Mechanism insight on licorice flavonoids release from Carbopol hydrogels: Role of "release steric hindrance" and drug solubility in the release medium.

The present study was to systematically evaluate different licorice flavonoids (LFs) compounds release behaviors from the single payload hydrogel and LFs extracts hydrogels based on the drug solubility in the release medium (DSRM), intermolecular strength of the hydrogel and the "release steric hindrance" (RSH). Two kinds of LFs (LFs 1: LFs 2 = 5:1, W/W) hydrogels were prepared with Carbopol 940 (CBP) as the thickener, and ten LFs single payload hydrogels were prepared according to the actual content in the LFs 1 extracts. The drug release mechanisms were confirmed by in vitro release experiments and molecular dynamic simulation analysis, and evaluated using novel indicators of ERLFs 1/Sin (the enhancement ratio (ER) of drug release percent of LFs 1-CBP hydrogel to the single payload hydrogel), ERLFs 2/ LFs 1 (ER of drug release percent of LFs 2-CBP hydrogel to LFs 1-CBP hydrogel) and ERrelease medium (ER of drug release percent in different release medium). We found that LFs 1-CBP possessed a significantly higher intermolecular strength and RSH than LFs 2-CBP, resulting in a higher viscosity, which had a positive correlation with the payload content and a negative correlation with the drug release percent. Therefore, the ERLFs 2/ LFs 1 values of ten LFs compounds were all higher than 1. For liquiritigenin and retrochalcone with higher DSRM, they displayed similar ERLFs 1/ Sin, ERLFs 2/ LFs 1 and ERrelease medium values (≈1). For formononetin, licoflavone A and licochalcone A with low DSRM, they exhibited ERLFs 1/Sin values >1. The low DSRM was the decisive factor to restrict their release from the single payload hydrogel. The presence of glycyrrhizin acid (GA) in the LFs could facilitate their release from the LFs extracts hydrogel. For isoliquiritin, isoliquiritigenin and glabridin with a lower content in the LFs extracts, they exhibited ERLFs 1/Sin values <1. The RSH predominantly restricted its release. The study provided guidelines for the reasonable design of LFs extracts hydrogel in pharmaceutical topical formulations.

[The preventive effects of one herbal compound on activities of myosin adenosine triphosphatase of muscle fibers and muscle atrophy in tail-suspended rat].

AIM: To study the effect of radix-astragali compound(RC) on muscle atrophy in tail-suspended rats. Muscle weight, fiber type distribution, cross-sectional area (CSA), and activity of myosin adenosine triphosphatase (ATPase) in rat soleus muscle were investigated. METHODS: The tail-suspended rats were subjected to a 14 days simulated weightlessness, during which period, RC or saltwater was given via intragastric instillation during tail suspension. The changes of soleus muscle weight were scaled by muscle-to-body weight ratio. The activities of myosin ATPase of muscle fibers were detected by method of Ca(2+) -ATPase. RESULTS: After a 14 days tail suspension it was found: in rats treated with RC, soleus muscle-to-body weight ratio rose by 33.33% (P < 0.01), both CSA of type I and II fiber drastically enhanced by(143.03%, P < 0.01; 83.25%, P < 0.01), the percentage of type I fiber significantly declined compared to the untreated rats. CONCLUSION: RC is able to effectively prevent muscle atrophy caused by tail suspension and restrain the increase in the myosin ATPase activities caused by simulated weightlessness.

Muscle composition after 14-day hindlimb unloading in rats: effects of two herbal compounds.

AIM: We studied the potential of two herbal compounds (HC-1 and HC-2) in different dosages (HC-1, containing ligustrazine; HC-2, containing radix astragali) as a countermeasure against muscle atrophy in a hindlimb unloading rat model. Soleus muscle weight, fiber type distribution, cross-sectional area (CSA), and myosin ATPase activity were measured. METHODS: Six rats each were assigned to a nine-group design: Control (CON); hindlimb unloading only (HLU); hindlimb unloading plus intragastric water instillation (HLU-W); and hindlimb unloading plus different dosages of instilled HC-1 (HLU-HC-1l, HLU-HC-1m, HLU-HC-1h) or HC-2 (HLU-HC-2l, HLU-HC-2m, HLU-HC-2h). RESULTS: As expected, in HLU and HLU-W, soleus muscle-to-body weight ratio and CSA of type I and II fiber went down, and myosin ATPase activity and the percentage of type II fibers went up, all compared with CON. Compared to untreated rats, high-dose HC-1 enhanced type I and II fiber CSA by 77% and 55%, respectively; myosin ATPase activity (type II fiber percentage) were lower, but soleus muscle-to-body weight ratio did not change. High-dose HC-2 enhanced soleus muscle-to-body weight ratio by 33%; and type I / type II fiber CSA by 143% and 83% above HLU-W values, respectively, and resulted in a slower myosin ATPase activity (corresponding to a lower type II fiber percentage). Low- to mid-dose HC-1 and HC-2 showed some preventive effects as well. CONCLUSION: HC-1 and HC-2 in proper dosages diminished muscle atrophy that otherwise occurs in simulated weightlessness.