Isoorientin

• Antioxidant
• Anti-inflammatory
• Neuroprotective
• Antidiabetic

• Cardioprotective
• Hepatoprotective
• Anticancer
• Antimicrobial
• Antiviral

Isoorientin (luteolin-6-C-glucoside) exerts its diverse biological effects through multiple molecular pathways. As a C-glycosylflavone, isoorientin possesses a unique structural feature where a glucose molecule is directly attached to the C-6 position of the luteolin 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 isoorientin’s distinct pharmacokinetic profile and biological activities. One of isoorientin’s most extensively studied mechanisms is its potent antioxidant activity.

Isoorientin scavenges reactive oxygen species (ROS) and free radicals through its hydroxyl groups, particularly those on the A and B rings of the flavone structure. The catechol structure in the B-ring (3′,4′-dihydroxy) is especially effective for neutralizing free radicals by donating hydrogen atoms and stabilizing the resulting phenoxyl radicals through electron delocalization. Isoorientin neutralizes superoxide anions, hydroxyl radicals, peroxynitrite, and other reactive species, preventing oxidative damage to cellular components including lipids, proteins, and DNA. Beyond direct scavenging, isoorientin 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), isoorientin 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, isoorientin 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.

Isoorientin 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. A particularly significant anti-inflammatory mechanism of isoorientin is its ability to inhibit the NLRP3 inflammasome, a multiprotein complex involved in the processing and secretion of pro-inflammatory cytokines IL-1β and IL-18. By suppressing NLRP3 inflammasome activation, isoorientin reduces the production of these potent inflammatory mediators, providing additional anti-inflammatory benefits beyond NF-κB inhibition. In metabolic regulation, isoorientin demonstrates significant antidiabetic effects through multiple mechanisms.

It enhances insulin sensitivity by activating the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, leading to increased glucose uptake in skeletal muscle and adipose tissue. Isoorientin also activates AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, which promotes glucose uptake and fatty acid oxidation while inhibiting gluconeogenesis in the liver. Additionally, isoorientin protects pancreatic β-cells from oxidative stress and inflammation, preserving insulin secretion capacity. It inhibits α-glucosidase and α-amylase, enzymes involved in carbohydrate digestion, potentially reducing postprandial glucose levels.

Isoorientin also reduces advanced glycation end-product (AGE) formation, which is implicated in diabetic complications. In the central nervous system, isoorientin exhibits neuroprotective effects through multiple mechanisms. It protects neurons from oxidative stress and excitotoxicity by reducing glutamate-induced calcium influx and maintaining mitochondrial function. Isoorientin also inhibits neuroinflammation by suppressing microglial activation and reducing the production of pro-inflammatory mediators in the brain.

Furthermore, it has been shown to enhance brain-derived neurotrophic factor (BDNF) expression and activate the PI3K/Akt/glycogen synthase kinase-3β (GSK-3β) pathway, promoting neuronal survival and synaptic plasticity. Isoorientin has demonstrated potential in protecting against neurodegenerative diseases by reducing the aggregation of misfolded proteins such as amyloid-beta and tau, which are implicated in Alzheimer’s disease. In the cardiovascular system, isoorientin demonstrates protective effects by improving endothelial function, reducing inflammation, and preventing oxidative damage. It enhances nitric oxide (NO) production by endothelial cells through activation of endothelial nitric oxide synthase (eNOS), promoting vasodilation and improving blood flow.

Isoorientin also inhibits platelet aggregation and thrombus formation, potentially reducing the risk of thrombotic events. Additionally, it protects cardiomyocytes from ischemia/reperfusion injury by preserving mitochondrial function and inhibiting apoptosis. In cancer cells, isoorientin demonstrates antiproliferative and pro-apoptotic effects. It induces cell cycle arrest primarily at the G0/G1 or G2/M phases by modulating the expression and activity of cell cycle regulators, including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors.

Isoorientin also triggers apoptosis through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways. It modulates the expression of Bcl-2 family proteins, decreasing anti-apoptotic proteins (Bcl-2, Bcl-xL) and increasing pro-apoptotic proteins (Bax, Bad), leading to mitochondrial membrane permeabilization, cytochrome c release, and activation of caspase cascades. Furthermore, isoorientin has been shown to inhibit angiogenesis by reducing vascular endothelial growth factor (VEGF) expression and signaling, potentially limiting cancer progression and metastasis. The C-glycosidic bond in isoorientin contributes to its unique pharmacological profile compared to its aglycone luteolin and its isomer orientin (luteolin-8-C-glucoside).

This structural feature affects its bioavailability, metabolism, and tissue distribution, potentially leading to different biological activities and therapeutic applications. The position of the glucose moiety at C-6 rather than C-8 (as in orientin) results in subtle differences in receptor binding and molecular interactions, which may explain some of the distinct pharmacological effects observed between these isomers.

Optimal dosage ranges for isoorientin in humans have not been well established through clinical trials. Most research has focused on isoorientin as a component of herbal extracts, particularly from rooibos tea, bamboo leaves, and passion flower (Passiflora species), rather than as an isolated compound. Based on preclinical studies and limited human research with herbal extracts containing isoorientin, estimated effective doses would range from 10-50 mg of isoorientin daily. For rooibos tea extracts, typical daily doses range from 300-900 mg of standardized extract containing 0.5-2% isoorientin, corresponding to approximately 1.5-18 mg of isoorientin daily.

For bamboo leaf extracts, typical daily doses range from 200-600 mg of standardized extract containing 0.5-2% isoorientin, corresponding to approximately 1-12 mg of isoorientin daily. For passion flower extracts, typical daily doses range from 300-800 mg of standardized extract containing 0.2-0.8% isoorientin, corresponding to approximately 0.6-6.4 mg of isoorientin daily. It’s important to note that isoorientin’s bioactivity may be influenced by other compounds present in herbal extracts, potentially leading to synergistic effects that allow for lower effective doses compared to isolated isoorientin.

Isoorientin has relatively low oral bioavailability, estimated at approximately 2-7% in animal studies. This limited bioavailability is primarily due to its C-glycosidic structure, which affects its absorption and metabolism. Unlike O-glycosides, the C-glycosidic bond in isoorientin (where the glucose is directly attached to the C-6 position of luteolin via a carbon-carbon bond) is resistant to hydrolysis by intestinal and hepatic glycosidases. This means that isoorientin is primarily absorbed intact rather than being converted to its aglycone (luteolin) in the gastrointestinal tract.

The glucose moiety enhances water solubility but reduces passive diffusion across cell membranes due to its hydrophilicity. Absorption occurs primarily through active transport mechanisms, including sodium-dependent glucose transporters (SGLTs) and possibly other transporters. Once absorbed, isoorientin undergoes limited phase II metabolism, primarily glucuronidation and sulfation, though to a lesser extent than many other flavonoids due to its already glycosylated structure. The catechol structure in the B-ring (3′,4′-dihydroxy) makes isoorientin particularly susceptible to methylation by catechol-O-methyltransferase (COMT) and conjugation by UDP-glucuronosyltransferases (UGTs), which can further reduce the amount of free isoorientin in circulation.

The C-glycosidic bond also makes isoorientin less susceptible to efflux by P-glycoprotein transporters in the intestine, which may partially compensate for its limited passive diffusion. In animal studies, isoorientin has demonstrated tissue distribution to various organs, including the liver, kidneys, and brain, though brain penetration is limited due to its hydrophilicity. The presence of other compounds in herbal extracts, particularly from rooibos tea, bamboo leaves, and passion flower, may influence isoorientin’s bioavailability through various mechanisms, including competitive inhibition of metabolic enzymes or transporters.

Nanoemulsion formulations – can increase bioavailability by 3-10 fold by improving solubility and enhancing intestinal permeability, Liposomal encapsulation – protects isoorientin from degradation and enhances cellular uptake, Self-emulsifying drug delivery systems (SEDDS) – improve dissolution and absorption in the gastrointestinal tract, Phospholipid complexes – enhance lipid solubility and membrane permeability, Microemulsions – provide a stable delivery system with enhanced solubility, Combination with piperine – inhibits P-glycoprotein efflux and intestinal metabolism, Cyclodextrin inclusion complexes – improve aqueous solubility while maintaining stability, Solid dispersion techniques – enhance dissolution rate and solubility, Co-administration with other flavonoids that may compete for metabolic enzymes, potentially extending isoorientin’s half-life, Nanoparticle formulations – improve stability and targeted delivery, particularly relevant for metabolic and neuroprotective applications

Isoorientin is best absorbed when taken with meals containing some fat, which can enhance solubility and stimulate bile secretion, improving dissolution and absorption. The presence of other flavonoids may enhance isoorientin’s bioavailability through competitive inhibition of metabolic enzymes or transporters. For antioxidant and anti-inflammatory effects, timing is less critical than consistency of use, though divided doses throughout the day may maintain more consistent blood levels due to isoorientin’s relatively short half-life (approximately 2-4 hours in animal studies). For metabolic support, particularly in diabetes management, taking isoorientin before meals may enhance its effects on postprandial glucose levels through α-glucosidase and α-amylase inhibition.

For cardiovascular benefits, consistent daily dosing is important, with some evidence suggesting that morning dosing may be beneficial due to potential effects on endothelial function and blood flow throughout the day. For neuroprotective effects, consistent daily dosing is important for maintaining protective mechanisms against oxidative stress and neuroinflammation. Enhanced delivery formulations like nanoemulsions or liposomes 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 use of herbs containing isoorientin often involves preparing them as teas or tinctures, which may have different absorption characteristics compared to modern extract formulations.

When consumed as a tea, particularly rooibos tea, the hot water extraction efficiently extracts isoorientin due to its good water solubility, but the absence of lipids may limit absorption compared to when taken with a meal.

• Gastrointestinal discomfort (mild, uncommon)
• Nausea (rare)
• Dizziness (rare)
• Headache (rare)
• Allergic reactions (rare)
• Mild hypoglycemia (uncommon, primarily in individuals with already low blood glucose or those taking antidiabetic medications)

• Pregnancy and breastfeeding (due to insufficient safety data)
• Scheduled surgery (discontinue 2 weeks before due to potential effects on blood glucose and mild antiplatelet effects)
• Individuals with severe hypoglycemia or unstable blood glucose levels (due to potential blood glucose-lowering effects)
• Individuals with known allergies to plants in the Fabaceae family (for rooibos-derived isoorientin), Poaceae family (for bamboo-derived isoorientin), or Passifloraceae family (for passion flower-derived isoorientin)
• Individuals with severe liver or kidney disease (due to limited data on metabolism and excretion in these populations)
• Individuals taking medications for diabetes (due to potential interactions)

• Antidiabetic medications (may enhance blood glucose-lowering effects, potentially leading to hypoglycemia)
• Anticoagulant and antiplatelet medications (may enhance antiplatelet effects, potentially increasing bleeding risk, though this effect appears to be mild)
• Cytochrome P450 substrates (limited evidence suggests potential mild inhibition of certain CYP enzymes)
• Antihypertensive medications (may enhance blood pressure-lowering effects)
• Antioxidant medications (potential for additive effects with other antioxidants)
• Drugs requiring active transport for absorption (potential competition for transporters)
• Immunomodulatory drugs (potential for interaction due to isoorientin’s effects on inflammatory pathways)
• Hepatically metabolized drugs (potential for competition for metabolic enzymes)

Due to limited human clinical data on isolated isoorientin, a definitive upper limit has not been established. Based on safety data for rooibos tea, bamboo leaf, and passion flower extracts (which contain isoorientin) and animal toxicity studies, doses up to 50 mg of isoorientin daily or 900 mg of standardized extract daily appear to be well-tolerated in most individuals. For general supplementation, doses exceeding these levels are not recommended without medical supervision due to potential drug interactions and limited long-term safety data at higher doses. It’s important to note that isoorientin has demonstrated a favorable safety profile in both preclinical and limited clinical studies, with a wide therapeutic window.

Acute toxicity studies in animals have shown very low toxicity, with LD50 values well above any reasonable supplemental dose. The presence of other bioactive compounds in herbal extracts may contribute to the overall safety profile, making it difficult to establish precise upper limits for isolated isoorientin. Traditional use of herbs containing isoorientin in moderate doses, particularly rooibos tea which has been consumed for centuries, has a long history of safe use, further supporting the generally favorable safety profile of isoorientin-containing preparations.

Isoorientin itself is not approved as a drug by the FDA and is not commonly available as an isolated supplement. Plant extracts containing isoorientin, such as rooibos tea, bamboo leaf, and passion flower extracts, 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 isoorientin specifically.

Rooibos tea is generally recognized as safe (GRAS) for food use, and passion flower and bamboo leaves are generally recognized as safe when used in traditional amounts as herbs or supplements.

Eu: In the European Union, isoorientin is not approved as a medicinal product. Rooibos tea is regulated as a food product, while passion flower extracts containing isoorientin are regulated as traditional herbal medicinal products under Directive 2004/24/EC in several EU countries, allowing them to be sold with specific health claims related to traditional use. The European Medicines Agency (EMA) has published a community herbal monograph on passion flower, recognizing its traditional medicinal use for relief of mild symptoms of mental stress and to aid sleep. Bamboo leaf extracts are primarily regulated as food supplements in the EU.

Germany: In Germany, passion flower extracts are approved by Commission E (the German regulatory authority for herbs) for nervousness and sleep disorders. They are available as registered herbal medicinal products with specific therapeutic indications. Rooibos tea is regulated as a food product, and bamboo leaf extracts are primarily available as food supplements.

Uk: In the United Kingdom, passion flower products may be registered as Traditional Herbal Medicinal Products (THMPs) under the Traditional Herbal Medicines Registration Scheme, allowing them to be sold with specific health claims based on traditional use. Rooibos tea is regulated as a food product, and bamboo leaf extracts are primarily regulated as food supplements.

Canada: Health Canada regulates passion flower, bamboo leaf, and rooibos extracts as Natural Health Products (NHPs). Several products containing these extracts have been issued Natural Product Numbers (NPNs), allowing them to be sold with specific health claims. For passion flower, these include ‘traditionally used in Herbal Medicine as a sleep aid’ and ‘helps relieve restlessness and nervousness.’ For rooibos, claims include ‘source of antioxidants for the maintenance of good health.’ Isolated isoorientin is not specifically approved as a standalone ingredient.

Australia: The Therapeutic Goods Administration (TGA) regulates passion flower, bamboo leaf, and rooibos extracts as complementary medicines. Several products containing these extracts are listed on the Australian Register of Therapeutic Goods (ARTG). Traditional use claims are permitted with appropriate evidence of traditional use. Isoorientin as an isolated compound is not specifically regulated.

South Africa: In South Africa, rooibos tea is regulated as a food product and is also recognized for its potential health benefits. The South African Department of Health has supported research into the health benefits of rooibos, including its antioxidant properties. Isoorientin as an isolated compound is not specifically regulated for therapeutic use.

China: In China, bamboo leaves (Zhu Ye) are officially listed in the Chinese Pharmacopoeia as a traditional Chinese medicine. They are approved for clearing heat, resolving phlegm, and calming the spirit. Various formulations containing bamboo leaves are approved for medicinal use. Rooibos tea and passion flower are less commonly used in traditional Chinese medicine. Isoorientin as an isolated compound is primarily used in research rather than as an approved therapeutic agent.

Medium

Isolated isoorientin is rarely available commercially for supplementation and is primarily sold as a research chemical at prices ranging from $250-$700 per 10-25 mg, making it prohibitively expensive for regular supplementation. Standardized rooibos tea extracts containing isoorientin along with other flavonoids typically cost $0.25-$1.00 per day for basic extracts and $1.00-$2.50 per day for premium, highly standardized formulations. Standardized bamboo leaf extracts containing isoorientin typically cost $0.30-$1.20 per day for basic extracts and $1.20-$3.00 per day for premium formulations. Standardized passion flower extracts containing isoorientin typically cost $0.25-$1.00 per day for basic extracts and $1.00-$2.50 per day for premium formulations.

Rooibos tea is the most cost-effective option, typically costing $0.10-$0.30 per day, though it provides less consistent and potentially lower amounts of isoorientin compared to standardized extracts.

The cost-effectiveness of isoorientin must be evaluated in the context of herbal extracts containing it, as isolated isoorientin is not practically available for regular supplementation due to its high cost and limited commercial availability. For antioxidant and anti-inflammatory benefits, there are likely more cost-effective options than isoorientin-containing extracts, as many other botanical antioxidants have similar potency at lower costs. However, for specific applications such as metabolic support in diabetes, isoorientin-containing extracts may offer unique value that justifies their moderate cost. For metabolic support, particularly in diabetes management, rooibos tea and its extracts containing isoorientin offer good value compared to many pharmaceutical interventions for mild to moderate metabolic conditions.

Preclinical studies have demonstrated significant improvements in insulin sensitivity, glucose tolerance, and protection against diabetic complications, though more clinical studies are needed to fully establish their efficacy in humans. The long-term benefits for metabolic health may justify the moderate cost of high-quality extracts. For neuroprotective effects, the value proposition is promising based on preclinical studies, but clinical evidence is still lacking. The long-term benefits for neurodegenerative conditions would need to be substantial to justify ongoing supplementation costs.

For cardiovascular support, isoorientin-containing extracts offer moderate value compared to other cardioprotective supplements. The preclinical evidence is promising, particularly for conditions like myocardial ischemia/reperfusion injury, but more clinical studies are needed to fully establish their efficacy in humans. When comparing the cost-effectiveness of rooibos tea, bamboo leaf, and passion flower extracts containing isoorientin to other supplements with similar indications: For metabolic support, they are comparably priced to alpha-lipoic acid and berberine, but with less clinical evidence. For neuroprotection, they are comparably priced to other neuroprotective botanicals like Bacopa monnieri or Ginkgo biloba, but with less clinical evidence supporting their use.

The most cost-effective way to consume isoorientin is through regular consumption of rooibos tea, which can be prepared from loose leaf tea at a fraction of the cost of processed extracts. However, the concentration of isoorientin and other active compounds may be lower and less consistent in tea preparations compared to standardized extracts. Green (unfermented) rooibos contains higher levels of isoorientin compared to traditional fermented rooibos, potentially offering better value for those specifically seeking isoorientin’s benefits. Enhanced delivery systems such as nanoemulsions, liposomes, or SEDDS offer better bioavailability and potentially superior therapeutic outcomes, which may justify their higher cost for specific health conditions, particularly those requiring significant tissue penetration of isoorientin.

Pure isoorientin is moderately stable, with a typical shelf life of 2-3 years when properly stored. The C-glycosidic bond (where the glucose is directly attached to the C-6 position of luteolin via a carbon-carbon bond) provides better stability compared to O-glycosides, as it is resistant to hydrolysis by acids and enzymes. However, the catechol structure in the B-ring (3′,4′-dihydroxy) makes isoorientin somewhat susceptible to oxidation, which can limit its long-term stability. Standardized herbal extracts containing isoorientin, such as rooibos tea, bamboo leaf, or passion flower extracts, typically have a shelf life of 1-2 years from the date of manufacture.

Dried herb material (e.g., rooibos leaves, bamboo leaves, passion flower) properly stored can maintain acceptable isoorientin content for 1-2 years. Tea preparations have a much shorter shelf life, with optimal potency maintained for only a few hours after preparation. Enhanced delivery formulations such as nanoemulsions or liposomes 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 isoorientin. Protect from moisture, heat, oxygen, and light exposure, which can accelerate degradation. For research-grade pure isoorientin, storage under inert gas (nitrogen or argon) at -20°C is recommended for maximum stability.

For dried herb material (e.g., rooibos leaves, bamboo leaves, passion flower), store in airtight containers away from light and moisture to preserve the isoorientin content. The addition of antioxidants such as vitamin E or ascorbic acid to formulations can help prevent oxidation and extend shelf life, particularly important due to the catechol structure in isoorientin’s B-ring, which is susceptible to oxidation. 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.

Exposure to UV light and sunlight – causes photodegradation, particularly affecting the catechol structure in the B-ring, 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 of the catechol structure in the B-ring, pH extremes – isoorientin 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, with the catechol structure being particularly susceptible to metal-catalyzed oxidation, Enzymatic activity – while the C-glycosidic bond is resistant to glycosidases, other enzymes may affect the flavone structure, particularly polyphenol oxidases that can degrade the catechol structure, Incompatible excipients in formulations – certain preservatives or other ingredients may interact negatively with isoorientin, Repeated freeze-thaw cycles – can destabilize enhanced delivery formulations such as nanoemulsions or liposomes

Synthesis Methods

Natural Sources

Quality Considerations

Isoorientin itself was not identified or isolated until the modern era, but it is a constituent of several plants that have been used in traditional medicine systems for centuries. While the specific contribution of isoorientin to the traditional uses of these plants was unknown to ancient practitioners, it is now recognized as one of the bioactive compounds in these historically important medicinal materials. Isoorientin is primarily found in rooibos tea, bamboo leaves, and passion flower, all of which have rich histories in traditional medicine across various cultures. Rooibos tea (Aspalathus linearis) has been used by indigenous peoples in South Africa for centuries.

The Khoisan people of the Cederberg region traditionally harvested wild rooibos and used it as a herbal tea. They discovered that fermenting the leaves and stems produced a sweet, aromatic tea with a reddish color. Rooibos was valued for its refreshing taste and perceived health benefits, including relief from allergies, digestive problems, and skin conditions. The Dutch settlers in South Africa adopted rooibos as an alternative to black tea in the 18th century, particularly when tea imports from Asia were difficult to obtain.

By the early 20th century, rooibos began to be commercially cultivated, and its popularity spread beyond South Africa. In traditional South African medicine, rooibos was used to treat colic in infants, allergies, asthma, and skin conditions. It was also used as a general health tonic and to promote relaxation and sleep. Bamboo has been used in traditional Asian medicine, particularly in China, Korea, and Japan, for thousands of years.

In Traditional Chinese Medicine (TCM), bamboo leaves (Zhu Ye) were first documented in the ‘Shennong Bencao Jing’ (Divine Farmer’s Classic of Materia Medica) around 200-300 CE. They were classified as herbs that clear heat, resolve phlegm, and calm the spirit. Bamboo leaves were traditionally used to treat fevers, coughs, phlegm, and irritability. The cooling properties of bamboo leaves made them particularly valuable for treating conditions associated with ‘heat’ in TCM theory, including inflammatory conditions, fevers, and thirst.

In Korean traditional medicine, bamboo leaves were used for similar purposes as in TCM, with additional applications for treating hypertension and diabetes. In Japanese Kampo medicine, bamboo leaves were included in various formulations for treating respiratory conditions and fevers. Passion flower has been used by indigenous peoples of the Americas for centuries before European contact. Native American tribes, including the Aztecs, Maya, and various North American groups, used passion flower for its calming and sedative properties.

The Aztecs used passion flower as a sedative and to treat insomnia, nervousness, and epilepsy. Various indigenous tribes in North America used passion flower to treat wounds, earaches, liver problems, and as a mild pain reliever. When European explorers arrived in the Americas in the 16th century, they quickly learned about passion flower from indigenous peoples and brought it back to Europe. The plant was named ‘passion flower’ by Spanish missionaries who saw in its unique flower structure symbols of the Passion of Christ.

By the 17th century, passion flower was being used in European herbal medicine for its calming and sleep-promoting effects. In the 19th and early 20th centuries, passion flower was included in various pharmacopeias and was commonly prescribed for nervousness, insomnia, and epilepsy. It was officially listed in the United States National Formulary from 1916 to 1936 and in the British Herbal Pharmacopoeia. Corn silk, another source of isoorientin, has been used in traditional medicine systems worldwide.

Native American tribes used corn silk tea for treating urinary tract infections, kidney stones, and as a diuretic. In TCM, corn silk (Yu Mi Xu) was used to promote urination, reduce edema, and treat urinary tract infections. Isoorientin was first isolated and characterized in the mid-20th century as part of the scientific investigation into the active components of these traditional medicinal plants. Its structure was elucidated as luteolin-6-C-glucoside, identifying it as a C-glycosylflavone with a unique carbon-carbon bond between the flavone backbone and the glucose moiety.

Modern scientific interest in isoorientin began to grow in the late 20th and early 21st centuries as research revealed its antioxidant, anti-inflammatory, antidiabetic, and neuroprotective properties. The discovery of isoorientin’s effects on AMPK signaling, oxidative stress, and inflammatory pathways has provided scientific explanations for some of the traditional uses of plants containing isoorientin, particularly their applications in metabolic conditions, inflammatory disorders, and general well-being.