Phellodendron amurense

Phellodendron amurense (Amur Cork Tree / Huang Bai): A Comprehensive Reference

1. Identity, Nomenclature, and Botanical Description

Phellodendron amurense is a species of tree in the family Rutaceae, commonly called the Amur cork tree. Its full botanical name is Phellodendron amurense Rupr., where the genus name derives from the Greek words phellos (cork) and dendron (tree). In commerce and herbal medicine it is also known by the names Amur Cork Bark, Amur Corktree, Cortex Phellodendri, Phellodendri Cortex, Huang Bai, and Huang Bo.

The species is native to eastern Asia, including northern China, northeast China, Korea, the Ussuri and Amur regions, and Japan. The Amur cork tree can grow up to 12 meters tall. It is a deciduous tree with pale gray-brown, cork-like bark. The tree has shiny, dark green, pinnate leaves composed of 9 to 13 smaller leaflets, and small greenish-yellow flowers grow in clusters. Male and female flowers are located on separate trees. The small round fruit is black and has a strong scent of turpentine.

According to the Chinese Pharmacopeia 2015 edition, Phellodendri Cortex (Huang Bai) has two main pharmacopeial species: Phellodendron amurense Rupr. ("Guan Huang Bai") and Phellodendron chinense Schneid. ("Chuan Huang Bai"), yielding the crude drug forms Phellodendri amurensis cortex (PAC) and Phellodendri chinense cortex (PCC), respectively. The medicinal part of the plant is the dried trunk bark.

Phellodendri amurensis Cortex is the dried bark of the cork tree (Phellodendron amurense Rupr.) from the Rutaceae family, and possesses traditional efficacy in clearing heat, drying dampness, purging fire, relieving steaming sensations, detoxifying, and healing sores.

Common Preparations and Dosage Forms

• Phellodendri Cortex is prepared from the dried cortex of plants from the Rutaceae family, including Phellodendron amurense, Phellodendron chinense, Phellodendron amurense var. sachalinense, and Phellodendron wilsonii.
• The bark is used in standardized extract capsules, standardized to berberine content, as well as in combination proprietary blends (discussed in later sections).
• Phellodendri Cortex is described as bitter in taste and nontoxic; the traditional treatment dose is typically 1 to 11 g per day.

2. Traditional and Historical Use

Traditional Chinese Medicine (TCM)

Phellodendron amurense is a major source of huáng bò (Chinese: 黄柏 or 黄檗), one of the 50 fundamental herbs used in traditional Chinese medicine. It is an important bark-derived TCM originating from Northeast China, renowned for its medicinal value in clearing heat, drying dampness, purging fire, relieving steaming sensations, detoxifying, and healing sores.

Medicinal plants containing its active compounds were documented as early as the Shennong Bencao Jing, the earliest extant Chinese pharmacopoeia. The Compendium of Materia Medica also elaborately describes therapeutic effects on diseases such as jaundice and dysentery.

Clinically in TCM, it is commonly used for treating symptoms such as damp-heat diarrhea and dysentery, jaundice with reddish urine, leukorrhea with vaginal itching, painful and difficult urination due to heat strangury, flaccidity and weakness of the lower limbs, bone-steaming and consumptive fever, night sweats and seminal emission, sores, ulcers, swellings, and toxins, eczema, damp sores, and urinary tract infections.

In TCM, phellodendron bark is one of the "three huangs," or bright yellow plants used for treating inflammation and infection — the other two being scute root and coptis rhizome.

Japanese and Korean Traditional Medicine

It is known as hwangbyeok in Korean and kihada (キハダ) in Japanese. As a core active metabolite of traditional Chinese medicines including Coptis chinensis Franch. and Phellodendron amurense Rupr., palmatine has been employed in Asian traditional medicine for centuries, primarily for treating jaundice, liver diseases, and inflammatory disorders.

Ainu (Indigenous Japan/Russia) Traditional Use

The Ainu people used its fruit, called "shikerebe-ni" (in Ainu, sikerpe), as a painkiller.

Historical Medicinal Applications

In Chinese traditional medicine, it has been used for the treatment of meningitis, bacillary dysentery, pneumonia, tuberculosis, tumours, jaundice, and liver cirrhosis. It was used orally to treat abdominal pain, diarrhoea, gastroenteritis, and urinary tract infections. The herbal medicine has also been used to prepare an eye wash, for strengthening the stomach and intestines to stimulate appetite, and as an astringent and anti-inflammatory.

3. Key Constituents and Active Compounds

Alkaloids

The major chemical constituents of its bark are the isoquinoline alkaloids: palmatine, jatrorrhizine, and phellodendorine, with berberine found within the leaves. To date, various active components have been isolated from PAC, including alkaloids, phenolics, terpenoids, phenylpropanoids, sterols, lignans, and flavonoids.

• Berberine: Berberine is an alkaloid extracted from the roots, rhizomes, and stem tubers of plants such as Coptis chinensis, Phellodendron amurense, Radix berberidis, and several other plants. The content of berberine in the methanol extract of P. amurense bark is abundant compared to other compounds, with a percentage yield detected at approximately 1.4%.
• Palmatine: Palmatine is a natural isoquinoline alkaloid belonging to the quaternary protoberberine class. Hydrochloric acid/methanol-ultrasonic extraction of fresh Phellodendron amurense Rupr. bark yields palmatine at 1.25 mg/g.
• Jatrorrhizine and Phellodendorine: These are additional protoberberine-type isoquinoline alkaloids present in the bark.
• Flavonoids: Compounds in the leaves — quercetin, quercetin-3-O-beta-D-glucoside, quercetin-3-O-beta-D-galactoside, and kaempferol-3-O-beta-D-glucoside — demonstrated significant free radical scavenging activity comparable to vitamin E.
• Other constituents: The oil contains a variety of biologically active substances, including flavonoids (diosmin), alkaloids (berberine, jatrorrhizine, palmatine), saponins, and coumarins. Various active components include alkaloids, phenolics, terpenoids, phenylpropanoids, sterols, lignans, and flavonoids.

Berberine-Free Fraction

Berberine comprises only about 0.6 to 2.5% of the plant's material. The berberine-free fraction of phellodendron bark has exhibited anti-ulcer activity, anti-inflammatory properties, reduction of gastric acid secretion, and anti-cholera toxin effects.

4. Mechanisms of Action

Anti-Inflammatory Pathways

The P. amurense stem bark extract demonstrates good anti-inflammatory activity by reducing nitric oxide, 3-nitrotyrosine, and NF-κB, and antioxidant activity by lowering oxidants and increasing antioxidants. Studies have investigated the effects of Phellodendron amurense in protecting cartilage, including regulating the levels of aggrecanases, matrix metalloproteinases (MMPs)/tissue inhibitor of metalloproteinase (TIMP), proinflammatory cytokines, and signaling of the mitogen-activated protein kinase (MAPK) pathway in human osteoarticular cartilage and chondrocytes.

Antimicrobial Mechanisms

Berberine not only exerts an antimicrobial effect by regulating host immunity but also has a significant direct antimicrobial effect. Berberine is found mainly in the form of hydrochloride in many medicinal plants, including Coptis chinensis, Phellodendron amurense, and Berberis vulgaris. It exhibits various pharmacological activities, including prominent anti-inflammatory and anti-infective effects, antagonizing a variety of pathogenic bacteria (including S. aureus), fungi, parasites, and even viruses.

Phellodendron amurense exhibits antifungal activity mainly through its bioactive components berberine hydrochloride and palmatine hydrochloride. Berberine and palmatine were found to inhibit CYP1A1.1- and CYP1B1.1-catalyzed 7-ethoxyresorufin O-deethylation (EROD) activities, and kinetic analysis revealed that berberine noncompetitively inhibited EROD activities of CYP1A1.1 and CYP1B1.1.

Anticancer and Antiproliferative Mechanisms

Phellodendron amurense extract is a Chinese herbal remedy studied for its antitumor, antimicrobial, and other biological activities. Its antiproliferative properties, and those of berberine, an isoquinoline alkaloid component of P. amurense, have been investigated in terms of bioavailability when delivered as a dietary component. Berberine, when administered orally through the diet, inhibits in vivo tumorigenesis of both p53-expressing and p53-null lung tumor xenografts equally, whether administered in its pure form or as a part of P. amurense extract. Berberine also induces G1 cell cycle arrest, inhibits proliferative kinase signaling, and arrests the growth of lung tumor cells in culture.

Multi-modal anti-tumor mechanisms of palmatine in cancer therapy include triggering programmed cell death in malignant cells, inhibiting cancer cell growth and division, impeding tumor cell migration and invasion, disrupting tumor vascularization, and modulating the tumor microenvironment.

Neuroprotective Mechanisms

Berberine, palmatine, and coptisine at a dose of 5 μg/mL enhanced neurite formation of rat pheochromocytoma (PC12) cells exposed to 10 ng/mL of nerve growth factor (NGF) by 30%, 5%, and 20%, respectively, suggesting transient activation of extracellular signal-regulated kinase (ERK1/2). Collective evidence suggests that the protoberberines — including palmatine, berberine, coptisine, groenlandicine, and jatrorrhizine — are potent AChE inhibitors on account of their charged quaternary amine and methoxyl moieties, which mimic acetylcholine.

Metabolic / AMPK Pathway

Berberine (BBR) has demonstrated remarkable therapeutic efficacy in the management of disorders affecting the nervous, cardiovascular, and endocrine systems, characterized by its high safety profile and minimal adverse effects. The berberine in phellodendron might lower blood sugar and cholesterol levels, as well as protect the liver.

Dermatological / Protease-Activated Receptor Signaling

Measurement of intracellular calcium concentration using human respiratory or skin cells can illustrate pollutant challenges by triggering Ca²⁺ influx. This signal is generated by proteinase-activated receptor-2 (PAR-2), and Phellodendron amurense bark extract was able to control the response and expression of PAR-2. Increase in proinflammatory cytokines and decrease in cell adhesion components suggest a severe damage status by air pollutants and protection by PAE.

5. Scientific Evidence by Area of Use

5.1 Stress, Cortisol, and Psychological Mood

Magnolia (Magnolia officinalis) and Phellodendron (Phellodendron amurense) barks are medicinal plants commonly used as traditional remedies for reducing stress and anxiety. The most-studied modern human application of P. amurense in this context involves the proprietary blend Relora®.

Relora® Study 1 (Talbott et al., 2013): Salivary cortisol exposure and psychological mood state were assessed in 56 subjects (35 men and 21 women) screened for moderate stress and supplemented with a standardized/patented MP combination (Relora®) or placebo for 4 weeks. The product was standardized to "not less than 1.5% honokiol and 0.1% berberine," and subjects ingested 500 mg/day at breakfast (250 mg) and dinner (250 mg). Salivary cortisol exposure was significantly (p<0.05) reduced by −18% in the Relora group, with significant (p<0.05) mood state improvements found for overall stress, global mood state, and vigor. Other indicators included overall stress (reduced by 11%), depression (reduced by 20%), confusion (reduced by 27%), and salivary cortisol exposure decreased by 18%. No adverse side effects were reported.

Relora® Study 2 (Kalman et al., 2008): This study measured the effects of the proprietary blend of extracts of Magnolia officinalis and Phellodendron amurense (Relora®) on anxiety, stress, and sleep in healthy premenopausal women. The randomized, parallel, placebo-controlled clinical study was conducted with healthy, overweight (BMI 25–34.9), premenopausal female adults aged 20–50 years. The intervention was Relora (250 mg capsules) or identical placebo three times daily for 6 weeks. Relora was effective, in comparison to placebo, in reducing temporary, transitory anxiety as measured by the Spielberger STATE anxiety questionnaire. It was not effective in reducing long-standing feelings of anxiety or depression as measured using the Spielberger TRAIT questionnaire. Other assessments including salivary cortisol and amylase levels, appetite, body morphology, and sleep quality/latency were not significantly changed by Relora in comparison to placebo.

Evidence characterization: Both studies used P. amurense only as part of a combination product (Relora®) alongside Magnolia officinalis. It is not possible to attribute observed effects to P. amurense alone. Both trials were small and of short duration. Findings are preliminary.

5.2 Osteoarthritis and Joint Health

NP 06-1 Osteoarthritis Trial (Oben et al., 2009): An 8-week, placebo-controlled, randomized, double-blind study was conducted with four groups comparing the effects of NP 06-1 to placebo in overweight and normal-weight subjects diagnosed with primary osteoarthritis of the knee. NP 06-1 (a combination of two botanical extracts: Phellodendron amurense bark and Citrus sinensis peel) or matching placebo was given in a dose of two capsules (370 mg each) twice daily. The outcome measures were the Lequesne Algofunctional Index (LAI) for joint pain and movement, and biomarkers of inflammation including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Eighty subjects were enrolled and 45 subjects completed the study.

Cardiovascular Outcomes in Same Trial (Oben et al., 2008): NP 06-1 administration was associated with a general improvement in lipid levels. In this pilot study, NP 06-1 had a beneficial effect on cardiovascular risk factors including lipid levels, blood pressure, and fasting glucose levels. Administration of NP 06-1 was also associated with weight loss.

Cartilage Protection Research: In vitro research investigated the effects of Phellodendron amurense in protecting cartilage, including regulating levels of aggrecanases, matrix metalloproteinases (MMPs)/tissue inhibitor of metalloproteinase (TIMP), proinflammatory cytokines, and signaling of the MAPK pathway. Explants from human osteoarthritis cartilage were cultured alone or in IL-1α for 7 days with or without Phellodendron amurense ethanol extract or celecoxib (40, 100, 200 μg/ml). Results showed that Phellodendron amurense displayed no evident cytotoxicity on human articular cartilage and significantly inhibited the IL-1α-induced degradation of GAG and type II collagen from human osteoarticular cartilage.

The proprietary product NP 06-1 (Citrofen®, Next Pharmaceuticals) consists of a blend of extracts of Phellodendron amurense tree bark and Citrus sinensis peel standardized to berberine and polymethoxylated flavones, respectively. Next Pharmaceuticals previously conducted bioassay-guided research on Phellodendron amurense tree bark resulting in a proprietary extract that demonstrated analgesic and anti-inflammatory activity both in vitro and in vivo, in unpublished studies.

Evidence characterization: The human osteoarthritis trials used combination products rather than P. amurense alone, had significant dropout rates (80 enrolled, 45 completed), and were pilot-scale. In vitro cartilage data is mechanistically informative but does not establish clinical efficacy. Evidence is preliminary.

5.3 Antimicrobial Activity

Studies have shown that berberine has demonstrated exceptional antimicrobial efficacy in the treatment of intestinal infections, conjunctivitis, and suppurative otitis media. Phellodendri Cortex has antibacterial, anti-inflammatory, and wound healing properties.

Phellodendron amurense exhibits antifungal activity mainly through its bioactive components berberine hydrochloride and palmatine hydrochloride. One study evaluated the antifungal effects of berberine hydrochloride, palmatine hydrochloride, and a mixture of both substances against Microsporum canis in vivo and in vitro.

P. amurense extract is widely used in traditional medicine for the treatment of pneumonia and diarrhea and for enhancing blood circulation, and is also used as a spasmolytic, anti-inflammatory, and as a bitter tonic for stomach problems.

Evidence characterization: Most antimicrobial evidence derives from in vitro and animal studies, or from the documented activity of isolated berberine rather than of P. amurense preparations specifically. Controlled human clinical evidence for infection treatment is very limited.

5.4 Dermatology: Acne and Skin Inflammation

One clinical trial — a single-center, single-arm study — has been published involving 18 patients with mild-to-moderate acne who used a face mask containing P. amurense (Amur cork tree) once daily for 8 weeks (every evening for the first 3 days and then every other evening thereafter). The results indicated that the mask led to a reduction in lesion counts and moderate to excellent improvements in the appearance of lesions on the forehead (67% of patients), cheek, and jaw (39% of patients for both) during the study period.

In vitro, berberine exhibited significant inhibition zones against four Cutibacterium acnes strains, with the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in the range of 6.25–12.5 μg/mL and 12.5–25 μg/mL, respectively. BBR-treated C. acnes exhibited obvious growth inhibition on the bacterial growth curve.

In cell research, Phellodendron amurense bark extract was able to control the response and expression of PAR-2 in skin cells. Increases in proinflammatory cytokines and decreases in cell adhesion components were observed following pollutant challenge, and protection was observed with PAE.

Evidence characterization: Human clinical evidence in dermatology consists of a single small, non-blinded, uncontrolled study (n=18). In vitro findings are supportive but insufficient to establish clinical efficacy. Evidence is very preliminary.

5.5 Neurological Function / Memory

Research has examined whether Phellodendron amurense and its major alkaloid compound, berberine, improve memory defects caused by administering scopolamine in rats. This investigation was conducted in an animal model only.

Palmatine exhibits particularly notable acetylcholinesterase (AChE) inhibition (IC50 = 36.6 μM), surpassing other Coptis rhizoma alkaloids such as berberine and coptisine in potency, and molecular docking studies confirm its strong binding affinity.

Modern research reveals that palmatine, as an isoquinoline alkaloid, exhibits multi-target regulatory properties, demonstrating broad therapeutic potential across various diseases. This includes systematically elucidated molecular mechanisms in treating digestive system disorders, neurological diseases, and metabolic diseases.

Evidence characterization: Neurological evidence for P. amurense specifically is limited to animal models and in vitro mechanistic studies. No robust controlled human clinical trials in cognitive or neurological endpoints have been identified for this botanical preparation.

5.6 Oncology: Antiproliferative and Cancer-Related Research

Extract from the bark of Phellodendron amurense showed antiproliferative and antiangiogenic effects. Results showed promising anticancer effects based also on the inhibition of angiogenesis with minimum negative effects.

Plant extracts of P. amurense were tested for their anticancer potential against 2D and 3D human skin melanoma (A375) and lung adenocarcinoma (A549) cell lines. The concentrations at which 50% of the cells are affected were determined by viability assay.

Nexrutine (bark extract from Phellodendron amurense) may have potential to prevent prostate tumor development. The Akt/cAMP-responsive element binding protein/cyclin D1 network has been identified as a novel target for prostate cancer inhibition in the transgenic adenocarcinoma of mouse prostate (TRAMP) model mediated by Nexrutine, a Phellodendron amurense bark extract.

Phellodendron amurense may prove to be a potentially important chemopreventive agent for lung cancer.

Evidence characterization: All identifiable anticancer evidence for Phellodendron amurense as a whole preparation derives from cell lines and animal models. There are no completed controlled human trials establishing anticancer efficacy of the botanical. This body of evidence is preclinical only.

5.7 Metabolic Health (Glucose, Lipids)

Several diseases such as diabetes, hormonal disorder, diarrhea, obesity, coronary heart disease, and hyperlipidemia were shown to have been effectively inhibited by berberine in recent studies. However, these data primarily reflect research on isolated berberine rather than on P. amurense preparations.

In the NP 06-1 pilot osteoarthritis study, NP 06-1 administration was associated with a general improvement in lipid levels, and was reported to have a beneficial effect on cardiovascular risk factors including lipid levels, blood pressure, and fasting glucose levels. No serious adverse events were reported.

Evidence characterization: The metabolic findings in the NP 06-1 trial are from a combination product in a secondary endpoint analysis of a pilot study. Direct evidence from P. amurense preparations on metabolic outcomes in humans is limited.

5.8 Urological Health

Phellodendron amurense is able to inhibit prostatic contractility, suggesting that it may be useful in the treatment of urological disorders caused by prostatic urethral obstruction such as benign prostatic hyperplasia (BPH).

Evidence characterization: Evidence is derived from pharmacological and preclinical studies; controlled human trials in urological conditions are not yet established.

5.9 Anti-Gout and Hepatoprotective Activity

The medicinal applications of PAC include antioxidant, hypoglycemic, antihypertensive, anti-inflammatory, antipyretic, anticancer, immunosuppressive, ulcer-protective, anti-gout, and antiviral activities.

Several studies show that total alkaloids obtained from the cortex of P. amurense have a protective effect on stomach ulcer.

Evidence characterization: The foregoing are largely based on preclinical or experimental studies; human evidence remains sparse for these endpoints.

6. Dosage Forms and Reported Study Dosages

• Traditional use: Phellodendri Cortex is described as bitter in taste and nontoxic, and the traditional treatment dose is typically 1 to 11 g per day (dried bark).
• Relora® cortisol/stress trial: 500 mg/day total (250 mg at breakfast, 250 mg at dinner) of a standardized blend (not less than 1.5% honokiol and 0.1% berberine) for 4 weeks.
• Relora® anxiety trial in women: 250 mg capsules three times daily for 6 weeks.
• NP 06-1 osteoarthritis study: two capsules (370 mg each) of the Phellodendron/Citrus combination, twice daily (total 1,480 mg/day) for 8 weeks.
• The NP 06-1 formulation was standardized to a minimum of 50% berberine from the Phellodendron amurense bark extract fraction.

7. Safety Considerations and Drug Interactions

Pregnancy and Neonatal Risk

Phellodendron contains a chemical called berberine, which can cross the placenta and might harm the fetus. Berberine can cause or worsen jaundice in newborn infants and could lead to a life-threatening problem called kernicterus. Berberine might also interact with medicines in negative ways.

Berberine crosses the placenta and can displace bilirubin from albumin in fetal blood, potentially causing kernicterus (a type of brain injury in newborns from bilirubin buildup). The NCCIH explicitly states that berberine is "likely to be unsafe for infants."

Drug Interactions via CYP450 Inhibition

Berberine may inhibit CYP3A4 and possibly other CYP450 enzymes, indicating a risk for interaction between berberine-containing plant preparations and various medicinal products. ANSES discouraged the use of berberine supplements in pregnant or breastfeeding women, diabetics, and individuals with hepatic or cardiac disorders, and warned against any concomitant drug treatment due to potential interaction.

Berberine has been shown to inhibit several CYP450 enzymes, such as CYP3A4, CYP2D6, and CYP2C9. When these enzymes are blocked or slowed down by berberine, medications that rely on them for clearance can stay in the system for longer than intended. This can lead to an accumulation of the drug in the bloodstream, effectively increasing the dose and the risk of toxic side effects.

Research has characterized BBR-induced CYP2D6 inhibition as quasi-irreversible in nature. BBR exhibited selective quasi-irreversible inhibition of CYP2D6 with inactivation rate constant (k_inact) of 0.025 min⁻¹, inhibition constant (K_I) of 4.29 μM, and k_inact/K_I of 5.83 mL/min/μmol.

Hypoglycemia Risk

When combined with glucose-lowering medications such as metformin, insulin, or sulfonylureas, combining berberine may cause hypoglycemia.

Genotoxicity Assessment by Regulatory Bodies

There is evidence for berberine genotoxicity in vitro, indicating gene mutation and chromosomal damage, which are supported by mechanistic evidence. Genotoxicity concern for berberine was identified in in vitro assays. Due to safety concerns and insufficient data, no safe intake can currently be established for any of these berberine-containing preparations by the relevant European regulatory panel.

Except for Hydrastis canadensis, the toxicity profiles of preparations of the plant species included in the [EFSA] mandate, beyond their berberine content, remain largely unknown due to the lack of adequate toxicity studies, resulting in significant uncertainty in the identification and characterisation of hazards associated with these preparations.

General Tolerability

When taken by mouth, phellodendron is possibly safe when used in combination with other ingredients short-term. There is not enough reliable information to know if phellodendron is safe or what the side effects might be when used as a single ingredient. No significant adverse events were observed in the Relora® pilot study in premenopausal women; the study concluded that Relora may offer some relief for premenopausal women experiencing mild transitory anxiety, with no safety concerns observed.

In one vascular irritancy study, at concentrations of 0.10 and 1.0 mg/mL the berberine extract showed no significant signs of irritancy such as vasoconstriction, hyperaemia, haemorrhage, or coagulation. Moderate irritancy was observed only at the highest applied concentration of 10 mg/mL.

8. Body Systems and Health Areas of Association

Modern pharmacological studies have demonstrated that extracts and monomeric compounds from Phellodendri amurensis Cortex possess antibacterial, anti-inflammatory, immunosuppressive, anticancer, and neuroprotective effects, with anti-inflammatory and anticancer activities being particularly prominent. Based on the body of evidence reviewed, P. amurense has been associated with the following body systems:

• Gastrointestinal system: Traditional and preliminary pharmacological evidence for diarrhea, dysentery, gastroenteritis, ulcer, and abdominal pain.
• Musculoskeletal system: Pilot clinical evidence from combination product trials in osteoarthritis; in vitro cartilage protection data.
• Nervous system: Animal and in vitro evidence for cognitive/memory support; AChE inhibition by key alkaloids.
• Endocrine and metabolic system: Preliminary human evidence from combination products for effects on blood glucose, lipids, and cortisol.
• Integumentary (skin) system: Limited clinical evidence in acne; in vitro evidence for anti-inflammatory effects in skin cells.
• Immune and oncological system: Extensive preclinical data on anticancer, immunomodulatory, and antimicrobial properties; no controlled human oncology trials.
• Urinary tract: Preliminary pharmacological evidence in urological disorders including BPH.
• Cardiovascular system: Secondary endpoint findings in pilot human studies; primarily driven by berberine content.

References

• Wikipedia – Phellodendron amurense
• Sun et al. (2026, Molecules) – An Updated and Comprehensive Review of Phellodendri amurensis Cortex: Ethnobotany, Geographical Distribution, Phytochemistry, Quality Control, and Pharmacology
• Sun Y, Lenon GB, Yang AWH (2019, Evidence-Based Complementary and Alternative Medicine) – Phellodendri Cortex: A Phytochemical, Pharmacological, and Pharmacokinetic Review (PMC6463642)
• Talbott SM, Talbott JA, Pugh M (2013, J Int Soc Sports Nutr) – Effect of Magnolia officinalis and Phellodendron amurense (Relora®) on cortisol and psychological mood state in moderately stressed subjects (PMC3750820)
• Kalman DS et al. (2008, Nutrition Journal) – Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial (PMC2359758)
• Oben J et al. (2009, Nutrition Journal) – Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study (PubMed 19682376)
• Oben J et al. (2008, Nutrition Journal) – Phellodendron and Citrus extracts benefit cardiovascular health in osteoarthritis patients: a double-blind, placebo-controlled pilot study (PMC2409365)
• Youn MJ et al. (2010, PubMed) – Dietary administration of berberine or Phellodendron amurense extract inhibits cell cycle progression and lung tumorigenesis (PubMed 21061266)
• Lee B et al. (2012, Korean J Physiol Pharmacol) – Phellodendron amurense and its major alkaloid compound, berberine, ameliorates scopolamine-induced neuronal impairment and memory dysfunction in rats (PubMed 22563252)
• Khayyal MT et al. (2011, ScienceDirect/PubMed) – Effect of Phellodendron amurense in protecting human osteoarthritic cartilage and chondrocytes (PubMed 21182922)
• Xiao CW et al. (2015, BMC Complementary and Alternative Medicine) – Antifungal activity of berberine hydrochloride and palmatine hydrochloride against Microsporum canis-induced dermatitis in rabbits (PMC4460627)
• Sojka M et al. (2022, PMC) – Antiproliferative Effect of Phellodendron amurense Rupr. Based on Angiogenesis (PMC9143060)
• Frontiers in Pharmacology (2025) – Pharmacological properties and therapeutic potential of berberine: a comprehensive review (PMC12391081)
• Frontiers in Pharmacology (2025) – From traditional remedy to modern therapy: a comprehensive review of palmatine's multi-target mechanisms and ethnopharmacological potential
• PMC12331620 – From traditional remedy to modern therapy: palmatine's multi-target mechanisms
• PMC11201499 – Pharmacological Potential of Three Berberine-Containing Plant Extracts (Berberis vulgaris, Mahonia aquifolium, Phellodendron amurense)
• NCCIH (NIH) – In the News: Berberine
• PMC – Quasi-Irreversible Inhibition of CYP2D6 by Berberine (PMC7600264)
• PMC10797013 – The antibacterial activity of berberine against Cutibacterium acnes: its therapeutic potential in inflammatory acne
• PMC – Phellodendron amurense Extract Protects Human Keratinocytes from PM2.5-Induced Inflammation via PAR-2 Signaling
• UK Committee on Toxicity – Draft Scientific Opinion on the safety of plant preparations containing berberine