Polyphenol-Rich Extracts of Xylopia and Aframomum Species Show Metabolic Benefits by Lowering Hepatic Lipid Accumulation in Diet-Induced Obese Mice

Abstract

Metabolic syndrome is a complex condition associated with a series of pathologies featuring glucose intolerance, diabetes, high blood pressure, dyslipidemia, microalbuminuria, overweight, and obesity. It is also related to nonalcoholic fatty liver disease (NAFLD), recognized as the most familiar cause of chronic liver disease worldwide. The overall prevalence of metabolic syndrome and, consequently, the one of NAFLD is constantly increasing worldwide. The initial management of these diseases involves lifestyle modifications, including changes in diet and physical exercise. In addition to conventional drugs like orlistat, botanicals are traditionally used to counteract these disorders, and some of them are currently under evaluation. The present work evaluated the in vivo beneficial effects of hydroalcoholic extracts of two Cameroonian spices, focusing on obesity-related hepatic lipid injury in high-fat-fed C57BL/6 mice. Hydroethanolic extracts were prepared and characterized by reverse phase-high-performance liquid chromatography (HPLC)-photodiode array detection and ultra performance liquid chromatography-triple time-of-flight electrospray ionization tandem mass spectroscopy (TOF-ESI-MS/MS) analysis. Plant extracts were orally administered for 30 days at different dose levels (100 and 200 mg kg –1 body weight (BW)) to obese C57BL/6 mice. Food intake (FI) and BW were recorded daily. Plasma biochemical parameters and lipid content were estimated at the beginning and at the end of the experiment. Liver tissues were subjected to histological examinations, lipid content, as well as oxidative stress markers, and FAME (fatty acid methyl esters) were estimated. Oral administration of extracts at 200 mg kg –1 BW significantly reduced FI and prevented BW gain. A decrease in the weight of the liver and a decrease in the hepatic and plasma lipid content were observed. Plasma enzyme (serum glutamic-oxaloacetic transaminase, SGOT; serum glutamic pyruvic transaminase, SGPT; alkaline phosphatase, ALP) activities were not indicative of any organ damage. Chemical analysis suggested that phenolic acids (4-caffeoylquinic acid, p-coumaric acid 4-O-glucoside, 5-caffeoylshikimic acid, caffeic acid hexose, and 4-O-methyl gallic acid) and flavonoids (morusin derivatives, naringenin-7-O-glucoside, and homoisoflavanone) identified in the extracts could potentially justify the biological properties observed. The main findings of this study showed that Xylopia parviflora (A. Rich.) Benth and Aframomum citratum (Pereira ex Oliv. et Hanb.) K. Shum decreased hepatic lipid accumulation in high-fat-diet (HFD)-induced obese C57BL/6 mice and confirmed, at least in part, our previous in vitro and ex vivo studies. The molecular mechanisms underlying these effects are still unclear and will be explored in the future.

Anti-Inflammatory, Antioxidant Activities, and Phytochemical Characterization of Edible Plants Exerting Synergistic Effects in Human Gastric Epithelial Cells

“…Compounds 5b and 2a gave typical fragmentation pattern at m/z 269 [M−H−146−H 2 O] − (loss of moiety of O-linked rhamnose) and m/z 287 [M−H−146] − (loss of a deoxyhexose moiety), characteristic of eriodictyol deoxyhexose derivatives [ 40 ]. Compounds 4d generated MS 2 fragments at m/z 271 [M−H−162] − indicating a loss of caffeoyl moiety, and according to the literature [ 17 , 21 , 33 ], this compound was assigned to naringenin-7-O glucoside. Compound 1c gave a [M−H] − at m/z 271.1.…”

“…Compound 8b (t R = 15.10 min) and compound 5a (t R = 15.75 min) ( Figure S1B,C ) revealed molecular ions at m/z 325.2 and m/z 295.2, respectively ( Table 1 ). Based on these data and comparing retention times and MS 2 fragments, they were tentatively assigned to hydroxycinnamic acid compounds [ 17 , 21 ]. Furthermore, compound 6d (t R = 12.58 min) and compound 10d (t R = 15.65 min) ( Figure S1D ) in X. parviflora spectra exhibited [M−H] − at m/z 335.2 and m/z 339.2, respectively ( Table 1 ) The MS 2 fragmentation patterns of compound 6d are typical of caffeoylshikimic acid [ 35 ].…”

“…The phenolic compounds content within each extract was analyzed as described above [ 17 ] by HPLC (Nexera X-2 LC-30A, Shimadzu, Japan), and chromatography separations were carried out on a Chromasol™ RP-C18 column (250 mm × 4.6 mm, 5 µm). The mobile phase was made up of water set at a pH of 2.65 with acetic acid (solvent A) and solvent B (20% solvent A and 80% acetonitrile).…”

“…The Kinetex C18 100A (30 × 2.1 mm 1.7 μm) Column (Phenomenex) was used for separation at a flow rate of 0.4 mL/min. The mobile phase was made up of a combination of two solvents: A (0.1% acetic acid in water) and B (0.1% acetic acid in acetonitrile and methanol in the ratio 8:2) [ 17 ]. The mass spectra analyses were performed in negative ion mode in the m/z range from 100 to 2000 m/z at an IRDx resolution of 15,000 using an LC/MS/MS Quadrupole-TOF Hybrid Mass Spectrometer (Sciex Triple ToF 5600, Singapore) and under the following conditions: gases were GS1-45, GS2-60, and Curtain GAS (CUR)-40, source voltage was 4.0 kV, Duospray ion source was set at 400 °C, and the collision energy was 10 V. CID-MS/MS experiments were carried out on mass-selected precursor ions using standard isolation and excitation configuration.…”

“…Chiov., and Aframomum citratum (C.Pereira) K.Schum were chosen for gastro-protective evaluation. Our early studies showed that hydro-ethanolic extracts from these plants exerted antioxidant, hepato-protective, and enzyme inhibition activities [ 14 , 15 , 16 , 17 ]. In addition to their anti-inflammatory effects, the combination of these dietary plants, suggested by traditional Cameroonian medicine, might provide phytochemicals (mainly polyphenols) with synergistic gastro-protective effects.…”