Combining In Vitro, In Vivo, and In Silico Approaches to Explore the Effect of <i>Ceratonia siliqua</i> and <i>Ocimum basilicum</i> Rich Phenolic Formula on Lipid Metabolism and Plasma Lipoprotein Oxidation in Mice Fed a High-Fat Diet: A Follow-Up Study

Background/Objectives: Hyperlipidemia is a serious risk factor for cardiovascular diseases and liver steatosis. In this work, we explored the effect of an herbal formula (CBF) containing immature <i>Ceratonia siliqua</i> pods and <i>Ocimum basilicum</i> extracts on lipid meta...

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Main Authors: Mohammadine Moumou, Amani Tayebi, Abderrahmane Hadini, Omar M. Noman, Abdulsalam Alhalmi, Hamza Ahmoda, Souliman Amrani, Hicham Harnafi
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Language:English
Published: MDPI AG 2025-01-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/1/36
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author Mohammadine Moumou
Amani Tayebi
Abderrahmane Hadini
Omar M. Noman
Abdulsalam Alhalmi
Hamza Ahmoda
Souliman Amrani
Hicham Harnafi
author_facet Mohammadine Moumou
Amani Tayebi
Abderrahmane Hadini
Omar M. Noman
Abdulsalam Alhalmi
Hamza Ahmoda
Souliman Amrani
Hicham Harnafi
author_sort Mohammadine Moumou
collection DOAJ
description Background/Objectives: Hyperlipidemia is a serious risk factor for cardiovascular diseases and liver steatosis. In this work, we explored the effect of an herbal formula (CBF) containing immature <i>Ceratonia siliqua</i> pods and <i>Ocimum basilicum</i> extracts on lipid metabolism disorders and lipoprotein-rich plasma (LRP) oxidation in mice. Methods: The phenolic composition was determined using HPLC-DAD analysis. The antioxidant activity was studied using various in vitro methods. Acute toxicity was evaluated in mice. Importantly, the effect of the CBF on lipid metabolism disorders was investigated in a high-fat diet (HFD) hyperlipidemia mouse model. An in silico study was carried out to predict underlying mechanisms. Results: The HPLC analysis revealed gallic acid, cinnamic acid, and naringenin as major phenolics of the carob pod aqueous extract. Concerning the basil hydro-ethanolic extract, rosmarinic, chicoric, caftaric, and caffeic acids were the main phenolics. Accordingly, the CBF prevented LRP oxidation in a concentration-dependent manner. This formula is not toxic in mice (LD<sub>50</sub> > 2000 mg/kg body weight). Moreover, animals administered the CBF at 200 mg/kg/day presented a significant decline in their body weight gain, adipose tissue weight, plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C) level, and glycaemia after 10 weeks’ treatment. Accordingly, the CBF decreased the plasma atherogenic index and the LDL-C to HDL-C ratio and reduced the level of fats accumulated in the liver. The molecular docking study revealed that chicoric, rosmarinic, and caftaric acids, and naringenin bound particularly strongly to many proteins involved in the regulation of lipid and cholesterol metabolism. This includes the HMG-CoA reductase, PPARα/γ, PCSK9, Cyp7a1, and ATP-citrate lyase. Conclusions: The CBF could be a good source of natural supplements, functional foods, and pharmaceuticals effective in managing hyperlipidemia and oxidative stress and preventing their related cardiovascular disorders.
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spelling doaj-art-eee38097cdf144c69ff9a3d8495f557e2025-01-24T13:41:14ZengMDPI AGMetabolites2218-19892025-01-011513610.3390/metabo15010036Combining In Vitro, In Vivo, and In Silico Approaches to Explore the Effect of <i>Ceratonia siliqua</i> and <i>Ocimum basilicum</i> Rich Phenolic Formula on Lipid Metabolism and Plasma Lipoprotein Oxidation in Mice Fed a High-Fat Diet: A Follow-Up StudyMohammadine Moumou0Amani Tayebi1Abderrahmane Hadini2Omar M. Noman3Abdulsalam Alhalmi4Hamza Ahmoda5Souliman Amrani6Hicham Harnafi7Laboratory of Bioresources, Biotechnologies, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed First, Oujda 60000, MoroccoLaboratory of Bioresources, Biotechnologies, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed First, Oujda 60000, MoroccoLaboratory of Bioresources, Biotechnologies, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed First, Oujda 60000, MoroccoDepartment of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaUniversitätsklinik für Viszerale Chirurgie und Medizin, Universität Bern, 3010 Bern, SwitzerlandLaboratory of Bioresources, Biotechnologies, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed First, Oujda 60000, MoroccoLaboratory of Bioresources, Biotechnologies, Ethnopharmacology and Health, Faculty of Sciences, University Mohammed First, Oujda 60000, MoroccoBackground/Objectives: Hyperlipidemia is a serious risk factor for cardiovascular diseases and liver steatosis. In this work, we explored the effect of an herbal formula (CBF) containing immature <i>Ceratonia siliqua</i> pods and <i>Ocimum basilicum</i> extracts on lipid metabolism disorders and lipoprotein-rich plasma (LRP) oxidation in mice. Methods: The phenolic composition was determined using HPLC-DAD analysis. The antioxidant activity was studied using various in vitro methods. Acute toxicity was evaluated in mice. Importantly, the effect of the CBF on lipid metabolism disorders was investigated in a high-fat diet (HFD) hyperlipidemia mouse model. An in silico study was carried out to predict underlying mechanisms. Results: The HPLC analysis revealed gallic acid, cinnamic acid, and naringenin as major phenolics of the carob pod aqueous extract. Concerning the basil hydro-ethanolic extract, rosmarinic, chicoric, caftaric, and caffeic acids were the main phenolics. Accordingly, the CBF prevented LRP oxidation in a concentration-dependent manner. This formula is not toxic in mice (LD<sub>50</sub> > 2000 mg/kg body weight). Moreover, animals administered the CBF at 200 mg/kg/day presented a significant decline in their body weight gain, adipose tissue weight, plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C) level, and glycaemia after 10 weeks’ treatment. Accordingly, the CBF decreased the plasma atherogenic index and the LDL-C to HDL-C ratio and reduced the level of fats accumulated in the liver. The molecular docking study revealed that chicoric, rosmarinic, and caftaric acids, and naringenin bound particularly strongly to many proteins involved in the regulation of lipid and cholesterol metabolism. This includes the HMG-CoA reductase, PPARα/γ, PCSK9, Cyp7a1, and ATP-citrate lyase. Conclusions: The CBF could be a good source of natural supplements, functional foods, and pharmaceuticals effective in managing hyperlipidemia and oxidative stress and preventing their related cardiovascular disorders.https://www.mdpi.com/2218-1989/15/1/36<i>Ceratonia siliqua</i><i>Ocimum basilicum</i>HPLC-DADpolyphenolslipid metabolism
spellingShingle Mohammadine Moumou
Amani Tayebi
Abderrahmane Hadini
Omar M. Noman
Abdulsalam Alhalmi
Hamza Ahmoda
Souliman Amrani
Hicham Harnafi
Combining In Vitro, In Vivo, and In Silico Approaches to Explore the Effect of <i>Ceratonia siliqua</i> and <i>Ocimum basilicum</i> Rich Phenolic Formula on Lipid Metabolism and Plasma Lipoprotein Oxidation in Mice Fed a High-Fat Diet: A Follow-Up Study
Metabolites
<i>Ceratonia siliqua</i>
<i>Ocimum basilicum</i>
HPLC-DAD
polyphenols
lipid metabolism
title Combining In Vitro, In Vivo, and In Silico Approaches to Explore the Effect of <i>Ceratonia siliqua</i> and <i>Ocimum basilicum</i> Rich Phenolic Formula on Lipid Metabolism and Plasma Lipoprotein Oxidation in Mice Fed a High-Fat Diet: A Follow-Up Study
title_full Combining In Vitro, In Vivo, and In Silico Approaches to Explore the Effect of <i>Ceratonia siliqua</i> and <i>Ocimum basilicum</i> Rich Phenolic Formula on Lipid Metabolism and Plasma Lipoprotein Oxidation in Mice Fed a High-Fat Diet: A Follow-Up Study
title_fullStr Combining In Vitro, In Vivo, and In Silico Approaches to Explore the Effect of <i>Ceratonia siliqua</i> and <i>Ocimum basilicum</i> Rich Phenolic Formula on Lipid Metabolism and Plasma Lipoprotein Oxidation in Mice Fed a High-Fat Diet: A Follow-Up Study
title_full_unstemmed Combining In Vitro, In Vivo, and In Silico Approaches to Explore the Effect of <i>Ceratonia siliqua</i> and <i>Ocimum basilicum</i> Rich Phenolic Formula on Lipid Metabolism and Plasma Lipoprotein Oxidation in Mice Fed a High-Fat Diet: A Follow-Up Study
title_short Combining In Vitro, In Vivo, and In Silico Approaches to Explore the Effect of <i>Ceratonia siliqua</i> and <i>Ocimum basilicum</i> Rich Phenolic Formula on Lipid Metabolism and Plasma Lipoprotein Oxidation in Mice Fed a High-Fat Diet: A Follow-Up Study
title_sort combining in vitro in vivo and in silico approaches to explore the effect of i ceratonia siliqua i and i ocimum basilicum i rich phenolic formula on lipid metabolism and plasma lipoprotein oxidation in mice fed a high fat diet a follow up study
topic <i>Ceratonia siliqua</i>
<i>Ocimum basilicum</i>
HPLC-DAD
polyphenols
lipid metabolism
url https://www.mdpi.com/2218-1989/15/1/36
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