Palmatine

• Anti-inflammatory
• Antioxidant
• Metabolic regulation
• Cardiovascular protection

• Blood glucose regulation
• Lipid profile improvement
• Liver protection
• Neuroprotection
• Antimicrobial
• Anti-cancer potential
• Bone health support

Palmatine, a quaternary protoberberine alkaloid, exerts its diverse biological effects through multiple molecular mechanisms. As an anti-inflammatory agent, palmatine inhibits the NF-κB signaling pathway, reducing the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. It also suppresses the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), further contributing to its anti-inflammatory properties. Palmatine’s antioxidant effects stem from its ability to scavenge reactive oxygen species (ROS) and enhance the activity of endogenous antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).

This dual action helps protect cells from oxidative damage and reduces oxidative stress markers such as malondialdehyde (MDA). In metabolic regulation, palmatine activates AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. This activation leads to improved glucose uptake in peripheral tissues, reduced hepatic glucose production, and enhanced fatty acid oxidation. Palmatine also inhibits α-glucosidase and α-amylase, enzymes involved in carbohydrate digestion, potentially slowing glucose absorption from the intestine.

For cardiovascular protection, palmatine improves endothelial function by increasing nitric oxide (NO) production through the activation of endothelial nitric oxide synthase (eNOS). It also exhibits anti-platelet aggregation effects and can reduce blood pressure through calcium channel blocking activity. In the liver, palmatine protects hepatocytes from injury by inhibiting lipid peroxidation, reducing inflammatory responses, and enhancing the activity of phase II detoxification enzymes. It may also inhibit hepatic stellate cell activation, potentially reducing liver fibrosis.

Palmatine demonstrates neuroprotective effects by reducing neuroinflammation, inhibiting acetylcholinesterase (AChE) activity, and protecting neurons from excitotoxicity and oxidative damage. Its antimicrobial properties are attributed to its ability to intercalate with DNA, disrupt bacterial cell membranes, and inhibit bacterial protein synthesis. The potential anti-cancer effects of palmatine involve multiple mechanisms, including induction of apoptosis through both intrinsic and extrinsic pathways, cell cycle arrest, inhibition of cancer cell migration and invasion, and modulation of various signaling pathways including PI3K/Akt, MAPK, and Wnt/β-catenin. For bone health, palmatine inhibits osteoclast differentiation and activity while potentially promoting osteoblast function, resulting in a net positive effect on bone formation and reduced bone resorption.

These diverse mechanisms of action explain palmatine’s wide range of pharmacological effects and its potential therapeutic applications in various conditions related to inflammation, oxidative stress, metabolic disorders, and beyond.

The optimal dosage of palmatine as a standalone supplement has not been firmly established through human clinical trials. Most research has been conducted in preclinical settings or using herbal preparations that contain palmatine along with other compounds. Based on the limited available data and traditional usage, dosages typically range from 20-100 mg per day of pure palmatine, though this should be considered preliminary.

Palmatine is typically taken with meals to reduce potential gastrointestinal discomfort and may enhance absorption. For multiple daily doses, spreading them throughout the day (morning, midday, and evening) may help maintain more consistent blood levels.

In traditional herbal preparations containing palmatine (such as goldenseal, barberry, or Chinese goldthread), the palmatine content varies significantly. These herbs typically contain 0.5-6% palmatine, meaning that a 500 mg capsule of herb might provide approximately 2.5-30 mg of palmatine. Traditional dosing of these herbs should be followed rather than attempting to calculate palmatine content.

It’s important to note that most dosage recommendations for palmatine are extrapolated from preclinical studies or based on traditional usage patterns. Well-designed human clinical trials specifically examining palmatine dosage for various conditions are limited. Future research is needed to establish more precise dosing guidelines.

Palmatine demonstrates relatively poor oral bioavailability, estimated at approximately 5-10% in animal studies. As a quaternary ammonium compound with a permanent positive charge, palmatine faces challenges crossing biological membranes, which limits its absorption from the gastrointestinal tract.

Liposomal formulations: Encapsulating palmatine in liposomes has been shown to increase bioavailability by up to 3-4 times in preclinical studies, Nanoparticle delivery systems: Various nanoparticle formulations can enhance palmatine absorption and tissue distribution, Co-administration with piperine: Black pepper extract containing piperine may inhibit P-glycoprotein efflux and first-pass metabolism, potentially improving palmatine bioavailability, Phytosomal complexes: Forming complexes with phospholipids may enhance membrane permeability and absorption, Taking with fatty meals: The presence of dietary fats may enhance absorption of palmatine

Palmatine is best taken with meals, particularly those containing some fat content, which may enhance absorption. Dividing the daily dose into 2-3 administrations throughout the day may help maintain more consistent blood levels due to its relatively short half-life.

Absorption: Primarily absorbed in the small intestine, though the process is limited by palmatine’s quaternary structure and positive charge

Distribution: Moderately distributed to tissues, with higher concentrations observed in the liver, kidneys, and intestinal tissues in animal studies

Metabolism: Undergoes hepatic metabolism primarily through demethylation and glucuronidation pathways. CYP3A4 and CYP2D6 are involved in its metabolism

Elimination: Primarily excreted via biliary and fecal routes, with a smaller portion eliminated through renal excretion

Half Life: The plasma half-life of palmatine is estimated to be approximately 4-6 hours in animal studies, though human data is limited

Palmatine shows similar bioavailability challenges to berberine, another quaternary protoberberine alkaloid. Both compounds have poor oral absorption due to their physicochemical properties. Some studies suggest palmatine may have slightly better absorption than berberine, but this difference is not substantial without formulation enhancements.

After absorption, palmatine shows preferential distribution to the liver, intestinal tissues, and kidneys. Lower concentrations are found in the brain due to limited blood-brain barrier penetration, though some central nervous system effects have been observed, suggesting that small amounts do reach the brain or that some effects are mediated through peripheral mechanisms.

Palmatine undergoes enterohepatic circulation, where it is excreted in bile, reabsorbed in the intestine, and returned to the liver. This recycling process may contribute to its prolonged presence in the body despite relatively poor initial absorption.

• Gastrointestinal discomfort (nausea, diarrhea, constipation)
• Headache
• Dizziness
• Dry mouth
• Potential hypoglycemia at higher doses
• Allergic reactions (rare)

• Pregnancy and breastfeeding (insufficient safety data)
• Children and adolescents (insufficient safety data)
• Hypoglycemia or history of severe hypoglycemic episodes
• Severe liver or kidney disease
• Biliary tract obstruction
• Known hypersensitivity to palmatine or related alkaloids
• Scheduled surgery (discontinue 2 weeks before due to potential effects on blood glucose and blood pressure)

• Anti-diabetic medications (may enhance hypoglycemic effects)
• Antihypertensive drugs (potential additive effects on blood pressure)
• Medications metabolized by CYP3A4 (potential for increased plasma levels of these drugs)
• P-glycoprotein substrates (may affect transport and bioavailability)
• Anticoagulants and antiplatelet drugs (potential increased bleeding risk due to palmatine’s mild antiplatelet effects)
• Sedatives and CNS depressants (theoretical additive effects)
• Medications with narrow therapeutic indices (caution due to potential metabolic interactions)

No established upper limit has been determined through clinical studies. Based on preclinical data and traditional usage, doses above 150 mg daily are not recommended without medical supervision. The long-term safety of palmatine at high doses has not been thoroughly evaluated.

Acute Toxicity: Animal studies suggest low acute toxicity with LD50 values (in rodents) typically exceeding 1000 mg/kg body weight when administered orally.

Chronic Toxicity: Limited long-term toxicity studies exist. Available data suggest that palmatine at moderate doses does not produce significant organ toxicity in animal models when used for periods of up to 3 months.

Genotoxicity: Mixed results in genotoxicity studies, with some suggesting potential DNA intercalation at high concentrations, though clinical relevance at therapeutic doses is unclear.

Reproductive Toxicity: Insufficient data on reproductive and developmental toxicity; hence the contraindication in pregnancy and breastfeeding.

Elderly: Start with lower doses and monitor more closely due to potential age-related changes in metabolism and increased likelihood of drug interactions.

Hepatic Impairment: Use with caution in mild to moderate liver impairment; not recommended in severe liver disease due to palmatine’s hepatic metabolism.

Renal Impairment: Limited data available; use with caution in mild to moderate kidney impairment and avoid in severe renal disease.

Diabetics: May have glucose-lowering effects; monitor blood glucose levels closely and adjust diabetes medications as needed under medical supervision.

Palmatine appears to have a similar safety profile to berberine, with comparable side effects and precautions. Some preliminary data suggest that palmatine may cause less gastrointestinal discomfort than equivalent doses of berberine, but more comparative studies are needed to confirm this observation.

For individuals taking palmatine regularly, particularly at higher doses or for extended periods, monitoring of liver function, blood glucose levels, and blood pressure may be advisable. Those taking multiple medications should be monitored for potential drug interactions.

In the United States, palmatine is not approved as a drug by the FDA.

When sold as a dietary supplement ingredient,

it falls under the Dietary Supplement Health and Education Act (DSHEA) of 1994. Like other dietary supplements, products containing palmatine must adhere to good manufacturing practices, cannot make disease treatment claims, and the FDA can take action if a product is found to be unsafe. Palmatine is not

specifically listed on the FDA’s list of generally recognized as safe (GRAS) substances, nor is

it on the list of prohibited ingredients.

Eu: In the European Union, palmatine does not have an approved health claim under the European Food Safety Authority (EFSA) regulations. It is primarily available as a component of traditional herbal medicinal products containing plants such as Berberis species or Coptis chinensis. The regulatory status may vary between individual EU member states, with some potentially having more restrictive policies.

Canada: Health Canada regulates palmatine-containing products under the Natural Health Products Regulations. Products containing palmatine as part of herbal extracts like goldenseal or barberry may be licensed as Natural Health Products (NHPs) with a Natural Product Number (NPN), provided they meet safety, efficacy, and quality requirements.

Australia: The Therapeutic Goods Administration (TGA) regulates palmatine-containing products as complementary medicines. These products must be listed or registered on the Australian Register of Therapeutic Goods (ARTG) before they can be marketed.

China: In China, palmatine is recognized as a component of various traditional Chinese medicines, particularly Coptis chinensis (Huang Lian) and related herbs. These herbs have official monographs in the Chinese Pharmacopoeia, which specifies quality standards including alkaloid content.

Japan: In Japan, palmatine-containing herbs may be regulated as Kampo medicines (traditional Japanese herbal medicines) or as ‘Foods with Functional Claims’ depending on the specific product formulation and claims.

Us: Products containing palmatine must be labeled as dietary supplements, include a Supplement Facts panel listing all ingredients, and cannot make disease treatment or prevention claims. Structure/function claims must be accompanied by the FDA disclaimer stating that the claims have not been evaluated by the FDA and that the product is not intended to diagnose, treat, cure, or prevent any disease.

Eu: Products must comply with the relevant EU directives on food supplements or herbal medicinal products, depending on their classification. Labeling must include recommended daily dose, warning statements, and must not attribute properties for preventing, treating, or curing human diseases.

Canada: NHPs containing palmatine must display an NPN, medicinal and non-medicinal ingredients, recommended use, cautions, and warnings as specified in their product license.

Across most jurisdictions, marketing of palmatine-containing supplements is restricted from making specific disease treatment or prevention claims. In the US, structure/function claims (e.g., ‘supports healthy inflammatory response’) are permitted with appropriate disclaimer statements, but claims about treating specific diseases are prohibited. Some jurisdictions may have additional restrictions on advertising supplements containing alkaloids.

As a plant alkaloid with pharmacological activity, palmatine faces regulatory challenges in some markets where there may be concerns about its safety or potential for misuse. The lack of extensive human clinical trials and safety data may limit regulatory approvals in some contexts. Additionally, the presence of palmatine alongside other alkaloids in plant extracts can create regulatory complexity regarding standardization and quality control.

As research on palmatine expands, regulatory status may evolve. Increased clinical evidence could potentially lead to consideration as a medical food or even a pharmaceutical ingredient in some jurisdictions, though this would require substantial additional research and regulatory submissions. Conversely, any emerging safety concerns could lead to increased restrictions.

International shipping of palmatine or palmatine-containing supplements may be subject to varying import regulations. Consumers and businesses should verify the legal status in destination countries before importing, as some countries may have restrictions on alkaloid-containing supplements. Customs documentation should clearly identify the nature of the product to avoid potential import issues.

Medium to high

Pure palmatine supplements are relatively uncommon in the market, but when available, typically cost $0.75-$2.50 per effective daily dose (20-100 mg). More commonly, palmatine is found as a component of whole herb extracts (such as Berberis or Coptis extracts), where the cost per dose ranges from $0.30-$1.00, though the exact palmatine content in these products varies.

The value proposition of palmatine must be considered in context of several factors:

1. Limited availability as a standalone supplement means most consumers access palmatine through whole herb extracts, where it works alongside other bioactive compounds that may provide synergistic effects.

2. The relatively poor bioavailability of palmatine means that higher doses may be required to achieve therapeutic effects, potentially increasing the cost per effective dose.

3. For specific conditions where palmatine has shown promise (such as metabolic syndrome or inflammatory conditions), the cost may be reasonable compared to some conventional treatments, though more clinical evidence is needed to fully establish its efficacy.

4. Enhanced formulations (such as liposomal delivery systems) may improve bioavailability and thus value, but typically come at a premium price.

Vs Berberine: Palmatine is generally more expensive than berberine on a per-gram basis, likely due to lower market demand and more limited commercial production. However, if future research demonstrates superior efficacy or fewer side effects for specific applications, this price differential may be justified.

Vs Whole Herbs: Isolated palmatine is significantly more expensive than whole herb extracts containing palmatine (such as barberry or goldthread). The whole herbs provide a complex of alkaloids and other compounds that may work synergistically, potentially offering better overall value despite lower palmatine content.

Vs Conventional Medications: For conditions like metabolic syndrome or inflammatory disorders, palmatine supplements are generally less expensive than many prescription medications, particularly for those without insurance coverage. However, the lack of robust clinical evidence and standardization makes direct cost-effectiveness comparisons difficult.

The market for palmatine and palmatine-containing supplements remains relatively niche but is gradually expanding as research interest grows. Prices have remained relatively stable, though increased demand and improved extraction technologies could potentially reduce costs in the future. The growing interest in natural alternatives to conventional medications may drive further market development.

Purchasing whole herb extracts standardized for alkaloid content (including palmatine) may provide better value than isolated palmatine, Combination products that include palmatine alongside synergistic compounds may offer better overall value than taking multiple separate supplements, Improved formulations focusing on enhanced bioavailability may provide better cost-efficiency despite higher upfront costs, Bulk purchasing of palmatine-containing supplements can often reduce the per-dose cost

Preventive Use: For preventive or wellness applications, the cost-benefit ratio of palmatine is difficult to establish given the limited human clinical evidence. Consumers should weigh the ongoing supplement cost against the uncertain preventive benefits.

Therapeutic Use: For specific therapeutic applications where some evidence exists (such as metabolic or inflammatory conditions), palmatine may offer reasonable value compared to some alternatives, though it should not replace proven medical treatments without healthcare provider guidance.

Research Use: For research purposes, higher-purity palmatine commands premium prices, with analytical grade (>95% purity) costing significantly more than supplement-grade material.

The economic factors affecting palmatine production and pricing include:

1. Limited natural concentration in source plants (typically 0.1-3% depending on the plant species and part used)

2. Labor-intensive cultivation and harvesting of source plants

3. Complex extraction and purification processes required to isolate palmatine from other alkaloids

4. Relatively small market demand compared to more mainstream supplements

5. Lack of efficient synthetic production methods, making botanical extraction the primary commercial source

Pure palmatine, when properly stored, typically has a shelf life of 2-3 years. In commercial supplement formulations, the shelf life may range from 1-2 years depending on the specific formulation, packaging, and storage conditions.

Store in a cool, dry place away from direct sunlight. Optimal storage temperature is between 59-77°F (15-25°C). Refrigeration is not necessary but may extend shelf life. Keep container tightly closed to protect from moisture and air exposure. Avoid frequent opening of the container to minimize exposure to air and humidity.

Light exposure: Palmatine is photosensitive and can degrade when exposed to direct sunlight or strong artificial light, Heat: Temperatures above 86°F (30°C) accelerate degradation, Moisture: Humidity can cause hydrolysis of palmatine, Oxidation: Prolonged exposure to air leads to oxidative degradation, pH extremes: Palmatine is most stable in slightly acidic conditions (pH 4-6); strongly acidic or alkaline environments accelerate degradation

Palmatine is a quaternary ammonium compound with a permanent positive charge, which contributes to its relative stability in certain conditions. However, this same feature makes it susceptible to specific degradation pathways:

1. Demethylation: Loss of methyl groups from the methoxy substituents can occur over time, especially under acidic conditions.

2. Photodegradation: The conjugated ring system absorbs light, making palmatine susceptible to photochemical reactions that can break down the molecule.

3. Oxidation: The methoxy groups and the isoquinoline ring system can undergo oxidation when exposed to air for extended periods.

When formulating supplements containing palmatine, consider these compatibility factors:

1. Compatible with most capsule materials including vegetable cellulose and gelatin.

2. May interact with certain excipients containing reactive groups that could bind to palmatine’s quaternary nitrogen.

3. Potential incompatibility with strongly oxidizing agents used as preservatives.

4. May form complexes with certain minerals (iron, calcium) if included in the same formulation.

5. Generally compatible with most other herbal extracts, though tannin-rich extracts may reduce bioavailability.

High-performance liquid chromatography (HPLC) to measure active compound content over time, Accelerated stability testing under various temperature and humidity conditions, Photostability testing to assess degradation under various light conditions, pH stability studies to determine optimal formulation pH, Real-time stability testing to confirm shelf life estimates

Appropriate packaging is crucial for maintaining palmatine stability:

1. Amber or opaque containers are recommended to protect from light.

2. Airtight containers with good moisture barriers are essential.

3. Some premium products may use blister packs to protect individual doses from environmental factors until use.

4. Inclusion of desiccants in the packaging can help maintain low humidity.

5. Nitrogen flushing during packaging can reduce oxidative degradation by removing oxygen.

Different formulations affect palmatine stability:

1. Solid formulations (capsules, tablets) generally provide better stability than liquid formulations.

2. Enteric-coated formulations may protect palmatine from stomach acid while potentially improving intestinal absorption.

3. Liposomal formulations may enhance stability while also improving bioavailability.

4. Inclusion of antioxidants (such as vitamin E or rosemary extract) in formulations may extend shelf life by reducing oxidative degradation.

Synthesis Methods

Natural Sources

Extraction Methods

Quality Considerations

Sustainability Considerations

Palmatine has a rich history of traditional use spanning thousands of years, primarily as a component of medicinal plants rather than as an isolated compound. Its presence in various traditional medicine systems reflects its importance in historical healing practices across different cultures.

In Traditional Chinese Medicine (TCM), palmatine-containing herbs have been used for over 2,000 years. Coptis chinensis (Huang Lian), one of the primary sources of palmatine, appears in the earliest known Chinese pharmacopeia, the Shennong Ben Cao Jing (Divine Farmer’s Materia Medica), compiled around 200-250 CE. These herbs were traditionally used to ‘clear heat and dry dampness,’ which in TCM terminology refers to treating conditions characterized by inflammation, infection, and digestive disorders. Specific applications included treating diarrhea, dysentery, jaundice, and various inflammatory conditions.

In Ayurvedic medicine from the Indian subcontinent, plants containing palmatine such as Berberis aristata (Indian Barberry or ‘Daruharidra’) have been used since at least 700 BCE, as documented in ancient texts like the Charaka Samhita. These plants were employed for treating eye disorders, skin diseases, jaundice, and various infectious conditions. The bitter properties of these herbs were believed to enhance digestion and purify the blood.

Native American healing traditions also utilized palmatine-containing plants, particularly Hydrastis canadensis (Goldenseal) and various Berberis species. These were used for treating digestive disorders, skin conditions, and infections. The Cherokee, Iroquois, and other indigenous peoples used these plants for their antimicrobial and anti-inflammatory properties long before the arrival of European settlers.

In European traditional medicine, Berberis vulgaris (European Barberry) was documented in medieval herbals and was used to treat liver and gallbladder disorders, as well as various infectious conditions. The 17th-century English herbalist Nicholas Culpeper recommended barberry for liver complaints and to ‘strengthen the stomach.’

The isolation and identification of palmatine as a distinct chemical compound occurred much more recently, in the late 19th and early 20th centuries, as part of the scientific investigation of traditional medicinal plants. The name ‘palmatine’ is derived from Coptis teeta (also known as Coptis palmata), one of the plants from which it was first isolated.

Modern scientific interest in palmatine began to accelerate in the latter half of the 20th century, with research focusing on its pharmacological properties and potential therapeutic applications. Studies have since confirmed many of the traditional uses, identifying antimicrobial, anti-inflammatory, and metabolic regulatory effects that align with historical applications.

Unlike some other alkaloids that have been developed into mainstream pharmaceutical drugs, palmatine has remained primarily in the domain of traditional medicine and dietary supplements. However, ongoing research continues to explore its potential in various therapeutic areas, bridging ancient wisdom with modern scientific understanding.

This historical context highlights how palmatine-containing plants have been valued across diverse healing traditions for similar applications, suggesting consistent biological activity that has been recognized empirically by different cultures throughout human history.

No formal meta-analyses specifically focused on palmatine have been published to date, reflecting the early stage of clinical research on this compound.

Limited information is available on registered clinical trials specifically investigating palmatine as a standalone intervention. Most current research appears to be at the preclinical stage or involves herbal preparations that contain palmatine among other compounds.

Human Clinical Trials: There is a significant lack of well-designed human clinical trials investigating palmatine’s efficacy, optimal dosing, and long-term safety.

Pharmacokinetics: More detailed studies on palmatine’s absorption, distribution, metabolism, and excretion in humans are needed.

Drug Interactions: Comprehensive evaluation of potential interactions between palmatine and commonly used medications is lacking.

Comparative Studies: Direct comparisons between palmatine and related compounds (such as berberine) would help clarify its relative efficacy and safety profile.

Formulation Research: Studies on improving palmatine’s bioavailability through various formulation strategies are needed to enhance its therapeutic potential.

Anti Inflammatory: Moderate preclinical evidence; limited clinical data

Metabolic Regulation: Moderate preclinical evidence; very limited clinical data

Cardiovascular Effects: Moderate preclinical evidence; insufficient clinical data

Antimicrobial: Strong in vitro evidence; limited in vivo confirmation

Anticancer: Emerging preclinical evidence; requires substantial clinical validation

Neuroprotection: Preliminary preclinical evidence; clinical studies lacking

Most researchers in the field consider palmatine a promising bioactive compound with diverse pharmacological activities, but acknowledge that its therapeutic potential requires substantial additional research, particularly human clinical trials. The compound is generally viewed as having similar properties to berberine but with some potentially distinct characteristics that warrant further investigation. Experts typically recommend caution in clinical application until more robust human data becomes available.