Pharmacological systemic analysis of gardenia fructus against non-alcoholic fatty liver disease and validation of animal models

Abstract

[Purpose] We aimed to investigate the systemic pharmacological analysis of gardenia fructus (GF) and the proof of concepts. We examined the antioxidant and anti-inflammatory effects in high-fat (HF) diet mice.[Methods] The active compounds of GF and the target genes were identified using the Traditional Chinese Medicine Database and Analysis Platform (oral bioavailability ≥ 30%, Caco-2 permeability ≥ -0.4, and drug-likeness ≥ 0.18). The rats were divided into four groups: untreated group, HF group, HF and metformin (17 mg/kg) treated group, and HF and treated with GF (28 mg/kg) for 8 weeks group. Hepatic lesion changes and markers were analyzed using hematoxylin and eosin staining and immunohistochemistry assay.[Results] In the systemic analysis, we identified 14 active compounds including A, B, and C. From these 14 compounds, 242 biological target genes were identified. The top 10 Gene Ontology were analyzed using GO-biological process analysis: removal of superoxide radicals, regulation of endothelial cell apoptotic process, and cellular response to lipopolysaccharide. GF extracts in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) mice models significantly regulated hepatic lesion markers, such as mTOR, 8-Hydroxy- 2'-deoxyguanosine as well as oxidative stress activities, TGF-β, and phosphorylation of ERK1/2.[Conclusion] These results suggest that GF, as an exercise supplement, can alleviate NAFLD disease or fatty liver inflammation. Further studies are required to verify the synergistic effect of GF treatment combined with exercise, which is known to alleviate NAFLD and fatty liver inflammation.

A sport supplement candidate of Erigeron breviscapus extract regulates lipogenesis in vitro and in vivo

“…Scorletti et al reported that the continuous storage of lipid droplets induces NFALD 15 . As shown in Figure 2, our re-Figure 3.…”

“…To analyze the components of EB and the target gene network, we used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Cytoscape. EB characteristics analyze of EB was analyzed as previously described [ 15 ]. The TCMSP ( http://ibts.hkbu.edu.hk/LSP/tcmsp.php ) was used to identify the active components of EB.…”

Rosae multiflorae fructus regulates the lipogenesis in high-fat diet-induced NAFLD mice model

“…To confirm the effects of RMF in the NAFLD mouse model, tissues were analyzed using a staining solution and specific antibodies. Immunohistochemistry was performed as previously described [ 16 ]. First, the mice were perfused and fixed in 10% formalin.…”

Recent Insights into the Biomarkers, Molecular Targets and Mechanisms of Non-Alcoholic Steatohepatitis-Driven Hepatocarcinogenesis

“…It has been recently reported that natural products, including phenols, flavonoids, glycosides, quinones, terpenoids, pyrazines, alkaloids, and phenylpropanoids, have antioxidant, energy-producing, anti-inflammatory, anti-apoptotic, and anti-aging effects, which mainly influence the AMPK/Nrf2/mTOR, Nrf2/HO-1, NAMPT/NAD(+)/SIRT, AMPK/SIRT1/PGC-1alpha and PKCs/PARPs/NF-kB signaling pathways, thereby regulating NAD(+) metabolism to prevent and treat NAFLD [ 117 ]. Hepatoprotective effects, caused by the inhibition of PI3K/Akt/mTOR signaling and effective alleviation of oxidative stress damage and ER stress induced by excessive lipid accumulation in hepatocytes, and activation of autophagy were observed for agonists of AMPK thymoquinone [ 118 ] and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) [ 119 ], agonist of GLP-1/glucagon cotadutide [ 120 ], an antagonist of sphingosine 1-phosphate receptor 2 (S1PR2) JTE-013 [ 26 ], activator of PI3K, autophagy-related genes (ATG) and agonist of Nrf2, PPARα and hemeoxygenase-1 (HO-1) pterostilbene [ 121 ], flavonoid with antioxidant properties involving CYP7A1, quercetin [ 122 ], Pueraria flavonoids [ 92 ], a novel gerotherapy compound, BIOIO-1001 [ 123 ], a natural nonenzymatic antioxidant with low toxicity schisandrin B (Sch B) [ 124 ], H1-antihistamines (AHs) [ 125 ], fat soluble polyphenol Tanshinone IIA (TsIIA) [ 126 ], purendan (PRD) [ 127 ], down-regulating the expression of p-mTOR, p-S6K1 and SREBP-1c, chrysin [ 128 ], red pepper seed extract (RPS) [ 129 ], Gardenia Fructus (GF) extracts [ 130 ], curcumin [ 131 ], and magnesium [ 132 ].…”

“…In a recent study, a dual inhibitor of soluble epoxide hydrolase (sEH) and cyclooxygenase 2 (COX-2), 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl)-benzenesulfonamide (PTUPB), significantly reduced the expression of liver senescence-related molecules p16, p53, and p21 in HFD mice and inhibited the PI3K/AKT/mTOR pathway through Sirt1 [ 130 ]. PTUPB improved autophagy, slowed down the senescence of hepatocytes, and alleviated NAFLD in vitro [ 133 ].…”