Dogwood

Dogwood (Cornus spp.): A Comprehensive Reference Article

1. Identity: Botanical Classification, Nomenclature, and Forms

1.1 Taxonomy and Key Species

The genus Cornus, colloquially known as dogwood due to its sturdy woody stem, belongs to the Cornaceae family. The dogwood genus (Cornus L., Cornaceae) comprises 59 subordinate taxa distributed throughout Asia, North and South America, Europe, and Africa, mainly in boreal and temperate climate regions, as well as at higher altitudes in subtropical and tropical zones.

The term "dogwood" in the context of dietary supplements and traditional medicine most commonly refers to three principal species, each with its own therapeutic tradition and phytochemical profile:

• Cornus florida L. — American Flowering Dogwood. The Western species, Cornus florida, is native to various parts of the United States. Its bark is the primary medicinal part used in North American traditions.
• Cornus officinalis Sieb. et Zucc. — Asiatic Dogwood, Japanese Cornel Dogwood, Shan Zhu Yu (山茱萸). Cornus officinalis, also known as Japanese cornel or Japanese cornelian cherry, is a species of dogwood that is native to China, Japan, and Korea. It is a highly valued plant used both as a food source and in traditional medicine.
• Cornus mas L. — Cornelian Cherry, European Dogwood. Cornelian cherry (Cornus mas L., CM) is an important plant, which belongs to the Cornaceae family, that grows in Europe and Southwest Asia.

These species are related but possess meaningfully different phytochemical compositions and therapeutic histories. CM and CO are the only two species that have been widely researched and used in the pharmaceutical and food fields.

1.2 Botanical Description

The plant has small inconspicuous yellow flowers that appear in late winter and early spring. The fruits of all dogwood trees are drupes. Native to China, Japan, and Korea, C. officinalis is a deciduous large shrub or small tree that showcases striking yellow flowers in late winter to early spring. Reaching heights and spreads of 15–25 feet, it displays an open, oval-to-round habit and distinctive exfoliating grayish-brown bark.

1.3 Plant Parts Used and Common Preparations

The bark of the dogwood tree (Cornus florida) is most commonly used in Western herbalism. In Asia, the bark and especially the fruit of the dogwood species, Cornus officinalis, is used. Parts most frequently used include bark, root bark, fruit, and rarely the leaf.

Common preparations across traditions include:

• Decoctions and teas: Historically, remedies utilizing Asiatic Dogwood involved decoctions or extracts of the dried fruit, which was considered to have astringent and tonifying effects.
• Tinctures: The bark was brewed into teas or tinctures to help reduce fever, alleviate chills, and support the body during convalescence.
• Dried fruit (Corni Fructus): C. officinalis, a deciduous tree or shrub, is renowned for its "Cornus flesh" fruit, which is widely acknowledged for its medicinal value when matured and dried. Leveraging C. officinalis as a foundational ingredient opens avenues for the development of environmentally friendly health foods, ranging from beverages and jams to preserves and canned products.
• Standardized extracts and capsules: Used in modern clinical research, particularly for C. mas and C. officinalis fruit extracts.
• Poultice: The bark has also been used as a poultice on external ulcers, wounds, etc.

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2. Traditional and Historical Use

2.1 North American Traditions (Cornus florida)

Flowering dogwood was employed medicinally by a number of Native North American Indian tribes who valued it especially for its astringent and antiperiodic properties. Historically, American Dogwood bark was most renowned as a natural substitute for quinine in the treatment of fevers, especially during times when malaria outbreaks were common and quinine was scarce.

During the American Civil War, Confederate soldiers would make tea from the bark to treat pain and fevers, and a poultice was made from the leaves that was used to cover wounds.

The glycoside "cornin" found in the bark has astringent properties. The inner bark was boiled and the tea drunk to reduce fevers and to restore a lost voice. A compound infusion of the bark and the root has been used in the treatment of various childhood diseases such as measles and worms.

People used American dogwood for headaches, fatigue, fever, and ongoing diarrhea. It is also used to increase strength, to stimulate appetite, and as a tonic. Some people apply American dogwood directly to the skin for boils and wounds.

2.2 Traditional Chinese Medicine (Cornus officinalis)

C. officinalis holds a significant position in traditional Chinese medicine, boasting a rich history in China. Its use dates back over a thousand years, where it was highly valued for its restorative and tonic properties. In Traditional Chinese Medicine (TCM), Asiatic Dogwood is known as "Shan Zhu Yu" and is classified as an herb that nourishes the liver and kidney, helping to stabilize and secure bodily essence ("jing").

It is often prescribed to treat conditions such as excessive sweating, dizziness, tinnitus, lower back pain, and urinary incontinence — symptoms commonly associated with deficiencies of the liver and kidney systems.

It is one of the key components of "Liu Wei Di Huang Wan" (Six-Ingredient Rehmannia Pill) and contains various beneficial substances, such as ursolic acid, gallic acid, malic acid, saponins, phenols, resins, vitamin A, vitamin C, and others. CO is known as the Asian dogwood and has been recorded for more than 2000 years.

It is used in TCM to treat a wide variety of conditions including impotence, heavy menstrual cycle, diarrhea, leukorrhea, fevers, and to help speed recovery after an illness.

2.3 European and Central Asian Traditions (Cornus mas)

CM has been used for more than 4,000 years in Europe and Asia Minor. The use of CM as a medicinal plant took root between 450 and 100 BCE. The leaves, flowers, and fruits of the plant have been widely used in traditional medicine for over 1,000 years for the treatment and prevention of diarrhea, sore throat, hemorrhoids, diabetes, measles, digestive ailments, chicken pox, anemia, rickets, liver and renal diseases, especially in the Caucasus and Central Asia.

In Slovakia, C. mas is used to treat fever, digestive disorders, and inflammation, and in Iran for the treatment of malaria, diarrhoea, inflammatory bowel disease, fever, kidney stones, urinary tract infections, and cancer. In Turkish folk medicine, the berries of C. mas and C. sanguinea are used as remedies for gastrointestinal disorders.

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3. Key Constituents and Active Compounds

3.1 Overview of Phytochemical Classes

Plants within the Cornus genus are known to contain a diverse array of phytoconstituents, including triterpenoids, iridoids, anthocyanins, tannins, flavonoids, phenolic compounds, carotenoids, and loganin.

Based on modern pharmacological studies, about 90 compounds have been isolated and identified from Corni Fructus (C. officinalis). In vivo and in vitro experimental studies indicate that Corni Fructus exhibits extensive pharmacological activities including hypoglycemic, antioxidant, anti-inflammatory, anticancer, neuroprotective, hepatoprotective, and nephroprotective activities.

3.2 Iridoid Glycosides (Primary Bioactives)

Iridoid glycosides are the main components with medicinal properties of C. officinalis. Among them, morroniside and loganin are the indicators for herb quality control according to the Pharmacopoeia of the People's Republic of China (2015).

It is used as a famous traditional Chinese medicine with iridoid glycosides (such as loganin, morroniside, cornuside, and sweroside) taken as the main active ingredients.

Morroniside, derived from C. officinalis, is an atypical secoiridoid that possesses a unique six-membered cyclic endoether fragment. This compound belongs to the class of iridoid glycosides and has been found to exhibit potent antioxidant properties.

Iridoids and secoiridoids are characteristic and active constituents of C. officinalis. They have been reported to possess anti-diabetic, antioxidant, and anti-inflammatory properties.

3.3 Polyphenols, Tannins, and Organic Acids

The other active ingredients in the pericarp of C. officinalis (e.g., total organic acid, gallic acid, oleanolic acid, and ursolic acid) also have antioxidant and anti-aging biological activities.

The fruits (berries) of C. mas are rich in anthocyanins including delphinidin-3-glucoside, cyanidin-3-rhamnoglucoside, cyanidin-3-glucoside, cyanidin-3-galactoside, and pelargonidin-3-galactoside.

Constituents of C. alba fruit extract include coumaroylquinic acid, kaempferol, and hydroxytyrosol derivatives.

3.4 Flavonoids Across Species

Quercetin-3-O-glucoside was abundant in C. kousa but absent in C. mas. Quercetin-3-O-rhamnoside was detected in significant amounts only in C. racemosa and C. amomum. Among the kaempferol derivatives, kaempferol-3-O-glucoside was the most abundant, with the highest concentration in C. coreana. Furthermore, C. racemosa and C. amomum were the richest sources of quercetin, while C. coreana was particularly rich in kaempferol.

3.5 Root and Leaf Compounds

Initially, the edible part of Cornus officinalis primarily consisted of fruit pulp. However, ongoing research has revealed the presence of varying levels of active substances in different parts of the plant. For instance, a study identified three active compounds, namely 3,3′-di-O-methylellagic acid 4-(5″-acetyl)-α-L-arabinofuranoside, 6α-dihydrocornic acid, and 6β-dihydrocornic acid, extracted from the roots of C. officinalis.

Other studies have focused on the leaves, resulting in the extraction of three new iridoids, one of which exhibited inhibitory effects on the lung cancer cell line A-549.

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4. Mechanisms of Action

4.1 Antioxidant Activity

Morroniside has been found to exhibit potent antioxidant properties. In studies investigating the effects of morroniside on cytotoxicity induced by hydrogen peroxide in human neuroblastoma tumor SH-SY5Y cells, it was observed that morroniside effectively reduced intracellular calcium accumulation, mitigated hydrogen peroxide-induced mitochondrial membrane potential (MMP) disruption, and decreased the percentage of apoptosis triggered by hydrogen peroxide.

4.2 Anti-Inflammatory Mechanisms

Iridoid glycosides, gallate derivatives, and triterpenoids are considered to be anti-inflammatory components of C. officinalis. Of these components, iridoid glycosides, including monomers and dimers, are the main anti-inflammatory active ingredients in C. officinalis. Total cornel iridoid glycoside and some iridoid glycosides including morroniside, loganin, cornuside, and iridoid dimers have been reported to show significant anti-inflammatory activity by regulating different inflammatory factors.

4.3 GLP-1 Receptor Activation (Neuropathic and Glycemic Relevance)

Iridoid glycoside compounds, including morroniside, activated GLP-1 receptors expressed in rat PC12 cells, human HEK293 cells, and mouse N9 cells, suggesting that iridoid compounds, like the peptide agonist exenatide and other non-peptide agonists, act as GLP-1 receptor agonists.

4.4 Inhibition of Carbohydrate-Digesting Enzymes

The ability of extracts from Cornus alba (CA), Cornus florida (CF), and Cornus sanguinea (CS) to inhibit digestive enzymes was studied, including α-amylase, pancreatic lipase, and α-glucosidase. Among the aqueous-ethanolic extracts, the activity of α-amylase was the most strongly inhibited by the fruit extract of CA (IC₅₀ = 115.20 ± 14.31 μg/mL) and the activity of α-glucosidase by the fruit of CF (IC₅₀ = 38.87 ± 2.65 μg/mL).

4.5 Anthocyanin-Mediated Insulin Sensitization

It has been shown that anthocyanins increase insulin secretion from pancreatic β-cells and improve insulin resistance. Animal studies support these findings and indicate enhanced insulin signaling and inhibition of carbohydrate-digesting enzymes as the mechanisms of action.

4.6 Renal Protective Mechanisms

A review of the literature showed that iridoid glycosides, low molecular weight polyphenols, and triterpene acids in C. officinalis had anti-inflammatory, anti-oxidative, anti-apoptotic, and anti-fibrosis effects by regulating the AGEs/RAGE, NF-κB/TGF-β, and PPARγ signaling pathways, thereby alleviating the injury of the intrinsic renal cells.

4.7 Neuroprotective Mechanisms

Cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway.

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5. Scientific Evidence by Area of Use

5.1 Glycemic Control and Diabetes

Evidence strength: Moderate for C. mas (human RCTs + meta-analysis); preliminary/preclinical for C. officinalis.

Fruits of Cornus mas and Cornus officinalis are representative plant materials traditionally used in Europe and Asia, respectively, in the treatment of diabetes and diabetes-related complications, which are often mediated by pathogenic inflammatory agents.

A 2024 meta-analysis of randomized controlled trials on C. mas examined the clinical evidence comprehensively. An extensive literature survey was carried out until 10 April 2024, and a total of 415 participants from six eligible studies were included. The overall results from the random-effects model indicated that cornelian cherry supplementation significantly reduced body weight (SMD = −0.27, p = 0.03), body mass index (SMD = −0.42, p = 0.007), fasting blood glucose (SMD = −0.46, p = 0.001), glycated haemoglobin (SMD = −0.70, p = 0.005), and HOMA-IR (SMD = −0.89, p = 0.02), while high-density lipoprotein cholesterol significantly increased (SMD = 0.38, p = 0.007).

A 2025 GRADE-assessed systematic review further extended this evidence. This study aimed to assess the potential of cornelian cherry in improving anthropometric parameters, lipid profile, glycemic indices, liver enzyme levels, and dietary intake. A systematic search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library for eligible RCTs published up to May 2025, using a random-effects model. The certainty of assessments was examined using the GRADE system, with seven RCTs included in the final analysis.

A randomized double-blind placebo-controlled trial on C. mas in type 2 diabetic patients was conducted. The plant Cornus mas L. (cornelian cherry) is traditionally used as an antidiabetic supplement; however, there was no related clinical trial at the time of that study's design.

A further RCT investigated the effect of lyophilized cornelian cherry on insulin resistance. The study was conducted with 84 women aged 18–45 who had been diagnosed with insulin resistance. Participants were randomized into four groups: MNT + 20 g lyophilized dried CM group (DCm, n = 22), MNT group (D, n = 21), only 20 g lyophilized dried CM group (Cm, n = 21), and the control group (C, n = 20). All participants were followed for 12 weeks.

For C. officinalis, modern pharmacology shows that CO has various effects such as lowering blood glucose, anti-inflammatory, antioxidant, and anti-apoptotic properties; and its main components, iridoid glycosides and polyphenols, can significantly improve the metabolic parameters of diabetic nephropathy (DN). CO effectively ameliorated insulin resistance, lowered blood glucose, and alleviated symptoms of DN patients. However, this evidence is largely derived from preclinical models and TCM combination studies. Despite these promising findings, clinical studies evaluating American Dogwood in humans remain limited. Most evidence is derived from laboratory or animal models, and there is a need for well-designed clinical trials to substantiate its efficacy and safety for specific health conditions.

5.2 Cardiometabolic Risk Factors and Lipid Profile

Evidence strength: Moderate (human RCTs + meta-analysis for C. mas).

A sensitivity analysis showed that cornelian cherry supplementation significantly reduced total plasma triglycerides, total cholesterol, low-density lipoprotein cholesterol, and insulin levels. Cornelian cherry supplementation did not significantly affect waist circumference and liver parameters among the participants.

One study investigated the impact of cornelian cherry on blood pressure, showing significant reductions in both systolic and diastolic blood pressure.

A randomized clinical trial in postmenopausal women evaluated the lipid profile effects of C. mas. This interventional, double-blinded, randomized clinical trial was carried out on 84 menopaused women aged 45–60 years old. The treatment group received three capsules of 300 mg of Cornus mas extract (CME), and the control group received three capsules of 300 mg of starch powder per day for 8 weeks.

Another trial assessed C. mas effects in patients with metabolic-associated fatty liver disease (MAFLD). The study aimed to evaluate the effect of lyophilized CM fruit powder with/without diet therapy on biochemical parameters and anthropometric measurements in patients with MAFLD. This randomized clinical trial was conducted on 87 patients with MAFLD and 21 healthy individuals.

Considering these findings, this meta-analysis indicates that supplementation with cornelian cherry may impact diverse cardiometabolic risk factors among individuals considered to be at high risk.

5.3 Neuroprotection and Cognitive Function

Evidence strength: Preliminary — animal and cell-based models only. No human clinical trials confirmed at the time of writing.

Cornus officinalis (CC) has a wide range of pharmacological activities, including antioxidant, neuroprotective, and anti-inflammatory effects. The present study was undertaken to elucidate the neuroprotective mechanism of CC and fermented CC (FCC) on stress and H₂O₂-induced oxidative stress damage in rats and SH-SY5Y cells. A dose of 100 mg/kg CC or FCC was orally administered to rats 1 hour prior to immobilization for 2 hours per day for 14 days. CC, especially FCC administration, decreased immobility time in forced swim test (FST), effectively alleviated oxidative stress, and remarkably decreased corticosterone and β-endorphin while increasing serotonin levels.

Cornuside, an iridoid glycoside from C. officinalis, has been studied in mouse models of Alzheimer's disease. Cornuside from Cornus officinalis Sieb. et Zucc is considered an anti-AD candidate. In the present study, AD mice were established by intracerebroventricular injection of Aβ₁₋₄₂ and treated with cornuside (3, 10, 30 mg/kg) for 2 weeks. Cornuside significantly ameliorated behavioral deficits, protected synaptic plasticity, and relieved neuronal damage in Aβ₁₋₄₂-induced mice. Importantly, cornuside decreased NLRP3 inflammasome activation, characterized by decreased levels of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β.

Administration of cornel iridoid glycoside (CIG) for 3.5 months improved cognitive impairments and the survival rate of P301S transgenic mice. Electrophysiological recordings and transmission electron microscopy studies showed that CIG improved synaptic plasticity and increased the ultrastructure and number of synapses. Moreover, CIG increased the expression levels of N-methyl-D-aspartate receptor (NMDAR) subunits GluN1, GluN2A, and GluN2B, and AMPA receptor subunit GluA1.

Loganin, an iridoid glycoside extracted from Cornus officinalis, is reported to have anti-inflammatory and memory-enhancing properties. One study aimed to explore the influence of loganin on cognitive function in 3xTg-AD mice and the underlying mechanism associated with its neuroprotection.

All neuroprotection findings to date are from preclinical models. No peer-reviewed human clinical trials specifically evaluating dogwood for cognitive outcomes had been published at the time of this writing.

5.4 Renal and Hepatic Protection

Evidence strength: Preclinical (animal and cell models). Clinical evidence limited to combination TCM formulas.

Some of the herb's ethnomedical indications have been confirmed by the herb's pharmacological effects, such as its hepatic and renal protection and the antidiabetic effects. In particular, the crude extract and its chemical composition have exerted good therapeutic effect in diabetic treatment.

A study in mice examined hepatoprotection. The hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented APAP (200 mg/kg)-induced hepatic damage as indicated by serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione.

In the context of diabetic nephropathy, common traditional Chinese medicine prescriptions containing Cornus officinalis for the clinical treatment of diabetic kidney disease (DKD) include Shenqi Dihuang Decoction, Jinkui Shenqi Pill, and Liuwei Dihuang Pill. Experiments have shown that Shenqi Dihuang Decoction can intervene in the inflammatory response of early DN patients, reduce proteinuria, protect renal function, and improve the patient's endothelial function and hemorheology, achieving normal recovery of microcirculation.

An animal study of diabetic nephropathy found that advanced glycation end products (AGE) are involved in the alterations of renal mesangial cell (MCs) growth, a feature of early stages of diabetic nephropathy (DN). Morroniside and loganin, two components extracted from Cornus officinalis, may ameliorate the detrimental effects of AGE-induced MC proliferation by preventing oxidative stress. Rat MCs cultured in AGE milieu were treated with morroniside and loganin; results showed that morroniside and loganin inhibited AGE-induced MC proliferation.

5.5 Antimicrobial Activity

Evidence strength: In vitro only.

The antimicrobial effects of a hydroalcoholic extract of C. mas fruits were investigated against 13 species of bacteria and yeast. The Gram-positive strains Listeria monocytogenes, Bacillus cereus, S. aureus, and Sarcina lutea and the Gram-negative strains Proteus vulgaris, Shigella sonnei, and Salmonella enteritidis were the most sensitive. A positive correlation between antimicrobial activity and total phenol content was found.

Cornus officinalis extract has demonstrated a significant inhibitory effect on hepatitis C virus protease activity through bioguided distillation. In addition, the ethanolic extract of C. officinalis has shown varying degrees of inhibition against bacterial strains such as E. coli and Listeria monocytogenes.

5.6 Bone Health

Evidence strength: One human RCT; preliminary.

Cornus mas extract is a potential candidate for treating menopausal-related bone complications because of its phytoestrogen and anti-inflammatory contents. It was evaluated in an interventional double-blind placebo-controlled randomized study.

5.7 Anti-Inflammatory Effects (General)

Evidence strength: In vitro and cell-based. Some human ex vivo data.

The aqueous-methanolic extract of C. officinalis fruit decreased IL-8 secretion by neutrophils to approximately 50% at concentrations of 5, 50, and 100 μg/mL, compared to the LPS-stimulated control (100%). The aqueous extract of C. officinalis fruit significantly inhibited TNF-α release by neutrophils at concentrations of 50 and 100 μg/mL.

5.8 Diabetes Prevention (Emerging Research)

Cornus officinalis (CO) is a highly popular ethnopharmacological treatment for diabetes and has been actively studied. Earlier findings revealed in vitro that CO application to the pancreatic 1.1B4 β-cell line can promote pancreatic β-cell viability, metabolic activity, prevention of cytokine-mediated cell death, and expression of important cytoprotective pathways through promotion of autophagy and the KEAP1-Nrf2 mediated antioxidant response.

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6. Body Systems and Health Areas Associated with Dogwood

Key biological activities attributed to the constituents of C. officinalis include safeguarding the cardiovascular system, boosting the immune system, and exhibiting anti-inflammatory, antibacterial, and antioxidant properties, as well as aiding in lowering blood lipids and enhancing human memory.

Based on the published literature, the following body systems are principally associated with dogwood's use and investigation:

• Endocrine/Metabolic system: Glycemic regulation, insulin sensitization, anti-obesity effects — most extensively evidenced in human trials for C. mas.
• Cardiovascular system: Lipid lowering, blood pressure reduction, cardioprotective effects.
• Renal system: Protection against diabetic nephropathy, anti-fibrotic signaling regulation.
• Hepatic system: Hepatoprotection, alleviation of nonalcoholic fatty liver disease markers.
• Nervous system: Neuroprotection, cholinesterase inhibition, potential role in neurodegenerative disease models.
• Immune system: Cytokine modulation, immunomodulatory activity of fruit extracts.
• Musculoskeletal system: Bone health in the context of postmenopausal women.
• Gastrointestinal system: Astringent and antidiarrheal properties (traditional).
• Reproductive and urinary systems: TCM applications for impotence, urinary incontinence, leukorrhea.

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7. Dosage Forms and Dosages Reported in Studies

The following dosages are reported directly from identified studies and should not be construed as therapeutic recommendations:

• Cornus mas extract (postmenopausal women, lipid/glycemic RCT): The treatment group received three capsules of 300 mg of Cornus mas extract (CME) per day for 8 weeks.
• Lyophilized dried cornelian cherry (insulin resistance RCT): 20 g/day of lyophilized dried cornelian cherry (MNT + CM group, CM-only group), followed for 12 weeks.
• Cornus mas extract for NAFLD (proposed protocol): The intervention group received cornelian cherry extract containing 320 mg/day anthocyanins per day for 12 weeks.
• Cornus officinalis (CC) extract in rats, neuroprotection study: 100 mg/kg CC or FCC was orally administered to rats 1 hour prior to immobilization for 14 days.
• Cornuside in AD mouse model: AD mice were treated with cornuside (3, 10, 30 mg/kg) for 2 weeks.
• Cornus officinalis ethanolic extract (ECO) hepatoprotection — mice: Pretreatment of mice with ECO at 100, 250, and 500 mg/kg for 7 days.
• Cornus officinalis for diabetic nephropathy in rats: Cornus officinalis group received 281.25 mg/kg for 6 weeks.

No standardized human dosage has been established for Cornus florida bark in the peer-reviewed literature. The 2024 meta-analysis on C. mas reflects the range of doses used across included human trials, but no single universally accepted dose has been codified in a pharmacopeia monograph for supplemental use.

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8. Safety Considerations and Interactions

8.1 Species-Specific Toxicity Differences

The toxicity of dogwood plants can vary, and it is important to identify the specific species. While some species produce fruit consumed by wildlife and having traditional culinary uses, others can be toxic. Specifically, the fruit of flowering dogwood (Cornus florida) is poisonous to humans and should be avoided. This is in contrast to the fruit of C. officinalis and C. mas, which are used medicinally and culinarily. Proper botanical identification is therefore critical.

8.2 Safety Profile of Cornus officinalis

Research on the pericarp of C. officinalis (Shan Pi) indicates it contains more flavonoids and terpenoid active ingredients and is non-toxic in the body. This discovery not only strengthens the safety foundation of its clinical application, but provides a solid scientific basis for the establishment of reasonable clinical dosage and the implementation of effective clinical toxicity monitoring.

Only about 18% of chemical constituents in Corni Fructus have been tested for pharmacological activity. This means the potential pharmacological activities and clinical values of Corni Fructus need to be further investigated.

8.3 Skin Sensitivity (Cornus florida)

The red berries of dogwood are not toxic when ingested, but some people can experience skin rashes after contact with the tree. This applies specifically in the context of Cornus florida.

8.4 Potential Interactions: Glucose-Lowering Agents

Given the demonstrated reductions in fasting blood glucose and HOMA-IR in human RCTs of C. mas, and preclinical evidence of antidiabetic activity in C. officinalis, there is a theoretical risk of additive hypoglycemic effects when combined with pharmaceutical antidiabetic agents. Supplementation significantly improved fasting blood glucose (FBG), HbA1c, and HOMA-IR. The researchers suggested that previous animal studies support these findings and indicated enhanced insulin signaling and inhibition of carbohydrate-digesting enzymes as the mechanism of action. This mechanism-based interaction has not been formally studied in controlled human trials but is biologically plausible.

8.5 Antiplatelet Considerations

Some of the pharmacological effects of the active components of C. officinalis include anti-oxidation, anti-apoptosis, anti-inflammatory, anti-cholinesterase, anti-diabetes, and vasorelaxant activity, and others are unique, such as the mucin secretion inhibitory effect and the antiplatelet aggregative effect. The antiplatelet aggregative effect, though demonstrated preclinically, suggests a theoretical interaction with anticoagulant or antiplatelet medications; this has not been confirmed in clinical studies.

8.6 Limitations in Safety Evidence

Formal toxicological studies in humans are limited for all Cornus species used as supplements. In some cases, Cornus has also been used for digestive system diseases and fever, mostly as an alternative treatment without side effects to chemical drugs. This characterization is based on traditional use rather than formal clinical safety trials. The absence of reported adverse events in the human RCTs reviewed for C. mas does not constitute a complete safety record.

Consumers should be careful not to confuse American dogwood (Cornus florida) with Jamaican dogwood (Piscidia piscipula), which belongs to an entirely different botanical family and has a distinct and more pronounced toxicity profile.

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