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Hypericum patulum has been used as a folk medicine for its varied therapeutic effects including antifungal, wound-healing, spasmolytic, stimulant, hypotensive activities. The water decoction is drank as tea could treat cold, infantile malnutrition. The present study aims to isolate the constituents of the plant and investigate their effects on the glucose consumption in insulin-resistant HepG2 cells, furthermore, lipid metabolism in oleic acid (OA)-treated HepG2 cells was also studied. The phytochemical investigation of the plant led to the isolation of eleven compounds, and their structures were identified by spectroscopic analysis as n-dotriacontanol (1), shikimic acid (2), 1-O-caffeoylquinic acid methyl ester (3), 5-O-caffeoylquinic acid methyl ester (4), 5-O-coumaroylquinic acid methyl ester (5), 5-O-caffeoylquinic acid butyl ester (6), quercetin-3-O-α-L-rhamnoside (7), quercetin (8), quercetin-3-O-(4״-methoxy)-α-L-rahmnopyranosyl (9), hyperoside (10), and rutin (11). The results revealed that compounds 7, 9, and 10 could enhance glucose consumption significantly in hyperglycemia induced HepG2 cells and insulin-resistant HepG2 cells. In addition, the western blotting analysis result exhibited that compounds 7, 9, and 10 in high concentration (5 μM, H) group could dramatically upregulate the expression of PPARγ protein, and even the effect of them had no significant difference compared with that of rosiglitazone. Furthermore, compounds 9 and 10 in middle concentration (2.5 μM, M) group and H group could dramatically promote triglyceride metabolism and decrease TG content in OA-treated HepG2 cells, and even in H group, reactive oxygen species (ROS) level were significantly decreased compared with model group. PRACTICAL APPLICATIONS: Hypericum patulum is a well-known plant of the genera Hypericum for its varied preventive and therapeutic potential activities. To study the chemical constituents and their effects on glucose and lipid metabolism in vitro, we detected glucose consumption in insulin-resistant HepG2 cells, triglyceride content and reactive oxygen species level in OA-treated HepG2 cells. In addition, PPARγ protein was also detected by western blotting analysis in the study. Compounds 1, 2, 3, 5, 6, 9, 10, and 11 were isolated from the plant for the first time. Quercetin-3-O-(4"-methoxy)-α-L-rahmnopyranosyl (9) and hyperoside (10) had potential therapeutic benefit against glucose and lipid metabolic disease. Therefore, this study might have certain guiding significance for further research and development of H. patulum.

The fruits of Swietenia macrophylla King have been processed commercially to a variety of health foods and healthcare products and exhibited antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. This study was aimed to examine the glucose consumption in human hepatoma HepG2 cells and the expression of PPARγ of limonoids isolated from the fruits of S. macrophylla. The phytochemical investigation of the fruits led to the isolation of ten limonoids which structures were elucidated by spectroscopic analysis as swietenine (1), khayasin T (2), 6-deoxyswietenine (3), 3-O-tigloylswietenolide (4), swietenolide (5), 3,6-O,O-diacetylswietenolide (6), 7-deacetoxy-7-oxogedunin (7), fissinolide (8), proceranolide (9), 7-deacetoxy-7α-hydroxygedunin (10), and compound 10 was isolated from this plant for the first time. The glucose consumption assay revealed that compounds 1, 2, 3, 5, and 9 could promote glucose consumption significantly in normal hyperglycemia-induced HepG2 cells, furthermore, compounds 1, 5, and 9 had a better effect on promoting glucose consumption in insulin-resistant HepG2 cells. In addition, compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells according to the western blotting analysis result. PRACTICAL APPLICATIONS: Swietenia macrophylla King belongs to the family Meliaceae and the fruits have been exhibited a wide range of biological activities, such as antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. Phytochemical investigations of S. macrophylla have revealed that limonoids and triterpenoids were effective antidiabetic agents. However, the mechanism of these limonoids to antidiabetic activity is unclear. In this study, limonoids were isolated from the fruit of S. macrophylla and their effects on the glucose consumption of insulin-resistant HepG2 cells were studied. The results showed that compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells, which will give aid to explore the mechanism of these limonoids in the treatment of type 2 diabetes. Therefore, this research might facilitate further research and development of S. macrophylla.

As drug abuse has become increasingly serious, carbamazepine (CBZ) is discharged into the aquatic environment with municipal sewage, causing potential harm to aquatic organisms. Here, we utilized zebrafish, an aquatic vertebrate model, to comprehensively evaluate the hepatotoxicity of CBZ. The larvae were exposed to 0.07, 0.13, and 0.26 mmol/L CBZ from 72 hpf to 144 hpf, and the adults were exposed to 0.025, 0.05, and 0.1 mmol/L CBZ for 28 days. The substantial changes were observed in the size and histopathology of livers, indicating that CBZ induced severe hepatoxicity in the larvae and adults. Oil red O staining demonstrated CBZ exposure caused severe lipid accumulation in the livers of both larvae and adults. Furthermore, CBZ exposure facilitated hepatocyte apoptosis through TUNEL staining, which was caused by rising ROS content. Subsequently, down-regulation of genes related to the Wnt pathway in exposure groups indicated that CBZ inhibited the development of liver via the Wnt/β-catenin signaling pathway. In conclusion, CBZ induced severe hepatotoxicity by promoting lipid accumulation, generating excessive ROS production, and inhibiting the Wnt/β-catenin signaling pathway in zebrafish. The results reveal the occurrence of CBZ-induced hepatotoxicity in zebrafish and clarify its mechanism of action, which potentially illustrate environmental concerns associated with CBZ exposure.