IngredientsThe name Cornus refers to a genus of flowering trees and shrubs belonging to the family Cornaceae. Among 65 species belonging to the genus Cornus, only two have a long tradition of medicinal use. These two species are Cornus officinalis Sieb. et Zucc. and Cornus mas L., and while they are closely related botanically, they originate from distinct geographic regions and developed their medicinal traditions independently.
Cornus mas (cornelian cherry) is native to southern Europe and southwest Asia, whereas C. officinalis (Asiatic dogwood, cornel dogwood) is a deciduous tree distributed in eastern Asia, mainly in China, as well as Korea and Japan. Based on the different geographic distribution of the closely related species but clearly distinct taxa, the ethnopharmacological use of C. mas and C. officinalis seems to have independently originated.
Cornus officinalis Sieb. et Zucc. is a deciduous tree or shrub, renowned for its "Cornus flesh" fruit, which is widely acknowledged for its medicinal value when matured and dried. In Traditional Chinese Medicine (TCM), the dried, ripe fruit pulp is the principal medicinal part and bears the official TCM drug name Corni Fructus (ε±±θ±θΈ; ShΔn ZhΕ« YΓΊ). Cornus mas is native to southern Europe and southwest Asia from the era of Virgil and Pliny (70β19 BC). This plant comes from the foothills of the Caucasus and from there it spreads over Turkey, Romania, Bulgaria, Italy, and to the inland European continent. The genus name comes from the Latin word cornu, meaning horn, possibly due to the strong, dense wood.
The C. officinalis fruit has been present in the Pharmacopoeia of the People's Republic of China since 1963. The 2020 edition of the Chinese Pharmacopoeia stipulates that the content of morroniside and loganin in the fruit should not be less than 1.2% when used medicinally.
Corni Fructus (ripened and dried fruits) is recognized as an essential herb medicine in Traditional Chinese Medicine and has been widely used for over 2,000 years. C. officinalis belongs to the liver and kidney meridians in TCM theory and has a mild warm nature. It is often used to tonify the liver and kidney, and arrest the loss of essence. Because of its excellent tonic effect, C. officinalis has been commonly used to treat asthenia, liver and kidney diseases, and reproductive system diseases since ancient times.
According to the basic theory of TCM, Corni Fructus usually participates in various Chinese medicinal formulae to exert essential roles in replenishing liver and kidney, arresting seminal emission and sweat. It has the effect of tonifying the liver and kidney, astringing the essence. It is mainly used for treating vertigo, tinnitus, lumbar and knee pain, impotence, spermatorrhea, internal heat, and diabetes.
Corni Fructus is a foundational ingredient in the classical formula Liuwei Dihuang Wan. Liuwei Dihuang Pill (LWDHP) is a TCM formula consisting of six herbs β Rehmannia glutinosa, Cornus officinalis, Dioscorea opposita, Poria cocos, Alismatis rhizoma, and Moutan cortex β and has a long history in treating multiple kinds of diseases in Asia, including diabetes, cancer, and osteoporosis. Liu Wei Di Huang Wan and Mai Wei Di Huang Wan are commonly used to treat chronic inflammation, oxidative stress, and to revitalize the kidney and liver, and to treat diabetes. C. officinalis is also an ingredient commonly found in TCM formulas for bone-related diseases such as Zuo Gui Pill (ZGP), You Gui Pill (YGP), and Liuwei Dihuang Pill (LWDHP), all known for kidney-nourishing properties.
Cornus mas L., native to southern Europe and southwest Asia and known as cornelian cherry, has been used since ancient times. The fruits of this plant were used for a broad variety of diseases and complaints in all areas of its geographical distribution. Preparations from C. mas were considered astringent, tonic, and antipyretic remedies.
Fruits of Cornus mas L. have been used for centuries as traditional cuisine and folk medicine in various countries of Europe and Asia. In folk medicine, the fruits and other parts of the plant have been used for the prevention and treatment of a wide range of diseases such as diabetes, diarrhea, gastrointestinal disorders, fevers, rheumatic pain, skin and urinary tract infections, kidney and liver diseases, and sunstroke, among others.
Biologically active compounds are present not only in fruits but also in flowers, leaves, stones, and bark. The use of these parts of the C. mas plant in folk medicine has been known and appreciated for many years, especially in Asia.
A total of 353 compounds have been identified in C. officinalis, including iridoids, tannins, monoterpenes, sesquiterpenes, flavonoids, phenolic acids, organic acids, polysaccharides, essential oils, as well as triterpenes and steroids. The fruits of C. mas and C. officinalis are characterized by the presence of secondary metabolites, in particular iridoids, anthocyanins, phenolic acids, and flavonoids.
Iridoids are regarded as the primary medicinal constituents of C. officinalis. Loganin and morroniside, both iridoid glycosides, are key bioactive constituents of Cornus officinalis. The main active iridoids of C. officinalis are morroniside and loganin. These compounds have similar hypoglycemic, nephroprotective, and neuroprotective activity. In addition, morroniside exhibits myocardial protection and antioxidant capacity.
The extract and active components of C. officinalis β such as vitamins, fatty acids, amino acids, and bioactive compounds, including loganin, loganic acid, cornin, sweroside, and cornuside β have numerous biological activities, including antioxidant and neuroprotective activities. Additional iridoids identified include cornuside and cornusfuroside. A number of cyclic enol ether terpene glycosides including morroniside, logmalicids, cornusfurosides, and cornuside are specific to Cornus and are closely related to the corresponding bioactivities.
Many tannins have been isolated from C. officinalis fruits. The richness of hydrolysable tannins in C. officinalis was considered a remarkable difference compared to C. mas. Specific compounds identified include cornuside, cornusiin G, methyl malate, and sedoheptulose gallate, highlighting the presence of dimeric hydrolyzable tannins and other molecular components.
Among flavonoids, flavonol glycosides are the major constituents, mainly with kaempferol or quercetin as aglycones. Anthocyanins, flavonoids, iridoids, and vitamin C are major bioactive constituents of C. mas fruits.
Similarly, flavonoids, tannins, and iridoids are the main chemical constituents of C. officinalis. In addition, the presence of organic acids, polysaccharides, sterols, phenylpropanoids, lignans, furans, and mineral substances has also been described. The fruits of C. officinalis have also yielded a new bisiridoid glucoside named cornutide, as well as 7Ξ²-O-dimethyl butanedioate morroniside and caffeoyltartaric acid dimethyl ester, which were structurally characterized using various spectroscopic analyses.
These components contribute to biofunctionality, including 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.
Two active ingredients from Cornus officinalis β loganin and morroniside β have been shown to have antidiabetic effects, such as promoting insulin secretion, improving insulin resistance, and regulating glucose and lipid metabolism. Total iridoid glycosides of C. officinalis can effectively reduce insulin levels in mice, reducing blood lipids and improving insulin resistance. These iridoid glycosides notably improved insulin resistance in DM mice and decreased the expression levels of p-ERK1/2, p-P65, p-P38, and p-JNK1/2 proteins in liver tissues. Oral administration of loganin and morroniside decreased fasting blood glucose levels in diabetes mellitus mice. Ursolic acid exhibited the highest reactive oxygen species scavenging activity and Ξ±-glucosidase inhibitory activity.
Morroniside, loganin, and 7-O-galloyl-D-sedoheptulose, the main active compounds of Corni Fructus, exhibit the same lowering effects on elevated triglyceride, oxidative stress, and advanced glycation endproduct (AGE) formation in the kidney of db/db mice. The effects of morroniside and 7-O-galloyl-D-sedoheptulose were mediated through modulation of renal sterol regulatory element binding proteins and nuclear factor-kappa B expression, while the effect of loganin was mediated by hypoglycemic and antioxidant effects in the kidney. Morroniside has a protective effect on podocyte apoptosis, and its mechanism may involve restoring blocked autophagy flux and inhibiting HβOβ-induced NADPH oxidase 4 (NOX4) overexpression to prevent podocyte apoptosis.
The background of many biological effects of both C. mas and C. officinalis appears to be the antioxidant activity, as well as an amelioration of inflammatory processes through regulation of NF-ΞΊB and MAPK signaling pathways by constituents of extracts from both species. Studies found that the level of reactive oxygen species (ROS) was significantly reduced after treatment with morroniside and loganin, and the activities of superoxide dismutase (SOD) and glutathione peroxidase were markedly increased.
Administration of C. officinalis extract effectively alleviated oxidative stress, remarkably decreased corticosterone and Ξ²-endorphin, and increased serotonin levels. In cells, the extract significantly inhibited reactive oxygen species (ROS) generation and markedly increased the gene expression of antioxidant and neuronal markers such as superoxide dismutase (SOD), catalase (CAT). Neuroprotection was also shown to be mediated through blocking the MAPK signaling pathway. The downregulation of mRNA expression of STIM1 and the inhibition of extracellular CaΒ²βΊ influx in PC12 cells by an aqueous extract from fruits of C. officinalis were proposed as the potential inducing mechanisms of neurite generation and differentiation.
In close relation to neuroprotection linked with antioxidant properties, antihyperlipidemic and cardioprotective activity of both C. mas and C. officinalis preparations were demonstrated by in vitro as well as in vivo experiments. In animal studies for both plant materials, evidence was shown for antihypertensive effects, decreasing blood pressure, and reduction of circulating cholesterol concentration.
Human/Clinical Evidence (Cornus mas):
The most direct clinical evidence comes from a randomized controlled trial (RCT) of C. mas. The trial was a randomized, double-blind, placebo-controlled clinical trial conducted in Isfahan Cardiovascular Research Center at Isfahan University of Medical Sciences, Iran, from December 2012 to September 2013. Sixty patients with type 2 diabetes were randomly assigned to two groups to receive either the extract or placebo capsules (2 capsules twice daily) for 6 weeks; each drug capsule contained 150 mg of anthocyanins. After 6 weeks of intervention, a significant increase in insulin level as well as decrease in HbAβC and triglyceride levels was observed in the drug group compared to placebo.
A subsequent meta-analysis of RCTs provided broader clinical context. The overall results from a random-effects model indicated that cornelian cherry supplementation significantly reduced fasting blood glucose (SMD = β0.46, CI: β0.74, β0.18, p = 0.001), glycated haemoglobin (SMD = β0.70, CI: β1.19, β0.22, p = 0.005), and HOMA-IR (SMD = β0.89, CI: β1.62, β0.16, p = 0.02), while high-density lipoprotein cholesterol significantly increased (SMD = 0.38, CI: 0.10, 0.65, p = 0.007). The same meta-analysis also found significant reductions in body weight and BMI. However, the number of eligible RCTs in these analyses remains small, limiting the strength of conclusions.
A GRADE-assessed systematic review and meta-analysis further corroborated some findings: a higher C. mas intake was associated with lower triglycerides (MD: β30.6 mg/dl, 95% CI: β61.0, β0.14; P = 0.049) and significantly increased HDL-C (MD: 2.03 mg/dl, 95% CI: 0.82, 3.25; P = 0.001). However, significant between-study heterogeneity was reported for triglycerides and LDL-C.
Overall evidence strength: The reported data reveal that the fruits are a potential source for treatment of diabetes, obesity, hyperlipidemia, and gastrointestinal disorders. Unfortunately, the pharmacological studies in these areas are still insufficient to substantiate these preventive effects in confirmatory trials on a mass-scale clinical setting.
Animal/Preclinical Evidence (C. officinalis):
Loganin and morroniside in C. officinalis had significant effects in improving insulin resistance in mice and promoting glucose consumption in liver cells. In addition, loganin and morroniside have shown potential therapeutic effects on several diabetic complications, including diabetic nephropathy, diabetic osteoporosis, diabetic testicular injury, diabetic neuropathy, and diabetes-related liver injury. This evidence is preclinical and has not been validated by dedicated human RCTs for C. officinalis as a single-herb intervention.
Research on C. officinalis and diabetic kidney disease is extensive at the preclinical level. Loganin and morroniside may jointly inhibit the apoptosis of podocytes in diabetic nephropathy (DN) by targeting AGEs/RAGE and its downstream pathways p38 MAPK and Nox4. Loganin and morroniside can significantly inhibit the proliferation of renal cortical endothelial cells in DN rats and protect the integrity of the endothelium.
At the clinical level, evidence comes not from C. officinalis alone, but from the multi-herb formula Liuwei Dihuang Wan. Clinical studies indicate effectiveness of Liuwei Dihuang Wan against diabetes and diabetic nephropathy, and its use was found to be safe in elderly as well as pediatric patients with diabetes. These outcomes, however, cannot be attributed solely to C. officinalis, since the formula contains multiple active herbs.
Evidence strength: Preclinical (animal/cell) evidence is substantial. Clinical evidence for C. officinalis alone is lacking; the multi-herb formula context limits attribution.
A systematic review and meta-analysis of animal studies specifically assessing lipid outcomes found: cornelian cherry supplementation significantly decreased LDL (WMD = β6.38 mg/dl; 95% CI, β9.93 to β2.84; p < .001), triglyceride (WMD = β52.36 mg/dl; 95% CI, β80.50 to β24.22; p < .005), and cholesterol level (WMD = β37.16 mg/dl; 95% CI, β51.19 to β23.13; p < .005) in treated rats compared with control groups. Human RCT meta-analyses have replicated some but not all of these effects at smaller magnitudes. The results of meta-analyses of RCTs suggested that cornelian cherry supplementation may contribute to beneficial effects on certain risk factors linked to cardiometabolic diseases, supporting a favourable impact on anthropometric measurements, lipid profile, and glycaemic parameters.
Evidence strength: Animal data are consistent and robust. Human evidence is promising but limited to small RCTs with heterogeneous populations and preparations.
Experimental studies showed that C. officinalis extract and its active components had various pharmacological effects including neuroprotection, but clinical studies are still needed to assess whether the reported pharmacological activities have confirmed efficacy.
At the preclinical level, a study examined the neuroprotective mechanism of C. officinalis (CC) and fermented C. officinalis (FCC) on stress-induced and HβOβ-induced oxidative stress damage in rats and SH-SY5Y neuroblastoma cells. A dose of 100 mg/kg CC or FCC was orally administered to rats 1 h prior to 2 h/day immobilization for 14 days. Isolated compounds from C. officinalis fruits were evaluated for neuroprotective activities against corticosterone-induced injury in PC-12 cells, with several compounds exhibiting significant neuroprotective activities.
Evidence strength: Entirely preclinical (animal/in vitro). No confirmed human clinical trials specifically targeting neurodegenerative outcomes have been identified in the reviewed literature.
C. officinalis is an ingredient commonly found in TCM formulas for bone-related diseases such as Zuo Gui Pill, You Gui Pill, and Liuwei Dihuang Pill, all of which are known for their kidney-nourishing properties; they exert beneficial effects in the prevention and treatment of osteoporosis by alleviating lumbar and knee discomfort. Recent research has highlighted the therapeutic potential of certain monomeric components derived from C. officinalis, independent of its inclusion in TCM formulations, including flavonoids, tannins, iridoids, organic acids, polysaccharides, and lignans.
Evidence strength: Evidence for anti-osteoporotic effects derives primarily from animal models and TCM formula clinical trials. Isolated C. officinalis clinical data for bone outcomes are lacking.
C. officinalis cyclic ether terpene glycosides significantly inhibit the secretion levels of AGEs-induced inflammatory factors, and dose-dependently alleviate AGEs-induced inflammation in rat mesangial cells HBZY-1. Polysaccharides from C. officinalis offer a range of benefits including immunomodulatory, cardiovascular protective, antioxidant, hypoglycemic, and anticancer properties in experimental models.
Evidence strength: Preclinical only. No clinical trials specifically targeting inflammatory or immune outcomes for C. officinalis or C. mas as solo interventions have been identified in the reviewed literature.
A randomized, double-blind, controlled trial conducted in Korea enrolled 76 obese female participants. The results showed that 12 weeks of administration of the mixture of C. officinalis and Ribes fasciculatum could significantly decrease the body fat of the participants. However, the clinical studies on the pharmacological effects of single-herb C. officinalis are still needed.
Evidence strength: One human trial (combination product). No clinical evidence yet from a single-herb C. officinalis intervention on weight.
The biologically active compounds found in fruits of Cornus mas have a wide range of pharmacological action, including hepatoprotective activity. Animal studies have examined this effect directly: groups receiving C. mas fruit extract at doses of 200 and 500 mg/kg orally for 14 days were tested against CClβ-induced hepatotoxicity in rodent models. In-depth studies on the pharmacodynamics and pharmacotoxicology of C. officinalis fruits and their derived bioactive compounds are still required to ascertain their efficacy and safety for human consumption.
Evidence strength: Preclinical only. No adequate human clinical data specifically for hepatoprotection.
Dosages vary considerably across studies and preparations. The following dosages are cited directly as reported in the scientific literature and do not constitute recommendations.
In-depth studies on the pharmacodynamics and pharmacotoxicology of C. officinalis fruits and their derived bioactive compounds are imperative to ascertain their efficacy and safety for human consumption.
Despite a wide spectrum of effects from specific compounds, research mainly focuses on in vitro and animal studies, with a lack of pharmacokinetics, clinical trials, quality control, and multi-component synergistic mechanism data.
Fruits of C. mas are non-toxic and safe as food on acute toxicity studies in rat and human models. However, this pertains specifically to the whole fruit consumed as food, not to concentrated extracts or standardized preparations.
The wide acceptance of TCM formulas such as Liuwei Dihuang Wan still faces challenges due to unclear efficacy and mechanism in scientific scope, including issues of purity, dosage, and safety. Despite the barriers derived from the unclear therapeutic mechanisms and some reported side effects, increasing studies have demonstrated the potential to study these formulas using advanced scientific approaches.
Regarding potential drug interactions and pharmacodynamic concerns, the antidiabetic properties of both C. officinalis and C. mas β including effects on insulin secretion, insulin resistance, and blood glucose levels β raise theoretical concerns about additive hypoglycemic effects when combined with antidiabetic medications. Loganin and morroniside have been shown to promote insulin secretion, improve insulin resistance, and regulate glucose and lipid metabolism in preclinical models, suggesting a plausible mechanism for pharmacodynamic interactions with antidiabetic drugs, though direct clinical interaction data are lacking.
The cardiovascular actions reported in animal models β including effects on blood pressure and cholesterol β present analogous theoretical concerns when combined with antihypertensive or lipid-modifying drugs. These interactions have not been systematically evaluated in human subjects.
While reviews enhance the understanding of C. officinalis as a prospective therapeutic agent, clinical applicability underscores the need for further research and clinical studies to validate findings and establish safe and effective clinical applications.
Experimental studies have shown that C. officinalis extract and its active components have various pharmacological effects including anti-oxidation, anti-apoptosis, anti-inflammation, anti-diabetes, anti-osteoporosis, immunoregulation, neuroprotection, and cardiovascular protection, but clinical studies are still needed to assess whether these reported pharmacological activities have confirmed efficacy.
C. officinalis has been so intensively studied that it appears almost as a panacea for many major conditions. Clinical trials are clearly needed to assess which of the reported pharmacological activities have confirmed efficacy and practical application in humans. For C. mas, a small number of human RCTs and meta-analyses of RCTs now provide preliminary human evidence β particularly in glycemic control and cardiometabolic risk factors β but sample sizes are small, study durations are short, and the heterogeneity of preparations complicates direct comparisons.
Pharmacological studies in these areas are still insufficient to substantiate preventive effects in confirmatory trials at a mass-scale clinical setting. Future studies on mechanisms of action, bioavailability, pharmacokinetics, and adverse effects of the extracts and their bioactive constituents, as well as their effective doses and long-term toxic effects in humans, are needed.
Health conditions that Cornus may help support.
Body systems that Cornus may help support.
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