The Isosteroid Alkaloid Imperialine from Bulbs of Fritillaria cirrhosa Mitigates Pulmonary Functional and Structural Impairment and Suppresses Inflammatory Response in a COPD-Like Rat Model.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world. Present therapies for COPD have limited effect on reducing the progression of COPD and suppressing the inflammatory response in the lung. Bulbs of Fritillaria cirrhosa D. Don (BFC) have been used in many Asian countries for a long time to treat pulmonary diseases, such as cough, expectoration, and asthma. Steroidal alkaloids are the major biological active constituents in BFC, whereby imperialine is one of the important steroidal alkaloids. So far, there are no studies reporting the effect of imperialine on COPD. In this study, we investigated the effect of imperialine on pulmonary function and structure and inflammation in a COPD-like rat model which was induced by the combination of exposure to CS and intratracheal administration of LPS. Our data show that imperialine mitigates pulmonary functional and structural impairment and suppressed inflammatory response in a COPD-like rat model by mediating expression of related cytokines in lung tissues of the COPD-like rats, such as IL-1ß, IL-6, IL-8, TNF-α, NF-κB, TGF-ß1, MMP-9, and TIMP-1.

Intestinal absorption characteristics of imperialine: in vitro and in situ assessments.

AIM: Imperialine is an effective compound in the traditional Chinese medicine chuanbeimu (Bulbus Fritillariae Cirrhosae) that has been used as antitussive/expectorant in a clinical setting. In this study we investigated the absorption characteristics of imperialine in intestinal segments based on an evaluation of its physicochemical properties. METHODS: Caco-2 cells were used to examine uptake and transport of imperialine in vitro, and a rat in situ intestinal perfusion model was used to characterize the absorption of imperialine. The amount of imperialine in the samples was quantified using LC-MS/MS. RESULTS: The aqueous solubility and oil/water partition coefficient of imperialine were determined. This compound demonstrated a relatively weak alkalinity with a pKa of 8.467±0.028. In Caco-2 cells, the uptake of imperialine was increased with increasing pH in medium, but not affected by temperature. The apparent absorptive and secretive coefficient was (8.39±0.12)×10(-6) cm/s and (7.78±0.09)×10(-6) cm/s, respectively. Furthermore, neither the P-glycoprotein inhibitor verapamil nor Niemann-Pick C1-Like 1 transporter inhibitor ezetimibe affected the absorption and secretion of imperialine in vitro. The in situ intestinal perfusion study showed that the absorption parameters of imperialine varied in 4 intestinal segments (duodenum, jejunum, ileum and colon) with the highest ones in the colon, where a greater number of non-ionized form of imperialine was present. CONCLUSION: The intestinal absorptive characteristics of imperialine are closely related to its physicochemical properties. The passive membrane diffusion dominates the intestinal absorption of imperialine.

[Comparison on pollen morphology among populations of Changium smyrnioides].

OBJECTIVE: To observe the pollen morphological differences among different populations of Changium smyrnioides. METHOD: The pollen morphology of 10 populations were examined through LM and SEM observations. RESULT: Pollens in different populations were distinguished from each other in the size, the largest average size was the pollen of the population cultivated in Hongshan, and the smallest was that of the population cultivated in Jiuhuashan. Pollens were oval-shaped in all of the populations, and P/E values were around 1.5. Typical feature of surface ornamentation was stripe-like structure, different populations were distinguished from each other in the texture depth and the gap. With different length and width in different populations, typical feature of germinal aperture was nearly square and 3 germinal furrows. Variation with 4 germinal apertures were found in the pollen of population cultivated in Hongshan. CONCLUSION: Diversity of pollen morphology was high, and differentiation was strong in Ch. smyrnioides.

Sipeimine-producing endophytic fungus isolated from Fritillaria ussuriensis.

Ten strains of endophytic fungi were isolated from the bulbs of the traditional Chinese medicinal plant Fritillaria ussuriensis. The extract from one of them, Fu7, showed a positive reaction with Dragendorff's reagent and the same Rf value in thin-layer chromatography (TLC) analysis as authentic sipeimine. A further TLC scan and high-performance liquid chromatography-evaporative light-scattering detection (HPLC-ELSD) showed that one ingredient of the extract of strain Fu7 had a similar absorption curve in the range 200-700 nm and the same retention time as authentic sipeimine. Thus, the fungus produces the bioactive ingredient sipeimine, as does its host plant, and could be used for the production of sipeimine by fermentation.