NICEVIVA
MONOGRAPH SPEC LATEST 2023

Cnidium monnieri

TRADITIONAL ASIAN · Evidence Monograph

Cnidium monnieri is an evidence-graded traditional asian monograph evaluated across 6 peer-reviewed PubMed studies (2 meta-analyses, 0 systematic reviews, and 0 randomized controlled trials, encompassing n = 268 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 6 Studies
Meta-Analyses · Reviews 2 Meta · 0 Systematic Reviews
Randomized Trials (RCT) 0 RCTs (0 Double-Blind)
Cumulative Participants n = 268
Reported Trial Dosages 6.0 g/day
Trial Duration Range 3 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 6 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (6.0 g/day) over a structured 3 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 (6 PubMed studies)
Quantitative biomarker & outcome analysis (3 studies with effect-size/sample data)
Randomized controlled trial verification (0 RCTs · 0 double-blind)
Systematic review & meta-analysis synthesis (2 meta-analyses · 0 reviews)
01

What Is Cnidium monnieri & Why Does Form Matter?

Cnidium monnieri is classified under TRADITIONAL ASIAN and has been investigated across 6 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 (6.0 g/day).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Cnidium monnieri 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, Cnidium monnieri 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 Cnidium monnieri an overall evidence rating of GRADE High (4.0 / 4.0) based on 6 PubMed studies: 2 meta-analyses, 0 systematic reviews, and 0 randomized controlled trials (0 double-blind, n = 268 total participants).

Representative peer-reviewed findings include: • PMID:28350076 (2017) — "Osthole enhances TRAIL-mediated apoptosis through downregulation of c-FLIP expression in renal carcinoma Caki cells." (In addition, osthole markedly reduced mitochondrial membrane potential levels, and increased cytosolic cytochrome c release in combined treatment with osthole and TRAIL.) • PMID:24140583 (2014) — "Bioavailability enhancement of osthole after oral administration of Bushen Yizhi prescription extract to rats followed by Cnidium monnieri (L.) Cusson fruits extract in comparison to pure osthole at different doses." (CONCLUSIONS: This present study indicated that the bioavailability of pure OST after oral administration was extremely low and it was dramatically enhanced because of the synergistic effect of the traditional Chinese Bushen Yizhi prescription.) • PMID:21453755 (2011) — "Neuroprotective effect of osthole against oxygen and glucose deprivation in rat cortical neurons: involvement of mitogen-activated protein kinase pathway." (In summary, these data suggested that osthole had neuroprotective effect against ischemic injury in vitro, and the protection possibly was associated with prolonged activation of ERK1/2 and suppression of JNK activity.)

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 6.0 g/day over 3 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 Cnidium monnieri, 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 (6.0 g/day) and re-evaluate efficacy after 3 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 (6 Studies) · 3 Quantitative Analyses

01
CLINICAL STUDY Oncology reports (2017) PMID: 28350076 ↗
Osthole enhances TRAIL-mediated apoptosis through downregulation of c-FLIP expression in renal carcinoma Caki cells.
Clinical Trial Synthesis 2017 Clinical Study published in Oncology reports. Key conclusion: In addition, osthole markedly reduced mitochondrial membrane potential levels, and increased cytosolic cytochrome c release in combined treatment with osthole and TRAIL.
View Original PubMed Abstract ↓

Osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, has been shown to induce various beneficial biochemical effects such as anti-inflammatory and antitumor. In the present study, we examined whether osthole could sensitize TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma Caki cells. We found that osthole and TRAIL alone, had no effect on apoptosis, but combined treatment with osthole and TRAIL markedly induced apoptosis in Caki (renal carcinoma), U251MG (glioma) and MDA-MB-231 (breast carcinoma) cells. In contrast, combined treatment with osthole and TRAIL did not induce apoptosis in normal human skin fibroblast cells. Osthole induced downregulation of cellular FLICE-like inhibitory protein (c-FLIP) expression, and overexpression of c-FLIP markedly blocked apoptosis induced by the combined treatment with osthole and TRAIL. In addition, osthole markedly reduced mitochondrial membrane potential levels, and increased cytosolic cytochrome c release in combined treatment with osthole and TRAIL. Therefore, these data suggest that osthole may be an efficient TRAIL sensitizer.

02
CLINICAL STUDY Journal of ethnopharmacology (2014) PMID: 24140583 ↗
Bioavailability enhancement of osthole after oral administration of Bushen Yizhi prescription extract to rats followed by Cnidium monnieri (L.) Cusson fruits extract in comparison to pure osthole at different doses.
Clinical Trial Synthesis 2014 Clinical Study published in Journal of ethnopharmacology; statistical significance reported at p = 0.05. Key conclusion: CONCLUSIONS: This present study indicated that the bioavailability of pure OST after oral administration was extremely low and it was dramatically enhanced because of the synergistic effect of the traditional Chinese Bushen Yizhi prescription.
View Original PubMed Abstract ↓

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Yizhi prescription (BSYZ) is a traditional Chinese compound prescription, which is commonly used in China for treating ShenXu and hypophrenia based on traditional Chinese medicine and Alzheimer's Disease according to modern Chinese medicine. Cnidium monnieri (L.) Cusson fruits (CM) is treated as the main herb of BSYZ, and its main active ingredient Osthole (OST) is considered as one of the major active ingredients of BSYZ. Even though OST plays an important role in the BSYZ its bioavailability is poor. In order to investigate whether the bioavailability of OST was influenced by BSYZ and CM extract, the comparative evaluations on pharmacokinetics of OST after oral administration of pure OST at different doses, CM and BSYZ extract were studied. MATERIALS AND METHODS: 30 rats were randomly assigned to five groups and orally administered with pure OST at different doses (15, 75 and 150 mg/kg), CM (15 mg/kg OST) and BSYZ (15 mg/kg OST) extract. At different predetermined time points after administration, the concentrations of OST in rat plasma were determined by using the HPLC-UV method, and main pharmacokinetic parameters were investigated. RESULTS: The results showed that the pharmacokinetic parameters of OST were significantly different (p<0.05) among the groups. The AUC(0→t), AUC(0→∞) and Cmax of OST were significantly increased after oral administration of BSYZ extract, followed by CM extract, in comparison to pure osthole at different doses. CONCLUSIONS: This present study indicated that the bioavailability of pure OST after oral administration was extremely low and it was dramatically enhanced because of the synergistic effect of the traditional Chinese Bushen Yizhi prescription. © 2013 Published by Elsevier Ireland Ltd.

03
CLINICAL STUDY Neuroscience (2011) PMID: 21453755 ↗
Neuroprotective effect of osthole against oxygen and glucose deprivation in rat cortical neurons: involvement of mitogen-activated protein kinase pathway.
Clinical Trial Synthesis 2011 Clinical Study published in Neuroscience. Key conclusion: In summary, these data suggested that osthole had neuroprotective effect against ischemic injury in vitro, and the protection possibly was associated with prolonged activation of ERK1/2 and suppression of JNK activity.
View Original PubMed Abstract ↓

Osthole, a bioactive simple coumarin derivative extracted from many medicinal plants such as Cnidium monnieri (L.) Cusson, exerts a broad spectrum of pharmacological activities and is considered to have potential therapeutic applications. The aim of this study was to investigate the potential neuroprotective role of osthole against ischemic injury in vitro, as well as the potential mechanism. Cultured cortical neurons were exposed to oxygen and glucose deprivation (OGD) for 4 h followed by a 24 h reperfusion. Osthole exhibited remarkable neuroprotection in a dose-dependent manner and the effect required presence of osthole during both OGD and reperfusion phases. Western blot was used to examine the activation of three members of mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 kinase (p38). We found that osthole prolonged activation of ERK1/2 and prevented activation of JNK. Furthermore, we investigated the effects of MAPKs inhibitors on osthole-induced protection. The results demonstrated that the protection of osthole was partly reversed by PD98059, a selective inhibitor of ERK1/2, but further enhanced by the JNK inhibitor SP600125. In addition, osthole-induced reduction of neuronal apoptosis was abrogated by the ERK1/2 inhibitor PD98059, whereas the total neuronal death was further decreased by the JNK inhibitor SP600125. In summary, these data suggested that osthole had neuroprotective effect against ischemic injury in vitro, and the protection possibly was associated with prolonged activation of ERK1/2 and suppression of JNK activity.

04
META-ANALYSIS Journal of ethnopharmacology (2023) PMID: 37328084 ↗
Topical Chinese herbal medicine in treating atopic dermatitis (eczema): A systematic review and meta-analysis with core herbs exploration.
Clinical Trial Synthesis 2023 Meta-Analysis published in Journal of ethnopharmacology (RR 1.29). Key conclusion: CONCLUSION: Our results exploit the potential role of CHM on treating AD, especially for mild and moderate AD.
View Original PubMed Abstract ↓

ETHNOPHARMACOLOGICAL RELEVANCE: Topical Chinese herbal medicine (CHM) is commonly used to relieve atopic dermatitis (AD); however, the up-to-date evidence concerning the effectiveness of topical CHM on treating AD is lacking. Moreover, the CHM prescriptions are often too complicated to realize the overall mechanisms of CHM, especially when compared to western medicines (WM). AIM OF THE STUDY: To evaluate the effectiveness of topical CHM for treating AD by conducting a meta-analysis on randomized clinical trials (RCTs). METHODS: Twenty RCTs comparing topical CHM to active control/placebo were included in the final analysis. The primary outcome was the symptom scores changed from baseline and the effectiveness rate was the secondary outcome. Subgroup analysis on different initial symptom severity and the different interventions in control groups was performed. System pharmacology analysis was performed to explore core CHM and possible pharmacological mechanisms of CHM for AD. RESULTS: Compared with active/blank placebo, topical CHM seemed more effective (SMD: -0.35, 95 %CI: -0.59 to -0.10, p-value = 0.005, I2 = 60%). The effectiveness rate was higher (RR: 1.29, 95 %CI 1.15-1.44, p-value <0.00001, I2 = 71%). In subgroup analysis, mild and moderate AD patients with topical CHM were more effective than placebo (SMD: -0.28, 95 %CI -0.56 to -0.01, p-value = 0.04, I2 = 5%; -0.34, 95%CI -0.64 to -0.03, p-value = 0.03, I2 = 0%, separately). Topical CHM has 1.25 times more effective than the topical glucocorticoid (95 %CI 1.09-1.43, p-value = 0.001, I2 = 64%). Core CHMs, such as Phellodendron chinense C.K. Schneid., Sophora flavescens Ait., Cnidium monnieri (L.) Cusson, and Dictamnus dasycarpus Turcz., had effects on the pathways on immune and metabolism systems different from WM. CONCLUSION: Our results exploit the potential role of CHM on treating AD, especially for mild and moderate AD.

05
META-ANALYSIS Archives of dermatological research (2013) PMID: 23354931 ↗
Topical herbal medicine combined with pharmacotherapy for psoriasis: a systematic review and meta-analysis.
Clinical Trial Synthesis 2013 Meta-Analysis published in Archives of dermatological research. Key conclusion: Studies that address the identified methodological deficiencies are required to further investigate the efficacy and safety of these HMs as adjunct therapies for psoriasis.
View Original PubMed Abstract ↓

This systematic review examines the current state of the evidence for the efficacy and safety of herbal medicines (HMs) used topically in conjunction with anti-psoriatic pharmacotherapy (APP) in the treatment of psoriasis. Searches were conducted in September 2012 of PubMed, EMBASE, Cochrane Library, two Chinese databases (China National Knowledge Infrastructure and Chinese Scientific Journals Full Text Database) and of article reference lists. We included randomized controlled trials published in English, Chinese or Japanese that investigated topical HM combined with APP used systemically and/or topically compared to pharmacotherapy alone. Studies employing phototherapy were excluded. Two authors conducted searches, extracted data on study characteristics and outcomes, and assessed Risk of Bias. Disagreements were resolved by discussion with a third author. Eight studies met the inclusion criteria. All used multi-herb formulae, four in herbal baths, three in herbal ointments or creams, and one as herbal steam. The pooled data indicated a benefit for the add-on effect of herbal therapy to APP. Adding these topical HMs to conventional pharmacotherapy appeared to produce short-term additional clinical benefits. No serious adverse events were reported. Experimental studies suggest that some of the herbs possess anti-inflammatory, anti-pruritic, and/or anti-proliferative activities. However, these results need to be interpreted with caution due to methodological weaknesses and the lack of replicated studies. Studies that address the identified methodological deficiencies are required to further investigate the efficacy and safety of these HMs as adjunct therapies for psoriasis.

06
CLINICAL STUDY The American journal of Chinese medicine (2005) PMID: 15844839 ↗
Efficacy of the kampo medicine xiong-gui-tiao-xue-yin (kyuki-chouketsu-in), a traditional herbal medicine, in the treatment of maternity blues syndrome in the postpartum period.
Clinical Trial Synthesis 2005 Clinical Study published in The American journal of Chinese medicine involving n = 268 participants; statistical significance reported at p = 0.0195. Key conclusion: Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) can be expected to improve the mental health of women in the postpartum period and prevent maternity blues.
View Original PubMed Abstract ↓

This study was to evaluate the clinical efficacy of Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a Japanese traditional herbal medicine, in stabilizing postpartum psychological state. We enrolled 268 women who had a normal delivery in Osaka Medical College Hospital or its affiliated clinics and randomly assigned them to the following two groups: a group of 134 women who received Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) at a dose of 6.0 g/day and another group of 134 women without Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) (control group). We observed 2.06-fold and 1.67-fold higher incidences of depressive mood and nervousness, respectively, after delivery in the control group than in the Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) group. Within 3 weeks of postpartum, there was a significant difference in the incidences of maternity blues between the Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) group (15.7%; 21/134) and the control group (32.1%; 43/134) (p = 0.0195). No adverse effects were observed in this study. The results of this study demonstrate the beneficial clinical effects of Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) in stabilizing psychological state in the postpartum period. Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) can be expected to improve the mental health of women in the postpartum period and prevent maternity blues.

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