Toxicity study of compound granules of Hedyotis diffusa: Acute toxicity and long-term toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical efficacy of the hospital preparation compound granules of Hedyotis diffusa (CGHD), which is composed of Hedyotis diffusa Willd, Smilax china L., Solanum lyratum Thunb., has accumulated a good reputation over the past decades. However, because it is a hospital preparation, few researchers have paid attention to it, resulting in a lack of systematic basic research studies. Thus, it is not clear whether there are safety concerns that restrict its clinical application, and toxicological evaluation of CGHD is needed. AIM OF THE STUDY: The aim of this study was to evaluate the safety of CGHD by conducting acute toxicity and long-term toxicity experiments, with the objective of providing evidence for its clinical safety and a theoretical foundation for its clinical application. MATERIALS AND METHODS: KM mice were selected for the acute toxicity experiment and were administered water or CGHD-E 3 times within 24 h. The reactions of the animals to CGHD treatment were observed and recorded within 1 h after administration and then once a day for 14 consecutive days. SD rats were selected to conduct the long-term toxicity experiment. The drug-treated groups were administered different doses of CGHD-E, which were equivalent to 10 times, 20 times and 50 times the clinical dose in humans. The rats were administered the drug for 28 consecutive days. After 28 days, the animals were sacrificed, and routine blood tests, blood coagulation function analysis, liver and kidney function tests, and glycolipid metabolism related tests were conducted. The major organs of the rats were collected to calculate organ coefficients and perform hematoxylin-eosin (HE) staining. RESULTS: In the CGHD-E acute toxicity experiment, the drug-treated groups did not show adverse reactions or poisoning symptoms, and the maximum tolerated dose of CGHD-E in mice was greater than 45.072 g/kg. In the long-term toxicity experiment, drug-treated rats generally exhibited a good condition, but continuous administration decreased on body weight and food intake, especially in male rats. Coagulation function alterations and the impact on the liver during long-term drug administration were also assessed, which should be emphasized in clinical applications. No significant toxic effects were observed according to routine blood tests or test of liver and kidney function, glucose and lipid metabolism, or ion metabolism. CONCLUSIONS: The results of this study showed that CGHD was nontoxic or had low toxicity, providing not only a scientific basis for its clinical application, determining the appropriate clinical dose and monitoring clinical toxicity but also theoretical support for subsequent clinical drug trials.

[Carbon Source Utilization Characteristics of Soil Microbial Community for Apple Orchard with Interplanting Herbage].

As soil fertility in apple orchard with clean tillage is declined continuously, interplanting herbage in orchard, which is a new orchard management model, plays an important role in improving orchard soil conditions. By using biolog micro-plate technique, this paper studied the functional diversity of soil microbial community under four species of management model in apple orchards, including clear tillage model, interplanting white clover model, interplanting small crown flower model and interplanting cocksfoot model, and the carbon source utilization characteristics of microbial community were explored, which could provide a reference for revealing driving mechanism of ecological process of orchard soil. The results showed that the functional diversity of microbial community had a significant difference among different treatments and in the order of white clover > small crown flower > cocksfoot > clear tillage. The correlation analysis showed that the average well color development (AWCD), Shannon index, Richness index and McIntosh index were all highly significantly positively correlated with soil organic carbon, total nitrogen, microbial biomass carbon, and Shannon index was significantly positively correlated with soil pH. The principal component analysis and the fingerprints of the physiological carbon metabolism of the microbial community demonstrated that grass treatments improved carbon source metabolic ability of soil microbial community, and the soil microbes with perennial legumes (White Clover and small crown flower) had a significantly higher utilization rate in carbohydrates (N-Acetyl-D-Glucosamine, D-Mannitol, ß-Methyl-D-Glucoside), amino acids (Glycyl-L-Glutamic acid, L-Serine, L-Threonine) and polymers (Tween 40, Glycogen) than the soil microbes with clear tillage. It was considered that different treatments had the unique microbial community structure and peculiar carbon source utilization characteristics.