Anti-oral common pathogenic bacterial active acetylenic acids from Thesium chinense Turcz.

Discovery of agents for oral infectious diseases is always encouraged in natural products chemistry. A bioassay-guided isolation led to the isolation of two new acetylenic acids (1, 2) along with seven known ones (3-9) from the ethanol extract of Thesium chinense Turcz, a commonly used oral anti-bacterial and anti-inflammatory herb. Their structures were elucidated on the basis of spectroscopic and chemical evidence. Exocarpic acid (3) demonstrated the most promising activity against three tested oral pathogenic bacterial strains, Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans, with minimum inhibitory concentration values of 0.86, 3.43, and 13.70 µg/mL, respectively. Compounds 1, 2, 4, 5 and 7 also showed potential activities against periodontal bacteria (P. gingivalis, F. nucleatum).

Survey on the Implementation of Preconception Care in Shanghai, China.

BACKGROUND: Recently, the Chinese government has promoted preconception care (PCC) to prevent birth defects. The objective of this study was to evaluate the implementation of PCC in Shanghai, China, following a 3-year municipal project providing 'Free Pre-pregnancy Health Evaluation Services' to 20 000 residents. METHODS: A retrospective questionnaire survey was undertaken among 12 309 pregnant women and 8997 of their partners during their initial prenatal visit in six hospitals with the most births in Shanghai. RESULTS: A total of 90% (n = 11 113) of the women and 87% (n = 7856) of the men were aware of PCC, and 40% (n = 4890) of the women and 35% (n = 3185) of the men had previously participated in PCC. Logistic regression showed that PCC participants were more likely to have a planned pregnancy, receive support from their partner for PCC services, were older, and have higher educational attainment and higher household incomes. Regardless of gender, there were significant differences between the participating and non-participating groups in terms of prepregnancy changes in lifestyle and behaviour, such as folic acid supplementation, smoking cessation (for men only), avoiding passive smoking, abstaining from alcohol/drugs, and rubella/hepatitis B immunity. CONCLUSIONS: The government-led efforts proved to be effective in promoting PCC participation and positive lifestyle and behavioural changes in couples of childbearing age. Future efforts should target couples who are young, poorly educated, and/or from low-income families. Strategies must ensure that the couples' knowledge of and positive attitudes toward PCC are translated into their practical participation in PCC.

Transcutaneous electrical nerve stimulation on acupoints relieves labor pain: a non-randomized controlled study.

OBJECTIVE: To investigate the efficacy of transcutaneous electrical nerve stimulation (TENS) on four specific acupuncture points Hegu (LI4), Neiguan (PC6), Danshu (BL19) and Weishu (BL21) for reducing pain in labor. METHODS: A total of 160 voluntary nulliparous women who were willing to receive TENS for analgesia were assigned to the treatment group after cervical dilation of more than 2 cm. Another 145 matched nullipara were recruited as the control group. Visual analogue scale (VAS) was used to assess the pain before and 0.5 h after the application of TENS. Then, VAS was assessed every one hour until delivery. Percentage of VAS score decreased by > 25% was the primary outcome, the delivery mode and neonatal outcome were measured as secondary outcomes. Adverse reactions were also recorded during TENS. RESULTS: The percentage of VAS score decreased by > 25% was 68.6% in the TENS treatment group. Maternal delivery mode and neonatal outcomes were not significantly different between the two groups. In addition, the incidence of postpartum hemorrhage in the TENS treatment group was less than the control group (P<0.05). There was no adverse reaction recorded with TENS on acupoints. CONCLUSION: As a novel and non-invasive approach, TENS on specific acupoints including Hegu (LI4), Neiguan (PC6), Danshu (BL19) and Weishu (BL21) was an effective method for analgesia in labor.

Effects of herbal products on the metabolism and transport of anticancer agents.

IMPORTANCE OF THE FIELD: Cancer patients on chemotherapy treatment often seek herbal therapies and this may alter the clearance of anticancer drugs. AREAS COVERED IN THIS REVIEW: Many anticancer drugs are metabolized by CYPs and are substrates of P-glycoprotein, breast cancer resistance protein and multi-drug resistance proteins. CYPs and drug transporters are subject to inhibition and/or induction by the herbal medicines used by cancer patients and the metabolism and pharmacokinetics of anticancer agents may be altered by herbal products. There are increased reports on the interaction of herbal medicines with anticancer agents. A clinical study in cancer patients reported that treatment of St John's wort at 900 mg/day orally for 18 days decreased the plasma levels of the active metabolite of irinotecan, SN-38, by 42%. In healthy subjects, treatment with St John's wort for 2 weeks significantly decreased the systemic exposure of imatinib by 32%. Induction and/or inhibition of CYPs and transporters is considered an important mechanism for these interactions. WHAT THE READER WILL GAIN: Potential interactions of herbal medicines with anticancer agents have become a safety concern in cancer chemotherapy. TAKE HOME MESSAGE: Further studies are warranted to investigate the efficacy and safety profiles of herbal medicines commonly used by cancer patients.

Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra.

Glabridin is a major constituent of the root of Glycyrrhiza glabra, which is commonly used in the treatment of cardiovascular and central nervous system diseases. This study aimed to investigate the role of P-glycoprotein (PgP/MDR1) in the intestinal absorption of glabridin. The systemic bioavailability of glabridin was approximately 7.5% in rats, but increased when combined with verapamil. In single-pass perfused rat ileum with mesenteric vein cannulation, the permeability coefficient of glabridin based on drug disappearance in luminal perfusates (P(lumen)) was approximately 7-fold higher than that based on drug appearance in the blood (P(blood)). Glabridin was mainly metabolized by glucuronidation, and the metabolic capacity of intestine microsomes was 1/15 to 1/20 of that in liver microsomes. Polarized transport of glabridin was found in Caco-2 and MDCKII monolayers. Addition of verapamil in both apical (AP) and basolateral (BL) sides abolished the polarized transport of glabridin across Caco-2 cells. Incubation of verapamil significantly altered the intracellular accumulation and efflux of glabridin in Caco-2 cells. The transport of glabridin in the BL-AP direction was significantly higher in MDCKII cells overexpressing PgP/MDR1 than in the control cells. Glabridin inhibited PgP-mediated transport of digoxin with an IC(50) value of 2.56 microM, but stimulated PgP/MDR1 ATPase activity with a K(m) of 25.1 microM. The plasma AUC(0-24h) of glabridin in mdr1a(-/-) mice was 3.8-fold higher than that in wild-type mice. These findings indicate that glabridin is a substrate for PgP and that both PgP/MDR1-mediated efflux and first-pass metabolism contribute to the low oral bioavailability of glabridin.

Quantitative analysis of 23-hydroxybetulinic acid in mouse plasma using electrospray liquid chromatography/mass spectrometry.

23-Hydroxybetulinic acid is a newly isolated derivative of betulinic acid. The agent exhibits potential anti-tumor activity and functions in this regard via apoptosis. In support of pharmacokinetic and toxicological evaluations, a new assay based on liquid chromatography/mass spectrometry (LC/MS) was developed for the quantitative analysis of 23-hydroxybetulinic acid. Sample preparation consisted of extraction of the plasma by the addition of methylene chloride followed by centrifugation. Aliquots of the supernatant were analyzed using an isocratic reversed-phase high-performance liquid chromatography (HPLC) system coupled to a negative ion electrospray mass spectrometer. Molecules of 23-hydroxybetulinic acid and the internal standard limonin were detected using selected ion monitoring at m/z 471 and 469, respectively. The limit of detection of 23-hydroxybetulinic acid was 0.05 pg (0.11 fmol) injected on-column (10 pg/mL, 5 microL injection volume), and the limit of quantitation was 10 pg (21.19 fmol, 2 ng/mL, 5 muL injection volume). 23-Hydroxybetulinic acid was stable in plasma samples at -20 degrees C for at least 3 weeks. The intra-day and inter-day coefficients of variation of the assay were 3.0 and 4.8%, respectively. The utility of the assay was demonstrated by measuring 23-hydroxybetulinicacid in mouse plasma following intragastric administration (IG) in vivo. Pharmacokinetic parameters were calculated using the 3P97 pharmacokinetic software package. A two-compartment, first-order model was selected for pharmacokinetic modeling. The result showed that after IG of 200 mg/kg 23-hydroxybetulinic acid, the plasma concentrations reached peaks at 2 h with C(max) of 3.1 microg/mL. The 200 mg/kg 23-hydroxybetulinic acid suspension IG doses were found to have long elimination half-lives of 25.6 h and low bioavailability of 2.3%. No interference was noted due to endogenous substances. These analytical methods should be of value in future studies related to the development and characterization of 23-hydroxybetulinic acid.

[Effects of Radix Salviae Miltiorrhizae on Ca2+ in hepatic stellate cells].

OBJECTIVE: To investigate the effects of Radix Salviae Miltiorrhizae (RSM) on intracellular free calcium in hepatic stellate cells (HSCs). METHODS: After the model of hepatic fibrosis was established in SD rats, RSM [20 ml/(kg x d)] was given via gastrogavage to the rats of treatment groups while the same volume of 0.9% NaCl was given to the rats of control groups twice a day for 6 consecutive days. Then the blood sample was drawn from the inferior vena cava, and the serum was extracted for pharmacological studies. After 24 h incubation with 10% drug serum, HSCs were loaded with Fluo-3/AM, a Ca2+ marker, and were observed with laser scanning confocal microscopy (LSCM). RESULTS: By comparison with controls, both RSM pharmacological serums decreased [Ca2+]i in HSCs significantly in the condition of using Ang II or not (P<0.05). CONCLUSION: RSM decreased [Ca2+]i in activated HSCs, which may be one of important ways to block liver fibrosis.

[Pharmacokinetics of oxymatrine and its metabolite in beagle dogs by LC-MS].

OBJECTIVE: To establish LC-MS method in the determination of oxymatrine and its metabolite in plasma and investigate their pharmacokinetics in beagle dogs. METHOD: Lichrospher C18 column (4.6 mm x 250 mm, 5 microm) was used as the analytical column maintained at 25 degrees C. The mobile phase consisted of 10 mmol x L(-1) CH3COONH4 and CH3OH (25:75). Flow rate was 1 mL x min(-1). Electrospray ionization (ESI) was carried out. The ESI ion source was set in positive ion polasity mode. The selective ion monitoring (SIM) was set at m/z 265.1 and 249.2. RESULT: The linearity ranged from 2 to 5000 ng x mL(-1) (r = 0.9991). The detection of oxymatrine and its metabolite were 0.6 and 0.3 ng x mL(-1). The RSD(%) within day and between day was less than 4.7%. The recovery of this method was more than 96.5%. The disposition was conformed to a two-compartment model. The T(1/2), Tmax, Cmax, MRT, AUC(0-->24 h) of oxymatrine were (5.5+/-1.58) h, (1.0+/-0.30) h, (2418.3 +/-970.78) ng x mL(-1), (3.2+/-0.64) h, (5797.4+/-908.16) ng x mL(-1) x h accordingly. The corresponding T(1/2), Tmax, Cmax, MRT, AUC(0-->24 h) of matrine were (9.8+/-2.77) h, (1.9+/-1.09) h, (1532.4+/-494.86) ng x mL(-1), (4.4+/-1.97) h, (5530.5+/-1042.65) ng x mL(-1) x h. CONCLUSION: This assay was highly sensitive, rapid, simple and specific enough for determining concentrations of oxymatrine and its metabolite matrine in plasma of beagle dog.

Clinical and experimental study of effect of Raondix Salviae Militiorrhiza and other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension.

AIM:To study the effects of Radix Salviae Militiorrhiza (RSM), other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension.METHODS:Portal pressure of cirrhotic dogs after chronic common bile duct ligation was measured directly; portal blood flow in patients with liver cirrhosis were detected by ultrasound Doppler.RESULTS:After administration of RSM and Radix Angelicae Sinensis (RAS) by intravenous infusion in cirrhosis dogs, the portal venous pressure (Ppv), wedge hepatic venous pressure (WHVP), hepatic venous pressure gradient (HVPG), were significantly decreased (P < 0.05-0.01), but the mean arterial pressure (MAP), and the heart rate (HR) remained unchanged. When nifedipine was used, Ppv, WHVP, MAP and HR were significantly decreased (P < 0.05), and the MVPG unchanged (P > 0.05). After administration of RSM, RSM+nifedipine and RSM+Hirudin+Nifedpin for 10-12 weeks, the diameter of portal vein (Dpv), spleen vein (Dsv), the portal venous flow (Qpv) and splenic venous flow (Qsv) in patients with hepatic cirrhosis were significantly lowered (P < 0.05-0.01), and the effect of RAS was weaker.CONCLUSIONS: The efficacy of decreasing Ppv by Chinese herbs RSM, RAS, etc. as compared with nifedipine, demonstrated that the Chinese herbs were slower in action than that of nifedipine, but more long-lasting and without side effects. Hence, long-term administration of Chinese herbs, would be more beneficial.