Delving into the Latest Updates on Evodiamine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

NLRP3 x TRPV1

Action

inhibitors, agonists

Mechanism

NLRP3 inhibitors(NACHT, LRR and PYD domains-containing protein 3 inhibitors), TRPV1 agonists(Transient receptor potential cation channel subfamily V member 1 agonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesNervous System Diseases+ [3]

Active Indication

Multiple SclerosisAtherosclerosisNon-Small Cell Lung Cancer+ [1]

Inactive Indication-

Originator Organization

Beijing University of TechnologyThe Institute of Radiation Medicine Academy of Military Medical Sciences PLA

Active Organization

Yunnan UniversityThe Institute of Radiation Medicine Academy of Military Medical Sciences PLA

Nanchang University

+ [3]

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC19H17N3O

InChIKeyTXDUTHBFYKGSAH-SFHVURJKSA-N

CAS Registry518-17-2

Ferroptosis, an iron dependent form of regulated cell death driven by lipid peroxidation, has emerged as a pivotal process in prostate cancer biology and therapy. This review summarizes the multifaceted regulation of ferroptosis in prostate cancer from molecular, metabolic, and microenvironmental perspectives. Core regulators such as GPX4, SLC7A11, and ACSL4 coordinate redox balance, glutathione metabolism, and lipid peroxidation, together determining ferroptotic sensitivity. Transcriptional, epigenetic, and post translational mechanisms including STAT3, the JMJD6 ATF4 axis, and TRIM family proteins further refine ferroptosis regulation. Metabolic reprogramming involving APOC1, SLC25A10, and BCAT2, as well as mitochondrial dynamics governed by VSTM2L and RPS6KC1, establishes metabolic dependencies that influence resistance or susceptibility to ferroptosis. Within the tumor microenvironment, cancer-associated fibroblasts and extracellular matrix components modulate ferroptosis through lactate signaling, exosomal microRNAs, and detachment resistance. Clinically, ferroptosis-related gene signatures provide valuable prognostic tools and predict responses to radiotherapy, antiandrogen therapy, and immunotherapy, linking ferroptotic dysregulation with immune suppression and treatment resistance. Emerging therapeutic strategies that inhibit GPX4 or system Xc-, modulate iron metabolism, and employ PSMA-targeted nanoplatforms have shown potent antitumor efficacy, especially in castration resistant disease. Repurposed drugs such as flubendazole and the ezetimibe derivative L14-8, along with natural compounds including evodiamine and luteolin, demonstrate translational potential for ferroptosis induction. Collectively, ferroptosis represents a promising therapeutic vulnerability for precision treatment of advanced prostate cancer.

01 Feb 2026·JOURNAL OF ETHNOPHARMACOLOGY

Inducible effects of evodiamine on the uptake of glutamine in Caco-2 cells

Article

Author: Makino, Toshiaki ; Mizukami, Hajime ; Ishida, Tomoaki ; Somehara, Sho ; Mizuno, Fumika

ETHNOPHARMACOLOGICAL RELEVANCE:

In traditional Chinese medicine (TCM) and traditional Japanese Kampo medicine, the symptoms associated with malabsorption syndrome correspond to "spleen deficiency", which can be treated with the prescriptions containing spleen-tonifying drugs. However, there is a lack of scientific evidence for this effect.

AIM OF THE STUDY:

We hypothesized that one potential mechanisms of action of spleen-tonifying drugs is to enhance nutrient transporter function in the gastrointestinal epithelium. Glutamine is an amino acid that aids in intestinal function. In addition, we develop crude drugs with this efficacy and to clarify the active ingredients and their mechanisms of action.

MATERIALS AND METHODS:

We screened 99 crude drugs used in Kampo preparations to identify those that promote the uptake of glutamine into human colon-derived Caco-2 cells.

RESULTS:

We found 7 active crude drugs on the promotion of glutamine uptake, however, no activity was observed for the representative spleen-tonifying drugs such as Ginseng Radix and Astragali Radix. Instead of spleen-tonifying drugs, we observed that the extract of Euodiae Fructus (dried fruit of Tetradium ruticarpum) had the strongest effect on glutamine uptake. Euodiae Fructus extract induced mRNA expression of the amino acid transporter B⁰ (ATB⁰), also known as system alanine-serine-cysteine transporter 2 or solute carrier 1A. The active ingredient in Euodiae Fructus was evodiamine, and when Caco-2 cells were incubated with medium containing evodiamine (3 μM) for 24 h, the glutamine uptake and the mRNA expression of ATB⁰ were significantly induced by 1.6-times and 4.1-times, respectively. The inducible effects of evodiamine were significantly suppressed by each inhibitor of protein tyrosine kinase, protein kinase C, phosphatidylinositol-3 kinase, or epidermal growth factor receptor (EGFR). Evodiamine induced mRNA expression level of EGFR.

CONCLUSIONS:

It is incorrect to interpret the spleen-tonifying effect as an effect of enhanced glutamine uptake. Evodiamine, an ingredient of Euodiae Fructus, promotes glutamine absorption in intestinal cells to improve malabsorption syndrome.

02 Jan 2026·DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY

Development and pharmacological evaluation of Evodia rutaecarpa extract-based transdermal gels: a novel approach for hypertension management

Article

Author: Yang, Zhixin

OBJECTIVE:

Alkaloids from Evodia rutaecarpa exhibit strong antihypertensive and antioxidant effects, but oral administration suffers from low bioavailability. This study aimed to develop and optimize a transdermal gel patch containing a vinegar-water extract of E. rutaecarpa to enhance therapeutic efficacy.

METHODS:

Gel formulations were optimized using single-factor tests and a Box-Behnken design (BBD), with adhesion and organoleptic properties as evaluation indices. In vitro permeation and kinetic modeling were used to characterize drug release, while antihypertensive effects were assessed in L-NAME-induced hypertensive rats. Serum lactate dehydrogenase (LDH), atrial natriuretic peptide (ANP), estradiol (E2), testosterone (T), and interleukin-6 (IL-6) were quantified by ELISA. Histopathological evaluation of the heart, kidney, and aorta was also performed.

RESULTS:

Optimized formulation: NP-700 (6.8 g), DAA (0.15 g), PVP K-90 (0.1 g), tartaric acid (0.15 g), glycerol (25 g), and distilled water (60 g). In vitro, the 72 h cumulative permeation of dehydroevodiamine, evodiamine, and rutaecarpine was 302.64 ± 0.74, 129.11 ± 0.41, and 41.50 ± 0.14 μg·cm^-2, respectively. The release kinetics fitted the Weibull model. In the L-NAME-induced hypertensive rats, patch treatment reduced systolic blood pressure (SBP) from 158.5 ± 4.9 to 122.5 ± 2.5 mmHg (p < 0.001) and significantly restored serum LDH, ANP, IL-6, E2, and T (p < 0.05). Histological analysis showed attenuation of myocardial hypertrophy and fibrosis, endothelial injury and smooth muscle proliferation, and reduced renal edema, tubular atrophy, and inflammatory infiltration.

CONCLUSIONS:

The E. rutaecarpa vinegar-water extract gel patch exhibited marked antihypertensive activity and protection against target organ damage, highlighting its promise as a novel transdermal therapy for hypertension.

100 Deals associated with Evodiamine

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple Sclerosis	Preclinical	China	Yunnan University	25 Jul 2025
Atherosclerosis	Preclinical	China	Guizhou University of Traditional Chinese Medicine	01 May 2025
Atherosclerosis	Preclinical	China	Shanghai Yuanye Bio-Technology Co., Ltd.	01 May 2025
Non-Small Cell Lung Cancer	Preclinical	China	Nanchang University	01 May 2025
Nervous System Diseases	Preclinical	China	The Institute of Radiation Medicine Academy of Military Medical Sciences PLA	-
Nervous System Diseases	Preclinical	China	Beijing University of Technology	-