Dataset Information

Aged Pericarpium Citri Reticulatae 'Chachi' Attenuates Oxidative Damage Induced by tert-Butyl Hydroperoxide (t-BHP) in HepG2 Cells.

ABSTRACT: This study investigated the protective effects of aged Pericarpium Citri Reticulatae 'Chachi' (PCR-C) on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells. According to HPLC analysis, PCR-C aged 10 years (PCR-C10) had the highest flavonoids content, especially polymethoxyflavones (PMFs), compared with the fresh peel of Citrus reticulata cv. 'Chachiensis' and PCR-C aged 1, 3, and 5 years. Then, flavonoids-rich PCR-C samples and non-flavonoids-rich PCR-C samples (NF) were prepared by extracting and purifying PCR-C of different aging periods, for further cell experiments. Pretreatment with flavonoids-rich PCR-C samples (particularly PCR-C10) considerably reversed t-BHP-induced oxidative damage in HepG2 cells by improving cell viability, increasing SOD activity and GSH levels and reducing the overproduction of ROS and MDA. Correlation analysis further indicated that the accumulation of PMFs, mainly 5,6,7,4'-tetramethoxyflavone and nobiletin, was the main reason that PCR-C10 maintained the redox balance in HepG2 cells. These findings provided direct evidence for the cellular antioxidant activity of aged PCR-C and a guide for PCR-C's classification, authentication and rational use.

SUBMITTER: Yu Q

PROVIDER: S-EPMC8834029 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Aged Pericarpium Citri Reticulatae 'Chachi' Attenuates Oxidative Damage Induced by tert-Butyl Hydroperoxide (t-BHP) in HepG2 Cells.

Yu Qian Q Tao Yexing Y Huang Yuting Y Zogona Daniel D Wu Ting T Liu Ruiting R Pan Siyi S Xu Xiaoyun X

Foods (Basel, Switzerland) 20220120 3

This study investigated the protective effects of aged Pericarpium Citri Reticulatae 'Chachi' (PCR-C) on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells. According to HPLC analysis, PCR-C aged 10 years (PCR-C10) had the highest flavonoids content, especially polymethoxyflavones (PMFs), compared with the fresh peel of Citrus reticulata cv. 'Chachiensis' and PCR-C aged 1, 3, and 5 years. Then, flavonoids-rich PCR-C samples and non-flavonoids-ric ...[more]

PMID: 35159424

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Project description:BackgroundPathological cardiac hypertrophy is a major risk factor for cardiovascular diseases, including heart failure. However, limited pharmacological therapies are available for reversing the maladaptive process and restoring cardiac function. Citri reticulatae Pericarpium (CRP) has been used in traditional Chinese medicine prescriptions for clinical treatment. Previous studies have shown that CRP and its ingredients have beneficial effects on the cardiovascular system. However, whether CRP has a protective effect against pathological cardiac hypertrophy remains unknown.MethodsPrimary neonatal rat cardiomyocytes (NRCMs) were treated with angiotensin II (Ang II) to induce pathological hypertrophy in vitro. Immunofluorescent staining and quantitative real-time PCR (qRT-PCR) were used to determine the cell size and the expression of hypertrophic gene markers (Anp and Bnp), respectively. Male C57BL/6 mice were subjected to the investigation of cardiac hypertrophy induced by Ang II (2.5 mg/kg/d for 4 weeks). CRP (0.5 g/kg/d for 4 weeks) was administrated to treat mice with or without peroxisome proliferator-activated receptors gamma (PPARγ) inhibitor T0070907 (1 mg/kg/d for 4 weeks treatment) infused with Ang II. Cardiac hypertrophy (hematoxylin-eosin staining and qRT-PCR), fibrosis (Masson's Trichrome staining, qRT-PCR, and western blot), and cardiac function (echocardiography) were examined in these mice. Western blot was used to determine the protein level of PPARγ and PGC-1α both in NRCMs and in mice.ResultsWe found that CRP could prevent Ang II-induced pathological cardiac hypertrophy evidenced by improving cardiac function, decreasing hypertrophic growth and reducing cardiac fibrosis. Also, we demonstrated that PPARγ was upregulated by CRP both in NRCMs and in hearts. Moreover, PPARγ inhibitor could abolish the inhibitory effects of CRP on Ang II-induced pathological cardiac hypertrophy.ConclusionsCRP attenuates Ang II-induced pathological cardiac hypertrophy by activating PPARγ.

Project description:Liver diseases are mostly triggered by oxidative stress and inflammation, leading to extracellular matrix overproduction and prone to develop into liver fibrosis, cirrhosis and hepatocellular carcinoma. Liver injury (LI) refers to various pathogenic factors leading to the destruction of stem cells that then affect the liver's normal function, causing a series of symptoms and abnormal liver function indicators. Citri Reticulatae Pericarpium (CRP) is one of the most commonly used traditional Chinese medicines; it contains flavonoids including hesperidin, nobiletin, and tangeretin. CRP has antibacterial, antioxidant, and antitumor effects that reduce cholesterol, prevent atherosclerosis and decrease LI. Here we analyzed the components of CRP and their targets of action in LI treatment and assessed the relationships between them using a systems pharmacology approach. Twenty-five active ingredients against LI were selected based on ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry results and databases. The drug targets and disease-related targets were predicted. The 117 common targets were used to construct a protein-protein interaction network. We identified 1719 gene ontology items in LI treatment, including 1,525 biological processes, 55 cellular components, and 139 molecular functions. These correlated with 49 Kyoto Encyclopedia of Genes and Genomes pathways. These findings suggest that CRP may counteract LI by affecting apoptotic, inflammatory, and energy metabolism modules. In vitro experiments suggested that the mechanism may involve hesperidin and naringenin acting on CASP3, BAX, and BCL2 to affect the apoptosis pathway, attenuating liver fibrosis. Naringenin significantly inhibited AKT1 phosphorylation, which in turn mediated activation of the phosphoinositide 3-kinase-Akt signaling pathways against LI. This study provides a reference for systematically exploring the mechanism of CRP's anti-LI action and is also expands of the application of systems pharmacology in the study of traditional Chinese medicine.

Project description:Edible herbal medicines contain macro- and micronutrients and active metabolites that can take part in biochemical processes to help achieve or maintain a state of well-being. Citri Reticulatae Pericarpium (CRP) is an edible and medicinal herb used as a component of the traditional Chinese medicine (TCM) approach to treating COVID-19 in China. However, the material basis and related mechanistic research regarding this herb for the treatment of COVID-19 are still unclear. First, a wide-targeted UPLC-ESI-MS/MS-based comparative metabolomics analysis was conducted to screen for the active metabolites of CRP. Second, network pharmacology was used to uncover the initial linkages among these metabolites, their possible targets, and COVID-19. Each metabolite was then further studied via molecular docking with the identified potential SARS-CoV-2 targets 3CL hydrolase, host cell target angiotensin-converting enzyme II, spike protein, and RNA-dependent RNA polymerase. Finally, the most potential small molecule compound was verified by in vitro and in vivo experiments, and the mechanism of its treatment of COVID-19 was further explored. In total, 399 metabolites were identified and nine upregulated differential metabolites were screened out as potential key active metabolites, among which isorhamnetin have anti-inflammatory activity in vitro validation assays. In addition, the molecular docking results also showed that isorhamnetin had a good binding ability with the key targets of COVID-19. Furthermore, in vivo results showed that isorhamnetin could significantly reduced the lung pathological injury and inflammatory injury by regulating ATK1, EGFR, MAPK8, and MAPK14 to involve in TNF signaling pathway, PI3K-Akt signalling pathway, and T cell receptor signaling pathway. Our results indicated that isorhamnetin, as screened from CRP, may have great potential for use in the treatment of patients with COVID-19. This study has also demonstrated that comparative metabolomics combined with network pharmacology strategy could be used as an effective approach for discovering potential compounds in herbal medicines that are effective against COVID-19.

Dataset Information

Aged Pericarpium Citri Reticulatae 'Chachi' Attenuates Oxidative Damage Induced by tert-Butyl Hydroperoxide (t-BHP) in HepG2 Cells.

Publications

Aged <i>Pericarpium Citri Reticulatae 'Chachi'</i> Attenuates Oxidative Damage Induced by <i>tert</i>-Butyl Hydroperoxide (<i>t</i>-BHP) in HepG2 Cells.

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