Aloesone is a major metabolic compound in Aloe vera, which has been widely used as a food source and therapeutic agent in several countries. Our recent study demonstrated that aloesone has anti-epileptic effects on glutamate-induced neuronal injury by suppressing the production of reactive oxygen species (ROS). Unless ROS are naturally neutralized by the endogenous antioxidant system, they lead to the activation of inflammation, polarization, and apoptosis. This study aimed to identify the multiple beneficial effects of aloesone and explore its molecular mechanism in macrophages. Hence, the murine macrophage cell line RAW264.7 was pretreated with aloesone and then exposed to lipopolysaccharides (LPS). The results demonstrated that aloesone, within a dosage range of 0.1–100 µM, dramatically decreased the LPS-induced elevation of ROS production, reduced nitric oxide (NO) release, inhibited the M1 polarization of RAW264.7 cells, and prevented cells from entering the LPS-induced early and late phases of apoptosis in a dose-dependent manner. Simultaneously, aloesone significantly decreased the mRNA expression of inflammation-related genes (iNOS, IL-1ꞵ, TNF-α) and increased the expression of antioxidant enzymes (Gpx-1 and SOD-1). The core genes HSP90AA1, Stat3, Mapk1, mTOR, Fyn, Ptk2b, and Lck were closely related to these beneficial effects of aloesone. Furthermore, immunofluorescence staining and flow cytometry data confirmed that aloesone significantly repressed the activation of mTOR, p-mTOR, and HIF-1α induced by LPS and inhibited the protein expression of TLR4, which is the target of LPS. In conclusion, aloesone demonstrated multiple protective effects against LPS-induced oxidative stress, inflammation, M1 polarization, and apoptosis in macrophages, suggesting its potential as a prodrug.

Two new pregnane glycosides, kidjoranin 3-O-α-diginopyranosyl-(1→4)-β-cymaropyranoside (1) and kidjoranin 3-O-β-digitoxopyranoside (2), together with one known compound caudatin 3-O-β-cymaropyranoside (3), were isolated from the roots of Cynanchum auriculatum. Their structures were established on the basis of NMR analyses. Compounds 1 - 3 were tested for their in vitro inhibitory activity against the growth of human tumor cell lines SMMC-7721, HeLa and MCF7; all of them displayed marked cytotoxic activities against cells SMMC-7721 and HeLa with IC₅₀ values ranging from 8.6 μM to 58.5 μM, yet no activity against the cell line MCF7 was detected.

The present study investigated the anti-hyperglycemic and anti-hyperlipidemia effects of the alkaloid-rich extract from Litsea glutinosa barks (CG) in ob/ob mice. CG was orally administrated (50, 100 and 200 mg/kg) to ob/ob mice for 4 weeks. Parameters of glucose metabolism, hepatotoxicity, hyperlipidemia and inflammation were measured. CG was chemically characterized using UPLC-QTOF-MS. CG dose-dependently decreased body and fat weights without reducing average food intake. CG (100–200 mg/kg) significantly reduced the serum levels of fasting glucose, glycosylated hemoglobin (HbAlc) and glycosylated serum protein (GSP). CG increased insulin sensitivity as manifested by decreased fasting serum insulin, reduced homeostasis model assessment-estimated insulin resistance (HOMA-IR) and improved oral glucose tolerance. CG also alleviated dyslipidemia, ameliorated liver steatosis, increased the activity of serum lipase and alleviated inflammation. The activities of liver pyruvate kinase and glucokinase as well as liver content of glycogen were increased after CG treatment. CG was rich in alkaloids and eight main alkaloids were identified, many of which had been demonstrated to possess adequate anti-diabetic activities. These results suggest that the alkaloid-rich extract of CG possesses potential anti-hyperglycemic and anti-hyperlipidemic effects and can be utilized as an effective agent for the treatment of type 2 diabetes.

Background: Galangin (3,5,7-trihydroxyflavone) is present in high concentrations in herbal medicine such as Alpinia officinarum Hance. Galangin shows multifaceted in vitro and in vivo biological activities. The number and position of hydroxyl groups in this molecule play an important role in these biological activities. However, these hydroxyl groups undergo glucuronidation and sulfation in in vitro assay system. However, the systemic exposure to galangin after dosing in animals and/or humans remains largely unknown. Thus it is not clear whether the galangin exists in the body at concentrations high enough for the biological effects. Furthermore, the metabolite identification and the corresponding plasma pharmacokinetics need to be characterized. Results: Two LC-MS/MS methods were developed and validated and successfully applied to analyze the parent drug molecules and aglycones liberated from plasma samples via β-glucuronidase hydrolysis. Our major findings were as follows: (1) The routes of administration showed significant influences on the systemic exposure of galangin and its metabolites. (2) Galangin was preferentially glucuronidated after p.o. dosing but sulfated after i.v. medication. (3) Kaempferol conjugates were detected demonstrating that oxidation reaction occurred; however, both glucuronidation and sulfation were more efficient. (4) Oral bioavailability of free parent galangin was very low. Conclusions: Systemic exposure to galangin and its metabolites was different in rat plasma between oral and intravenous administration. Further research is needed to characterize the structures of galangin conjugates and to evaluate the biological activities of these metabolites.