Puerarina

Puerarin

1. Identity: Chemical Name, Botanical Source, and Physical Properties

Puerarin's chemical name is 8-(β-D-glucopyranosyl)-4′,7-dihydroxyisoflavone, and its molecular formula is C₂₁H₂₀O₉. Its structural formula is 8-β-D-glucopyranose-4,7-dihydroxy isoflavone; it presents as a white needle crystal, is slightly soluble in water, and its aqueous solution is colorless or light yellow. Puerarin (7,4′-dihydroxy-8-C-glucosylisoflavone) belongs to the chemical class of isoflavones. At positions 7 and 4′ there are hydroxy group substitutions, and at position 8 it is accompanied by a beta-D-glucopyranosyl residue through a C-glycosidic linkage. This C-glycosidic bond — attaching glucose directly to the carbon ring skeleton rather than through an oxygen atom — is a key distinguishing structural feature that affects its metabolic behavior and stability.

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. Puerarin is the most abundant secondary metabolite, which was isolated from the rhizome of Pueraria lobata in the 1950s. Kudzu (Pueraria montana var. lobata) is used as a traditional medicine in China and Southeast Asia. It produces both O- and C-glycosylated isoflavones, with puerarin (C-glucosyl daidzein) as an important bioactive compound.

The chemical structural characteristics of puerarin contribute to its poor water-solubility and liposolubility, thereby leading to poor oral absorption and low bioavailability, which eventually restricts its wide application in clinical settings. Puerarin can be categorized as a Class IV drug of the Biopharmaceutics Classification System based on its low solubility and low intestinal permeability values, with an aqueous solubility of 0.46 mg/mL and a maximum solubility of 7.56 mg/mL at pH 7.4.

1.1 Botanical Source and Related Species

Gegen, the root of Pueraria lobata (Willd.) Ohwi, a perennial liana in the family Leguminosae, is used as a traditional Chinese medicine with various medicinal purposes. Dried root of P. thomsonii is also known as thomson kudzuvine root or Fengen and is used extensively in southern Chinese cuisines, whereas dried root of P. lobata is employed as the major source for therapeutic applications. Chemical analysis suggests isoflavonoids, including puerarin, daidzin, daidzein, and genistin, are the major constituents in P. thomsonii. However, 3-hydroxypuerarin and 3′-methoxypuerarin, which are normally found in P. lobata, were absent in the water extract of P. thomsonii.

Among the isoflavones quantified in Pueraria root, puerarin is present at the highest concentration, followed by puerarin 6″-O-xyloside, 3′-methoxy puerarin, and 3′-hydroxy puerarin. Of all the isoflavones, puerarin is the most abundant; it represents up to 60% of the total of these compounds in the root.

1.2 Common Forms and Preparations

So far, only puerarin injections and eye drops are on the market as approved pharmaceutical products. For example, Puerarin Injection, Puerarin and Glucose Injection, as well as Puerarin and Sodium Chloride Injection have been approved as clinical drugs for the treatment of certain cardiovascular diseases (CVDs) in China. In dietary supplement markets outside China, puerarin is available in oral forms including capsules, tablets, and standardized root extracts. Various nanotechnologies and preparation technologies — including microemulsions, self-microemulsifying drug delivery systems (SMEDDS), dendrimers, nanoparticles, and nanocrystals — have been researched to improve the bioavailability of puerarin.

To improve solubility of puerarin, cosolvents such as propylene glycol, ethylene glycol, and polyvinylpyrrolidone have been added to the clinical injection formulation. Puerarin is also metabolized to daidzein by intestinal bacteria. In traditional culinary contexts, the starch of Pueraria root is a food ingredient widely used in Japan; it has a mild taste that does not conflict with delicate and subtle flavors, creates a smooth consistency, and crisps well when used as a coating for deep-fried foods.

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2. Traditional and Historical Use

2.1 Chinese Medicine: Texts and Indications

The tea of Radix Puerariae was first recorded in the Chinese materia medica Shen Nong Ben Cao Jing (Pharmacopeia of Shen Nong, approximately 200 BC) and used as an antipyretic, antidiarrhetic, diaphoretic, and antiemetic agent. The roots of kudzu (Radix Puerariae) have been used in Chinese herbal medicine for the treatment of fever, acute dysentery, diarrhea, diabetes, and cardiovascular diseases for more than 2,000 years.

Indications and properties of Puerariae lobatae Radix as a traditional Chinese medicine include: sweet, pungent, cool; entering lung and stomach meridians; acting to release the muscles, cure fever, discharge measles, promote production of fluid and relieve thirst, ascend Yang to stop diarrhea; applicable for treating high fever of exterior syndromes, muscle pain of the upper back and neck, measles with incomplete eruption, thirst due to warm diseases, diarrhea due to heat, and diarrhea due to spleen deficiency.

In Chinese traditional medicine, kudzu root (Gen) is one of the 50 fundamental herbs. Kudzu root (Pueraria lobata (Willd.) Ohwi) is commonly used as an adjunctive treatment for fever, diarrhea, and inflammatory diseases in traditional Chinese medicine. A classical formula context is the Shanghan Lun (Treatise on Cold Damage), a foundational text of classical Chinese medicine, where pueraria features as an ingredient in traditional Chinese medicine formulas.

2.2 Use for Alcohol-Related Conditions

Kudzu (Pueraria lobata) is one of the earliest medicinal plants used to treat alcohol abuse in traditional Chinese medicine for more than a millennium. Over the centuries it has been used to treat alcoholism, hangover, gastric distress, high blood pressure and other circulatory problems, colds, flu, diabetes, skin rashes, kidney disease, and diabetic retinopathy, among other conditions.

2.3 Use in Other Asian Traditions

Kudzu has been used in Thai folklore medicine for its rejuvenating qualities in aged women and men for nearly one hundred years. It is native to Southeast Asia and has been utilized as a food source, fodder, and medicine for thousands of years. Kudzu is also used traditionally for the treatment of menopausal symptoms.

The plant's traditional use across these cultures spans both internal medicine (fever management, gastrointestinal complaints, thirst, metabolic conditions) and externally-observed symptomatic relief (inebriation, skin conditions). It is important to note that the traditional use preceded the isolation and characterization of puerarin as a discrete chemical compound; these uses applied to whole-root preparations (Radix Puerariae / Gegen) containing a complex mixture of phytochemicals.

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3. Key Constituents and Active Compounds

While puerarin is the principal bioactive isoflavone in the root of Pueraria lobata, the root contains a broader phytochemical profile. Its main components include isoflavones (particularly puerarin, daidzein, and genistein), responsible for many of its pharmacological actions and its nature as a phytoestrogen; triterpene saponins with hepatoprotective and anti-inflammatory action; starch, which constitutes between 15% and 35% of the root; and micronutrients such as phosphorus, iron, and calcium.

Chemical analysis confirms that isoflavonoids, including puerarin, daidzin, daidzein, and genistin, are among the major constituents. The plant produces both O- and C-glycosylated isoflavones, with puerarin (C-glucosyl daidzein) as an important bioactive compound. Puerarin is structurally the C8-glucoside of daidzein, distinguishing it from daidzin (the O-glucoside of daidzein). This structural distinction significantly affects its pharmacokinetic behavior. Puerarin is metabolized to daidzein by intestinal bacteria.

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4. Established Mechanisms of Action

4.1 Phytoestrogenic and Estrogen Receptor-Mediated Activity

Contemporary pharmacological research has demonstrated that puerarin is the most important phytoestrogen extracted from Pueraria lobata (Willd.) Ohwi, and has protecting functions on the cardiovascular system, nervous system, osteoporosis, liver injury, and inflammation in vivo and in vitro. Research indicates that puerarin stimulates eNOS (endothelial nitric oxide synthase) phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Because of its estrogenic activity, puerarin can regulate the apoptosis of MG-63 cells through the estrogen receptor-dependent PI3K/Akt pathway.

4.2 Anti-inflammatory Pathways

The efficacy of puerarin for treating multiple cardiovascular diseases may be mainly mediated by modulation of Na⁺, K⁺, and Ca²⁺ channels, NF-κB, PI3K/Akt, BCL-2, and BAX. Furthermore, it may be related to the regulation of other targets such as PPAR, AMPK, AT1, ACE2, Nrf2, TNF-α, IL-8, COX-2, and P2X3. Puerarin can attenuate angiotensin II-induced cardiac hypertrophy by inhibiting the activation of the redox-sensitive ERK1/2, p38, and the NF-κB signaling pathways.

4.3 Antioxidant Mechanisms

Puerarin enhances the expression of Nrf2 and promotes the synthesis of antioxidants (such as CAT, GSH, and γ-GCS) through the Nrf2/ARE signaling pathway to combat oxidative stress. One pathway that has been elucidated is that puerarin increases the phosphorylation of GSK-3β at Ser9, resulting in a decrease in GSK-3β activity, which in turn leads to the inhibition of Fyn phosphorylation, so that Fyn is unable to enter the nucleus and promote nuclear expulsion of Nrf2, thereby allowing Nrf2 to accumulate in the nucleus.

4.4 PI3K/Akt Signaling

The PI3K/Akt signal pathway is a crucial signal transduction mechanism that regulates biological processes such as cell regeneration, apoptosis, and cognitive memory in the central nervous system, and is closely related to the pathogenesis of nervous system diseases. Accumulating evidence suggests that the excellent neuroprotective effect of puerarin may be related to the regulation of the PI3K/Akt signal pathway.

4.5 Glucose and Metabolic Regulation

It is possible that puerarin can enhance glucose uptake and improve insulin resistance via increasing glucose transporter 4 (GLUT4) mRNA and protein expressions. Puerarin increased GLUT4 levels on the plasma membrane in skeletal muscle and adipocyte membrane to reduce insulin resistance and enhance glucose absorption from blood circulation.

4.6 Vascular and Cardiac Signaling

Puerarin can decrease blood pressure, heart rate, and myocardial oxygen consumption. Puerarin injection also plays an important role in inhibiting platelet aggregation, decreasing blood viscosity, and improving microcirculation. The antiarrhythmic effects of puerarin could be partly attributed to its influences on Na⁺ and K⁺ channels.

4.7 Neuroprotective Mechanisms

Puerarin has demonstrated different pharmacological effects in animal models of many types of CNS disorders, including ischemic stroke, subarachnoid hemorrhage (SAH), epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), brain trauma, and CNS damage caused by neurotoxic agents. Its efficacy is mediated by its pluripotent pharmacological potential, including anti-apoptosis, anti-oxidative stress, inhibition of proinflammatory mediators, regulation of autophagy, and reduction of calcium influx.

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5. Scientific Evidence by Health Area

5.1 Cardiovascular Disease

Preclinical evidence: Emerging studies over the past few decades have shown that puerarin plays a critical role in protecting humans and animals from CVDs, including atherosclerosis, cardiac hypertrophy, heart failure, diabetic cardiovascular complications, myocardial infarction (MI), stroke, and hypertension. Preclinical findings demonstrate that puerarin administration reduces myocardial infarction size, improves cardiac function, and attenuates key pathological processes, including oxidative stress, inflammation, and cardiomyocyte apoptosis.

Clinical evidence — angina pectoris: Puerarin injection has usually been integrated with Western medicines (nitroglycerin, isosorbide nitrate, nifedipine, aspirin, trimetazidine, metoprolol, etc.) for the treatment of unstable angina pectoris (UAP) in China. Multiple randomized controlled trials (RCTs) have reported positive results on the therapeutic effect of puerarin injection for UAP. A systematic review and meta-analysis of these RCTs (published in PMC, 2022) synthesized available trial data and found broadly favorable outcomes in this context, though trials were largely conducted in China and many had methodological limitations.

Clinical evidence — CVD risk factors: Cell culture and animal studies suggest puerarin could prevent CVD. However, trials in humans are scarce, not primarily designed for prevention, and inadequately powered. A crossover trial assessed the effect of puerarin supplementation on CVD risk factors in 217 Chinese men aged 18–50 years without a history of CVD. This was a randomized, double-blind, placebo-controlled, two-way crossover trial design, representing one of the more rigorous human studies to date.

Clinical evidence — endothelial function and inflammation in CAD: One study investigated the effects of puerarin on vascular endothelial function and inflammatory factors in coronary artery disease (CAD) patients with stable angina pectoris (SAP). This study was conducted at multiple Chinese institutions and measured endothelial and inflammatory markers as primary outcomes.

Evidence strength summary: Meta-analyses and systematic reviews of small randomized clinical trials in ischemic stroke and unstable angina pectoris indicate that puerarin is a promising herbal medicine for the prevention or treatment of cardiovascular and cerebrovascular disorders. However, well-designed, multicenter, large-sample, randomized controlled trials are required to evaluate the efficacy and adverse effects of puerarin in the treatment of ischemic cardiomyopathy. The overall human evidence base remains preliminary, with most trials being small, single-center, and of moderate methodological quality.

5.2 Neuroprotection and Cerebrovascular Disease

Preclinical evidence: Growing evidence indicates that puerarin efficiently alleviates the initiation and progression of obesity, type II diabetes, hypertension, atherosclerosis, cardiac ischemia, cardiac arrhythmia, cardiac hypertrophy, ischemic stroke, and cognitive decline via suppression of oxidative stress and inflammation. In animal models, puerarin exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury. In one study, rat models of middle cerebral artery ischemia/reperfusion injury were established using the suture method, and puerarin (100 mg/kg) was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion.

Clinical evidence — stroke: Results from a recent clinical trial showed that the combined treatment of puerarin and naloxone exhibited better efficacy in patients with traumatic cerebral infarction than conventional therapy. Another trial also reported that dual therapy with puerarin and aspirin improved neurological functions in patients with acute cerebral infarction, along with decreased levels of von Willebrand factor and thrombomodulin, indicating damaged vascular endothelial cells in the blood serum. Despite these positive signals, the evidence supporting the therapeutic efficacy of puerarin on survival or dependency in people with ischemic stroke is still inconclusive.

Neurodegenerative diseases: Extensive cellular, animal, and some clinical research has provided insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, and depression. However, for Alzheimer's and Parkinson's disease specifically, human clinical trial data remain very limited and most evidence is from animal or cell-based studies. The clinical use of puerarin as a neuroprotective agent is limited by its low water solubility, poor lipid solubility, and poor intestinal permeability.

Evidence strength summary: The neuroprotection evidence base is predominantly preclinical (animal models, cell culture). Clinical trials that exist are small, often combine puerarin with other agents, and originate predominantly from China. Evidence is preliminary and insufficient to draw firm clinical conclusions.

5.3 Diabetes and Metabolic Disorders

Mechanisms and preclinical evidence: Puerarin is a predominant component of Radix Puerariae. Despite its anti-tumor and anti-virus effects and efficacy in improving cardiovascular or cerebrovascular diseases and preventing osteoporosis, it has been shown to protect against diabetes and its complications. Puerarin increased GLUT4 levels on the plasma membrane in skeletal muscle and adipocyte membrane to reduce insulin resistance and enhance glucose absorption from blood circulation. Puerarin also protected against diabetic complications such as osteoporosis, nephropathy, macroangiopathy, and cardiomyopathy.

Evidence strength summary: Most of the diabetes-related evidence for puerarin comes from in vitro cell studies and animal models. Modern pharmacological studies have shown that puerarin has a variety of bioactive effects, for instance, estrogen-like activity, anti-inflammation, antioxidant response, blood pressure control, blood glucose reduction, and cancer reduction. Rigorous human clinical trials specifically targeting blood glucose and insulin resistance outcomes with puerarin as a primary intervention are lacking, and this area remains a subject of ongoing preclinical and early-phase investigation.

5.4 Bone Health and Osteoporosis

Preclinical evidence: Based on the available data obtained from in vitro studies and animal models, it can be clearly shown that puerarin is an effective compound in inhibiting bone resorption and improving bone structure. Consumption of puerarin may be associated with the prevention of bone mass loss and thus can reduce the risk of developing osteoporosis.

Animal model meta-analysis: A 2026 systematic review and meta-analysis in Frontiers in Pharmacology evaluated puerarin in rodent models of osteoporosis. 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: 2.32–3.58, p < 0.00001) and improved 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.

In animal studies examining mechanisms, results showed improved bone density and reduced bone loss in rats treated with puerarin. There were also significant increases in serum levels of osteocalcin (OC) and bone alkaline phosphatase (BALP), indicating enhanced osteogenesis. Furthermore, there was a decrease in activation of the JAK2/STAT3 pathway in femoral tissue. These findings indicate that puerarin may combat osteoporosis by promoting osteogenesis and inhibiting activation of the JAK2/STAT3 pathway.

Evidence strength summary: It is necessary to conduct human intervention studies to confirm the effectiveness of puerarin's action on bone. The evidence is currently entirely preclinical (animal models and cell studies) and no published human clinical trials on puerarin and bone mineral density have been identified in the peer-reviewed literature. The preclinical signal is strong, but direct translation to humans is unconfirmed.

5.5 Liver Disease and Hepatoprotection

Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. Its pharmacological effects on various liver diseases act through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy.

In the context of alcohol-related liver injury specifically, antidipsotropic isoflavones isolated from Radix Puerariae, including puerarin, daidzin, and daidzein, suppressed the ethanol intake of rodents, abolished the development of alcohol withdrawal symptoms, increased the antioxidant enzymes (such as Cu/Zn SOD and catalase), and mitigated hepatic oxidant injury in ethanol-treated rats.

Evidence strength summary: Hepatoprotection evidence is primarily from animal and cell-culture studies. Clinical trials are discussed in the literature, highlighting some unique advantages, but human data in this area are limited and based largely on small studies or clinical observations from China. The evidence is promising but insufficient for definitive clinical claims.

5.6 Alcohol Use and Craving Reduction

One of the more studied human applications relates to alcohol use. A pilot study published in peer-reviewed literature examined whether the isoflavone puerarin reduces alcohol intake in heavy drinkers (ResearchGate/original publication reference). This intersection of pharmacological interest — reducing alcohol craving — derives from puerarin's traditional use in managing inebriation and its demonstrated effects in animal models. Kudzu is one of the earliest medicinal plants used to treat alcohol abuse in traditional Chinese medicine. Animal studies show suppression of ethanol intake, and limited human pilot work has been conducted, though the evidence base for puerarin specifically (vs. whole kudzu extract) in humans is restricted to a small number of trials.

5.7 Anti-inflammatory Effects

The beneficial anti-inflammatory effects of puerarin are the fundamental mechanism for retarding the clinical relevance of chronic inflammation in the heart, brain, and arteries in the pathogenesis of obesity, type II diabetes, hypertension, atherosclerosis, myocardial ischemia, myocardial infarction, and cerebral ischemia. These effects have been extensively characterized in preclinical models, with puerarin inhibiting major pro-inflammatory signaling nodes including NF-κB, COX-2, and TNF-α. Human clinical evidence of anti-inflammatory effects from puerarin supplementation remains limited to biomarker-based outcomes in small trials.

5.8 Oncology (Anti-tumor Activity)

Puerarin (8-(β-D-glucopyranosyl)-4′,7-dihydroxyisoflavone), a natural flavonoid compound isolated from the traditional Chinese herb Radix puerariae, has been demonstrated to have potential anti-tumor effects via induction of apoptosis and inhibition of proliferation. In pancreatic ductal adenocarcinoma models, puerarin treatment significantly repressed cancer cell proliferation; puerarin induced mitochondrial-dependent apoptosis of pancreatic cancer cells by causing a Bcl-2/Bax imbalance; and puerarin inhibited cancer cell migration and invasion by antagonizing epithelial-mesenchymal transition (EMT). These findings are entirely preclinical (cell lines and xenograft mouse models). No clinical trial evidence for puerarin as an anti-cancer agent in humans has been identified in the peer-reviewed literature.

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6. Body Systems and Health Areas of Association

• Cardiovascular system: Puerarin causes vasodilation, cardioprotection, and antioxidative effects, and is associated with the prevention and management of cardiovascular diseases including hypertension and arteriosclerosis.
• Central nervous system: Accumulating evidence has indicated that puerarin demonstrates multiple pharmacological effects and exhibits treatment potential for various neurological disorders, including ischemic stroke, Alzheimer's disease, and Parkinson's disease (primarily preclinical).
• Skeletal system: Puerarin is an effective compound in inhibiting bone resorption and improving bone structure, and may be associated with the prevention of bone mass loss.
• Endocrine/metabolic system: Puerarin is associated with insulin resistance management and glucose metabolism through GLUT4 upregulation.
• Hepatic system: Puerarin has significant hepatoprotective effects against metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma.
• Immune system: Puerarin has biological activities that include immunity improvement.
• Reproductive/hormonal system: Puerarin's phytoestrogenic properties have been associated with menopausal symptom management (traditional and limited clinical evidence).
• Ophthalmic system: Puerarin eye drops are among the approved pharmaceutical products on the market, used for certain ocular conditions.

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7. Pharmacokinetics

Puerarin's pharmacokinetics in rats after oral administration is characterized by rapid absorption, quick elimination, and minimal accumulation. Puerarin has many pharmacokinetic advantages, such as a short half-life, rapid elimination, and it is not easily accumulated in the body, all of which make it a suitable candidate for clinical use as a medication.

The chemical structural characteristics of puerarin contribute to its poor water-solubility and liposolubility, thereby leading to poor oral absorption and low bioavailability, which restricts its wide application in clinical settings. As an active substrate of P-glycoprotein (P-gp), multidrug resistance-associated protein, and multiple metabolic enzymes, the pharmacokinetics of puerarin can be influenced by different pathological conditions and drug-drug interactions.

To overcome these limitations, oral formulations with improved absorption of puerarin have attracted widespread attention. Various nanotechnologies and preparation technologies including microemulsions and SMEDDS, dendrimers, nanoparticles, and nanocrystals have been researched to improve bioavailability.

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8. Dosage Forms and Doses Reported in Studies

The following dosages are reported directly from scientific sources and should not be interpreted as therapeutic recommendations.

• Oral (tablet form, clinical applications in CVD): Pueraria flavones were given in tablets at a dose of 30–40 mg each time, three times daily (total daily dose 90–120 mg) to patients with coronary heart disease and angina pectoris; for hypertension, 50 mg of pueraria flavones were given twice per day (total daily dose 100 mg) for several weeks; hypertensive patients suffering from angina were given a daily dose of 150 mg/day. The maximum daily dose recommended in a survey of such applications appears to be 300 mg/day.
• Injectable (approved pharmaceutical form in China): In reported clinical cases involving hemolysis studies, patients received puerarin injection at intravenous infusion doses of 100–700 mg dissolved in 0.9% sodium chloride or 5% glucose, with drug-use duration of 5–10 days in most cases.
• Animal study doses (osteoporosis meta-analysis): Subgroup analysis of a rodent meta-analysis revealed that the most pronounced BMD improvement occurred at doses ≥50 mg/kg/day administered for ≥8 weeks.
• Animal study doses (cerebral ischemia): In a rat model of middle cerebral artery ischemia/reperfusion injury, puerarin (100 mg/kg) was administered intraperitoneally 30 minutes before occlusion and 8 hours after reperfusion.

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9. Safety Considerations and Drug Interactions

9.1 General Safety Profile — Oral Use

Puerarin has very low toxicity and high safety, providing a solid foundation for its further development. 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.

9.2 Adverse Reactions from Injectable Forms

To improve solubility of puerarin, cosolvents such as propylene glycol, ethylene glycol, and polyvinylpyrrolidone have 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.

A collection and analysis of 62 papers related to adverse drug reactions of puerarin injection 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, including drug-induced immune hemolytic anemia (DIIHA). Hemolysis largely limited the clinical use of puerarin injections.

Puerarin is the major isoflavonoid derived from the Chinese medical herb Radix Puerariae, and has been reported as associated with drug-induced immune hemolytic anemia (DIIHA). These results suggest that puerarin may be a cause of severe hemolysis and should be used with caution.

Due to its poor water solubility and low oral bioavailability, the formulation of puerarin has been in an injection dosage form, while the injection has poor clinical compliance with patients, occasionally causing adverse drug reactions. Due to the frequent occurrence of side effects of traditional Chinese medicine injections, China has restricted the use of such injections in recent years.

9.3 Pregnancy Concerns

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.

9.4 Drug Interactions — CYP Enzyme Inhibition

In previous studies, puerarin has been reported to have inhibitory effects on the CYP 450 enzymes, such as CYP3A4, CYP2B6, CYP2C9, and P-gp, which are related to the metabolism and absorption of drugs. Previous studies have reported that puerarin could inhibit the activity of CYP3A4 and P-gp, which might lead to drug-drug interactions when they are co-administered with other herbs or drugs that are P-gp substrates. These interactions are particularly relevant for drugs with narrow therapeutic windows that are metabolized by CYP3A4 or transported by P-gp.

9.5 Pharmacokinetic Drug Interactions

As an active substrate of P-gp, multidrug resistance-associated protein, and multiple metabolic enzymes, the pharmacokinetics of puerarin can be influenced by different pathological conditions and drug-drug interactions. Studies in rats have also shown bidirectional interactions between puerarin and co-administered herbal compounds, including astragaloside IV, which are relevant to traditional combination preparations.

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10. Limitations of the Current Evidence Base

Trials in humans are scarce, not primarily designed for prevention, and inadequately powered. The majority of published pharmacological research on puerarin derives from in vitro cell models and animal studies. Human clinical trials that do exist tend to be small in sample size, conducted in Chinese clinical settings, often combine puerarin with conventional treatments making it difficult to isolate puerarin's specific contribution, and are frequently of limited methodological rigor. Well-designed, multicenter, large-sample, randomized controlled trials are required to evaluate the efficacy and adverse effects of puerarin. Further research utilizing metabolomics, proteomics, genomics, and network pharmacology should be conducted to elucidate its pharmacological activity and molecular mechanisms.

Additionally, the predominant use of male animals in preclinical studies restricts the generalizability of findings to both sexes; this approach does not address potential sex-based differences, and therefore caution is required when translating preclinical results to clinical contexts.

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References

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