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Citrus grandis ‘Tomentosa’
PLANT PHYSIOLOGY AND BIOCHEMISTRY · 2023 · IF 6.5

Integrated transcriptomic and metabolomic analyses reveal key genes controlling flavonoid biosynthesis in Citrus grandis ‘Tomentosa’ fruits

Ruiyi Fan,Congyi Zhu,Diyang Qiu,Genlin Mao,Bernd Mueller-Roeber,Jiwu Zeng

As a well-recognized traditional Chinese medicine (TCM), immature fruits of Citrus grandis ‘Tomentosa’ (CGT) serve to cure chronic cough in humans. Specialized metabolites including flavonoids may have contribute to this curing effect. Knowledge about the molecular mechanisms underlying flavonoid biosynthesis in ‘Tomentosa’ fruits will, therefore, support the breeding of varieties with improved medicinal properties . Hence, we profiled the transcriptomes and metabolites of the fruits of two contrasting C. grandis varieties, namely ‘Zheng-Mao’ (‘ZM’) used in TCM production, and a locally cultivated pomelo, namely ‘Guang-Qing’ (‘GQ’), at four developmental stages. A total of 39 flavonoids, including 14 flavanone/flavone, 5 isoflavonoids , 12 flavonols, and 6 anthocyanins , were identified, and 16 of which were quantitatively determined in the fruits of the two varieties. We found that ‘ZM’ fruits contain more flavonoids than ‘GQ’. Specifically, rhoifolin levels were significantly higher in ‘ZM’ than in ‘GQ’. We annotated 31,510 genes, including 1,387 previously unknown ones, via transcriptome sequencing of ‘ZM’ and ‘GQ.’ A total of 646 genes were found to be differentially expressed between ‘ZM’ and ‘GQ’ throughout at all four fruit developmental stages, indicating that they are robust expression markers for future breeding programs. Weighted gene co-expression network analysis identified 18 modules. Combined transcriptional and metabolic analysis revealed 25 genes related to flavonoid biosynthesis and 16 transcriptional regulators (MYBs, bHLHs, WD40) that may be involved in the flavonoids biosynthesis in C. grandis ‘Tomentosa’ fruits.

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JOURNAL OF FOOD SCIENCE · 2024 · IF 3.2

Diversity in storage age enables discrepancy in quality attributes and metabolic profile of Citrus grandis “Tomentosa” in China

Liyang Wei,Qian Hu,Lei He,Guoping Li,Jiukai Zhang,Ying Chen

The folk proverb “the older, the better” is usually used to describe the quality of Citrus grandis “Tomentosa” (CGT) in China. In this study, CGT aged for 6-, 12-, 16-, and 19-years were collected for the investigation of infusion color, main bioactive components, antioxidant activity, metabolic composition, and pathway. The results found that infusion color, the total phenolic and flavonoid, and antioxidant activity of CGT were obviously changed by aging process. Through untargeted metabolomics, 55 critical metabolites were identified to in discrimination of CGT with different storage ages, mainly including phenylpropanoids, lipids, and organic oxygen compounds. Twenty compounds that showed good linear relationships with storage ages could be used for year prediction of CGT. Kyoto encyclopedia of genes and genomes enrichment pathway analysis uncovered important metabolic pathways related to the accumulation of naringin, kaempferol, and choline as well as the degradation of benzenoids, thus supporting that aged CGT might be more beneficial to health. Correlation analysis provided that some key metabolites with bitter taste and biological activity were involved in the darkening and reddening of CGT infusion during aging, and total phenolic and flavonoid were more strongly associated with the antioxidant activity of CGT. This study systematically revealed the quality changes and key metabolic pathways during CGT aging at first time. Practical Application This study reveals the differences in quality attributes and metabolic profile between CGT with different storage ages, providing guidance for consumers' consumption, and also providing more scientific basis for the quality evaluation and improvement of CGT.

CAS / MDL: 529-59-9 520-18-3
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MOLECULAR NUTRITION & FOOD RESEARCH · 2023 · IF 5.2

Ethanol Extract of Citrus grandis ‘Tomentosa’ Exerts Anticancer Effects by Targeting Skp2/p27 Pathway in Non-Small Cell Lung Cancer

Da Huang,Pei-En Wu,Zi-Jie Chen,Yan-Chun Pang,Zi-Wei Xu,Jingbo Tan,Zhi-Hua Jiang,Bing-Bing Yang,Ruoting Zhan,Hui Xu,Yong-Qiang Liu

Scope This study aims to investigate the anticancer properties of Citrus grandis ‘Tomentosa’ (CGT) in non-small cell lung cancer (NSCLC). Methods and results The ethanol extract of CGT (CGTE) is prepared by using anhydrous ethanol and analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), revealing that the main chemical components in CGTE are flavonoids and coumarins, such as naringin, rhoifolin, apigenin, bergaptol, and osthole. CGTE at concentrations without inducing cell death significantly inhibits cell proliferation via inducing cell cycle G1 phase arrest by MTT, colony formation, and flow cytometry assays, implying that CGT has anticancer potential. CGTE markedly inhibits the activity of Skp2-SCF E3 ubiquitin ligase, decreases the protein level of Skp2, and promotes the accumulation of p27 by co-immunoprecipitation (co-IP) and in vivo ubiquitination assay; whereas Skp2 overexpression rescues the effects of CGTE in NSCLC cells. In subcutaneous LLC allograft and A549 xenograft mouse models, CGTE, without causing obvious side effects in mice, significantly inhibits lung tumor growth by targeting the Skp2/p27 signaling pathway. Conclusion These findings demonstrate that CGTE efficiently inhibits NSCLC proliferation both in vitro and in vivo by targeting the Skp2/p27 signaling pathway, suggesting that CGTE may serve as a therapeutic candidate for NSCLC treatment.

CAS / MDL: 64-18-6
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INTERNATIONAL JOURNAL OF FOOD PROPERTIES · 2019 · IF 1.398

Comparison of the bioactive chemical components and antioxidant activities in three tissues of six varieties of Citrus grandis ‘Tomentosa’ fruits

Ruiyi Fan,Congyi Zhu,Diyang Qiu,Jiwu Zeng

The total phenolic, flavonoid, coumarin, and volatile contents and antioxidant activities in three tissues of six Citrus grandis ‘Tomentosa’ (CGT) fruit varieties were investigated. Two flavones, 3 coumarins and 147 volatiles were identified. The exocarp contained 3 coumarins, however, no coumarins were identified in the mesocarp, and only isoimperatorin was found in the pulp. In the exocarp, mesocarp and pulp, 104, 79 and 71 volatiles were identified, respectively. FuMao (FM) contained the highest total phenolic, naringin and rhoifolin amounts; HouYeZhengMao (HY-ZM) contained the highest meranzin hydrate and bergapten amounts; and XiYangZhengMao (XY-ZM) contained the highest isoimperatorin amount. The ABTS radical scavenging power of HuangLongZhengMao (HL-ZM) was the strongest, and FM had the strongest DPPH radical scavenging effect and ferric ion reducing antioxidant power. According to overall performance, FM and HY-ZM are the top two varieties with the highest total phenolic, flavonoid, and coumarin contents and antioxidant capacities.

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RSC Advances · 2025 ·Vol. 15 ·期 51 ·44049-44060 · IF 4.6

Development and optimization of green extraction of naringin in Citrus grandis ‘Tomentosa’ using natural deep eutectic solvents (NADES) and investigation of lung cancer therapeutics mechanisms

Jiaqi Yang,Guihua Zhang,Yanghuan Xing,Bixing Gao,Hua Du,Guihua Jiang

Natural bioactive compounds derived from traditional Chinese medicine have garnered widespread research interest. In this study, a green and efficient method for extracting naringin from Citrus grandis ‘Tomentosa’ (CGT) was developed using ultrasonic-assisted extraction (UAE) with the natural deep eutectic solvent (NADES) composed of choline chloride and levulinic acid (ChCl–Le). The extraction was carried out under the conditions of 40% (w/w) water content in NADES, a solid-to-liquid ratio of 1 : 65 (w/v), a temperature of 60 °C, an extraction time of 40 minutes, and an ultrasonic power of 300 W. Despite optimized and practical conditions, a high naringin yield of 4.7% was attained. This yield remains significantly greater than those obtained with methanol (4.1%) or ethanol (4.0%). Furthermore, the CGT extracts were evaluated for lung cancer therapeutics activity, leading to the identification of several key bioactive compounds, including poncirin, isosinensetin, sinensetin, nobiletin, didymin, neohesperidin, and naringenin. These components are known to exert therapeutic effects against lung cancer by targeting CYP17A1, CYP19A1, and AR, as well as by modulating pathways such as EGFR tyrosine kinase inhibitor resistance and prostate cancer. This study successfully establishes an eco-efficient extraction method for naringin and clarifies the multi-target mechanism of action of CGT extracts against lung cancer.

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