Anti-proliferation and anti-migration effects of an aqueous extract of Cinnamomi ramulus on MH7A rheumatoid arthritis-derived fibroblast-like synoviocytes through induction of apoptosis, cell arrest and suppression of matrix metalloproteinase.

CONTEXT: Cinnamomi ramulus, the dry twig of Cinnamomum cassia Presl. (Lauraceae), has been reported to exert several activities such as antitumor, anti-inflammatory, and analgesic effects. OBJECTIVE: This study investigates the effects of an aqueous extract of Cinnamomi ramulus (ACR) on rheumatoid arthritis (RA). MATERIALS AND METHODS: TNF-α-induced RA-derived fibroblast-like synoviocyte MH7A cells were incubated with ACR (0.1-2 mg/mL) for 24 h. The proliferation was tested using CCK-8 and colony formation assays. The migration and invasion abilities were measured using transwell tests and wound healing assays. Apoptosis and cell cycle were examined by flow cytometry. The potential mechanisms were determined by western blotting and quantitative real-time PCR. UPLC-QE-MS/MS was used for chromatographic analysis of ACR and its compounds were identified. Molecular docking strategy was used to screen the potential anti-RA active compounds of ACR. RESULTS: We found that ACR induced apoptosis in MH7A cells at concentrations of 0.4, 0.8, and 1.2 mg/mL. The proliferation of MH7A cells was reduced and the cell cycle was blocked in the G2/M phase at concentrations of 0.2, 0.4, 0.6 mg/mL. Migration and invasion of MH7A cells were reduced through inhibiting the expression of MMP-1, MMP-2, and MMP-3. The molecular docking strategy results showed that 9 compounds in ACR have good affinity with protein crystal, and benzyl cinnamate (10-100 µg/mL) could inhibit cell migration and induce apoptosis. CONCLUSIONS: The anti-RA effect of ACR may be attributed to its anti-proliferative and anti-migration effects on synovial fibroblasts. These data suggest that Cinnamomi ramulus may have therapeutic value for the treatment of RA.

The traditional uses, phytochemistry, pharmacology and toxicology of Cinnamomi ramulus: a review.

OBJECTIVES: Cinnamomi ramulus (called Guizhi in Chinese) is a traditional medicine used to treat gastrointestinal dysfunction, cancer, arthritis, osteoporosis, spleen deficiency, Alzheimer's disease and obesity. This review aimed to provide a systematic summary on the geographical distribution, botany, traditional application, phytochemistry, pharmacology, pharmacokinetics, toxicology and other aspects of Cinnamomi ramulus. KEY FINDING: So far, more than 121 chemical compounds have been isolated from Cinnamomi ramulus, including volatile oil, organic acids, triterpenoid saponins, coumarins, tannins, flavonoids and flavonoid glycosides, steroids and polysaccharides. This paper reviews the pharmacological effects of Cinnamomi ramulus on antibacterial, anti-inflammatory, antiviral, antitumour, antipyretic and analgesic, antidiabetic and antiplatelet aggregation effects. Furthermore, the present review also indicates that Cinnamomi ramulus has the potential to develop into drugs for treating various diseases with high efficacy and low toxicity. SUMMARY: The convictive evidence from modern pharmacology research supports the traditional application of Cinnamomi ramulus. However, further studies on the structure-activity relationship of some of the isolated compounds may improve their biological potency. More toxicological studies will also contribute to the progress of clinical trial studies.

Study of forced degradation behavior of pramlintide acetate by HPLC and LC-MS.

Pramlintide acetate (Symlin®), a synthetic analogue of the human hormone amylin. It was approved in March 2005 as a subcutaneous injection for the adjunctive treatment of patients who have type 1 or 2 diabetes mellitus. The objective of current investigation was to study the degradation behavior of pramlintide acetate under different ICH recommended stress conditions by HPLC and LC-MS. Pramlintide acetate was subjected to stress conditions of hydrolysis (acidic or alkaline), oxidation, photolysis and thermal decomposition. Extensive degradation products were observed under the hydrolysis, oxidation or thermal stress conditions, while minimal degradation was found in the photolytic conditions. Successful separation of drug from the degradation products was achieved by the validated chromatography (RP-HPLC and SCX-HPLC) methods. Subsequent to isolation, the molecular weight of each component was determined by LC-MS. The LC-MS m/z values and fragmentation patterns of 4 impurities matched with the predicted degradation products of pramlintide acetate.

Chemical constituents from Cimicifuga foetida.

From the rhizoma of Cimicifuga foetida L. (Ranunculaceae) a new chromone, 6'-hydroxylangelicain (18), has been isolated together with 20 known compounds. The structure of 18 has been elucidated on the basis of spectroscopic and chemical evidence.