Berberine is one of the most studied original natural drugs in China in recent years. It is a new lipid-lowering drug with completely different mechanism from statins, which has been used in the multi-center clinical trials. However, berberine is poorly absorbed in the intestinal tract after oral administration leading a significant pharmacokinetic characteristic of low blood concentration (1%) and bioavailability (< 5%). That is to say, it is difficult to explain the therapeutical effect in vivo by the current pharmacokinetic results. In fact, this phenomenon also exists in a number of clinically effective natural drugs. This review introduces the pharmacokinetic characteristic of berberine by focusing on the gut microbiota to mediate the metabolic process of berberine in vivo. Meanwhile, taking berberine as an example, we emphasized the important role of intestinal bacteria on the pharmacokinetic study on the oral chemical drugs, and put forward a new research mode of drug PK-PD mediated by the gut microbiota.

The study was designed to explore the influence of high-fat diet on the metabolism profile of feces and intestinal contents of golden hamster to provide new information for the mechanism of drug action. Twelve golden hamsters fed with high-fat diet and twelve golden hamsters fed with normal diet were used as model group and control group, respectively. Serum samples were collected from the normal group and the model group at 2 weeks, 4 weeks and 8 weeks after the induction of high-fat diet. Serum biochemical parameters were measured in the control and model groups. The levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels in model group were higher than the control group. After 8 weeks, the feces and intestine contents were taken. The intestine was divided into four sections:jejunum, ileum, cecum and colon. The changes of endogenous metabolites in intestinal contents were analyzed by ¹H NMR based metabolomics combined with multivariate statistical analysis to find the significant differences in metabolites. The metabolic profiles of hyperlipidemia model group and control group were significantly distinguished by the othorgonal partial least squares-discriminate analysis, (OPLS-DA). Compared with the control group, the endogenous metabolites in feces such as amino acids, fatty acids, tricarboxylic acid cycle intermediates and nucleotides related to intestinal microflora were changed significantly (P < 0.05), and the amino acid metabolites, protein spoilage products and choline metabolites in intestinal contents had significant changes (P < 0.05). The data suggest that the intestinal microflora plays an important role in the development of hyperlipidemia in golden hamsters from the molecular level of metabolites. This result provides useful information for the clinical treatment of hyperlipidemia and development of hyperlipidemia drug.

This study was designed to explore the intervention of muscle fatigue in rats with Astragali Radix using ¹H NMR metabolomics methods. The fatigue model was induced in rats by forced swimming plus food restriction, and the effects of Astragali Radix (3, 6 and 12 g·kg^-1) were investigated using the exhaustive time of rat swimming. After 3 weeks, the gastrocnemius was collected for ¹H NMR detection, and the anti-fatigue effects of Astragali Radix were explored using multivariate statistical analysis. Astragali Radix significantly improved the exhaustive swimming time of rats. Compared with control group, the levels of isoleucine, leucine, creatine, phosphatidylcholine, trimethylamine oxide, taurine, guanidinoacetate, AMP, inosine, histidine, hypoxanthine, anserine in rat gastrocnemius of model group were increased. While the levels of lactate, acetone, choline, glycerophosphocholine, glycine were decreased. These 6, 11, 5 potential biomarkers could be reversely regulated by treatment with Astragali Radix (high dose, middle dose, low dose), respectively. Metabolomics analysis revealed that Astragali Radix has a certain anti-fatigue effects and the mechanism may be related to regulation of amino metabolism.

Nobiletin is a kind of polymethoxyflavonoid with many pharmacological effects, such as antiinflammatory and antioxidation activities. This study was carried out to investigate the inhibitory effects of nobiletin on P-glycoprotein (P-gp) in vitro and in vivo. The molecular mechanism for structure-inhibition relationships of nobiletin with P-gp was investigated. Nobiletin exhibited significant inhibition (IC₅₀=2.21 μmol·L^-1) on P-gp in MDR1-MDCKⅡ cells. In the cell toxicity test, the paraquat-treated cell viability was decreased with nobiletin by inhibiting P-gp activity. In the rats PK study, the AUC_0-t of digoxin was increased 2.02 folds while the C_max of digoxin was increased 3.29 folds, when nobiletin was used in the pretreatment of SD rats. Molecular docking analysis elucidated that the formation of Pi-Pi bonds with Phe974 was the key factor for P-gp inhibition. The research findings provide important guideline for prediction of potential interaction between nobiletin and P-gp.

The chemical constituents of Sabia limoniacea var. ardisioides were investigated using chromatographic methods, such as silica gel, Sephadex LH-20 and preparative HPLC. Eight compounds were isolated and their structures were elucidated by spectral data and physicochemical properties, which were identified as 5-methoxy-1, 2-methylenedioxyl oxoaporphine (1), fuseine (2), N-p-feruloyltyramine (3), N-trans-coumaroyl tyramin (4), quercetin (5), rutin (6), mutabiloside (7), and protocatechuic acid (8). Among those, compound 1 is a new compound, compounds 2-8 were isolated from this plant for the first time.

Two novel Mannich base derivatives of silybin, SLB-DEA and DHSLB-PIP, were designed and synthesized. All the structures of new Mannich base derivatives of silybin were characterized by ¹H NMR and HR-MS. Their protective action against CCl₄-induced liver injury in mice were investigated. The changes of alanine aminotransferase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), total cholesterol (TC) and triglyceride (TG) were determined and the histopathological changes in liver tissues were examined. Pretreatment with a higher dosage of DHSLB-PIP (40 mg·kg^-1) prevented CCl₄-induced liver injury as indicated by the reduced levels of ALT, AST, LDH and TG. Meanwhile, liver histopathological improvement was observed in the model groups. The pharmacokinetics study in rats showed that the relative bioavailability of SLB-DEA and DHSLB-PIP were 172.5% and 259.8% compared with silybin. All the results suggest that SLB-DEA and DHSLB-PIP may protect liver against injury by CCl₄ and the relative bioavailability was significantly increased, which is worth of further investigation for their druggability.

The study was designed to investigate the effect of IMPDH1 gene polymorphism on the pharmacodynamics of mycophenolic acid in the renal transplant patients. 315 patients with renal transplantation were treated with triple immunotherapy (mycophenolic acid + tacrolimus + prednisone). The Agena MassARRAY assay was used to detect the IMPDH1 genotypes in patients above. The plasma drug concentration of mycophenolic acid (MPA) and its main metabolite mycophenolic acid glucuronide (MPAG) was detected by high performance liquid chromatography (HPLC). The correlation between IMPDH1 gene polymorphism (rs10954183, rs12536006, rs13242340, rs2278293, rs2288549) and rejection and postoperative infection in renal transplant recipients were analyzed by SPSS 21 software. The result showed that IMPDH1 rs2288549 GG is a risk factor for acute rejection after renal transplantation (P < 0.05), and IMPDH1 rs2278293 CT is a risk factor for infection after renal transplantation (P < 0.05). Above all, IMPDH1 rs2288549 is an important factor of acute rejection after renal transplantation, IMPDH1 rs2278293 is an important factor affecting the emergence of infection after renal transplantation. The SNPs may help to optimize clinical medication to reduce the incidence of adverse reaction.

HIV-1 reverse transcriptase (RT) plays an important role in HIV-1 life cycle. At present, the listed NRTIs and NNRTIs targeting the RT showed high efficiency as clinical first-line drugs. However, the rapid emergence of multidrug-resistant viruses and significant cumulative drug toxicities compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, there is an urgent demand for new types of RT inhibitors with novel mechanism of action to address this challenge. In recent years, additional inhibitors with novel mechanism of action have been reported, including nucleic acid competitive inhibitors, reverse transcriptase-directed mutagenesis inhibitors, primers/templates-competitive reverse transcriptase inhibitors, polymerase-RNase H inhibitors, reverse transcription initiation process inhibitors, peptide inhibitors etc., which have brought new hope to the development of novel anti-HIV drugs. This article focuses on the development of these inhibitors.

In this study, multivariate statistical analysis was applied to characterize the flowability of different types of microcrystalline cellulose (MCC), and the visualization of R language was used to explore the intrinsic correlation on its performances. To verify the operability of multivariate statistical analysis, we compared the results of the conventional methods such as repose angle method, Hausner ratio method, Carr's index method and the parameter a of Kawakita equation to determine whether there are significant differences between the conventional ones and multivariate statistical analysis. Moreover, the fillibility and compressibility were characterized by parameters 1/b of Kawakita equation and the means of pressure-tensile strength and compressibility curve method, respectively. The data was analyzed through R language for visualizing the correlation among the performance parameters of MCC. The flowability of the series of microcrystalline cellulose PH (MCCPH) were superior to the series of microcrystalline cellulose WJ (MCCWJ), the compressibility of MCCPH-302 was optimum, and the flowability and fallibility of MCCPH-102 were better than others. The results of conventional methods were consistent with multivariate statistical analysis. The fillibility was positively correlated with flowability, both negatively correlated with compressibility by analyzing correlation coefficient diagram, which was statistically significant (P < 0.01). It is reasonable that adopting multivariate statistical analysis to character the flowability of powders, which is more objective than the traditional approach. The correlation visualization of performance parameters of powders provides convenience for screening preparation material via the visualization of R language.

Shengmaiyin is widely used in the treatment of arrhythmia and has achieved a good effect. Due to the complexity of traditional Chinese medical formula, the pharmacological mechanism of Shengmaiyin in the treatment of arrhythmia is unclear. In this study, we used the internet-based Computation Platform (www.tcmip.cn) to explore the molecular mechanism. Shengmaiyin was found to treat the arrhythmia by modulating the pathway related to energy metabolism such as carbon metabolism, purine metabolism, carbohydrate metabolism, or by regulating the level of ATP. In this study, we find that the main active drug component in Shengmaiyin may be ginseng.