The pharmacokinetics profiles, pharmacological properties, and toxicological risks of dehydroevodiamine: A review

Abstract

Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from Evodiae Fructus (EF, Wuzhuyu in Chinese, Rutaceae family), a well-known traditional Chinese medicine (TCM) which is clinically applied to treat headache, abdominal pain, menstrual pain, abdominal distension, vomiting, acid regurgitation, etc. Modern research demonstrates that DHE is one of the main components of EF. In recent years, DHE has received extensive attention due to its various pharmacological activities. This review is the first to comprehensively summarize the current studies on pharmacokinetics profiles, pharmacological properties, and toxicological risks of DHE in diverse diseases. Pharmacokinetic studies have shown that DHE has a relatively good oral absorption effect in the mean concentration curves in rat plasma and high absorption in the gastrointestinal tract. In addition, distribution re-absorption and enterohepatic circulation may lead to multiple blood concentration peaks of DHE in rat plasma. DHE possesses a wide spectrum of pharmacological properties in the central nervous system, cardiovascular system, and digestive system. Moreover, DHE has anti-inflammatory effects via downregulating pro-inflammatory cytokines and inflammatory mediators. Given the favorable pharmacological activity, DHE is expected to be a potential drug candidate for the treatment of Alzheimer’s disease, chronic stress, amnesia, chronic atrophic gastritis, gastric ulcers, and rheumatoid arthritis. In addition, toxicity studies have suggested that DHE has proarrhythmic effects and can impair bile acid homeostasis without causing hepatotoxicity. However, further rigorous and well-designed studies are needed to elucidate the pharmacokinetics, pharmacological effects, potential biological mechanisms, and toxicity of DHE.

Therapeutic Effects of the major alkaloid constituents of Evodia rutaecarpa in Alzheimer's disease

“…Numerous studies have reported the significant cognitive‐enhancing effects of dehydroevodiamine in various cognitive impairment models. It has also demonstrated good blood–brain barrier permeability 52 . In 2000, Park et al .…”

“…It has also demonstrated good blood-brain barrier permeability. 52 In 2000, Park et al conducted the initial study on the therapeutic effects of orally administered dehydroevodiamine in various rat models of cognitive impairment. The results showed that oral administration of dehydroevodiamine significantly improved cognitive impairments induced by scopolamine in an AD rat model.…”

Research progress of plant‐derived natural alkaloids in central nervous system diseases

“…In toxicity studies, it was found that it can promote arrhythmia and impair bile acid homeostasis without hepatotoxicity. Studies of long‐term and high‐dose toxicity in animal models, however, remain blank and need further research (Fu et al, 2023). Nie et al analyzed Dendrobium nobile Lindl alkaloid (DNLA) ( 78 ) extracted from Dendrobium nobile by LC–MS/MS and determined that alkaloids accounted for 79.8% of DNLA and identified the structure and proportion of various alkaloids (Nie et al, 2016).…”

“…In toxicity studies, it was found that it can promote arrhythmia and impair bile acid homeostasis without hepatotoxicity. Studies of long-term and high-dose toxicity in animal models, however, remain blank and need further research(Fu et al, 2023).Nie et al analyzed Dendrobium nobile Lindl alkaloid (DNLA) (78) extracted from Dendrobium nobile by LC-MS/MS and determined that alkaloids accounted for 79.8% of DNLA and identified the structure and proportion of various alkaloids(Nie et al, 2016). In later studies, the team found that DNLA improved cognitive deficits in aged SAMP8 mice by downregulating the stress-related PERK signaling pathway by inhibiting cal-pain1, GSK-3β, and CDK5 activities and ultimately reducing tau hyperphosphorylation(Liu et al, 2020).…”

Dehydroevodiamine Targeting ACHE and ALDH3A1 Regulate Glycolytic Metabolism to Inhibit Hepatocellular Carcinoma Cell Apoptosis

“…20 Recent studies have shown that DHE has good pharmacological activity and it is expected to become a potential therapeutic drug for the treatment of Alzheimer's disease, chronic stress, amnesia, chronic atrophic gastritis, gastric ulcers, and rheumatoid arthritis. 21 Moreover, DHE has demonstrated significant antitumor activity in various cancers, including colorectal cancer (CRC) and gastric cancer. 22 However, the therapeutic effect of DHE on liver cancer remains unclear.…”