[Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats].

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats / 中国中药杂志

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Rutaecarpine enhances the anti-diabetic activity and hepatic distribution of metformin via up-regulation of Oct1 in diabetic rats.

Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.

Fabrication of food-grade Pickering high internal phase emulsions stabilized by the mixture of ß-cyclodextrin and sugar beet pectin.

Food-grade Pickering high internal phase emulsions (HIPEs) stabilized by a mixture of ß-cyclodextrin (ß-CD) and sugar beet pectin (SBP) were fabricated for the first time. The factors affecting the microstructures, mechanical properties, and stabilities of the Pickering HIPEs were systematically investigated. The corresponding hybrid particles were also separated and characterized to reveal the formation mechanism. The results indicated that the mixture could induce the formation of HIPEs with an oil phase volume fraction (φ) of 75% using a one-step high-speed shearing process at room temperature. The composition (the mass ratio of ß-CD to SBP, Rc/s) and concentration (W) of the mixture had significant effects on the formation and properties of HIPEs. When W ≥ 1.0% and Rc/s = 2:2 or 3:1, HIPEs had smaller oil droplets, higher gel strengths, better centrifugation stabilities and lutein protection effects. The spectral analysis suggested that SBP could adhere to the surface of ß-CD particles to form hybrid particles during the homogenization. Compared with native ß-CD particles, these hybrid particles had higher ζ-potential absolute values, and the SBP could also increase the viscosity of the aqueous phase, which contributed to the formation and properties of these HIPEs.

[Guiding mechanism of platycodin D in treatment of mouse lung cancer with doxorubicin].

This study is to observe whether platycodin D has the guiding role in treatment of mouse lung cancer with doxorubicin and explore its guiding mechanism. In vitro, platycodin D and doxorubicin(alone or in combination) were added into Lewis lung cancer(LLC) cells to detect the cell proliferation and doxorubicin uptake. Cell morphological changes were analyzed by cell holographic analysis system; cell gap junctional intercellular communication(GJIC) was tested by fluorescent yellow tracer; lyso-tracker red was used to examine lysosomal function; LC-3 B(Light chain 3 beta)and P62(heat shock 90-like protein)staining were used to test auto-phagy and autophagic degradation respectively; and P-glycoprotein(P-gp) expression was examined by Western blot. In vivo, lung solid tumor was formed in mouse LLC cells via intravenous injection. Platycodin D and doxorubicin(alone or in combination) were used to treat tumor-bearing mice for four weeks, and then the tumor size was examined, mouse survival time was recorded, doxorubicin uptake in lung tissues was tested, and lung tissues were stained for observation by HE(hematoxylin-eosin) and immunohistochemistry. The results showed that platycodin D at the experimental concentration had no effect on LLC cell proliferation but decreased LLC cell volume, promoted the cells to uptake doxorubicin and enhanced the inhibitory action of doxorubicin on cell proliferation. Platycodin D could promote GJIC and lysosomal function, increase autophagy and autophagic degradation and suppress P-gp expression. Platycodin D at the experimental dose in this study had no effect on LLC lung solid tumors in mice, increased doxorubicin uptake in lung tissues and enhanced the therapeutic efficacy of doxorubicin on lung solid tumors. Platycodin D could improve the extracellular matrix deposition in lung solid tumors, decreased the lung mucin 5 AC secretion and pulmonary vessel permeability. In summary, platycodin D had the guiding role in treating mouse lung cancer with doxorubicin, and its guiding mechanism may be associated with the promotion of cell communication, lysosomal function, and improvement of extracellular environment.

Three common caffeoylquinic acids as potential hypoglycemic nutraceuticals: Evaluation of α-glucosidase inhibitory activity and glucose consumption in HepG2 cells.

The demand for plant-derived antidiabetic nutraceuticals is increasing. In this study, the effects of three common caffeoylquinic acids (CQAs) (chlorogenic acid, isochlorogenic acid A, and cynarin) on α-glucosidase activity and glucose consumption in HepG2 cells were systematically compared. Their α-glucosidase inhibitory activities followed the order of isochlorogenic acid A > chlorogenic acid > cynarin. The fluorescence analysis indicated that they exerted the inhibitory role by forming the complex with α-glucosidase at the molar ratio of 1:1. Isochlorogenic acid A possessed the highest binding capacity, followed by chlorogenic acid and cynarin. The effect of caffeoyl group distribution on the α-glucosidase inhibitory activity was clarified by the molecular docking results. In the HepG2 cells, isochlorogenic acid A also showed the best glucose consumption with negligible cytotoxicity, which might be related to its reactive oxygen species scavenging capacity in cells. Our results confirm its potential application as the antidiabetic nutraceutical. PRACTICAL APPLICATIONS: The hypoglycemic activities of three common CQAs (chlorogenic acid, isochlorogenic acid A, and cynarin) were systemically evaluated in this study. Isochlorogenic acid A exhibited the strongest α-glucosidase inhibitory activity and highest glucose consumption in HepG2 cells with low cytotoxicity. The results suggest that isochlorogenic acid A can be used as the potential hypoglycemic nutraceutical in functional foods.

Structuring of sunflower oil by stearic acid derivatives: Experimental and molecular modelling studies.

Structuring of vegetable oils has potential application in food, pharmaceutical and cosmetic products. In this study, structuring effects of stearic acid derivatives on sunflower seed oil were systematically investigated by experimental and molecular simulation methods. Stearic acid (SA), 12-hydroxy stearic acid (HSA) and 2-hydroxyethyl stearate (HES) were able to structure sunflower seed oil, among which the structuring ability of HES was reported for the first time. The oleogel formed with HSA exhibited good mechanical properties (such as hardness, fracturability, adhesiveness, chewiness and storage modulus), which coincided with its highest solid fat content and degree of crystallinity. Oleogels containing SA and HES showed similar mechanical properties. Both the molecular dynamics (MD) simulation and independent gradient model (IGM) confirmed that the HSA dimer possessed the strongest interaction during the self-assembly process while the dimers of HES and SA had similar interactions, which could explain their structuring performance.

Preparation and characterization of lutein ester-loaded oleogels developed by monostearin and sunflower oil.

The marigold (Tagetes erecta L.) flower is rich in lutein ester with many health-promoting activities. In this study, the effects of vegetable oil type and extracting the temperature on the extraction efficiency of lutein ester in the marigold flower were evaluated. Then, the structuring of the lutein ester-loaded sunflower oil with the addition of different amounts of monostearin and cooling temperatures (4 and 20°C) was investigated. The XRD analysis suggested that these oleogels were stabilized by the network formed by monostearin crystals in the sunflower oil. The textural properties (firmness, cohesiveness, and hardness) of oleogels were positively related to the monostearin dosage, but negatively related to the cooling temperature. According to the rheological results, the oleogels belonged to the pseudoplastic gel and their gelation temperature (Tg ) was only related to the concentration of monostearin. The light stability of lutein ester in the oleogels was also significantly improved in a monostearin dosage-dependent manner. PRACTICAL APPLICATIONS: The edible lutein ester-loaded oleogel for foods developed by structuring the sunflower oil with monostearin is introduced in this study. Its texture and rheological properties can be adjusted to cater to different requirements in the food industry by changing the monostearin dosage and cooling temperature. This study provides a reference for the development of other liposoluble nutraceuticals.

[Effect of Saposhnikoviae Radix on pharmacokinetics and tissue distributions of active components in Tongxie Yaofang in rats].

Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However, the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs, we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis. The results revealed that Saposhnikoviae Radix could enhance Cmax, AUC0-t, and AUC0-∞ of paeoniflorin and hesperidin, and increase the distribution of atractylenolide-I, paeoniflorin and hesperidin in liver, spleen, brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I, paeoniflorin and hesperidin. Meanwhile, it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix, and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.

Effect of Saposhnikoviae Radix on pharmacokinetics and tissue distributions of active components in Tongxie Yaofang in rats / 中国中药杂志

Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However, the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs, we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis. The results revealed that Saposhnikoviae Radix could enhance Cmax, AUC0-t, and AUC0-∞ of paeoniflorin and hesperidin, and increase the distribution of atractylenolide-I, paeoniflorin and hesperidin in liver, spleen, brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I, paeoniflorin and hesperidin. Meanwhile, it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix, and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.

[Advance in studies on antibacterial effect of flavonoids].

As antibiotic drug resistance has become one of the most serious threats to global public health, there is a pressing need to look for new effective therapeutic drugs. Flavonoids are a large class of chemicals widely exist in plants, and have such effects as direct antibiotics, synergistic antibiotics and inhibition of bacterial activity. In this article, we made a summary for the advance in studies on the antibacterial effects of flavonoids and their mechanism.

[Brief summary on ancient moxibustion for treatment of fabei].

To formulate the theory and experiences of physicians of successive dynasties on moxibustion for treatment of fabei, the medical cases and theory of ancient physicians are analyzed. It is found that moxibustion treatment has unique efficiency on fabei, which can come back to life, advert a danger, be easy to implement with low cost and be well worth studying futher and promoting the application. The concrete manipulation of the moxibustion treatment are garlic separated moxibustion, direct moxibustion, mori moxibustion and so on.

Brief summary on ancient moxibustion for treatment of fabei / 中国针灸

To formulate the theory and experiences of physicians of successive dynasties on moxibustion for treatment of fabei, the medical cases and theory of ancient physicians are analyzed. It is found that moxibustion treatment has unique efficiency on fabei, which can come back to life, advert a danger, be easy to implement with low cost and be well worth studying futher and promoting the application. The concrete manipulation of the moxibustion treatment are garlic separated moxibustion, direct moxibustion, mori moxibustion and so on.