Fingerprint Analysis of Cnidium monnieri (L.) Cusson by High-Speed Counter-Current Chromatography.

Cnidium monnieri (L.) Cusson is a popular Traditional Chinese Medicine (TCM) with a variety of bioactivities. However, there are some problems that have affected the development of Cnidium monnieri (L.) Cusson. At present, many methods have been reported for the analysis of coumarins in Cnidium monnieri (L.) Cusson. However, the quality control of coumarins in Cnidium monnieri (L.) Cusson by high-speed counter-current chromatography (HSCCC) has not been reported. In this study, analytical high-speed counter-current chromatography (HSCCC) was successfully used for fingerprint of Cnidium monnieri (L.) Cusson with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water at 4:6:6.5:3.5 (v/v). The UV wavelength was set at 254 nm. Six coumarin compounds with high biological activity were selected as indicator compounds for the quality control. The HSCCC fingerprint of the Cnidium monnieri (L.) Cusson was successfully established and there were some differences according to the results of the fingerprint analysis. The present results demonstrate that HSCCC is an established and efficient technique for the fingerprint analysis of Cnidium monnieri (L.) Cusson and can be used to control the quality of Cnidium monnieri (L.) Cusson. In brief, HSCCC is a useful technology for the fingerprint analytical method for TCM.

Two new chromones and a new coumarin from the fruit of Cnidium monnieri (L.) Cusson.

Two new chromones named cnidimol G (1) and cnidimol H (2), one new coumarin, 7-methoxy-8-(3-methoxy-3-methyl-2-oxobutyl)coumarin (3), and twenty known compounds were isolated from MeOH extract of the fruit of Cnidium monnieri (L.) Cusson. The structures of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, HRESIMS, IR and UV. Anti-inflammatory activity of the selected isolated compounds were evaluated. Compounds 1 and 8 exhibited inhibitory activities against nitric oxide production.

Osthole inhibits bone metastasis of breast cancer.

Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.), exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potential mechanism of this inhibition. In the murine model of breast cancer osseous metastasis, mice that received osthole developed significantly less bone metastases and displayed decreased tumor burden when compared with mice in the control group. Osthole inhibited breast cancer cell growth, migration, and invasion, and induced apoptosis of breast cancer cells. Additionally, it also regulated OPG/RANKL signals in the interactions between bone cells (osteoblasts and osteoclasts) and cancer cells. Besides, it also inhibited TGF-ß/Smads signaling in breast cancer metastasis to bone in MDA-231BO cells. The results of this study suggest that osthole has real potential as a therapeutic candidate in the treatment of breast cancer patients with bone metastases.

Bioavailability enhancement of osthole after oral administration of Bushen Yizhi prescription extract to rats followed by Cnidium monnieri (L.) Cusson fruits extract in comparison to pure osthole at different doses.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Yizhi prescription (BSYZ) is a traditional Chinese compound prescription, which is commonly used in China for treating ShenXu and hypophrenia based on traditional Chinese medicine and Alzheimer's Disease according to modern Chinese medicine. Cnidium monnieri (L.) Cusson fruits (CM) is treated as the main herb of BSYZ, and its main active ingredient Osthole (OST) is considered as one of the major active ingredients of BSYZ. Even though OST plays an important role in the BSYZ its bioavailability is poor. In order to investigate whether the bioavailability of OST was influenced by BSYZ and CM extract, the comparative evaluations on pharmacokinetics of OST after oral administration of pure OST at different doses, CM and BSYZ extract were studied. MATERIALS AND METHODS: 30 rats were randomly assigned to five groups and orally administered with pure OST at different doses (15, 75 and 150 mg/kg), CM (15 mg/kg OST) and BSYZ (15 mg/kg OST) extract. At different predetermined time points after administration, the concentrations of OST in rat plasma were determined by using the HPLC-UV method, and main pharmacokinetic parameters were investigated. RESULTS: The results showed that the pharmacokinetic parameters of OST were significantly different (p<0.05) among the groups. The AUC(0→t), AUC(0→∞) and Cmax of OST were significantly increased after oral administration of BSYZ extract, followed by CM extract, in comparison to pure osthole at different doses. CONCLUSIONS: This present study indicated that the bioavailability of pure OST after oral administration was extremely low and it was dramatically enhanced because of the synergistic effect of the traditional Chinese Bushen Yizhi prescription.