Polymethoxyflavones in citrus extract has a beneficial effect on hypercholesterolemia rats by promoting liver cholesterol metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia is characterized by the disorder of lipid metabolism accompanied by oxidative stress damage, and low-grade inflammation, with the pathway of cholesterol and bile acid metabolic are an important triggering mechanism. Polymethoxyflavones (PMFs) are the active constituents of Aurantii Fructus Immaturus, which have many biological effects, including anti-inflammatory, antioxidant activities, anti-obesity, suppressing adipogenesis in adipocytes, and ameliorate type 2 diabetes, with potential roles for regulation of lipid metabolism. However, its associated mechanisms on hyperlipidemia remain unclear. AIM OF THE STUDY: This study aims to identify the anti-hypercholesterolemia effects and mechanisms of PMFs in a hypercholesterolemia model triggered by high-fat compounds in an excessive alcohol diet (HFD). MATERIALS AND METHODS: A hypercholesterolemia rat model was induced by HFD, and PMFs was intragastric administered at 125 and 250 mg/kg daily for 16 weeks. The effects of PMFs on hypercholesterolemia were assessed using serum lipids, inflammatory cytokines, and oxidative stress levels. Hematoxylin & eosin (H&E) and Oil Red O staining were performed to evaluate histopathological changes in the rat liver. The levels of total cholesterol (TC) and total bile acid (TBA) in the liver and feces were determined to evaluate lipid metabolism. RAW264.7 and BRL cells loaded with NBD-cholesterol were used to simulate the reverse cholesterol transport (RCT) process in vitro. The signaling pathway of cholesterol and bile acid metabolic was evaluated by Western Blotting (WB) and qRT-PCR. RESULTS: Lipid metabolism disorders, oxidative stress injury, and low-grade inflammation in model rats were ameliorated by PMFs administration. Numerous vacuoles and lipid droplets in hepatocytes were markedly reduced. In vitro experiments results revealed decreased NBD-cholesterol levels in RAW264.7 cells and increased NBD-cholesterol levels in BRL cells following PMFs intervention. PMFs upregulated the expression of proteins associated with the RCT pathway, such as LXRα, ABCA1, LDLR, and SR-BI, thereby promoting TC entry into the liver. Meanwhile, the expression of proteins associated with cholesterol metabolism and efflux pathways such as CYP7A1, CYP27A1, CYP7B1, ABCG5/8, ABCB1, and BSEP were regulated, thereby promoting cholesterol metabolism. Moreover, PMFs treatment regulated the expression of proteins related to the pathway of enterohepatic circulation of bile acids, such as ASBT, OSTα, NTCP, FXR, FGF15, and FGFR4, thereby maintaining lipid metabolism. CONCLUSIONS: PMFs might ameliorate hypercholesterolemia by promoting the entry of cholesterol into the liver through the RCT pathway, followed by excretion via metabolism pathways of cholesterol and bile acid. These findings provide a promising therapeutic potential for PMFs to treat hypercholesterolemia.

Trans-Nasion-Complex Approach for Endoscopic Modified Lothrop Procedure: Conception, Anatomy, and Technique.

Background: The endoscopic modified Lothrop procedure (EMLP) is an important procedure used to address frontal and anterior skull-base lesions. Two techniques were established, namely, the inside-out approach and the outside-in approach. The former technique take the frontal recess and the first olfactory filament (FOF) as key landmarks while the latter use the FOF as posterior boundary. In some cases, however, these two landmarks are not available. Therefore, we supplement the outside-in approach and named it trans-nasion-complex approach (TNCA) for EMLP that can be performed without locating these two landmarks. Methods: Two dry human skulls were used to observe the bony nasion complex. Then, five colored silicon-injected human head specimens were dissected via TNCA for EMLP. Finally, the outcomes of patients who underwent TNCA were reviewed. Results: The nasion complex is an osseous complex that consists of the nasion and its adjacent structures, including the bilateral root of nasal bones, nasal process of frontal bones, anterior portion of the perpendicular plate of the ethmoid bone that connects with the inferior aspect of the nasal bones, and portions of the bilateral frontal process of the maxillary bones. Surgical landmarks for TNCA include the anterior superior portion of the nasal septum, anterior margin and axilla of the middle turbinate, frontal process of the maxilla bone, nasal process of the frontal bone and upper part of the nasal bone. These structures form a "mushroom sign" during cadaveric dissection and surgery. Twenty-one patients underwent TNCA, of whom 9 had tumors and 12 had chronic rhinosinusitis with nasal polyps (CRSwNP). None of them had major complications. Conclusion: TNCA is expected to be a safe, and direct route for EMLP. Adequate understanding of the nasion complex and "mushroom sign" will be helpful to complete TNCA.