Isoschaftoside

• Antioxidant
• Anti-inflammatory
• Hepatoprotective
• Metabolic support

• Neuroprotective
• Antimicrobial
• Antiviral
• Skin barrier protection
• Anticancer

Isoschaftoside (apigenin-8-C-glucoside-6-C-arabinoside) exerts its diverse biological effects through multiple molecular pathways. As a di-C-glycosylflavone, isoschaftoside possesses a unique structural feature where two sugar molecules—a glucose at the C-8 position and an arabinose at the C-6 position—are directly attached to the apigenin backbone via carbon-carbon bonds, rather than through oxygen atoms as in O-glycosides. These C-glycosidic bonds are resistant to hydrolysis by glycosidases, contributing to isoschaftoside’s distinct pharmacokinetic profile and biological activities. One of isoschaftoside’s most extensively studied mechanisms is its antioxidant activity.

Isoschaftoside scavenges reactive oxygen species (ROS) and free radicals through its hydroxyl groups on the flavone 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, isoschaftoside 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), isoschaftoside 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, isoschaftoside 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. Isoschaftoside 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 isoschaftoside 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, isoschaftoside reduces the production of these potent inflammatory mediators, providing additional anti-inflammatory benefits beyond NF-κB inhibition. In the liver, isoschaftoside demonstrates potent hepatoprotective effects through multiple mechanisms. Recent studies have shown that isoschaftoside can significantly ameliorate non-alcoholic fatty liver disease (NAFLD) by activating the AMP-activated protein kinase (AMPK) signaling pathway.

AMPK activation leads to increased fatty acid oxidation, reduced lipogenesis, and improved insulin sensitivity in the liver. Isoschaftoside also reduces hepatic inflammation by inhibiting the NF-κB pathway and decreasing the production of pro-inflammatory cytokines in liver cells. Additionally, it enhances autophagy in hepatocytes, promoting the clearance of damaged organelles and lipid droplets, which further contributes to its beneficial effects in NAFLD. Isoschaftoside also protects against drug-induced liver injury by reducing oxidative stress and maintaining glutathione levels in hepatocytes.

In metabolic regulation, isoschaftoside demonstrates significant effects on lipid and glucose metabolism. It activates AMPK, a key regulator of cellular energy homeostasis, which leads to increased glucose uptake in skeletal muscle and adipose tissue, reduced hepatic glucose production, and improved insulin sensitivity. Isoschaftoside also enhances the expression and activity of peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor that plays a crucial role in adipocyte differentiation, lipid metabolism, and insulin sensitivity. By modulating these pathways, isoschaftoside helps maintain metabolic homeostasis and may benefit conditions like metabolic syndrome, type 2 diabetes, and obesity.

In the central nervous system, isoschaftoside exhibits neuroprotective effects through multiple mechanisms. It protects neurons from oxidative stress and excitotoxicity by reducing glutamate-induced calcium influx and maintaining mitochondrial function. Isoschaftoside 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 phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, promoting neuronal survival and synaptic plasticity.

Isoschaftoside has demonstrated antimicrobial and antiviral properties against various pathogens. The mechanisms include direct inhibition of microbial growth, disruption of bacterial cell membranes, and interference with viral entry and replication. The presence of two different sugar moieties at different positions on the apigenin backbone may contribute to isoschaftoside’s ability to interact with microbial proteins and disrupt their function. In skin cells, isoschaftoside has been shown to improve barrier function and hydration.

It enhances the expression of filaggrin, involucrin, and other proteins essential for skin barrier integrity. Isoschaftoside also activates the aryl hydrocarbon receptor (AhR) pathway, which plays a role in skin homeostasis and protection against environmental stressors. Additionally, it reduces inflammation and oxidative stress in keratinocytes, potentially benefiting various skin conditions. In cancer cells, isoschaftoside demonstrates antiproliferative and pro-apoptotic effects.

It induces cell cycle arrest by modulating the expression and activity of cell cycle regulators, including cyclins and cyclin-dependent kinases (CDKs). Isoschaftoside 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, isoschaftoside has been shown to inhibit angiogenesis and metastasis by reducing vascular endothelial growth factor (VEGF) expression and matrix metalloproteinase (MMP) activity.

The unique di-C-glycosidic structure of isoschaftoside, with different sugar moieties at different positions compared to its isomer schaftoside (apigenin-6-C-glucoside-8-C-arabinoside), contributes to its distinct pharmacological profile. This structural feature affects its bioavailability, metabolism, and tissue distribution, potentially leading to different biological activities and therapeutic applications. The presence of both glucose and arabinose moieties may allow isoschaftoside to interact with a broader range of molecular targets, potentially explaining its diverse biological effects.

Optimal dosage ranges for isoschaftoside in humans have not been well established through clinical trials. Most research has focused on isoschaftoside as a component of herbal extracts, particularly from fig leaves, passion flower (Passiflora species), bamboo leaves, and wheat leaves, rather than as an isolated compound. Based on preclinical studies and limited human research with herbal extracts containing isoschaftoside, estimated effective doses would range from 5-30 mg of isoschaftoside daily. For fig leaf extracts, typical daily doses range from 250-750 mg of standardized extract containing 0.1-0.3% isoschaftoside, corresponding to approximately 0.25-2.25 mg of isoschaftoside daily.

For passion flower extracts, typical daily doses range from 300-800 mg of standardized extract containing 0.05-0.2% isoschaftoside, corresponding to approximately 0.15-1.6 mg of isoschaftoside daily. For bamboo leaf extracts, typical daily doses range from 200-600 mg of standardized extract containing 0.05-0.15% isoschaftoside, corresponding to approximately 0.1-0.9 mg of isoschaftoside daily. For wheat leaf extracts, typical daily doses range from 250-750 mg of standardized extract containing 0.05-0.15% isoschaftoside, corresponding to approximately 0.125-1.125 mg of isoschaftoside daily. It’s important to note that isoschaftoside’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 isoschaftoside.

Isoschaftoside has relatively low oral bioavailability, estimated at approximately 1-5% in animal studies. This limited bioavailability is primarily due to its di-C-glycosidic structure, which affects its absorption and metabolism. Unlike O-glycosides, the C-glycosidic bonds in isoschaftoside (where glucose is directly attached to the C-8 position and arabinose to the C-6 position of apigenin via carbon-carbon bonds) are resistant to hydrolysis by intestinal and hepatic glycosidases. This means that isoschaftoside is primarily absorbed intact rather than being converted to its aglycone (apigenin) in the gastrointestinal tract.

The presence of two sugar moieties—glucose and arabinose—further increases the molecular weight and hydrophilicity of isoschaftoside, reducing passive diffusion across cell membranes. Absorption occurs primarily through active transport mechanisms, including sodium-dependent glucose transporters (SGLTs) and possibly other transporters, though the efficiency of this process is limited due to the complex structure. Once absorbed, isoschaftoside 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 C-glycosidic bonds also make isoschaftoside less susceptible to efflux by P-glycoprotein transporters in the intestine, which may partially compensate for its limited passive diffusion.

In animal studies, isoschaftoside has demonstrated tissue distribution to various organs, including the liver, kidneys, and brain, though brain penetration is limited due to its hydrophilicity and relatively large molecular size. The liver appears to be a primary site of accumulation, which may contribute to its pronounced hepatoprotective effects. The presence of other compounds in herbal extracts, particularly from fig leaves, passion flower, bamboo leaves, and wheat leaves, may influence isoschaftoside’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 isoschaftoside 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 isoschaftoside’s half-life, Nanoparticle formulations – improve stability and targeted delivery, particularly relevant for hepatoprotective and metabolic applications

Isoschaftoside 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 isoschaftoside’s bioavailability through competitive inhibition of metabolic enzymes or transporters. For hepatoprotective effects, particularly in NAFLD, taking isoschaftoside with meals may enhance its delivery to the liver through the portal circulation. Consistent daily dosing is important for maintaining therapeutic levels, with some evidence suggesting that morning dosing may be beneficial due to diurnal variations in liver metabolism.

For metabolic support, taking isoschaftoside before meals may enhance its effects on postprandial glucose and lipid metabolism. 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 isoschaftoside’s relatively short half-life (approximately 2-4 hours in animal studies). 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 isoschaftoside 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 fig leaf tea, the hot water extraction efficiently extracts isoschaftoside 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 drowsiness (uncommon, primarily when taken with passion flower extracts)

• Pregnancy and breastfeeding (due to insufficient safety data)
• Scheduled surgery (discontinue 2 weeks before due to potential mild sedative effects when present in passion flower extracts)
• Individuals with known allergies to plants in the Moraceae family (for fig leaf-derived isoschaftoside), Passifloraceae family (for passion flower-derived isoschaftoside), Poaceae family (for bamboo or wheat-derived isoschaftoside), or Pennisetum genus (for pearl millet-derived isoschaftoside)
• Individuals with severe liver or kidney disease (due to limited data on metabolism and excretion in these populations)
• Individuals taking medications that act on the central nervous system (due to potential additive effects when present in passion flower extracts)
• Individuals with latex allergies (due to potential cross-reactivity with fig leaf extracts)

• Sedatives and hypnotics (potential for additive sedative effects when isoschaftoside is present in passion flower extracts)
• 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)
• Antidiabetic medications (may enhance blood glucose-lowering effects, particularly relevant for fig leaf extracts which have known hypoglycemic properties)
• Antioxidant medications (potential for additive effects with other antioxidants)
• Hepatoprotective medications (potential for additive effects with other hepatoprotective agents)
• Drugs requiring active transport for absorption (potential competition for transporters)
• Immunomodulatory drugs (potential for interaction due to isoschaftoside’s effects on inflammatory pathways)
• Lipid-lowering medications (potential for additive effects on lipid metabolism, particularly relevant for fig leaf extracts)

Due to limited human clinical data on isolated isoschaftoside, a definitive upper limit has not been established. Based on safety data for fig leaf, passion flower, bamboo leaf, and wheat leaf extracts (which contain isoschaftoside) and animal toxicity studies, doses up to 30 mg of isoschaftoside daily or 800 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 isoschaftoside 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 isoschaftoside. Traditional use of herbs containing isoschaftoside in moderate doses has a long history of safe use, further supporting the generally favorable safety profile of isoschaftoside-containing preparations. Fig leaf extracts, which are particularly rich in isoschaftoside, have been used traditionally for various health conditions with a good safety record, though individuals with latex allergies should exercise caution due to potential cross-reactivity.

Isoschaftoside itself is not approved as a drug by the FDA and is not commonly available as an isolated supplement. Plant extracts containing isoschaftoside, such as fig leaf, passion flower, bamboo leaf, and wheat leaf 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 isoschaftoside specifically.

Fig leaves, passion flower, and bamboo leaves are generally recognized as safe (GRAS) when used in traditional amounts as herbs or supplements.

Eu: In the European Union, isoschaftoside is not approved as a medicinal product. However, passion flower extracts containing isoschaftoside 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. Fig leaf, bamboo leaf, and wheat 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. Fig leaf tea is recognized in German traditional medicine for its potential benefits in metabolic conditions, though it is not officially approved by Commission E. Bamboo leaf and wheat 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. Fig leaf, bamboo leaf, and wheat leaf extracts are primarily regulated as food supplements.

Canada: Health Canada regulates passion flower, fig leaf, bamboo leaf, and wheat leaf 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 fig leaf, claims include ‘traditionally used in Herbal Medicine to help lower blood glucose levels.’ Isolated isoschaftoside is not specifically approved as a standalone ingredient.

Australia: The Therapeutic Goods Administration (TGA) regulates passion flower, fig leaf, bamboo leaf, and wheat leaf 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. Isoschaftoside as an isolated compound is not specifically regulated.

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. Fig leaf and passion flower are less commonly used in traditional Chinese medicine. Isoschaftoside as an isolated compound is primarily used in research rather than as an approved therapeutic agent.

Turkey: In Turkey, fig leaf tea has a long history of traditional use for diabetes and is recognized in Turkish traditional medicine. It is regulated as a traditional herbal product and is widely available in markets and pharmacies. Isoschaftoside as an isolated compound is not specifically regulated for therapeutic use.

Middle East: In various Middle Eastern countries, fig leaf preparations are traditionally used for diabetes, hypertension, and liver disorders. They are generally regulated as traditional herbal products, though specific regulations vary by country. Isoschaftoside as an isolated compound is not specifically regulated for therapeutic use.

Medium to high

Isolated isoschaftoside is rarely available commercially for supplementation and is primarily sold as a research chemical at prices ranging from $300-$800 per 10-25 mg, making it prohibitively expensive for regular supplementation. Standardized fig leaf extracts containing isoschaftoside along with other flavonoids typically cost $0.30-$1.20 per day for basic extracts and $1.20-$3.00 per day for premium, highly standardized formulations. Standardized passion flower extracts containing isoschaftoside typically cost $0.25-$1.00 per day for basic extracts and $1.00-$2.50 per day for premium formulations. Standardized bamboo leaf extracts containing isoschaftoside typically cost $0.30-$1.20 per day for basic extracts and $1.20-$3.00 per day for premium formulations.

Standardized wheat leaf extracts containing isoschaftoside typically cost $0.25-$1.00 per day for basic extracts and $1.00-$2.50 per day for premium formulations. Dried herbs for tea preparation (fig leaves, passion flower) are the most cost-effective option, typically costing $0.15-$0.50 per day, though they provide less consistent and potentially lower amounts of isoschaftoside.

The cost-effectiveness of isoschaftoside must be evaluated in the context of herbal extracts containing it, as isolated isoschaftoside is not practically available for regular supplementation due to its high cost and limited commercial availability. For hepatoprotective effects, particularly in NAFLD, fig leaf extracts containing isoschaftoside offer promising value compared to other interventions. The emerging clinical evidence for fig leaf tea in NAFLD management, combined with its relatively low cost and favorable safety profile, suggests good cost-effectiveness for this specific application. When compared to pharmaceutical interventions for NAFLD, which can cost hundreds of dollars per month and often come with significant side effects, fig leaf extracts represent a potentially valuable complementary approach.

For metabolic support, particularly in conditions like metabolic syndrome and type 2 diabetes, fig leaf extracts containing isoschaftoside offer moderate value. Traditional use of fig leaf tea for diabetes has a long history in various cultures, and recent scientific studies are beginning to validate these applications. When compared to other natural supplements for metabolic support, fig leaf extracts are moderately priced and offer a unique mechanism of action through AMPK activation. For antioxidant and anti-inflammatory benefits, there are likely more cost-effective options than isoschaftoside-containing extracts, as many other botanical antioxidants have similar potency at lower costs.

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. When comparing the cost-effectiveness of fig leaf, passion flower, bamboo leaf, and wheat leaf extracts containing isoschaftoside to other supplements with similar indications: For NAFLD, fig leaf extracts are generally more expensive than milk thistle (silymarin) extracts, which have more extensive clinical evidence for liver conditions, but the unique mechanism of action through AMPK activation may justify the higher cost for specific cases. For metabolic support, fig leaf extracts are comparably priced to other natural supplements like berberine or alpha-lipoic acid, with emerging evidence supporting their efficacy.

For neuroprotection, passion flower extracts containing isoschaftoside 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 isoschaftoside is through traditional fig leaf or passion flower tea, which can be prepared from dried herb at a fraction of the cost of processed extracts. However, the concentration of isoschaftoside and other active compounds may be lower and less consistent in tea preparations compared to standardized extracts. 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 isoschaftoside.

Pure isoschaftoside is moderately stable, with a typical shelf life of 2-3 years when properly stored. The C-glycosidic bonds (where glucose is directly attached to the C-8 position and arabinose to the C-6 position of apigenin via carbon-carbon bonds) provide better stability compared to O-glycosides, as they are resistant to hydrolysis by acids and enzymes. Standardized herbal extracts containing isoschaftoside, such as fig leaf, passion flower, bamboo leaf, or wheat leaf extracts, typically have a shelf life of 1-2 years from the date of manufacture. Dried herb material (e.g., fig leaves, passion flower, bamboo leaves, wheat leaves) properly stored can maintain acceptable isoschaftoside 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 isoschaftoside. Protect from moisture, heat, oxygen, and light exposure, which can accelerate degradation. For research-grade pure isoschaftoside, storage under inert gas (nitrogen or argon) at -20°C is recommended for maximum stability.

For dried herb material (e.g., fig leaves, passion flower, bamboo leaves, wheat leaves), store in airtight containers away from light and moisture to preserve the isoschaftoside 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.

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, pH extremes – isoschaftoside 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 bonds are resistant to glycosidases, other enzymes may affect the flavone structure, Incompatible excipients in formulations – certain preservatives or other ingredients may interact negatively with isoschaftoside, Repeated freeze-thaw cycles – can destabilize enhanced delivery formulations such as nanoemulsions or liposomes, Microbial contamination – particularly relevant for liquid formulations, can lead to degradation of active compounds

Synthesis Methods

Natural Sources

Quality Considerations

Isoschaftoside 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 isoschaftoside 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. Isoschaftoside is primarily found in fig leaves, passion flower, bamboo leaves, and wheat leaves, all of which have rich histories in traditional medicine across various cultures. Fig leaves (Ficus carica) have been used in traditional medicine systems throughout the Mediterranean region, Middle East, and parts of Asia for thousands of years.

In ancient Greece and Rome, fig leaves were used to treat various ailments, including liver disorders, digestive problems, and skin conditions. Hippocrates, the father of Western medicine, recommended fig leaves for their medicinal properties. In traditional Middle Eastern medicine, fig leaf tea was used to treat diabetes, high blood pressure, and bronchitis. The ancient Egyptians used fig leaves in poultices for wounds and inflammatory conditions.

In traditional Turkish medicine, fig leaf tea was used for its hypoglycemic effects and to treat respiratory disorders. In the Bible, fig leaves are mentioned as being used for covering, but they also had medicinal applications in ancient Hebrew medicine. In traditional Indian medicine (Ayurveda), fig leaves were used for their cooling properties and to treat various conditions, including diabetes, liver disorders, and diarrhea. 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.

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. Wheat, one of the world’s oldest cultivated crops, has been used not only as a staple food but also for medicinal purposes in various cultures.

In ancient Egypt, Greece, and Rome, wheat was used in poultices for wounds and inflammatory conditions. The young wheat leaves, which contain isoschaftoside, were used in traditional European folk medicine for their nutritive and healing properties. In some traditional systems, wheat grass juice, derived from young wheat leaves, was used for detoxification, improving digestion, and enhancing overall health. Isoschaftoside 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 apigenin-8-C-glucoside-6-C-arabinoside, identifying it as a di-C-glycosylflavone with unique carbon-carbon bonds between the flavone backbone and the sugar moieties. Modern scientific interest in isoschaftoside began to grow in the late 20th and early 21st centuries as research revealed its antioxidant, anti-inflammatory, hepatoprotective, and metabolic regulatory properties. The discovery of isoschaftoside’s effects on AMPK signaling, Nrf2 pathway, and lipid metabolism has provided scientific explanations for some of the traditional uses of plants containing isoschaftoside, particularly their applications in liver disorders, diabetes, and inflammatory conditions.

No meta-analyses specifically on isoschaftoside are currently available; most analyses focus on herbal extracts containing isoschaftoside or flavonoids as a group.

Limited ongoing trials specifically investigating isoschaftoside; most research remains at the preclinical stage, Several clinical trials investigating fig leaf tea (containing isoschaftoside) for metabolic disorders, including non-alcoholic fatty liver disease, type 2 diabetes, and metabolic syndrome, Preclinical studies investigating isoschaftoside’s potential in neurodegenerative diseases, particularly focusing on its anti-inflammatory and neuroprotective properties in microglial cells, Research on isoschaftoside’s hepatoprotective effects in various liver disease models, including drug-induced liver injury and alcoholic liver disease, Investigations into isoschaftoside’s antiviral properties against respiratory viruses, including influenza and coronaviruses, Studies on novel delivery systems to enhance isoschaftoside’s bioavailability and targeted delivery