Mechanism of Wuling Capsules against hepatic fibrosis based on network pharmacology and animal experiments / 中国中药杂志

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.

Determination of Rosmarinic Acid in Wuling Capsules by HPLC / 中国药师

Objective:To establish an HPLC method to determine the content of rosmarinic acid in Wuling capsules. Methods:The chromatographic column was Linksil-ODS (250 mm × 4. 6 mm,5 μm) with a gradient elution mode at the flow rate of 0. 8 ml· min-1,and the mobile phase was acetonitrile-water (32∶68) including 0. 5% acetic acid. The detection wavelength was 319 nm, the column temperature was 25 ℃ and the injection volume was 20 μl. Results: The linear range was 2-80 μg·ml-1 and the standard curve showed good linear regression within the range(r=0. 999 8). And the average recovery was 97. 07﹪ (n=6) with the inter-day precision (RSD) of 1. 35 %. Conclusion:The method is accurate and rapid with good reproducibility in the determination of ros-marinic acid in Wuling capsules, which can be used to control the quality of rosmarinic acid in Wuling capsules.

Influence of Wuling Capsules Combined with Calcitriol on Urine Marker Proteins in Early Diabetic Ne-phropathy / 中国药师

Objective:To observe the effect of Wuling capsules combined with calcitriol on urine marker proteins in early diabetic nephropathy ( DN) . Methods: Totally 64 patients with early DN were randomly divided into the control group and the observation group with 32 cases in each. The two groups were with appropriate diet and exercise, relatively stable protein intake and optimal hypo-glycemic program. The observation group was additionally treated with Wuling capsules (0. 9 g, po tid) and calcitriol 0. 25 μg,po qd, with the treatment course of eight weeks. The levels of FBG and 2hBG, HbA1c, hs-CRP, urinary protein, ALB, β2-MG and RBP were observed in the two groups before and after the treatment. Results:After the treatment, FBG, 2hBG, HbA1c, hs-CRP, total pro-tein, Alb and RBP in the two groups were improved when compared with those before the treatment, and the difference had statistical significance(P<0. 05). The total protein, ALB,β2-MG, RBP and hs-CRP in the observation group were better than those in the con-trol group after the treatment, and the difference was statistically significance (P<0. 05). Conclusion: Wuling capsules combined with calcitriol can effectively reduce glomerular and renal tubular damage in early DN patients.

Clinical Research of Lingdan Tablets and Wuling Capsules in the Treatment of Alopecia Areate / 中国药师

Objective:To analyze the clinical effect and safety of Lingdan tablets and Wuling capsules in the treatment of alopecia areate. Methods:Totally 84 patients with alopecia areate were divided into the observation group and the control group with 42 ones in each. Minoxidil tincture was used for external in the two groups. The control group were treated with 0. 9 g Lindan tablets, tid, for 4 months and the treatment group was additionally treated with 0. 99 g Wuling capsules,po,tid, for 4 months. The changes in the area and position of trichomadesis, light pull test, the tissue growth score and Pittsburgh Sleep Quality Index ( PSQI) score were compared before and after the treatment. Results:The efficacy of the observation group was better than that of the control group(P<0. 05). Af-ter the treatment, the evaluated indices in the two groups were lower than those before the treatment(P<0. 01), and the reduction of the observation group was more significant than that of the control group(P<0. 01) . There was no notable adverse reaction appeared in the observation group. Conclusion:Lingdan tablets and Wuling capsules can improve sleeping quality, promote the growth of halr and enhance the curative effect.

Pharmacokinetic of saikosaponin d in Wuling Capsules in mouse / 中成药

AIM To investigate the pharmacokinetic characters of saikosaponin d in Wuling Capsules in mouse. METHODS Wuling Capsules were given by irrigated (ig) administered to mouse, the blood plasma was collected at different time and the sample solution was prepared by extract adding amine sulfate and the mix fluid of acetonitrile-methyl alcohol (4∶ 1), the content of saikosaponin d was detected by RP-HPLC. The pharmacokinetic parameter was fitted by SIP7 software. RESULTS After ig administered the Wuling Capsules (5.5 g/kg) to mouse, the blood plasma concentration-time course fitted well to one compartment model with the 1st order absorption. The pharmacokinetic parameters of the first absoption in mouse was as following: Ka=2.34_ 1/h ,Ke=0.08_ 1/h ,T_ max =1.45_h,C_ max =83.81_ ?g/ml ,T_ 1/2Ke =7.9 h; and that of the second absorption was as following Ka=1.32_ 1/h ,Ke=0.08_ 1/h ,T_ max =6.48h,C_ Max =119.63_ ?g/ml , T_ 1/2 Ke =7.76 h. CONCLUSION The boipharmaceutics characters of saikosaponin d of Wuling Capsules were absorption slow and elimination was also slow.