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Atherosclerosis (AS) is a major cause of mortality worldwide. Geniposide (GP) has lipolytic and anti-inflammatory effects and is widely administered for the treatment of cardiovascular disease. There is considerable evidence for the importance of autophagy in the cardiovascular system, and GP can promote autophagy and improve AS. However, the underlying mechanism is still unclear; network pharmacology and molecular docking suggest that GP may play anti-atherosclerotic roles by regulating the PI3K/Akt/mTOR pathway, which is a typical autophagy signal transduction approach. We further hypothesized that GP ameliorates AS by regulating autophagy through the PI3K/Akt/mTOR pathway. Oil Red O, Sirius Red, and Masson's trichrome staining revealed that GP can inhibit atherosclerotic lipid accumulation and stabilize plaques. Macrophages absorb lipids, form foam cells, and destabilize plaques. Immunohistochemical staining revealed that GP reduces the expression of F4/80, a major macrophage marker. We used western blotting (WB) and immunofluorescence (IF) to measure the protein levels of PI3K/Akt/mTOR, sequestosome-1, Beclin1, and long-chain base 3 (LC3). The experimental results revealed that GP can increase the expression of LC3, increase the expression of Beclin1, and decrease P62. Additionally, it inhibits the phosphorylation of PI3K/Akt/mTOR. In conclusion, GP can effectively treat AS by enhancing autophagy through the PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

Objective To explore the regulatory effects of Guanxinkang (a patent Chinese medicine based on the Trichosanthes, Chinese Chive and Pinellia Decoction) and its composite formulas on liver cholesterol reverse transport and its mechanism. Methods 60 LDLR-/- mice, half male and half female, were induced by high-fat diet for 12 weeks to establish the hyperlipidemia model. After verifying the model, three composite formulas were obtained from the complete formula of Guangxinfang according to the commonly encountered clinical patterns of hyperlipidemia, i. e. Yiqi Huatan (qi-reinforcing and phlegm-resolving, YQHT) formula, Huatan Huoxue (phlegm-resolving and blood-activating, HTHX) formula, and Yiqi Huoxue (qi-reinforcing and blood-activating, YQHX) formula. The 60 mice were randomly divided into the model group, Guanxinkang (GXK) group, Yiqi Huatan (YQHT) group, Huatan Huoxue (HTHX) group, Yiqi Huoxue (YQHX) group, and simvastatin group, 10 mice in each group, and another 10 C57BL/6J mice with the same genetic background formed the normal group. Guanxinkang, its composite formulas and simvastatin were given to the corresponding groups respectively. Peripheral blood and liver of the mice were collected 12 weeks later. Biochemical method was used to detect the blood lipid content of mice in different groups, HE staining to observe liver pathological changes,real-time PCR to detect liver PERK, eIF2α, SREBP-2, ABCA1 gene expressions, and Western Blotting to detect liver phosphorylation PERK, phosphorylation eIF2α, ABCA1 and SREBP-2 protein expressions. Results Guanxinkang and its composite formulas can regulate blood lipids to different extents. The liver tissues of the mice in the GXK group and the YQHT group were relatively complete. In the liver of the mice in the HTHX group and YQHX group, a large number of lipid droplet vacuoles were seen, accompanied by obvious loose cells with network-like changes. Compared with the model group, the liver PERK, eIF2α, SREBP-2 gene and protein expressions of mice in the GXK group were significantly reduced, and the ABCA1 protein was significantly increased (P <0. 05), but there was no such statistically significant difference in the three groups taking the composite formulas (P >0. 05). Conclusion Guanxinkang can effectively regulate blood lipids and maintain liver cholesterol homeostasis. Guanxinkang' s regulation of blood lipids and its" stabilizing" effects on liver cholesterol may be related to the activation of ABCA1 and inhibition of PERK-eIF2α-SREBP-2 signaling pathway, which reduces the synthesis and uptake of cholesterol and promotes the transport and metabolism of cholesterol. In addition, the herbal ingredients of Guanxinkang that invigorate qi and activate blood, including Huangqi (Astragalus Root, Radix Astragali), Yimucao (Motherwort Herb, Herba Leonuri), and Danshen (Danshen Root, Radix et Rhizoma Salviae Miltiorrhizae) inhibited the PERK-eIF2α-SREBP-2 signaling pathway more significantly. [ABSTRACT FROM AUTHOR]

In patients with severe acute respiratory syndrome coronavirus 2 (which causes coronavirus disease 2019 [COVID-19]), oxidative stress (OS) is associated with disease severity and death. OS is also involved in the pathogenesis of atherosclerosis (AS). Previous studies have shown that geniposide has anti-inflammatory and anti-viral properties, and can protect cells against OS. However, the potential target(s) of geniposide in patients with COVID-19 and AS, as well as the mechanism it uses, are unclear. We combined pharmacology and bioinformatics analysis to obtain geniposide against COVID-19/AS targets, and build protein-protein interaction network to filter hub genes. The hub genes were performed an enrichment analysis by ClueGO, including Gene Ontology and KEGG. The Enrichr database and the target microRNAs (miRNAs) of hub genes were predicted through the MiRTarBase via Enrichr. The common miRNAs were used to construct the miRNAs-mRNAs regulated network, and the miRNAs' function was evaluated by mirPath v3.0 software. Two hundred forty-seven targets of geniposide were identified in patients with COVID-19/AS comorbidity by observing the overlap between the genes modulated by geniposide, COVID-19, and AS. A protein-protein interaction network of geniposide in patients with COVID-19/AS was constructed, and 27 hub genes were identified. The results of enrichment analysis suggested that geniposide may be involved in regulating the OS via the FoxO signaling pathway. MiRNA-mRNA network revealed that hsa-miR-34a-5p may play an important role in the therapeutic mechanism of geniposide in COVID-19/AS patients. Our study found that geniposide represents a promising therapy for patients with COVID-19 and AS comorbidity. Furthermore, the target genes and miRNAs that we identified may aid the development of new treatment strategies against COVID-19/AS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)