ABSTRACT
Objective:Screen out the antitumor constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma base on system pharmacology with chemical constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma as study objects, in order to provide the theoretical basis for the development of antitumor and nontoxic activities of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma. Method:The small molecule ligand library of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma was built based on Traditional Chinese Medicine Systems Pharmacology(TCMSP), energy of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma was matched with the key protein targets of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signal pathway by molecular docking (SYBYL2.1, Tripos), the Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma-targets network model was established based on Cytoscape 3.5.1, and the physicochemical properties of the antitumor activity in Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma were predicted by using SwissADME and admetSAR. Result:There were 25 small molecule constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma. Through the energy match, key antitumor constituents of Pinelliae Rhizoma were gondoic acid, 10,13-eicosadienoic, baicalin, 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid. Key antitumor constituents of Aconiti Lateralis Radix Praeparata were deltoin, sitosterol, neokadsuranic acid B, 11,14-eicosadienoic acid. Phosphatidylinositol 3-kinase (PI3Kα), phosphatase and tensin homolog deleted on chromosome ten (PTEN), phosphoinositide dependent protein kinase 1 (PDK1) were key antitumor targets of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma. There were 8 key antitumor constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma, which had a low CYP450 inhibition and basically followed the Lipinski rule. Conclusion:Antitumor nontoxic constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma and key targets are screened out from the molecular level, which provides the new ideas for the effective use of nontoxic traditional Chinese medicine(TCM) and breaks the restrictions in using nontoxic TCM.
ABSTRACT
Objective Diminished ovarian reserve (DOR) severely affects the life of women and the estrogen replacement therapy for it has obvious adverse effects. This article aimed to study the effect of polygoni multiflori radix preparata (PMRP) on DOR in rats and provide a therapeutic option for clinical medication. Methods Sixty female SD rats were randomly divided into six groups of equal number,normal control,DOR model control,high-dose PMRP (4 g/kg),medium-dose PMRP (2 g/kg),low-dose PMRP (1 g/kg),and positive control. The DOR model was established by gavage of tripterygium glycosides as 75 mg/kg every morning,followed by administration of PMRP in the PMRP groups,Estradiol valerate at 0.18 mg/kg in the positive control group and distilled water in the model control group in the afternoon,all for 30 consecutive days. The estrous cycle of the rats was observed,the levels of serum estradiol (E2),follicle-stimulating hormone (FSH),luteinizing hor-mone (LH),anti-Müllerian hormone (AMH) and inhibin-B (INH- B) were determined by ELISA,the ovarian and uterine indexes were obtained,and the ovarian morphology was observed by HE stai-ning,and the counts of follicles at different stages were recorded. Results Compared with the normal controls,the DOR model rats showed modeling time-related lengthening,irregularity and even disorder of the estrous cycle,with a few epithelial cells or keratino-cytes and leucocytes on the vaginal smear at 11-30 days. The estrous cycle was normal in the PMRP and positive control groups at 1-10 days and relatively prolonged at 11-30 days. In comparison with the normal control group,the DOR model rats exhibited a signifi-cantly decreased levels of serum E2 ([302.6±42.9] vs [155.7±46.8] pg/mL,P<0.05) and INH-B ([494.5±84.1] vs [299.2± 106.8] pg/mL,P<0.05) but increased levels of FSH ([7.2±0.5] vs [21.7±1.2] mIU/mL,P<0.05) and LH ([17.4±1.2] vs [25.0±1.0] mU/mL,P<0.05). The INH-B level was markedly elevated in the PMRP and positive control groups as compared with that in the DOR models (P<0.05). The counts of follicles and corpora lutea were remarkably lower in the DOR model rats (P<0.05) while that of developing follicles markedly higher in the PMRP and positive control groups than in the normal control group (P<0.05). The numbers of atretic follicles+corpora lutea were significantly increased in the high-dose PMRP group but decreased in the low-dose PMRP group (P<0.05) and positive controls (P<0.05). The counts of primordial and developing follicles were dramatically higher in the PMRP and positive control groups than in the DOR model controls (P<0.01) and so were the numbers of atretic follicles+corpora lutea in the high-and medium-dose PMRP groups (P<0.05). Conclusion Polygoni multiflori radix preparata can effectively protect the reproductive function of female rats by inhibiting tripterygium glycosides-induced toxicity to the ovary.
ABSTRACT
<p><b>OBJECTIVE</b>To optimize the different components proportions of the Realgar floating tablets for gastric retention by uniform design and correlation analysis.</p><p><b>METHOD</b>With the different dosage of hydroxypropyl methyl cellulose (HPMC) as the tablets frame matrix, uniform design and correlation analysis were used to optimize the best component proportions of formula, and to measure the dissolution of the tablets in vitro.</p><p><b>RESULT</b>Dissolution of the tablets in vitro was conformed to the expectation of experiment. The drug-release mechanism was by diffusion and corrosion at the same time.</p><p><b>CONCLUSION</b>The Realgar floating tablets for gastric retention achieved the goal of design, which demand sustained release and safety.</p>