NICEVIVA
MONOGRAPH SPEC LATEST 2024

Phellodendron amurense

TRADITIONAL ASIAN · Evidence Monograph

Phellodendron amurense is an evidence-graded traditional asian monograph evaluated across 7 peer-reviewed PubMed studies (0 meta-analyses, 0 systematic reviews, and 0 randomized controlled trials, encompassing n = 130 cumulative participants). Current clinical evidence is rated GRADE Low (2.0 / 4.0) for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

Evidence Grade (GRADE) Low (2.0 / 4.0)
Indexed PubMed Studies 7 Studies
Meta-Analyses · Reviews 0 Meta · 0 Systematic Reviews
Randomized Trials (RCT) 0 RCTs (4 Double-Blind)
Cumulative Participants n = 130
Reported Trial Dosages 370 mg · 250 mg
Trial Duration Range 8 weeks · 6 weeks
Reading Time ~4 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support (supported by 7 indexed PubMed studies, GRADE Low).
  2. 02 Adults matching clinical trial dosing protocols (370 mg · 250 mg) over a structured 8 weeks evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Clinically Standardized Formulation
Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.
Dose Adjustment Signal: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.
CHRONOBIOLOGY · Optimal Dosing Window PM 12:30
With Breakfast or Lunch
Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary traditional asian clinical efficacy (7 PubMed studies)
Quantitative biomarker & outcome analysis (4 studies with effect-size/sample data)
Randomized controlled trial verification (0 RCTs · 4 double-blind)
Systematic review & meta-analysis synthesis (0 meta-analyses · 0 reviews)
01

What Is Phellodendron amurense & Why Does Form Matter?

Phellodendron amurense is classified under TRADITIONAL ASIAN and has been investigated across 7 peer-reviewed PubMed publications for its role in targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (370 mg, 250 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Phellodendron amurense frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (0 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Phellodendron amurense acts on pathways governing targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Phellodendron amurense an overall evidence rating of GRADE Low (2.0 / 4.0) based on 7 PubMed studies: 0 meta-analyses, 0 systematic reviews, and 0 randomized controlled trials (4 double-blind, n = 130 total participants).

Representative peer-reviewed findings include: • PMID:38465436 (2024) — "Safety Issues of Herb-Warfarin Interactions." (Besides, HWIs were also found to decrease International Normalised Ratio (INR) levels following the consumption of Persea americana or avocado.) • PMID:34757861 (2021) — "Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp." (DISCUSSION AND CONCLUSIONS: The adverse interaction between rhynchopylline and pellodendrine draws attention to the co-administration of these two herbs and provides a reference for further investigations with a broader study population.) • PMID:39590314 (2024) — "Exploring the Benefits of Herbal Medicine Composite 5 (HRMC5) for Skin Health Enhancement." (The topical application of HRMC5 cream offered potential advantages over ingested phytoestrogens by reducing the systemic side effects.)

05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Clinically Standardized Formulation. Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 370 mg · 250 mg over 8 weeks · 6 weeks. Optimal timing window: PM 12:30 · With Breakfast or Lunch (Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.

Adjustment & Discontinuation Signals: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Phellodendron amurense, but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 12:30 · With Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (370 mg · 250 mg) and re-evaluate efficacy after 8 weeks.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (7 Studies) · 4 Quantitative Analyses

01
CLINICAL STUDY Current drug metabolism (2024) PMID: 38465436 ↗
Safety Issues of Herb-Warfarin Interactions.
Clinical Trial Synthesis 2024 Clinical Study published in Current drug metabolism. Key conclusion: Besides, HWIs were also found to decrease International Normalised Ratio (INR) levels following the consumption of Persea americana or avocado.
View Original PubMed Abstract ↓

Warfarin is a popular anticoagulant with high global demand. However, studies have underlined serious safety issues when warfarin is consumed concomitantly with herbs or its formulations. This review aimed to highlight the mechanisms behind herb-warfarin interactions while laying special emphasis on its PKPD interactions and evidence on Herb-Warfarin Interaction (HWI) with regards to three different scenarios, such as when warfarin is consumed with herbs, taken as foods or prescribed as medicine, or when used in special situations. A targeted literature methodology involving different scientific databases was adopted for acquiring information on the subject of HWIs. Results of the present study revealed some of the fatal consequences of HWI, including post-operative bleeding, thrombosis, subarachnoid hemorrhage, and subdural hematomas occurring as a result of interactions between warfarin and herbs or commonly associated food products from Hypericum perforatum, Zingiber officinale, Vaccinium oxycoccos, Citrus paradisi, and Punica granatum. In terms of PK-PD parameters, herbs, such as Coptis chinensis Franch. and Phellodendron amurense Rupr., were found to compete with warfarin for binding with plasma proteins, leading to an increase in free warfarin levels in the bloodstream, resulting in its augmented antithrombic effect. Besides, HWIs were also found to decrease International Normalised Ratio (INR) levels following the consumption of Persea americana or avocado. Therefore, there is an urgent need for an up-to-date interaction database to educate patients and healthcare providers on these interactions, besides promoting the adoption of novel technologies, such as natural language processing, by healthcare professionals to guide them in making informed decisions to avoid HWIs.

02
CLINICAL STUDY Pharmaceutical biology (2021) PMID: 34757861 ↗
Pharmacokinetic interaction between rhynchopylline and pellodendrine via CYP450 enzymes and P-gp.
Clinical Trial Synthesis 2021 Clinical Study published in Pharmaceutical biology. Key conclusion: DISCUSSION AND CONCLUSIONS: The adverse interaction between rhynchopylline and pellodendrine draws attention to the co-administration of these two herbs and provides a reference for further investigations with a broader study population.
View Original PubMed Abstract ↓

CONTEXT: Rhynchopylline and pellodendrine are major extractions of commonly used Chinese medicine in gynaecology. The interaction between these two compounds could affect treatment efficiency and even result in toxicity during their co-administration in gynaecological prescription. OBJECTIVE: The pharmacokinetic interaction between rhynchopylline and pellodendrine and the potential mechanism were investigated in this study. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into four groups to investigate the pharmacokinetic interaction between rhynchopylline (30 mg/kg) and pellodendrine (20 mg/kg) with single dose of these two drugs as the control. The transport of rhynchopylline was evaluated in the Caco-2 cell model. Additionally, the metabolic stability and the activity of corresponding CYP450 enzymes were assessed in rat liver microsomes. RESULTS: The pharmacokinetic profile of rhynchopylline was dramatically affected by pellodendrine with the increased area under the pharmacokinetic curve (3080.14 ± 454.54 vs. 1728.08 ± 220.598 μg/L*h), Cmax (395.1 ± 18.58 vs. 249.1 ± 16.20 μg/L), prolonged t1/2 (9.74 ± 2.94 vs. 4.81 ± 0.42 h) and the reduced clearance rate (from 11.39 ± 1.37 to 5.67 ± 1.42 L/h/kg). No significant changes were observed in the pharmacokinetics of pellodendrine. The transport of rhynchopylline was significantly inhibited by pellodendrine with a decreasing efflux ratio (1.43 vs. 1.79). Pellodendrine significantly inhibited the activity of CYP1A2 and CYP2C9 with IC50 values of 22.99 and 16.23 μM, which are critical enzymes responsible for the metabolism of rhynchopylline. DISCUSSION AND CONCLUSIONS: The adverse interaction between rhynchopylline and pellodendrine draws attention to the co-administration of these two herbs and provides a reference for further investigations with a broader study population.

03
CLINICAL STUDY Current issues in molecular biology (2024) PMID: 39590314 ↗
Exploring the Benefits of Herbal Medicine Composite 5 (HRMC5) for Skin Health Enhancement.
Clinical Trial Synthesis 2024 Meta-Analysis published in Current issues in molecular biology. Key conclusion: The topical application of HRMC5 cream offered potential advantages over ingested phytoestrogens by reducing the systemic side effects.
View Original PubMed Abstract ↓

The skin, as the body's largest organ, is vital for protecting against environmental stressors, regulating temperature, and preventing water loss. Here, we examined the potential of a mixture of five traditional Korean herbal extracts-Cimicifuga racemosa, Paeonia lactiflora, Phellodendron amurense, Rheum rhaponticum, and Scutellaria baicalensis-referred to as herbal medicine composite 5 (HRMC5) for enhancing skin health and managing menopausal symptoms. High-performance liquid chromatography identified 14 bioactive compounds, including flavonoids, phenolic acids, anthraquinones, and alkaloids. In vitro studies revealed an optimal concentration of 0.625 g/L for cell survival and UV protection, with the mixture demonstrating significant wound-healing properties comparable to epidermal growth factor. HRMC5 exhibited anti-inflammatory effects by downregulating COX2 expression and upregulating the key skin barrier proteins. A 4-week clinical trial involving 20 postmenopausal women showed significant improvements in skin redness, hemoglobin concentration, and skin moisture content. Visual analog scale assessments indicated substantial reductions in facial flushing severity and the associated sweating. The topical application of HRMC5 cream offered potential advantages over ingested phytoestrogens by reducing the systemic side effects. These findings suggest that HRMC5 is a promising non-invasive treatment for vasomotor symptoms in menopausal women and overall skin health, warranting further research on its long-term efficacy and safety in larger populations. The efficacy of herbal medicines on anxiety and depression in peri- and postmenopausal women: A systematic review and meta-analysis. Shahmohammadi A(1), Ramezanpour N(2), Mahdavi Siuki M(2), Dizavandi F(3), Ghazanfarpour M(4), Rahmani Y(1), Tahajjodi R(5), Babakhanian M(6). Author information: (1)Clinical Research Development Center, Imam Ali and Taleghani Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. (2)Mashhad University of Medical Sciences, Mashhad, Iran. (3)Department of Nursing and Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran. (4

04
CLINICAL STUDY Nutrition journal (2009) PMID: 19682376 ↗
Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study.
Clinical Trial Synthesis 2009 Randomized Controlled Trial (RCT) published in Nutrition journal involving n = 45 participants; statistical significance reported at p = 0.0001. Key conclusion: Administration of NP 06-1 was also associated with weight loss, which may have been a contri
View Original PubMed Abstract ↓

BACKGROUND: The objective of this clinical study was to assess the potential benefit of a dietary supplement, NP 06-1, on joint health in overweight and normal weight adults diagnosed with osteoarthritis. METHODS: An 8-week placebo-controlled, randomized, double-blind study was conducted with four groups comparing the effects of NP 06-1 to placebo on 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 were 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 as well as biomarkers of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]). RESULTS: Eighty (80) subjects were enrolled and 45 subjects completed the study. No serious adverse events were reported. The mean total LAI scores at baseline for the four groups ranged from 11.4 to 12.4 (SD 1.2 to 2.4). Treatment for 8 weeks resulted in a statistical improvement in the LAI score in the overweight treatment group compared to placebo (6.3 +/- 2.3 vs 11.8 +/- 1.5; p < 0.0001). At 8 weeks, a similar result was observed in the normal weight groups (7.7 +/- 1.4 vs 9.9 +/- 0.9; p < 0.0001). There was a reduction in CRP levels with treatment in the overweight treatment group at 8 weeks (-0.62 +/- 0.2; 49%) compared to baseline (p < 0.001) and to placebo (p < 0.001). For the normal weight participants, there were significant reductions in CRP compared to baseline, but not to the matched placebo group. Both overweight and normal weight treatment groups lost a significant amount of weight compared to their placebo groups. The overweight treatment group lost an average of 5% body weight after 8 weeks. There was no significant change in ESR in any of the groups. CONCLUSION: In this pilot study, NP 06-1 had beneficial effects on symptoms of osteoarthritis of the knee as measured using LAI scores and had anti-inflammatory effects as measured using CRP. Administration of NP 06-1 was also associated with weight loss, which may have been a contri

05
CLINICAL STUDY Nutrition journal (2008) PMID: 18492265 ↗
Phellodendron and Citrus extracts benefit cardiovascular health in osteoarthritis patients: a double-blind, placebo-controlled pilot study.
Clinical Trial Synthesis 2008 Randomized Controlled Trial (RCT) published in Nutrition journal involving n = 45 participants. Key conclusion: Administration of NP 06-1 was also associated with weight loss.
View Original PubMed Abstract ↓

BACKGROUND: The objective of this clinical study was to assess the potential benefit of a dietary supplement, NP 06-1, on cardiovascular protective properties in overweight and normal weight adults diagnosed with osteoarthritis of the knee. METHODS: 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 reported are lipid levels, weight, BMI, blood pressure and fasting glucose. Analyses of variance were used to compare changes of physiological measures over the trial period and between groups. RESULTS: Eighty (80) subjects were enrolled and 45 subjects completed the study. No serious adverse events were reported. NP 06-1 administration was associated with a general improvement in lipid levels. Both the overweight and normal weight treatment groups had significant reductions in triglycerides and LDL-cholesterol, as well as a significant increase in HDL-cholesterol compared to their respective control groups. Overall there were decreases in blood pressure in both overweight and normal weight treatment groups compared to respective placebo groups. There was also a significant decrease in fasting glucose levels in the overweight treatment group compared to the start of the study and to the overweight placebo group. There was no change in fasting blood sugar for the normal weight groups. Both overweight and normal weight treatment groups lost a significant amount of weight compared to their respective placebo groups. The overweight treatment group lost an average of 5% body weight after 8 weeks, which was associated with a significant loss in BMI over time. CONCLUSION: In this pilot study NP 06-1 had a beneficial effect on cardiovascular risk factors; namely lipid levels, blood pressure and fasting glucose levels. Administration of NP 06-1 was also associated with weight loss.

06
CLINICAL STUDY Nutrition journal (2008) PMID: 18426577 ↗
Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial.
Clinical Trial Synthesis 2008 Randomized Controlled Trial (RCT) published in Nutrition journal involving n = 40 participants. Key conclusion: There were no safety concerns or significant adverse events observed in this study.
View Original PubMed Abstract ↓

BACKGROUND: Recent research has established correlations between stress, anxiety, insomnia and excess body weight and these correlations have significant implications for health. This study measured the effects of a proprietary blend of extracts of Magnolia officinalis and Phellodendron amurense (Relora) on anxiety, stress and sleep in healthy premenopausal women. METHODS: This randomized, parallel, placebo controlled clinical study was conducted with healthy, overweight (BMI 25 to 34.9), premenopausal female adults, between the ages of 20 and 50 years, who typically eat more in response to stressful situations and scores above the national mean for women on self-reporting anxiety. The intervention was Relora (250 mg capsules) or identical placebo 3 times daily for 6 weeks. Anxiety as measured by the Spielberger STATE-TRAIT questionnaires, salivary amylase and cortisol levels, Likert Scales/Visual Analog Scores for sleep quality and latency, appetite, and clinical markers of safety. The study was conducted by Miami Research Associates, a clinical research organization in Miami, FL. RESULTS: The intent-to-treat population consisted of 40 subjects with 26 participants completing the study. There were no significant adverse events. 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 conducted in this study including salivary cortisol and amylase levels, appetite, body morphology and sleep quality/latency were not significantly changed by Relora in comparison to placebo. CONCLUSION: This pilot study indicates that Relora may offer some relief for premenopausal women experiencing mild transitory anxiety. There were no safety concerns or significant adverse events observed in this study.

07
CLINICAL STUDY Alternative therapies in health and medicine (2006) PMID: 16454147 ↗
Effect of a proprietary Magnolia and Phellodendron extract on weight management: a pilot, double-blind, placebo-controlled clinical trial.
Clinical Trial Synthesis 2006 Randomized Controlled Trial (RCT) published in Alternative therapies in health and medicine; statistical significance reported at p = 0.89. Key conclusion: Bedtime cortisol levels decreased in the treatment group and increased in the placebo group.
View Original PubMed Abstract ↓

OBJECTIVE: To determine the efficacy of a dietary supplement ingredient containing proprietary extracts of Magnolia officinalis and Phellodendron amurense in helping overweight, otherwise healthy, premenopausal female adults, who typically eat more in stressful situations manage their body weight. DESIGN: Randomized, double-blind, placebo-controlled clinical study. Setting Miami Research Associates, a clinical research organization consisting of 32 board-certified physicians, Miami, Fla. SUBJECTS: Healthy, overweight (BMI 25 to 34.9), premenopausal female adults, between the ages of 20 and 50 years, who typically eat more in response to stressful situations and scored above the national mean for women on self-reported anxiety. INTERVENTIONS: Two-hundred-fifty-mg capsules or identical placebo capsules 3 times a day for 6 weeks. MAIN OUTCOME MEASURES: Salivary cortisol levels, weight change, psychological measures of stress and anxiety. RESULTS: Twenty-eight subjects completed the study. Extracts of M officinalis and P amurense were well tolerated. There was a significant weight gain during the study for the placebo group (P < ,01), but no significant weight gain for the group receiving extracts of M officinalis and P amurense (P < .89). Paired t-tests comparing baseline to post-treatment weight showed an average gain of 1.5 kg in the placebo group and no change in the treatment group (P = .89). When groups were divided into gainers (ie, participants who gained at least 1 kg or more) and maintainers or losers, 75% of the control group were gainers versus 37% of the treatment group (P < .04). There was a nonsignificant trend for lowered average cortisol in the treatment group at the end of the study (group X time interaction, F = 1.1, P < .15). This difference was due to a treatment effect on evening cortisol. There was a marginally significant group X time interaction (P = .06), showing the treatment group tended to have lower levels of cortisol in the evening, whereas the control group tended to have higher levels of cortisol in the evening. Bedtime cortisol levels decreased in the treatment group and increased in the placebo group. Participants in both the treat

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