kudzu root (Pueraria lobata, also known as Ge Gen in Chinese), which has been used in traditional medicine systems for thousands of years. While the specific contribution of puerarin to the traditional uses of kudzu was unknown to ancient practitioners, it is now recognized as one of the primary compounds responsible for many of kudzu’s medicinal properties. Kudzu has a rich history of use in traditional Chinese medicine (TCM) dating back over 2,000 years. It was first documented in the ‘Shennong Bencao Jing’ (Divine Farmer’s Classic of Materia Medica), one of the earliest Chinese pharmacopeias, compiled around 200-300 CE.

In this ancient text, kudzu root was classified as a superior herb, indicating its high value and relative safety. In TCM, kudzu root was traditionally used to treat fevers, headaches, neck stiffness, thirst, and diarrhea. It was considered to have properties that release the exterior, promote eruption of measles, generate fluids, and relieve thirst. Kudzu was particularly valued for its ability to treat the early stages of febrile illnesses, especially those affecting the upper body and neck region.

The ‘Mingyi Bielu’ (Supplementary Records of Famous Physicians), compiled around 500 CE, expanded on kudzu’s applications, noting its use for treating alcohol intoxication. This represents one of the earliest documented uses of kudzu for alcohol-related conditions, a application that has been validated by modern research on puerarin’s effects on alcohol metabolism and consumption. By the Tang Dynasty (618-907 CE), kudzu root had become an important herb in many classical TCM formulations. The famous physician Sun Simiao included kudzu in numerous prescriptions in his works ‘Qianjin Yaofang’ (Thousand Golden Prescriptions) and ‘Qianjin Yifang’ (Supplement to the Thousand Golden Prescriptions).

During this period, kudzu was increasingly used for cardiovascular conditions, a use that aligns with modern understanding of puerarin’s cardiovascular benefits. In the Song Dynasty (960-1279 CE), the ‘Taiping Shenghuifang’ (Taiping Holy Prescriptions for Universal Relief) documented kudzu’s use for hypertension-like symptoms, described as ‘ascending qi and dizziness.’ The ‘Bencao Gangmu’ (Compendium of Materia Medica), compiled by Li Shizhen in the 16th century during the Ming Dynasty, provided comprehensive information on kudzu’s medicinal properties and uses. Li Shizhen noted kudzu’s effectiveness for treating ‘heat in the blood,’ stroke, and various cardiovascular conditions. In traditional Japanese Kampo medicine, which evolved from TCM, kudzu root (known as kakkonto) has been used since at least the 8th century CE.

It is a key ingredient in kakkonto, a classical formula used to treat the common cold, influenza, and headaches. In Korean traditional medicine, kudzu (known as galgeun) has been used similarly to its applications in Chinese medicine, primarily for febrile conditions, muscle stiffness, and thirst. In North America, Native American tribes in the southeastern United States, where kudzu was introduced in the late 19th century, adopted the plant for some medicinal uses, including treatments for muscle pain and inflammation. However, kudzu’s use in North American folk medicine is much more recent and limited compared to its long history in Asian medical traditions.

The modern scientific study of kudzu and the isolation of puerarin began in the mid-20th century. Puerarin was first isolated from kudzu root in the 1950s, and its chemical structure was elucidated as daidzein-8-C-glucoside. Since then, extensive research has been conducted on puerarin’s pharmacological properties, particularly in China, where it has been developed into pharmaceutical preparations. In China, puerarin injection has been approved as a pharmaceutical drug since the 1990s for treating cardiovascular and cerebrovascular conditions, including coronary heart disease, angina pectoris, and ischemic stroke.

This represents a modern pharmaceutical application of a compound derived from an herb with thousands of years of traditional use. In recent decades, research on puerarin has expanded globally, with studies investigating its potential for treating alcohol use disorder, diabetes, neurodegenerative diseases, and other conditions. This research has provided scientific validation for many of the traditional uses of kudzu root while also identifying new potential applications based on puerarin’s diverse pharmacological activities.

Clinical trials investigating puerarin’s effects on cognitive function and neuroprotection in mild cognitive impairment and early Alzheimer’s disease, Studies on puerarin’s potential in alcohol use disorder, focusing on craving reduction and neurobiological mechanisms, Investigations into puerarin’s cardioprotective effects in various cardiovascular conditions, including coronary artery disease, heart failure, and hypertension, Research on puerarin’s effects on metabolic syndrome and type 2 diabetes, particularly focusing on insulin resistance and pancreatic β-cell function, Studies on novel delivery systems to enhance puerarin’s bioavailability and targeted delivery, Investigations into puerarin’s potential in osteoporosis prevention and treatment, particularly in postmenopausal women