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Evodiamine

Also known as: Evodiamine, Euodia rutaecarpa, Evodia, Wu Zhu Yu, C19H17N3O3

Overview

Evodiamine is a bioactive alkaloid derived from the fruit of *Euodia rutaecarpa*, a plant used in traditional Chinese medicine. It is recognized for its potential pharmacological properties, particularly as an anticancer and anti-inflammatory agent. Preclinical studies suggest that evodiamine exhibits analgesic, anti-inflammatory, anti-tumor, and anti-microbial effects. It has been shown to induce apoptosis, arrest cell cycles, and regulate various cellular pathways involved in cancer and other diseases. However, research is predominantly preclinical, with most studies conducted in animal models and in vitro experiments. More clinical trials are needed to fully understand its efficacy and safety in humans. Evodiamine's poor solubility in aqueous media may affect its absorption and bioavailability, necessitating pharmaceutical strategies to improve its solubility.

Benefits

Evodiamine has demonstrated significant antitumor effects in preclinical studies, particularly in mice models, with notable reductions in tumor volume and weight. A meta-analysis of 13 studies showed a standardized mean difference (SMD) of -5.99 (95% CI: -8.89 to -3.10) for tumor volume and -3.51 (95% CI: -5.13 to -3.90) for tumor weight. It also induces apoptosis in various cancer cell lines, including lung, liver, breast, and ovarian cancer cells, through intrinsic and extrinsic apoptotic pathways. Additionally, evodiamine exhibits anti-inflammatory and analgesic effects, potentially beneficial in treating pain and inflammatory conditions. While it has shown promise in regulating metabolic diseases and providing heart protection, further research is needed to fully elucidate these effects and translate them into clinical benefits for human populations.

How it works

Evodiamine induces apoptosis through both the intrinsic mitochondrial-dependent pathway and the extrinsic death receptor pathway. It increases mitochondrial membrane depolarization and the Bax/Bcl-2 ratio, leading to the activation of caspases. The compound regulates various cellular pathways, including the AKT/NF-κB and SHH/GLI1 pathways, which are involved in cell proliferation and survival. Evodiamine interacts with multiple body systems, including the immune system (through anti-inflammatory effects) and the metabolic system (through regulation of metabolic diseases). Known molecular targets include DNA methyltransferase 3A (DNMT3A), topoisomerase I (topo I), and various protein kinases such as PI3K/AKT and MEK/ERK pathways.

Side effects

Evodiamine has shown significant hepatotoxicity and cardiotoxicity in preclinical studies, necessitating careful monitoring in any potential clinical applications. There is limited data on common side effects in humans, but preclinical studies suggest potential liver and heart toxicity. Specific uncommon and rare side effects are not well-documented due to the lack of human clinical trials. Potential drug interactions are not well-studied, but evodiamine's effects on various cellular pathways suggest possible interactions with other medications. Given its hepatotoxicity and cardiotoxicity, evodiamine should be used with caution in patients with liver or heart conditions. Special care should be taken when considering evodiamine for use in pregnant or breastfeeding women, as well as in children, due to the lack of safety data.

Dosage

The minimum effective dose in animal studies ranges from 3 to 100 mg/kg body weight, effective in inhibiting tumor growth. However, the optimal dosage range for humans is not established and requires further clinical research. The maximum safe dose is also undefined due to limited clinical data. The timing of administration in animal studies varied, including subcutaneous injection, intraperitoneal injection, and gavage. Improving the solubility of evodiamine is crucial for its effective administration, and pharmaceutical formulations aimed at enhancing its solubility are being developed. Poor aqueous solubility affects its absorption, and strategies to improve solubility are necessary to enhance bioavailability. There is no specific information on required cofactors for evodiamine, but its interaction with various cellular pathways suggests potential synergies or antagonisms with other compounds.

FAQs

Is Evodiamine safe for human consumption?

Evodiamine is not currently approved for human use, and its safety and efficacy need to be established through clinical trials. It should not be used without medical supervision due to potential hepatotoxicity and cardiotoxicity.

What are the primary safety concerns with Evodiamine?

The primary safety concerns are related to liver and heart toxicity, which necessitate careful monitoring. Preclinical studies have indicated potential adverse effects on these organs.

What results can I expect from taking Evodiamine?

In preclinical studies, evodiamine has shown significant antitumor effects, but human clinical trials are needed to confirm these results. It is not a proven treatment for cancer or other diseases in humans yet.

How should Evodiamine be administered?

The optimal timing and administration methods for humans are not yet established. Research is ongoing to determine the best ways to improve its solubility and bioavailability.

Is Evodiamine a proven treatment for cancer?

Evodiamine is not a proven treatment for cancer or other diseases in humans and should not be used as such without further clinical validation. More research is needed.

Research Sources

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.774201/pdf – This systematic review and meta-analysis of 13 preclinical studies (n=267) found that evodiamine significantly inhibited tumor growth in mice. The treatment courses ranged from 14 to 70 days, showing a standardized mean difference (SMD) of -5.99 for tumor volume and -3.51 for tumor weight, indicating a robust antitumor effect in animal models.
https://pubmed.ncbi.nlm.nih.gov/32738391/ – This systematic review highlights evodiamine's various pharmacological activities, including analgesic, anti-inflammatory, anti-tumor, and anti-microbial effects. However, it also points out significant hepatotoxicity and cardiotoxicity, emphasizing the need for more research on toxic mechanisms, pharmacokinetics, and clinical applications.
https://pubmed.ncbi.nlm.nih.gov/34900724/ – This review article discusses the antiproliferative effects of evodiamine, noting that it induces apoptosis and cell cycle arrest in various cancer cell lines through multiple cellular pathways. The review emphasizes the need for clinical validation, as the findings are primarily based on in vitro and in vivo studies.
https://www.researchgate.net/post/When_performing_a_formal_systematic_review_is_there_a_minimal_number_of_databases_that_must_be_included_in_the_search – This ResearchGate post discusses the methodological considerations for performing systematic reviews, particularly regarding the number of databases to include in the search. While not specific to evodiamine, it provides context on the rigor required for comprehensive literature reviews in scientific research.
https://www.mdpi.com/1422-0067/19/11/3403 – This review explores the molecular mechanisms of evodiamine, detailing how it induces apoptosis and cell cycle arrest in cancer cells. It highlights evodiamine's interaction with various cellular pathways, including intrinsic and extrinsic apoptotic pathways, while emphasizing the need for further clinical research to validate these findings.