morphinans and magnoflorine

Sinomenium acutum stem is a popular traditional Chinese medicine used to treat bone and joint diseases. Sinomenine is considered the only chemical marker for the quality control of S. acutum stem in mainstream pharmacopeias. However, higenamine in S. acutum stem is a novel stimulant that was banned by the World Anti-Doping Agency in 2017. Therefore, enhancing the quality and safety control of S. acutum stem to avoid potential safety risks is of utmost importance. In this study, a fast, sensitive, precise, and accurate method for the simultaneous determination of 11 alkaloids in S. acutum stem by ultrahigh-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-QQQ-MS/MS) was established. This method successfully analyzed thirty-five batches of S. acutum stem samples. The average contents of sinomenine, magnoflorine, coclaurine, acutumine, higenamine, sinoacutine, palmatine, magnocurarine, columbamine, 8-oxypalmatine, and jatrorrhizine were 24.9 mg/g, 6.35 mg/g, 435 μg/g, 435 μg/g, 288 μg/g, 44.4 μg/g, 22.5 μg/g, 21.1 μg/g, 15.8 μg/g, 9.30 μg/g, and 8.75 μg/g, respectively. Multivariate analysis, including principal component analysis (PCA), orthogonal partial least square method-discriminant analysis (OPLS-DA), and hierarchical cluster analysis (HCA), were performed to characterize the importance and differences among these alkaloids in S. acutum stem samples. As a result, sinomenine, magnoflorine, coclaurine, acutumine, and higenamine are proposed as chemical markers for quality control. Higenamine and coclaurine are also recommended as chemical markers for safety control. This report provides five alkaloids that can be used as chemical markers for improving the quality and safety control of S. acutum stem. It also alerts athletes to avoid the risks associated with consuming S. acutum stem.

Topics: Alkaloids; Aporphines; Chromatography, High Pressure Liquid; Cluster Analysis; Drugs, Chinese Herbal; Isoquinolines; Least-Squares Analysis; Morphinans; Plant Extracts; Plant Stems; Principal Component Analysis; Sinomenium; Solvents; Spiro Compounds; Tandem Mass Spectrometry; Tetrahydroisoquinolines

The effects of the water extract of Sinomeni Caulis et Rhizoma (SCR-WE) and its major constituents, sinomenine (SIN) and magnoflorine (MAG), on moderate hemolysis induced by lysophosphatidylcholine (LPC) were investigated in rat erythrocytes and compared with the anti-hemolytic effects of lidocaine (LID) and propranolol (PRO) as reference drugs. LPC caused hemolysis at concentrations above the critical micelle concentration (CMC), and the concentration of LPC producing moderate hemolysis (60 %) was approximately 10 μM. SCR-WE at 1 ng/mL-100 μg/mL significantly inhibited the hemolysis induced by LPC. SIN and MAG attenuated LPC-induced hemolysis in a concentration-dependent manner from very low to high concentrations (1 nM-100 μM and 10 nM-100 μM, respectively). In contrast, the inhibiting effects of LID and PRO on LPC-induced hemolysis were observed at higher concentrations (1-100 μM) but not at lower concentrations (1-100 nM). Neither SIN nor MAG affected micelle formation of LPC, nor, at concentrations of 1 nM-1 μM, did they attenuate the hemolysis induced by osmotic imbalance (hypotonic hemolysis). Similarly, SCR-WE also did not modify micelle formation or hypotonic hemolysis, except at the highest concentration. These results suggest that SIN and MAG potently protect the erythrocyte membrane from LPC-induced damage and contribute to the beneficial action of SCR-WE. The protective effects of SIN and MAG are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.

Topics: Animals; Aporphines; Cytoprotection; Drug Evaluation, Preclinical; Erythrocyte Membrane; Erythrocytes; Hemolysis; Lysophosphatidylcholines; Male; Micelles; Morphinans; Plant Extracts; Plant Stems; Rats; Rats, Sprague-Dawley; Rhizome; Sinomenium

Boi and its original plant Sinomenium acutum from Japan were compared with Seifuto and its botanical origins from China in terms of their internal transcribed spacer (ITS) sequences and major chemical components. Boi, Seifuto, and their botanical origins overall showed seven variable sites in the ITS sequence and six genotypes. Japanese S. acutum and Boi had one nucleotide variation at position 593 to show two genotypes (J1 and J2) and their heterozygote (J3). Seifuto samples and their botanical origins, S. acutum and S. acutum var. cinereum from China, showed three genotypes (C1, C2, and C3), which did not agree with the botanical classification, indicating that they cannot be distinguished according to their ITS sequences. All Seifuto samples from Henan market showed the same ITS genotype (C1). The Japanese and Chinese genotypes differed in the nucleotide position 424, which can be used to distinguish the country of origin of these materials. In the HPLC analysis of six major components, sinomenine (1), magnoflorine (2), menisperine (3), 6-O-methyllaudanosoline glucoside (4), liriodendrin (5), and menisdaurin (6), all were detected in Boi, whereas five (all except for menisdaurin) were detected in Seifuto. The main component in the rhizome of Seifuto was sinomenine, whereas magnoflorine was the main component in the rhizome and the climbing stem of Boi. The content of sinomenine in Seifuto was almost twice that in Boi. Although the individual content of alkaloids 1-4 differed between Boi and Seifuto, the total contents of these alkaloids were comparable between them both in the climbing stem and rhizome.

Topics: Alkaloids; Aporphines; China; Chromatography, High Pressure Liquid; DNA, Ribosomal Spacer; Furans; Genotype; Glucosides; Glycosides; Japan; Morphinans; Sinomenium

Cardiac actions of the constituents of Sinomeni Caulis et Rhizome (SCR) and Mokuboi-to, a traditional herbal drug, were investigated. In voltage-clamp experiments, sinomenine (1 mM) and tetrandrine (100 microM) inhibited the ionic currents concentration-dependently. The constituents affected the action potential configurations. In multicellular preparations, SCR (1 mg/ml) decreased the maximum rate of depolarization. Tetrandrine (30 microM) and sinomenine (300 microM) also had similar effects, but magnoflorine (1 mM) had less or no effect. Dysrhythmias were abolished under Ca(2+) overload conditions by sinomenine. These results indicate that at even acute administrations, these drugs exert the active electropharmacological actions and cardioprotections.

Topics: Action Potentials; Alkaloids; Animals; Aporphines; Benzylisoquinolines; Calcium Channel Blockers; Drugs, Chinese Herbal; Guinea Pigs; Heart; Ion Channels; Morphinans; Papillary Muscles

We report a case of drug eruption caused by the crude drug Boi. A 41-year-old female patient had been diagnosed with chronic rheumatoid arthritis in the department of internal medicine. After ingestion of a decoction of the crude drug Boi for the alleviation of arthralgia, a slight fever developed, which was followed by systemic edematous erythema with itching. HPLC showed that the main components of the crude drug Boi are sinomenine and magnoflorine. The results of patch tests were negative for all oral drugs that the patient had been taking. Oral ingestion tests showed that the patient showed positive reactions to the as-is Boi boiling-water decoction and 1/10-volume sinomenine. Based on this, the drug eruption was judged to be caused by sinomenine. It is considered the first time that the causative component of a drug eruption was confirmed by oral ingestion tests with components of a crude drug of Kampo medicine (Sino-Japanese traditional medicine).

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aporphines; Arthritis, Rheumatoid; Chromatography, High Pressure Liquid; Drug Eruptions; Drugs, Chinese Herbal; Erythema; Female; Humans; Morphinans; Plant Roots; Plant Shoots; Pruritus