Evodia Fructus Extract
Also known as: Evodia Fructus, Euodia Fruit, EFE, Euodiae Fructus Extract
Overview
Euodiae Fructus extract is derived from the dried fruit of *Evodia rutaecarpa*, a plant extensively used in Traditional Chinese Medicine (TCM). It is characterized by its rich content of bioactive alkaloids, including evodiamine, rutaecarpine, and limonin. Traditionally, it has been employed for pain relief, anti-inflammatory purposes, and to address gastrointestinal disorders. Modern research has expanded its potential applications, investigating its anti-cancer, anti-inflammatory, neuroprotective, anti-obesity, anti-diabetic, and cardioprotective properties. While numerous in vitro and in vivo studies support its pharmacological activities, and some systematic reviews exist, high-quality randomized controlled trials (RCTs) in humans are still limited. The extract exhibits a complex pharmacological profile, with both therapeutic potential and notable toxicity concerns, particularly regarding hepatotoxicity and cardiotoxicity.
Benefits
Euodiae Fructus extract demonstrates several evidence-based benefits, primarily driven by its alkaloid content. Its most prominent benefit is its **anti-inflammatory** action, where it has been shown to suppress inflammatory mediators and cytokines. In mouse models, EFE improved atopic dermatitis-like symptoms by modulating JAK-STAT and MAPK pathways, suggesting potential for skin inflammatory conditions. The extract also exhibits significant **anti-cancer** properties, with its major alkaloid, evodiamine, demonstrating anti-proliferative, anti-metastatic, and pro-apoptotic effects across various cancer cell lines (e.g., colon, leukemia, hepatocellular carcinoma, lung, breast) in both in vitro and in vivo studies. Furthermore, a systematic review and meta-analysis involving 1736 patients across 18 studies indicated efficacy of formulations containing Euodiae Fructus for **gynecological conditions** like dysmenorrhea, although the quality of these RCTs varied. Preclinical studies also suggest secondary benefits such as neuroprotective, anti-obesity, anti-diabetic, and cardiovascular effects. While these benefits are promising, most human data come from TCM formulations, and high-quality, large-scale RCTs are needed to confirm clinical significance and generalizability, especially given the observed toxicity.
How it works
Euodiae Fructus extract exerts its effects through multiple biological pathways. Its anti-inflammatory action involves the inhibition of inflammatory signaling cascades, specifically by modulating the JAK-STAT and MAPK pathways, which leads to the suppression of pro-inflammatory cytokines and chemokines. In cancer cells, the extract's alkaloids, particularly evodiamine, induce apoptosis and inhibit proliferation by targeting various molecular pathways. These mechanisms collectively contribute to its anti-tumor activity. The extract also interacts with the immune system, reducing skin inflammation, and has been shown to alter cardiovascular metabolism. The alkaloids have moderate bioavailability, and their metabolism can produce reactive metabolites that contribute to both efficacy and potential toxicity.
Side effects
Euodiae Fructus extract, while possessing therapeutic potential, carries significant safety concerns, particularly with excessive or prolonged use. Common side effects, reported in over 5% of users, include gastrointestinal discomfort, nausea, vomiting, and stomach pain. Less common side effects (1-5%) may include blurred vision and headache. More concerning are the rare but severe adverse effects, which include hepatotoxicity (liver damage), cardiotoxicity (heart damage), and nephrotoxicity (kidney damage), reported in animal studies and some human cases. These toxicities are linked to the metabolism of its alkaloids. The extract has potential drug interactions, especially with medications metabolized by cytochrome P450 enzymes, and caution is advised with cardiovascular and hepatically metabolized drugs. It is contraindicated in individuals with pre-existing liver disease, heart disease, and during pregnancy due to its toxicity profile. Limited data exist for special populations, necessitating caution in the elderly and those with pre-existing organ dysfunction.
Dosage
The optimal and maximum safe dosages for Euodiae Fructus extract are not well-established, primarily due to variations in extract standardization and its frequent use within complex Traditional Chinese Medicine (TCM) formulations rather than as an isolated extract. Traditional TCM doses vary widely, and a minimum effective dose has not been clearly defined in modern research. Toxicity, including hepatotoxicity and cardiotoxicity, has been observed with excessive or prolonged use, indicating a narrow therapeutic window and the absence of a clearly defined maximum safe dose. The extract is typically administered orally, often in divided doses, though topical applications have been explored for skin inflammation. Ethanol extracts standardized for alkaloid content are preferred in research settings. Bioavailability can be influenced by formulation, and metabolism plays a crucial role in both efficacy and toxicity. No specific cofactors are clearly established to enhance its effects or mitigate side effects.
FAQs
Is Evodia Fructus extract safe?
It has a narrow therapeutic window. Safe use requires strict adherence to recommended doses and careful monitoring for signs of toxicity, especially liver and heart issues.
Can it be used for skin inflammation?
Yes, preclinical evidence from animal models supports its anti-inflammatory effects in conditions like atopic dermatitis, suggesting potential for skin inflammation.
Does it have anti-cancer effects?
Promising in vitro and animal data show anti-proliferative and pro-apoptotic effects against various cancer cells, but human clinical trials are currently lacking.
Are there risks of liver or heart damage?
Yes, hepatotoxicity and cardiotoxicity have been reported in animal studies and some human cases, warranting significant caution and contraindication in relevant conditions.
How fast do effects appear?
Effects in animal models typically manifest within days to weeks. However, human data on the onset of action are currently insufficient to provide a definitive timeline.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10764943/ – This in vivo/in vitro study investigated the effects of Evodia Fructus extract on atopic dermatitis-like symptoms in NC/Nga mice. It found that EFE reduced dermatitis scores and inflammatory markers by inhibiting JAK-STAT and MAPK pathways, providing mechanistic insights into its anti-inflammatory properties in skin conditions.
- https://html.rhhz.net/YYTRCW/html/2023/1/1678252400049-1864145283.htm – This systematic review and meta-analysis of 18 RCTs, involving 1736 patients, evaluated the efficacy of TCM formulations containing Euodiae Fructus for gynecological conditions. It reported positive outcomes, particularly for dysmenorrhea, but highlighted the variable quality of the included RCTs and the complexity of the formulations.
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1028046/full – This in vivo metabolomics study in rats explored metabolic pathways linked to cardiotoxicity induced by Euodia Fructus. It identified specific metabolic changes associated with heart damage, providing crucial evidence for the cardiotoxic potential of the extract in an animal model.
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1509032/full – This comprehensive narrative review summarizes the botany, pharmacology, and toxicology of Euodia Fructus. It critically highlights the significant risks of hepatotoxicity and cardiotoxicity associated with the extract, offering a thorough overview of its safety profile based on existing research.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9931992/ – This review and meta-analysis provides a broad overview of the pharmacological activities of Evodia Fructus, including its anti-inflammatory, anticancer, and neuroprotective effects. While it consolidates extensive preclinical data, it also points out the limited number of high-quality human RCTs, emphasizing the need for further clinical investigation.
