Amelioration of rat experimental arthritides by treatment with the alkaloid sinomenine

Zhou

Journal of Ethnopharmacology

et al. 2005

Self Cite

Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutum Rehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and sinomenine, respectively) provide empirical evidence to support their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague-Dawley rats (n = 6, 250-300 g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of sinomenine, the peak plasma concentration of paeoniflorin was elevated (P < 0.01), the peak time was delayed (P < 0.01), the AUC 0-t was increased (P < 0.001), the mean residence time (MRT) was prolonged (P < 0.01), the C L was decreased (P < 0.01) and the V d was reduced (P < 0.05). These results indicate that sinomenine hydrochloride at 90 mg/kg significantly improved the bioavailability of paeoniflorin in rats.

Section: Introductionmentioning

confidence: 99%

Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats

Zhou

Journal of Ethnopharmacology

et al. 2005

Self Cite

“…Due to its antiinflammatory and immunosuppressive effects, sinomenine has been widely used for the treatment of various rheumatic diseases, such as atrophic arthritis, with few side effects [1][2][3] .…”

Section: Introductionmentioning

confidence: 99%

HPLC and LC-MS analysis of sinomenine and its application in pharmacokinetic studies in rats

Long

Chen

et al. 2010

Acta Pharmacol Sin

Aim: To improve and validate analytical methods based on HPLC and liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the quantitative measurement of sinomenine in rat plasma and brain tissue. Methods: The separation of analytes and the internal standard (IS), chloramphenicol, was performed on an Agilent TC-C18 column (250×4.6 mm, 5 µm). Blood samples were measured with a Surveyor photodiode array (PDA) detector at a wavelength of 263 nm. The LCQ DECA XP Plus mass spectrometer was operated in the multiple reactions monitoring mode using positive electrospray ionization, and the transition from the precursor ion (m/z 279) to the product ion (m/z 224) for sinomenine was measured in brain tissue. Results: Measurements were linear over the concentration range of 0.1-100 µg/mL for sinomenine in plasma and over the range of 0.01-5.00 µg/g for sinomenine in brain tissue. The intra-and inter-day variabilities were less than 10% of the relative standard deviation (RSD), and the extraction and recovery of sinomenine was 72.48%-80.26% from plasma and 73.75%-80.26% from brain tissue. The limit of quantification (LOQ) was 0.1 µg/mL for plasma, and 0.01 µg/g for brain tissue. Identification of sinomenine was reproducible at 0.5, 5, and 50 μg/mL in the plasma and at 0.05, 0.50, and 2.00 μg/g in brain tissue. The concentration of sinomenine measured in brain tissue after a single ip dose had a neuroprotective effect on H 2 O 2 -induced injury in PC12 cells in vitro. Conclusion: Our methods offered a sensitivity within a wide linear concentration range for sinomenine. These methods were successfully applied to evaluate sinomenine pharmacokinetics over time in rat brain tissue after a single ip dose of 30 mg/kg.

“…Although many in vivo studies have demonstrated that SIN can significantly improve RA [10][11][12] , the specific mechanism of SIN has not been established. The purpose of this 436 www.nature.com/aps Ou YQ et al study was to investigate the effects of SIN on the invasion and migration ability of activated human monocytic THP-1 cells (A-THP-1) and to evaluate the underlying mechanism.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have demonstrated that SIN has a variety of pharmacological effects, including anti-inflammatory effects, immunosuppression, and prevention of cartilage destruction [1][2][3][4] . As an immunosuppressive agent, SIN has been used extensively in China for the treatment of rheumatoid arthritis [5,6] .…”

Section: Introductionmentioning

confidence: 99%

“…This protein stimulates the production of matrix metalloproteinases (MMPs). CD147 has also been reported to play an important role in the invasion and migration ability of cells in both animal models and cancer patients [9] .Although many in vivo studies have demonstrated that SIN can significantly improve RA [10][11][12] , the specific mechanism of SIN has not been established. The purpose of this 436 www.nature.com/aps Ou YQ et al study was to investigate the effects of SIN on the invasion and migration ability of activated human monocytic THP-1 cells (A-THP-1) and to evaluate the underlying mechanism.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Sinomenine influences capacity for invasion and migration in activated human monocytic THP-1 cells by inhibiting the expression of MMP-2, MMP-9, and CD147

Chen

et al. 2009

Acta Pharmacol Sin

Aim:The aim of this study was to investigate the mechanism of the effects of Sinomenine (SIN) on the invasion and migration ability of activated human monocytic THP-1 cells (A-THP-1). Sinomenine is a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Cells were treated with different concentrations of SIN. The invasion and migration ability of cells was tested by in vitro transwell assays. The levels of CD147 and MMPs were evaluated by flow cytometric analysis and zymographic analysis, respectively. The mRNA expression of CD147, MMP-2, and MMP-9 was measured by RT-PCR. Results:The invasion and migration ability of A-THP-1 cells was significantly inhibited by SIN in a concentration-dependent fashion; at the same time, the levels of CD147, MMP-2, and MMP-9 were markedly down-regulated. This inhibitory effect was most notable at concentrations of 0.25 mmol/L and 1.00 mmol/L (P<0.01). Conclusion: A possible mechanism of the inhibitory effect of SIN on cell invasion and migration ability is repression of the expression of MMP-2 and MMP-9, which strongly correlates with the inhibition of CD147 activity. IntroductionSinomenine (SIN,7, C 19 H 23 NO 4 ), an alkaloid isolated from the Chinese medicinal plant, Sinomenium acutum, has been utilized to safely treat arthritis for many years. Previous studies have demonstrated that SIN has a variety of pharmacological effects, including anti-inflammatory effects, immunosuppression, and prevention of cartilage destruction [1][2][3][4] . As an immunosuppressive agent, SIN has been used extensively in China for the treatment of rheumatoid arthritis [5,6] .Rheumatoid arthritis (RA) is a systemic, immune and inflammatory disease characterized by joint swelling, synovial inflammation and joint destruction, leading to significant disability [7] . The regulation of cell migration and invasion is a critical process throughout the development of RA.Enhanced migration and invasion of peripheral macrophages contribute to joint destruction in RA by directly degrading the cartilage matrix and indirectly promoting angiogenesis. Elevated gene expression of gelatinase A (also called matrix metalloproteinase-2, MMP-2) and gelatinase B (also called matrix metalloproteinase-9, MMP-9) is critical for the progression of RA [8] .The extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a heavily glycosylated protein containing two immunoglobulin super family domains. It is enriched on the surface of macrophages and is associated with differentiation of human monocytic THP-1 cells when treated with phorbol 12-myristate 13-acetate (PMA). This protein stimulates the production of matrix metalloproteinases (MMPs). CD147 has also been reported to play an important role in the invasion and migration ability of cells in both animal models and cancer patients [9] .Although many in vivo studies have demonstrated that SIN can significantly improve...