Objective To build an HPLC-ELSD method for simultaneous determination of 8-O-acetylharpagide and harpagide inAjuga decumbens Thunb.;To determineAjuga decumbens Thunb. samples from different area and of different batches.Methods Chromatographic separation was achieved on a Dikma C18 column (4.6 mm×150 mm, 5μm). The mobile phase consisted of water (A) and acetonitrile (B), using a gradient elution of 5% B at 0-6 min, 5%-15% B at 6-11 min, 15% B at 11-17 min, and the flow rate was 1.0 mL/min. An evaporative light scattering-detector (ELSD) was used with the temperature of drift tube at 103℃ and the gas flow rate of air was at 1.6 L/min.Results Good linearity was shown at the concentration range of 0.017-17.32μg for 8-O-acetylharpagide, and 0.003-1.62μg for harpagide. The validated method was of great precision and accuracy. The contents of 8-O-acetylharpagide and harpagide inAjuga decumbens Thunb. from Fujian province were higher than the contents in other localities.Conclusion The content of harpagide can be used as index component to monitor quality control ofAjuga decumbens Thunb..

Objective To investigate the evolution of surgical treatment and it's influence on prognosis in reptured liver cystic echinococcosis.Method Clinical data of 110 surgically treated cases of reptured liver cystic echinococcosis from January 1990 to December 2008 were retrospectively analysed,and these cases were divided into three groups by different surgical approach;Group A(22 cases):removal of internal capsule,with formaldehyde or hydrogen peroxide regional anthelminthic,with residual cavity side edge of lock stitching or greater omentum filling or drainage after residual cavity closure;Group B (65 cases):Removal of intemal capsule,with hypertonic saline regional anthelminthic,with external capsule extrahepatic partial resection,with residual cavity bile leakage sutured,and with residual cavity open drainage,Group C(23 cases):the total or subtotal external capsule stripping operation,with hypertonic saline regional anthelminthic and drainage.Result The rate of overall postoperative complications of residual cavity was 40.9%、16.9%、0.0%(P<0.05)respectively and the recurrence rate was 18.2%、4.6%、0.0%(P<0.05)respectively;drainage time needed was the longest in group A,and shortest in group C,whereas the operation time was the longest in group C and it costed higher blood loss.Intraabdominal implantation of the hydatid significantly decreased with hypertonic saline treatment.Conclusion Total or near total removal of the external capsule of the hydatic cyst and hypertonic saline treatment with postoperative external drainage is the therapy of choice for reptured liver cystic echinococcosis.

8-O-acetylharpagide and harpagide are two kinds of effective component of Ajuga decumbens extract. A sensitive LC-MS/MS method has been established for pharmacokinetics of 8-O-acetylharpagide and harpagide in beagle dog after oral administration of from A. decumbens extract. Female beagle dogs received orally 12.9, 25.7 mg x kg(-1) p. o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartment analysis. The mobile phase consisted of 0.1% formic acid in water (A) and acetonitrile (B), which was run at a flow rate of 0.3 mL x min(-1). Chromatographic separation was achieved on an Agilent ZORBAX XDB-C18 column (2.1 mm x 50 mm, 3.5 microm) using a gradient elution of 5% B at 0-2 min, 95% B at 2. 1-5 min and 5% B at 5. 1-10 min. All analytes, including the IS, were monitored under positive ionization conditions and quantified in MRM mode with transitions of m/z 429.2-369.2 for 8-O-acetylharpagide, m/z 387.2-207.2 for harpagide, and m/z 149.2-103.1 for IS. High purity nitrogen was employed as both the nebulizing and drying gas. Other parameters of the mass spectrometer were optimized as follows: drying gas flow 10.0 L x min(-1); drying gas temperature 300 degrees C; capillary voltage 4 000 V. Results showed that 8-O-acetylharpagide and harpagide showed a dose-dependence profile. T(max) of 8-O-acetylharpagide is 1.7 h, and T(max) of harpagide is 1.57 h, which was higher than T(max) of 8-O-acetylharpagide and harpagide after oral administration of from A. decumbens extract in rats. The different pharmacokinetic parameters may be due to the species differences of rat and beagle dog.
Administration, Oral ; Ajuga ; Animals ; Dogs ; Female ; Iridoid Glycosides ; pharmacokinetics ; Plant Extracts ; metabolism ; Pyrans ; pharmacokinetics ; Rats ; Species Specificity

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.