Sponsored by Chinese Pharmaceutical Association
ISSN 0513-4870 CN 11-2163/R
12 issues per year
Discipline(s): Medical Science
Current Issue: Issue 02, 2019
Acta Pharmaceutica Sinica, Launched in July 1953, it is supervised by China Association for Science and Technology and sponsored by Chinese Pharmaceutical Association. Its editorial board is composed of 120 well-known pharmaceutical experts at home and abroad, including 9 academicians, 9 foreign member experts. It is devoted to original research articles on pharmaceutical sciences including pharmacology, toxicology, pharmacy, pharmacognosy, antibiotics, chemistry of natural products, pharmaceutical chemistry and pharmaceutical analysis. Research articles, communications, reviews and commentaries introducing new theories and technologies. Readers of Acta Pharmaceutica Sinica are mainly those involved in scientific research and those pertaining to higher education. The journal is included in CA, JST, Pж(AJ), CSCD.
Sang Guowei;Zhou Tonghui
Bi Kaishun;Chen Shilin
Chen Kaixian;Ding Jian
Guo Zongru;Jiang Jiandong
Yang Baofeng;Yu Dequan
Zhang Qiang;Zheng Ailian
Beneficial effect of nanosuspension of honokiol in mice on high fat diet through suppression of hepatic gluconeogenesis
Vol 54,No. 02
To investigate the potential hypoglycemic effect of honokiol nanosuspension and explore the underlying mechanisms, C57BL/6J mice were divided into the following five groups: normal diet (ND), high fat diet (HFD), HFD/honokiol-sodium carboxymethyl cellulose (CMC-Na) (Hono-CMC, 100 mg·kg −1), HFD/honokiol nanosuspension (Hono-Nano, 80 mg·kg −1), and HFD/metformin (HFD/Met, 200 mg·kg −1). Fasting blood glucose (FBG) and fasting body weight (FBW) of mice were measured every seven days. After 30-day treatment, an oral glucose tolerance test (OGTT) was performed, and blood and tissue samples were collected for analysis. All animal experiments were approved by the Animal Ethics Committee of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. The data showed honokiol nanosuspension and metformin reduced FBG and FBW, and significantly improved OGTT of mice compared with the HFD group ( P < 0.05). CMC-Na suspension of honokiol had no significant impact on FBG and FBW of mice, while OGTT of mice was improved by CMC-Na suspension of honokiol ( P < 0.05). Meanwhile, serum insulin levels in the administration groups had no significant difference from that in the HFD group, and serum glucagon levels were significantly decreased compared with that in the HFD group ( P < 0.05). Western blotting result revealed that honokiol up-regulated the levels of p-AMPK and p-FOXO1 in liver tissues of HFD mice ( P < 0.05), which resulted in activation of AMPK and inhibition of FOXO1. Moreover, the expression of PEPCK (a key enzyme of gluconeogenesis) was decreased by honokiol ( P < 0.05). In summary, our findings demonstrated that nanosuspension of honokiol was more effective than CMC-Na suspension of honokiol in blood glucose controlling in HFD mice. The hypoglycemic effect of honokiol might rely on suppressing hepatic gluconeogenesis via activating AMPK and inhibiting FOXO1.
Vol 54,No. 02
Nifedipine, a calcium channel antagonist, is metabolized mainly by CYP3A4 to dehydronifedipine. A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine nifedipine and dehydronifedipine in human plasma using d6-nifedipine/ d6-dehydronife‐dipine as internal standards. After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on a Hypersil Gold C 18 (50 mm × 2.1 mm, 1.9 μm). The mobile phase consisted of methanol and 5 mmol·L −1 ammonium acetate aqueous solution (0.1% formic acid). Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 347.3→254.1 for nifedipine, m/z345.2→283.9 for dehydronifedipine, m/z 353.3→257.1 for d6-nifedipine, and m/z 351.2→286.9 for d6-dehydronife‐dipine. The method had a linear calibration curves over the concentrations of 0.10–80.0 ng·mL −1 for nifedipine and 0.050–40.0 ng·mL −1 for dehydronifedipine. The validated LC-MS/MS method has been successfully used to study pharmacokinetic interactions of apatinib (CYP3A4 inhibitor) and nifedipine (CYP3A4 substrate) in human. This clinical trial was approved by the society of ethics and conducted in the first hospital of China Medical University.
Differential mechanism of toxicity in normal and blood-stasis mice following Rhizoma Curcumae exposure based on “YOU-GU-WU-YUN” theory
Vol 54,No. 02
We were interested in ascertaining differences in developmental neurotoxicity in normal and blood-stasis pregnant mice administered orally with Rhizoma Curcumae (RC) and the underlying molecular biology mechanisms of any differences. To answer these questions, a blood stasis model was induced by their immersion in ice water. C57BL/6 mice with blood stasis, normal C57BL/6 mice, Nrf2 knock out (KO) mice with blood stasis were randomized into control groups and RC exposure groups. The pregnant mice were administered with RC during pregnant days 5–18. The neurodevelopment reflex was examined by the positive occurring time of avoidance precipice reflex tests. Measurement of glutathione (GSH) in brain of the offspring was performed by colorimetric assays. Transcription factor NF-E2-related factor 2 (Nrf2), glutamate cysteine ligase catalytic subunit (GCLc), and glutamate cysteine ligase modifier subunit (GCLm) mRNA and protein expression in brain of the offspring were examined by real-time RT-PCR and Western blot, respectively. All animal care and experiments procedures were reviewed and approved by the Animal Care and Use Committee of Qiqihar Medical College. Our results demonstrated for the first time evidence that RC (10.0 g·kg −1) extended the positive occurring time of avoidance precipice reflex tests of offspring mice as compared with that in the normal control group ( P < 0.05). We could not find any significant change in positive occurring time of avoidance precipice reflex of blood-stasis pregnant mice offspring as compared with that in the normal control group ( P > 0.05). Compared with the normal control group, levels of glutathione, mRNA and protein expressions of Nrf2, GCLc, and GCLm were significantly increased in brain of the offspring of blood-stasis pregnant mice (all P < 0.05). However, offspring of mice treated with RC (10.0 g·kg −1) did not experienced significant changes (all P >0.05). Knock out Nrf2 based on CRISPR/Cas9 extended the positive occurring time of avoidance precipice reflex tests of offspring of blood-stasis pregnant mice ( P < 0.05). In conclusion, developmental neurotoxicity of RC to the blood-stasis pregnant mice offspring was weaker than that to the normal pregnant mice offspring. Cold-induced Nrf2 activation played an important role in “YOU-GU-WU-YUN” phenomenon of RC.
Vol 54,No. 02
A mouse model of cholestatic liver fibrosis was established by bile duct ligation (BDL) method. The effect of ginsenoside Rg1 in the disease progress and the mechanism of cholestatic liver fibrosis are investigated in this mouse model. All animal experiments in this paper have been approved by the Unit Ethics Committee. Analysis of serum biochemical indicators and pathological sections assessed liver function, liver damage and fibrosis in mice. Immunohistochemistry and Western blot assays were used to detect vascular cell adhesion molecule-1 (VCAM-1) in BDL-induced mice. Nuclear factor- κB (NF- κB) and inflammatory factors were detected to investigate related mechanism of Rg1. The results showed that expression of VCAM-1 was up-regulated and peaked on the 7th day, followed by decreased expression, but still efficiently expressed as compared to that in the sham-operated group. Compared with the model group, 40 mg·kg −1·d −1 Rg1 reduced serum aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin (T. Bili) levels ( P < 0.05 or P < 0.01) and liver function damage, alleviated BDL-induced liver fibrosis, significantly down-regulated the expression of VCAM-1 ( P < 0.05), and inhibited the inflammatory response. In addition, Rg1 significantly reduced NF- κB p65 level in the cellular nucleus ( P < 0.05). This study demonstrates that VCAM-1 is dynamically altered during BDL-induced liver fibrosis. Rg1 could dampen inflammation and alleviate cholestatic liver fibrosis via regulation of the NF- κB/VCAM-1 pathway. The results provide an experimental basis for Rg1 application for treating liver fibrosis.
Vol 54,No. 02
This study offers preliminary insight into the phytoestrogen activity and mechanism of rehmapi‐crogenin. In this study, we characterized the estrogenic activity of rehmapicrogenin using immature female mice in vivo and MCF-7 cell proliferation assay in vitro. All the procedures for the care of the mice were conducted in accordance with the Regulations of Experimental Animal Administration issued by the State Committee of Science and Technology of the People’s Republic of China. Uterine wet weight/body mass ratios, Western blot assay for estrogen receptor, and serum estrogen levels of estradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were investigated. The effects of rehmapicrogenin, and the estrogen receptor antagonist ICI182, 780, the estrogen receptor alpha antagonist MPP, the estrogen receptor beta antagonist THC, the G-protein coupled receptor 30 antagonist G15 combined with rehmapicrogenin on cell proliferation were examined in MCF-7 cells. Rehmapicrogenin (50 mg·kg −1) treatments demonstrated significant estrogenic activity by promoting the development of uterus in immature female mice, as well as increasing the expression of estrogen receptor alpha (ER α) and G-protein coupled receptor 30 (GPR30) at the protein level in uterus, and decreasing FSH and LH compared with the control group. Meanwhile, rehmapicrogenin (6 and 8 μmol·L −1) promoted the proliferation of MCF-7 cells, which were significantly antagonized by ICI182, 780, MPP and G15. This study demonstrates rehmapicrogenin exerts estrogenic effects through ER α and GPR30.
Vol 54,No. 02
To investigate the effect of scutellarin (Scu) on diabetic cardiomyopathy in mice, type 2 diabetes mellitus was induced by intraperitoneal injection of 50 mg∙kg −1 streptozotocin (STZ) into a high-fat diet. Scu was injected intraperitoneally. After 8 weeks, fasting blood glucose and serum biochemical parameters were measured. Masson staining was performed on myocardial tissue. The expression levels of Nrf2, NFκB, AKT and p-AKT in myocardium of mice were observed by Western blot. All the procedures were approved by the Laboratory Animal Ethics Committee of the Peking Union Medical College. The results showed that Scu significantly decreased the heart-body ratio, increased myocardial contractile function, decreased the level of myocardial fibrosis and the expression of collagen Ⅰ and collagen Ⅲ in myocardium of diabetic mice. Scu can effectively reduce the levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA) in serum of diabetic mice, increase the level of antioxidant enzymes in serum, and inhibit the release of inflammatory factors. Further studies showed that Scu significantly increased Nrf2 nuclear translocation, inhibited NFκB nuclear translocation and increased AKT phosphorylation. It indicates that Scu has significant effect on diabetic cardiomyopathy in mice.
Feasibility exploration of discriminating red yeast rice for different applications by secondary metabolite fingerprints
Vol 54,No. 02
Though red yeast rice (RYR)has been used as medicine for centuries, few study has been reported about its biological activities related to traditional medicinal application and marketed RYR showed poor consistency in quality. In this study, with comprehensive investigation of their production processes and field acquisition samples including those from genuine producing area, an ultra performance liquid chromatographic (UPLC) method was established for the first time to discriminate RYR for different applications based on their secondary metabolites fingerprint. It was performed on a CAPCELL CORE AQ column (100 mm × 4. 6 mm, 2. 7 μm), with PDA (range: 200–650 nm, extracted: 237 nm) and ELSD detection. The mobile phase used was water (A) and acetonitrile (B)both containing 0. 1% formic acid at gradient elution (0–15 min, 50% B→85% B (linear); 15–16 min, 85 % B→50% B (linear) and maintained until 21 min), with a flow rate of 0. 5 mL∙min −1. The method established was fully validated in agreement with guidelines of Chinese Pharmacopeia. Common metabolites were found in RYR for same application and the fingerprints of RYR for food coloring or brewing from various manufacturers had similarities above 0. 90. Meanwhile, significant differences were observed among the fingerprints for various applications and discrimination could be achieved by principal component analysis (PCA). Lovastatin was absence in RYRs for food coloring or brewing, and the fingerprint of traditional medicinal RYR was similar to that of RYR for brewing. However, standardization was required for RYR containing lovastatin because of their significant differences from various manufacturers in fingerprints and lovastatin content. The results demonstrated the feasibility to discriminate RYR for different applications by the secondary metabolites fingerprint method established in this study, which provides a scientific basis to investigate the relationship between biological activities of medicinal RYR and their corresponding secondary metabolites, and further aid their quality standardization and improvement.
Vol 54,No. 02
In order to determine the difference in structure and optimal isolation conditions of Glycyrrhiza uralensis endophytic fungi from different habitats, plate-separation method was used to identify endophytic fungi in G. uralensis from Gansu, Ningxia, Inner Mongolia, Xinjiang, and Beijing. The isolation parameters were defined by investigating various concentration gradients and sterilization time of NaClO solution. The strains were identified with morphological and molecular biological methods. The results showed that 5% NaClO solution and sterilization time of 5 min were the optimal surface sterilization conditions. Among the 129 strains of G. uralensis from five habitats, 438 strains of endophytic fungi were isolated and belonged to 11 species in 7 genera of 5 orders. Among them, 4 taxa were firstly isolated from the G. uralensis in China. Fusarium was a common genus among the five regions. There was difference in the composition and structure of the endophytic fungi of G. uralensis from different habitats. Diversity analysis showed that the endophytic fungus diversity in Gansu was the highest and that in Beijing was the lowest. The comprehensive analysis indicated that the endophytic fungi of G. uralensis were diverse, and there was difference in the number, composition, and population of endophytic fungi among the five habitats of Gansu, Ningxia, Inner Mongolia, Xinjiang, and Beijing.