Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

Rapid characterization of the absorbed chemical constituents of Tangzhiqing formula following oral administration using UHPLC-Q-TOF-MS.

Tangzhiqing formula, a Chinese herbal formula, is used for the treatment of type II diabetes and prediabetes. Although its effectiveness has been certified by clinical use, its absorbed chemical constituents are not comprehensively represented. Thence, in order to reveal potential bioactive components and metabolism of Tangzhiqing formula, an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry method was developed. A total of 86 absorbed components, including 38 prototype compounds and 48 metabolites, were identified in rat plasma, urine, and feces after oral administration of Tangzhiqing formula. This was the first systematic study on the chemical constituents and metabolic profiling of Tangzhiqing formula. The results indicated that alkaloids and flavonoids were main absorbed components, and glucuronidation and sulfation were the major metabolites. Moreover we concluded that alkaloids and flavonoids first underwent demethylation and hydrolysis reactions before biotransformed to phase II metabolites. This study provided valuable data for safety estimation of Tangzhiqing formula, which will be advantageous for clinical application.

[Absorption of aqueous extracts from Salviae Miltiorrhizae Radix et Rhizoma by everted intestinal sac method].

To study the absorptive characteristics of aqueous extracts from Salviae Miltiorrhizae Radix et Rhizoma by in vitro rat everted intestinal sac model. Three representative ingredients in aqueous extracts from Salviae Miltiorrhizae Radix et Rhizome--protocatechuic aldehyde (PAL), posmarinic acid (RA) and salvianolic acid B (SAB), were selected as the study objects. An UPLC method was established to determine and measure their cumulative absorption amount, in order to explain the absorption characteristics of ingredients in different intestinal sections. According to the experimental result, RA and SAB showed the passive absorption in ileum, which conformed to the first-order absorption rate; with low and medium doses, they showed a zero-order absorption rate in jejunum, which was reflected in the coexistence of both positive and passive absorptions; PAL showed a passive absorption manner both in ileum and jejunum. According to the experiment for absorption in different intestinal sections, RA and SAB were mainly absorbed in jejunum, while PAL was absorbed mainly in ileum. All of the three ingredients in aqueous extracts from Salviae Miltiorrhizae Radix et rhizome--PAL, RA and SAB could be absorbed in intestines, but with differences in the absorption rate and mechanism, which indicated that the intestinal absorption of aqueous extracts from Salviae Miltiorrhizae Radix et rhizome was selectivity, instead of a simple semi-permeable membrane penetration process.

[Progress of mesoporous silica nanoparticles in targeting drug delivery system of antitumor drug].

Currently, chemotherapy is one of the main therapy for cancer. But the traditional antitumor drugs are systemic distribution in vivo, they are difficult to achieve an effective drug concentration in the tumor tissue and don't have the ability to distinguish normal cells and tumor cells by themselves, that cause systemic toxicity easily and can not meet the clinical needs. With the research on mesoporous silica nanoparticles (MSNs) deepening, more and more attention in the drug delivery system have been payed to in recent years, because of its unique physicochemical structure characteristics, it has the effect on specific targets, directly inhibits the tumor cell growth, reduces the side effects to normal cells, tissues and organs and can be long-term medication, etc. It is expected to be excellent carriers of antitumor drugs. MSNs application in the field of cancer treatment has now become a hot research field of medicine. In this paper, the latest research about MSNs in antitumor drugs targeting delivery system from 2008 to 2015 is summarized, including the application of MSNs separately in antitumor drug targeting, passive targeting, active targeting, physical or chemical conditions response targeting and other compound targeting drug delivery system. We expect it to provide a reference to the toxicity reducing and efficacy enhancing and further development of chemical medicine, natural medicine and monomeric compound of chinese herbal medicine.

[Effects of Ca2+ on photosynthetic parameters of Pinellia ternata and accumulations of active components in heat stress].

OBJECTIVE: To study the effect of exogenous Ca2+ on photosynthetic parameters of Pinellia ternate and accumulations of active components under high temperature stress. METHOD: The pigment contents of P. ternata leaves, photosynthesis parameters and chlorophyll fluorescence parameters of P. ternata leaves, the contents of guanosine, adenosine and polysaccharide in P. ternata tubers were measured based on different concentrations of exogenous Ca2+ in heat stress when the plant height of P. ternata was around 10 cm. RESULT: The contents of total chlorophyll and ratio of chlorophyll a/b were relatively higher by spaying Ca2+. Compared with the control, spaying 6 mmol x L(-1) Ca2+ significantly enhanced the net photosynthetic rate (Pn), transpiration (Tr) and stomatal limitation (L8), but reduced intercellular CO2 concentration (C) in P. ternata leaves. With the increase of Ca2+ concentration, maximal PS II efficiency (Fv/Fm), actual photosynthetic efficiency (Yield) and photochemical quenching coefficient (qP) initially increased and then decreased, however, minimal fluorescence (Fo) and non-photochemical quenching coefficient (NPQ) went down first and then went up. The contents of guanosine and polysaccharide and dry weight of P. ternata tubers showed a tendency of increase after decrease, and the content of adenosine increased with the increase of Ca2+ concentration. The content of guanosine and polysaccharide in P. ternata tubers and its dry weight reached maximum when spaying 6 mmol x L(-1) Ca2+. CONCLUSION: With the treatment of calcium ion, the inhibition of photosynthesis and the damage of PS II system were relieved in heat stress, which increased the production of P. ternata tubers.

[Indirect and direct effects of absorption components of composite for activating blood and removing stasis on coronary microvascular dysfunction and myocardial cell apoptosis].

It has been found that in case of targeted for coronary microvascular dysfunction and myocardial cell apoptosis, the anti-apoptosis effect of Guanxin No. 2, a Chinese herbal composite for activating blood and removing stasis (ABRS), is identical to that of its three absorption components (ferulic acid, Danshensu and hydroxylcarthamin yellow), and there exists a dose/myocardial flow-dependent direct or indirect acting path. Based on which, a hypothesis regarding the dose/myocardial flow related direct/indirect action of Chinese ABRS composite, with the same targets as before, was put forward by the authors in this paper, that is, the myocardial protective effect of acute high dose administration of the composite is acted through indirectly path by increasing the myocardial flow (MF); while that of chronic low dose administration is realized directly without change of MF. The evidence and significance of this hypothesis were discussed.

Pharmacokinetic comparison of puerarin after oral administration of Jiawei-Xiaoyao-San to healthy volunteers and patients with functional dyspepsia: influence of disease state.

OBJECTIVES: An investigation has been designed and conducted to compare the pharmacokinetics of puerarin after oral administration of Jiawei-Xiaoyao-San to healthy volunteers and to patients with functional dyspepsia. METHODS: Quantification of puerarin in serum was achieved using a simple and rapid HPLC method for pharmacokinetic study. KEY FINDINGS: After oral administration of decoctions of Jiawei-Xiaoyao-San to healthy volunteers and patients with functional dyspepsia, puerarin was absorbed and reached a maximum concentration of 56.47+/-15.60 and 29.40+/-8.89 ng/ml at 51.00+/-8.22 and 50.00+/-12.25 min, respectively. Compared with the value of AUC0-360 (5.55+/-1.47 microg/ml min) in healthy volunteers, a smaller value of AUC0-360 (3.35+/-1.17 microg/ml min) was observed in patients with functional dyspepsia. CONCLUSIONS: There were statistically significant differences in the pharmacokinetic parameters of puerarin including the values for Cmax, AUC0-360, Cl/F and MRT0-360 between healthy volunteers and patients with functional dyspepsia. The pharmacokinetic parameters showed that functional dyspepsia reduced the absorption of puerarin after oral administration of Jiawei-Xiaoyao-San.

Cardioprotection by Guanxin II in rats with acute myocardial infarction is related to its three compounds.

AIM: We tested the hypothesis that cardioprotection afforded by traditional Chinese Guanxin II (GXII) formula is related to absorbed bioactive compounds (ABCs). METHODS: Sprague-Dawley rats with acute myocardial infarction (AMI) were induced by coronary occlusion. ABCs including ferulic acid (F), hydroxyl safflor yellow A (A), tanshinol (T), protocatechualdehyde (P) and paeoniflorin (E) were measured in blood after oral GXII. The effects of GXII and FATPE, alone and in combination, and of some components of FATPE on infarct size, myocardial apoptosis and caspase-3 activity were determined. Myocardial blood flow (MBF) in AMI rat was detected 2h after oral GXII and FAT. RESULTS: FATPE was found in rat blood. FAT was similar to FATPE and GXII in decreasing infarct size, myocardial apoptosis and caspase-3 activity of AMI. Both FAT and GXII were similar in increasing of MBF. CONCLUSION: GXII and FAT protect the heart from ischemic injury by increasing MBF, and decrease infarct size by inhibiting myocardial apoptosis and caspase-3 activity. These findings provide a potential cardioprotective cocktail.

[Analysis of prescription for special disease/syndrome--compatibility of absorbed/metabolized components from original formula--a thinking of research].

What is the pharmacodynamic active components in Chinese medical prescription is a key problem in urgent need to solve for the development of traditional Chinese medicine (TCM). A new thinking of TCM research, "analysis of prescription for special disease/syndrome--compatibility of absorbed/metabolized components from original prescription", was proposed firstly, to analyze and seek out the components or metabolites originated from the administered prescription in blood serum of the organisms with special disease and syndrome. Secondly, to study the compatibility of these absorbed/metabolized components. Then, using a homogeneous design to find out the contribution of each component to the effectiveness of the prescription, eliminate the irrespective or contra-orientation effected components, so as to form the best combination of various components for the prescription with the optimal therapeutic efficacy. By this way, the validity of the prescription with new formed combination could be ensured, not only the predominance and characteristic of combined utilization of traditional Chinese drugs be retained, but also the pharmacodynamic components of the refined prescription be identified, a new prescription with clear pharmacodynamic constitution be obtained and the dispensing relation among various components be explained clearly and quantitatively.

[Mechanism of Shenqi compound recipe anti-earlier diabetic artherosclerosis in GK rats].

OBJECTIVE: To explore the mechanism of Shenqi compound recipe (SQCR) anti-earlier diabetic artherosclerosis in GK rats. METHOD: Four-month specefic pathogen free (SPF) GK rats were divided randomly according to blood glucose level into four groups: model group (5 mL x kg(-1) x d(-1) sterile water), ramipril group (positive control, 1 mg x kg(-1) x d(-1)), SQCR low dosage (0.72 g x kg(-1) x d(-1)) and SQCR high dosage group (2.88 g x kg(-1) x d(-1)) and Wistar rats as normal control group(5 mL x kg(-1) x d(-1) sterile water). GK rats took high-fat diet freely and meanwile were injected N-omega-nitro-L-arginine methyl ester (L-N-AME) intra-peritoneally with the dose of 10 mg x kg(-1) x d(-1) in order to induce earlier diabetic artherosclerosis, while normal control group took regular diet and were injected normal saline intra-peritoneally. In the experiment periods, each group was administrated correspondent substance respectively for 32 d. At the end, sampling blood by abdominal aorta and picking aorta on ice. Determined monocyte chemoattractant protein-1 (MCP-1) concentration by ELISA, messenger ribonucleic acid (mRNA) expression of MCP-1 and peroxisome proliferator-activated receptor gamma (PPARgamma) in aorta by reverse transcriptase PCR (RT-PCR). RESULT: Concentrations of MCP-1 in serum in SQCR low and high dosage groups and the mRNA expression of MCP-1 in SQCR high dosage group were all decreased significantly compared with model group (P < 0.05). The mRNA expression of PPARgamma in SQCR low and high dosage groups all increased compared with model group (P < 0.05 or P < 0.01). CONCLUSION: Inhibiting the mRNA and protein expression of MCP-1 and upregulating the mRNA expression of PPARgamma in aorta might be contribute to SQCR anti-earlier diabetic artherosclerosis in GK rats partly.

[Effects and mechanism of ShenQi compound recipe on inflammation maker in GK rats].

OBJECTIVE: To explore the effects and mechanism of ShenQi Compound Recipe on inflammation maker of type 2 diabetes mellitus in GK rats. METHODS: Rats were ranodmly divided into Model group, Ramipril group (positive control, 1 mg/kg x d), SQCR low dosage (0.72 g/kg x d), SQCR high dosage group (2.88 g/kg x d) and Wistar control group. Each group was administrated correspondent substance respectively for 32 days. Determined C-reactive protein (CRP) by ELISA and tumour necrosis factor (TNF)-alpha by radioimmunassay. The mRNA expression of nuclear factor (NF)-kappaB p65 in aorta was determined by real time RT-PCR, and activation of it using immunohistochemistry staining. RESULTS: Concentrations of CRP and TNF-alpha in serum and the expression of mRNA and activation of NF-kappaB were all decreased in SQCR low and high dosage groups compared with model group (P < 0.05 or P < 0.01). CONCLUSION: These results suggest that SQCR can decrease the level of inflammation maker in serum, which may be resulted from reducing the mRNA expression and activation of NF-kappaB.

[Effects of bushen huoxue recipe on proliferation, differentiation and mineralization of osteoblasts in rats].

OBJECTIVE: To observe the effects of bushen huoxue recipe (BHR) on cell proliferation, differentiation, maturation and mineralization in osteoblasts of rats cultured in vitro. METHODS: Osteoblasts from cranium of newborn SD rats were cultured by collagenase method. MTT, PNPP and ARS were used to observe the proliferation, activity of alkaline phosphatase (ALP) and the formation of mineral node of cultured osteoblasts effected by different concentrations of BHR at different time points (24, 48, 72 hrs after medication). RESULTS: Different concentrations of BHR could enhance the cell proliferation rate and ALP activity, the effects of BHR in high and moderate concentration were more significant in enhancing the cell proliferation rate (P < 0.01). And the number of mineral node of cultured osteoblasts treated by high and moderate concentration BHR was much more than that of the untreated osteoblasts (P < 0.01). CONCLUSION: BHR could promote the proliferation, differentiation, and mineralization of the osteoblasts.