Traditional Chinese medicine Euodiae Fructus: botany, traditional use, phytochemistry, pharmacology, toxicity and quality control.

Euodiae Fructus, referred to as "Wuzhuyu" in Chinese, has been used as local and traditional herbal medicines in many regions, especially in China, Japan and Korea, for the treatment of gastrointestinal disorders, headache, emesis, aphtha, dermatophytosis, dysentery, etc. Substantial investigations into their chemical and pharmacological properties have been performed. Recently, interest in this plant has been focused on the different structural types of alkaloids like evodiamine, rutaecarpine, dehydroevodiamine and 1-methyl-2-undecyl-4(1H)-quinolone, which exhibit a wide range of pharmacological activities in preclinical models, such as anticancer, antibacterial, anti-inflammatory, anti-cardiovascular disease, etc. This review summarizes the up-to-date and comprehensive information concerning the botany, traditional uses, phytochemistry, pharmacology of Euodiae Fructus together with the toxicology and quality control, and discusses the possible direction and scope for future research on this plant.

Systematic analysis of chemical profiles of Sophorae tonkinensis Radix et Rhizoma in vitro and in vivo using UPLC-Q-TOF-MSE.

Sophorae tonkinensis Radix et Rhizoma (S. tonkinensis) has been recorded as a 'poisonous' Chinese herbal medicine in Chinese Pharmacopoeia 2020. The clinical reaction reports of S. tonkinensis indicated its neurotoxicity; however, there still exists dispute about its toxic substances. At present, no report is available on the blood and brain prototype research of S. tonkinensis. Most studies focused on alkaloids and less on other compounds. Moreover, the constituents absorbed into the blood and brain have been rarely investigated so far. This study established a rapid and efficient qualitative analysis method using UPLC-Q-TOF-MSE to characterize the ingredients of S. tonkinensis and those entering into the rat's body after oral administration. A total of 91 compounds were identified in S. tonkinensis, of which 28 were confirmed by the standards. In addition, 30 and 19 prototypes were also first identified in the rat's blood and brain, respectively. It was found that most flavonoids, except alkaloids, were detected in the rat's body and distributed in the cerebrospinal fluid, suggesting that flavonoids may be one of the important toxic or effective substances of S. tonkinensis. This finding provides new clues and data for clarifying the toxicity or efficacy of this medicinal plant.

[Metabolites and metabolic pathways of maackiain in rats based on UPLC-Q-TOF-MS].

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to investigate the metabolites of maackiain in rats based on the prediction function of UNIFI data processing system and liver microsomal incubation in vitro. Ten metabolites of maackiain after oral absorption were reasonably deduced and characterized. It was found that the biotransformation of maackiain mainly included phase Ⅰ oxidation, dehydrogenation, phase Ⅱ sulfate conjugation, glucosylation conjugation, and glucuronic acid conjugation. Among them, the product of glucosylation conjugation, trifolirhizin, was identified by comparison with the reference for the first time. Liver microsomal incubation in vitro further confirmed the metabolites and metabolic pathways of maackiain in rats. The metabolites in the blood, urine, and feces complemented each other, which revealed the migration, metabolism, and excretion modes of maackiain in rats. This study lays a foundation for the further investigation of the metabolic mechanism of maackiain in vivo and the in-depth research on the mechanism of pharmacodynamics and toxicity.

3,4-Secocycloartane Triterpenoids from the Cones of Pseudolarix amabilis.

Four new 3,4-secocycloartane triterpenoids, pseudolactones A-D (1-4), were isolated from the ethanol extract of the cones of Pseudol arixamabilis. Their structures were established by extensive 1D- and 2D-NMR experiments. The cones of P. arixamabilis are enriched in the ring-expanded or cleaved cycloartane triterpenoids. This work provides new insight into cycloartane triterpenoids from the cones of P. arixamabilis.

Systematic characterization of metabolic profiles of ingenol in rats by UPLC-Q/TOF-MS and NMR in combination with microbial biotransformation.

Ingenol, as the precursor of the marketed drug ingenol mebutate, has been proven to have a variety of bioactivities. The purpose of this study was to identify the metabolites of ingenol using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) combined with UNIFI software. Plasma, urine and fecal samples of rats were obtained and analyzed. A total of 18 metabolites were detected and identified in rat, including five phase II metabolites (M14-M18). Moreover, as microbial biotransformation is helpful to obtain sufficient reference standards of metabolites, the co-culture of ingenol with the fungus Cunninghamella elegans bio-110930 was also studied and yielded 4 phase I metabolites, in which reference standards of three metabolites were further obtained by preparative scale biotransformation. By matching their retention times, accurate masses, and fragment ions with metabolites in rat, the structures of three metabolites (M2, M3 and M4) were unambiguously confirmed by NMR technology. The results revealed that C. elegans bio-110930 functioned as an appropriate model to mimic and prepare phase I metabolism of ingenol in vivo to a certain extent. It also revealed that hydroxylation, oxygenation, sulfonation, and glucuronidation were the major metabolic pathways of ingenol. Furthermore, the first systematic metabolic study of ingenol is of great significance to elucidate the metabolites and metabolic pathways in vivo, which is helpful to predict metabolites of ingenol in humans, understand the elimination mechanism of ingenol, and clarify its effectiveness and toxicity.

Triterpenoid saponins from the roots of Psammosilene tunicoides.

Seven oleanane-type triterpenoid saponins, tunicosaponins B-D (1-3), F-I (4-7), along with eight known triterpenoid saponins (8-15), were isolated from the roots of Psammosilene tunicoides. The structures of compounds 1-7 were determined by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry and chemical methods. Triterpene glycosides have been considered as major active constituents of P. tunicoides. This work provides a more complete insight into the saponin constituents of P. tunicoides.

Triterpenoids from Ainsliaea latifolia and Their Cyclooxyenase-2 (COX-2) Inhibitory Activities.

Eight new triterpenoids were isolated from Ainsliaea latifolia. The structures of these compounds were elucidated by interpretation of spectroscopic data, including HRESIMS and NMR data. Compounds 4-6 are identified as rare trinorcucurbitane or tetranorcucurbitane triterpenoids. The absolute configurations of compounds 1 and 2 were confirmed by Snatzke's method. All compounds were evaluated for their inhibition against cyclooxyenase-2 (COX-2), in which compound 4 showed significant inhibitory effect against COX-2 with IC50 value of 3.98 ± 0.32 µM, comparable to that of positive control NS-398 (IC50 4.14 ± 0.28 µM).