neotuberostemonine and croomine

To compare the contents of four alkaloids and antitussive activities of Stemona tuberosa from different habitats of Guangxi Province.. The HPLC separation was performed on a Merck Purospher STAR RP18 (250 mm x 4. 6 mm, 5 µm) column by gradient elution using 0. 05% ammonia-acetonitrile as the mobile phase. The flow rate was 1. 0 mL/min, the dectection wave-length was set at 210 nm,and the column temperature was 40 °C. The antitussive potency of total alkaloids of Stemonae Radix from different habitats was evaluated on guinea pigs with citric acid aerosol to induce cough.. The range of recoveries of this mehtod was 98. 24% ~ 101. 21%, with all the constituents showing good linearity(the correlation coefficents above 0. 999). The major chemotype of Stemonae Radix in Guangxi was stemoninine, following by tuberostemonine and croomine, and finally neotuberostemonine. The antitussive activitiy of Stemona tuberosa was in a concentration-dependent manner.. Stemonae Radix from Dongxing, Fangcheng can reduce cough times and prolong cough incubation period, and thus Dongxing, Fangcheng is the best habitat in Guangxi in the present experiments.

Topics: Alkaloids; Animals; Antitussive Agents; China; Chromatography, High Pressure Liquid; Cough; Drugs, Chinese Herbal; Ecosystem; Guinea Pigs; Heterocyclic Compounds, 3-Ring; Lactones; Plant Roots; Pyrrolidines; Spiro Compounds; Stemonaceae

Stemonae Radix (Stemona tuberosa Lour, Bai Bu) is an important traditional Chinese medicinal (TCM) plant known for its antitussive activity. Croomine, neotuberostemonine and tuberostemonine alkaloids of Stemonae Radix are major components responsible for antitussive action. In this work, plasma pharmacokinetic and biodistribution characteristics of the three alkaloids after oral administration of Stemonae Radix are investigated using a rapid and sensitive UPLC-Q-TOF-HDMS method. Mass spectrometry (MS) was performed on a Waters Micromass high-definition technology with an electrospray ionization source in positive ion mode, with excellent MS mass accuracy and enhanced MS data acquisition. Separation of main alkaloids was achieved on a Waters BEH C(18) column by linear gradient elution. Data were analyzed and estimated by compartmental methods and pharmacokinetic parameters calculated using WinNonlin Professional version 5.1. It was found that croomine, neotuberostemonine and tuberostemonine had faster absorbed into the bloodstream, maintain the high plasma concentration, and pose a large AUC value. The biodistribution of neotuberostemonine and tuberostemonine showed that the higher levels were in liver, and lung. Croomine was discovered in brain and showed that it could cross the blood-brain barrier, indicating that croomine plays an antitussive effect as acting on the central nervous system. Neotuberostemonine and tuberostemonine were not discovered in brain, demonstrating that they play an antitussive effect as peripheral antitussive. This work suggests that the pharmacokinetics and biodistribution based-UPLC-Q-TOF-HDMS can provide a reliable tools for screening bioactive components contributing to pharmacological effects of medicinal herbs.

Topics: Administration, Oral; Alkaloids; Animals; Area Under Curve; Chromatography, Liquid; Half-Life; Lactones; Male; Medicine, Chinese Traditional; Molecular Structure; Plant Roots; Pyrrolidines; Rats; Rats, Wistar; Spiro Compounds; Stemonaceae; Tandem Mass Spectrometry; Tissue Distribution

Stemona alkaloids with distinctly different chemical skeletons are recently reported as the active components in the antitussive herb Baibu derived from the root-tubers of Stemona tuberosa. This study aims to determine if alkaloids of this herb contribute equally to the antitussive functions, act on the same sites of cough reflex, and play any role in inducing central respiratory depressant effects.. Antitussive potency of four major alkaloids was evaluated on guinea pigs with citric acid aerosol to induce cough. The action sites of the alkaloids on cough reflex pathway were tested with electrical stimulation of the superior laryngeal nerve in guinea pigs. The central respiratory effects of croomine were also tested on guinea pigs.. Croomine, neotuberostemonine and stemoninine showed similar antitussive potency, while tuberostemonine showed much weaker antitussive potency. Neotuberostemonine, tuberostemonine and stemoninine acted on the peripheral cough reflex pathway, while croomine acted on the central part. Croomine also showed obvious central respiratory depressant effects.. The four major Stemona alkaloids in Stemona tuberosa do not contribute equally to antitussive potency in guinea pigs. Neotuberostemonine, tuberostemonine and stemoninine target on peripheral cough reflex pathway. Croomine acts on central sites in the cough reflex pathway and demonstrates central respiratory depressant effects, which can partly account for the adverse reactions reported for the herb.

Topics: Alkaloids; Animals; Antitussive Agents; Central Nervous System Agents; Citric Acid; Cough; Guinea Pigs; Lactones; Laryngeal Nerves; Plant Roots; Pyrrolidines; Respiratory System; Spiro Compounds; Stemonaceae

A high-performance liquid chromatography coupled with diode array detection and evaporative light scattering detection (HPLC-DAD-ELSD) method was developed to simultaneously quantify six major bioactive alkaloids belonging to different structure types in Radix Stemonae, Bai-Bu in Chinese, a traditionally used antitussive and insecticidal medicinal material in China and other countries of Southeast Asia. Diode array detector (DAD) with the wavelengths at 307 and 260 nm was used to monitor the conjugated system of protostemonine (2) and maistemonine (4), respectively, whereas evaporative light scattering detector (ELSD) was employed to detect croomine (1), stemoninine (3), neotuberostemonine (5) and tuberostemonine (6), the other four analytes with no or poor chromophores. The assay was validated to be sensitive, precise and accurate, with a detection limit of 3.64-0.04 microg/mL depending on the individual analytes. The overall intra- and inter-day variations were less than 9.3%, and the overall recoveries higher than 91.2%, respectively. The correlation coefficients of the calibration curves were better than 0.996 for all analytes. The newly established method was successfully utilized to determine six major components in the genuine sources of Radix Stemonae: Stemona japonica, S. sessilifolia and S. tuberosa. Significant variations of contents of these components were demonstrated in samples of these three species. This simple, rapid, low-cost and reliable method is suitable for the routine quality control of herbal medicines containing bioactive components with different structure types such as Radix Stemonae.

Topics: Alkaloids; Antitussive Agents; Chromatography, High Pressure Liquid; Equipment Design; Lactones; Light; Medicine, Chinese Traditional; Molecular Structure; Plant Roots; Pyrrolidines; Quality Control; Reproducibility of Results; Scattering, Radiation; Sensitivity and Specificity; Solvents; Spectrophotometry, Ultraviolet; Spiro Compounds; Stemonaceae

The root tubers of Stemona tuberosa, Stemona japonica and Stemona sessilifolia are recognized by the Pharmacopoeia of the People's Republic of China as authentic sources of the herb Radix Stemonae (Baibu). Careful anatomical analyses of these three species, whose identities were confirmed by flowering and fruiting samples, revealed that the root tubers of Stemona tuberosa could be distinguished from those of the other two species by the presence of scattered fibers in the cortex and pith and by the absence of thickened striations on the surface of velamen cells. HPLC analyses demonstrated that the total alkaloid profiles could be grouped into four types represented as the major component by stenine-type Stemona alkaloids such as tuberostemonine (4) and neotuberostemonine (3), or by non-stenine types such as croomine (1) and stemoninine (2). Nevertheless, all these samples demonstrated different degrees of antitussive properties in guinea pigs. These results suggested that non-stenine-type of Stemona alkaloids also contributed to the antitussive properties. The variations in chemical profiles among herb samples add difficulty in ensuring quality control in botanical products.

Topics: Alkaloids; Animals; Antitussive Agents; Female; Flowers; Guinea Pigs; Lactones; Male; Molecular Structure; Phytotherapy; Plant Preparations; Plant Tubers; Pyrrolidines; Spiro Compounds; Stemonaceae