Deciphering the molecular mechanism of tetrandrine in inhibiting hepatocellular carcinoma and increasing sorafenib sensitivity by combining network pharmacology and experimental evaluation.

CONTEXT: The mechanism of tetrandrine (TET) in hepatocellular carcinoma (HCC) progression and sorafenib (Sora) chemosensitivity deserves investigation. OBJECTIVE: Using network pharmacology approaches to elucidate the mechanisms of TET in HCC. MATERIALS AND METHODS: CCK-8, colony formation, and flow cytometry assays were used to measure cell phenotypes. BALB/c nude mice were divided into Control, Sora (10 mg/kg), TET (50 mg/kg), and TET + Sora (10 mg/kg Sora plus 50 mg/kg TET) groups to evaluate the antitumor effects of TET for 21 days. Sora and TET were given by intraperitoneal injection or oral gavage. RESULTS: For SMMC7721 (IC50 = 22.5 µM) and PLC8024 (IC50 = 18.4 µM), TET (10, 20 µM) reduced colony number (0.68 ± 0.04- and 0.50 ± 0.04-fold, 0.56 ± 0.04- and 0.42 ± 0.02-fold), induced cell cycle arrest at G0/G1 stage (1.22 ± 0.03- and 1.39 ± 0.07-fold, 1.37 ± 0.06- and 1.55 ± 0.05-fold), promoted apoptosis (2.49 ± 0.26- and 3.63 ± 0.33-fold, 2.74 ± 0.42- and 3.73 ± 0.61-fold), and inactivated PI3K/AKT/mTOR signalling. Sora (10 µM) decreased cell proliferation, enhanced apoptosis, and inhibited PI3K/AKT/mTOR signalling, and these effects were further aggravated in the combination group. Activating PI3K/AKT/mTOR reversed the effects of TET on cell proliferation and Sora sensitivity. In the combination group, tumour volumes and weights were decreased to 202.3 ± 17.4 mm3 and 151.5 ± 25.8 mg compared with Sora (510.6 ± 48.2 mm3 and 396.7 ± 33.5 mg). DISCUSSION AND CONCLUSIONS: TET enhances Sora sensitivity by inactivating PI3K/AKT/mTOR, suggesting the potential of TET as a chemosensitizer in HCC.

Efficacy of an Oral Solution Prepared from the Ultrasonic Extract of Radix dichroae roots against Eimeria tenella in Broiler Chickens.

This study was conducted to determine the optimal dose of the oral solution of the ultrasonic extract of Radix dichroae (UERD) and to provide experimental support for a safe clinical dose for anticoccidial treatment of broiler chickens. Radix dichroae root extracts were prepared using the ultrasonic extraction method. The anticoccidial activity of the oral solution prepared from the ultrasonic extract of Radix dichroae roots was tested in broiler chickens following oral infection with a field isolate of E. tenella. Ninety Lingnan yellow broiler chickens (14 days old) were randomly divided into nine groups (n = 10), including six UERD oral solution treatments (0.25, 0.50, 1.50, 2.50, 3.50, and 5.00%), a toltrazuril group (0.10%), an E. tenella-infected control group, and a healthy control group. All groups were inoculated orally with 7 × 104 sporulated E. tenella oocysts (Guangdong strain) except for the healthy control group. The chickens in the seven drug-treated groups were administered a UERD oral solution or toltrazuril in drinking water for 7 days. The anticoccidial efficacy of the UERD oral solution was evaluated by the bloody diarrhoea severity level, relative body weight gain (rBWG), lesion score, oocyst per gram (OPG), and anticoccidial index (ACI). Compared with the infected control group, there were no significant differences in the groups treated with UERD oral solution or toltrazuril with regard to the lesion changes in the caecal regions (P > 0.05); however, the blood contents, OPG, and oocyst score in three UERD oral solution treatment groups (0.50, 1.50, and 2.50%) were significantly reduced, and the bloody diarrhoea was also alleviated. The ACI in three UERD oral solution treatment groups (0.50%, ACI = 143.7; 1.50%, ACI = 151.0; and 2.50%, ACI = 144.3) was higher than that in the toltrazuril group (ACI = 127.0), and the rBWG in the 1.50% UERD oral solution treatment group (95.0%) was similar to that in the healthy control group (100%), which was also 12.5% higher than that in the toltrazuril group (82.5%). The findings of this study demonstrated that the UERD oral solution (0.50% ～ 2.50% dose range) showed better prevention, anticoccidial efficacy, and growth promotion effects than toltrazuril (0.10%), and the 1.50% dose level of UERD oral solution in water is the clinically recommended dose according to the present study conditions.