Abstract
Turning agricultural and food processing by-products into health-promoting ingredients is pivotal for developing sustainable food systems. This study developed an integrated multi-dimensional evaluation framework to assess whether the common pomelo peel by-product (Citrus grandis (L.) Osbeck, CGO) can serve as a functionally equivalent alternative to the rare Citrus grandis ‘Tomentosa’ (CGT) for functional food ingredient development. The framework combined comparative metabolomics and delayed luminescence profiling to characterize chemical and physical properties, alongside multi-parametric in vivo bioactivity and safety assessment in a diet-induced vertebrate model. Analyzes confirmed CGO and CGT as distinct chemotypes and physicotypes, with differential enrichment in bioactive pathways like phenylpropanoid biosynthesis. Crucially, both extracts demonstrated statistically equivalent efficacy in alleviating hepatic steatosis, oxidative stress, and inflammation in a high-cholesterol diet-induced zebrafish model, and modulated key genes related to lipid metabolism, antioxidant response, and inflammation. Safety assessment revealed CGO’s significantly wider safety margin. Data integration across dimensions demonstrates that despite compositional differences, the net bioactivity converges on similar beneficial outcomes for liver metabolic health. This work provides a validated strategy for transforming underutilized residues into a multi-target, dietary-relevant ingredient, offering a replicable framework for resource-efficient development of sustainable functional crops and food supply chains.

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Data availability
The datasets generated and/or analyzed during the current study are not publicly available due to they are part of an institutional database for ongoing projects but are available from the corresponding author on reasonable request.
References
Sarangi, P. K., Srivastava, R. K., Sahoo, U. K. & Vivekanand, V. Resource recovery from Pomelo byproducts for zero waste biorefinery and bioeconomic perspectives. Process Saf. Environ. Prot. 186, 1330–1344 (2024).
Tocmo, R., Pena-Fronteras, J., Calumba, K. F., Mendoza, M. & Johnson, J. J. Valorization of pomelo (Citrus grandis Osbeck) peel: a review of current utilization, phytochemistry, bioactivities, and mechanisms of action. Compr. Rev. Food Sci. Food Saf. 19, 1969–2012 (2020).
Rinella, M. E. & Sookoian, S. From NAFLD to MASLD: updated naming and diagnosis criteria for fatty liver disease. J. Lipid Res. 65, 100485 (2024).
Geng, Y., Faber, K. N., de Meijer, V. E., Blokzijl, H. & Moshage, H. How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease? Hepatol. Int. 15, 21–35 (2021).
El-Sehrawy, A. et al. Combating oxidative stress in non-alcoholic fatty liver disease: From mechanisms to therapeutic strategies. Pathol. Res. Pract. 272, 156053 (2025).
Oladipupo, S. O., Ezenabor, E. H., Ojo, A. B., Ogunlakin, A. D. & Ojo, O. A. Interplay of the pathophysiological mechanisms of non-alcoholic fatty liver disease, diabetes mellitus, and inflammation: a growing threat to public health. Obes. Med. 100613, https://doi.org/10.1016/j.obmed.2025.100613 (2025).
Ghosh, D. et al. Phytotherapy for non-alcoholic fatty liver disease: A review of mechanisms, efficacy, and future directions. Nat. Ther. Adv. 8, 6 (2025).
Miryan, M., Azizi, A., Pasdar, Y. & Moradi, M. Adherence to plant based diets reduce the risk of hepatic fibrosis in nonalcoholic fatty liver disease. Sci. Rep. 15, 17403 https://doi.org/10.1038/s41598-025-02613-8 (2025).
Feng, Q. et al. Discovery of pharmacological effects and targets of Citri Grandis Exocarpium based on SYSTCM and virtual screening. Food Nutr. Res. 68, 10.29219 (2024).
Deng, G. et al. Exocarpium Citri Grandis alleviates the aggravation of NAFLD by mitigating lipid accumulation and iron metabolism disorders. J. Ethnopharmacol. 313, 116559 (2023).
Hu, M., Zhang, L., Ruan, Z., Han, P. & Yu, Y. The regulatory effects of citrus peel powder on liver metabolites and gut flora in mice with non-alcoholic fatty liver disease (NAFLD). Foods 10, 3022 (2021).
Tian, D. et al. Coumarin analogues from the Citrus grandis (L.) Osbeck and their hepatoprotective activity. J. Agric. Food Chem. 67, 1937–1947 (2019).
Li, Y. J. et al. Exocarpium Citri Grandis ameliorates alcoholic liver disease by modulation of hepatic lipid metabolism and iron homeostasis. Chin. Med. 20, 174 (2025).
Xian, L. et al. The draft genome and multi-omics analyses reveal new insights into geo-herbalism properties of Citrus grandis ‘Tomentosa. Plant Sci. 325, 111489 (2022).
Liu, G. et al. Sequential grade evaluation method exploration of Exocarpium Citri Grandis (Huajuhong) decoction pieces based on “network prediction --> grading quantization --> efficacy validation”. J. Ethnopharmacol. 291, 115149 (2022).
Huang, H. et al. Evaluation of the authenticity of Citri Grandis Exocarpium based on metabolomics and transcriptomics. Med. Plant Biol. 4, 1 (2024).
Su, W.-W. et al. The potential application of the traditional Chinese herb Exocarpium Citri grandis in the prevention and treatment of COVID-19. Tradit. Med. Res. 5, 160–166 (2020).
Hu, S. et al. Analysis of volatile compounds in Citri grandis from different regions in South China and the response of volatile compounds to ecological factors. Molecules 30, 622 (2025).
Fan, R., Zhu, C., Qiu, D. & Zeng, J. Comparison of the bioactive chemical components and antioxidant activities in three tissues of six varieties of Citrus grandis ‘Tomentosa’ fruits. Int. J. Food Prop. 22, 1848–1862 (2019).
Temirbayeva, D., Ibrayev, N. & Kucherenko, M. Distance dependence of plasmon-enhanced fluorescence and delayed luminescence of molecular planar nanostructures. J. Lumin. 243, 118642 (2022).
Committee, C. P. Pharmacopoeia of the People’s Republic of China. 2025 edn (China Medical Science Press, 2025).
Popp, F.-A. & Yan, Y. Delayed luminescence of biological systems in terms of coherent states. Phys. Lett. A 293, 93–97 (2002).
Zhu, J. et al. Quality-grade analysis of velvet antler materials using ultra-weak delayed luminescence combined with chemometrics. Qual. Assur. Saf. Crops Foods 15, 1–10 (2023).
Fu, Y. et al. Delayed luminescence: An effective measurement for determining the growth ages of forest cultivated ginseng. Microchem. J. 210, 112921 (2025).
Sun, Q. et al. Investigation of the dynamic alteration in delayed luminescence property and their correlation with ginsenoside over the classical nine-cycle steaming and drying processing of black ginseng. LWT 218, 117474 (2025).
Sun, M. et al. Delayed luminescence: an experimental protocol for Chinese herbal medicines. Luminescence 31, 1220–1228 (2016).
Sun, M. et al. Characterization of ginsenoside extracts by delayed luminescence, high-performance liquid chromatography, and bioactivity tests. Photochem. Photobiol. Sci. 18, 1138–1146 (2019).
Wang, L. et al. Investigation of processing duration on red ginseng quality utilizing delayed luminescence combined with chemometrics and immunomodulatory assessment. J. Food Compos. Anal. 143, 107655 (2025).
Shi, F. et al. Dictamnine-induced hepatotoxicity in mice: the role of metabolic activation of furan. Toxicol. Appl. Pharmacol. 364, 68–76 (2019).
He, K. et al. Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem. Res. Toxicol. 11, 252–259 (1998).
Liang, Y. et al. Bergapten: A review of its pharmacology, pharmacokinetics, and toxicity. Phytother. Res. 35, 6131–6147 (2021).
Katoch, S. & Patial, V. Zebrafish: an emerging model system to study liver diseases and related drug discovery. J. Appl. Toxicol. 41, 33–51 (2021).
Shimizu, N., Shiraishi, H. & Hanada, T. Zebrafish as a useful model system for human liver disease. Cells 12, 2246 (2023).
Ko, J. H., Nam, D., Um, J. Y., Jung, S. H. & Ahn, K. S. Bergamottin inhibits adipogenesis in 3T3-L1 cells and weight regulation in diet-induced obese mice. Am. J. Chin. Med. 46, 601–615 (2018).
Yazıcı, E., Şahin, E., Alvuroğlu, E., Yuluğ, E. & Menteşe, A. Bergamottin reduces liver damage by suppressing inflammation, endoplasmic reticulum and oxidative stress in cafeteria diet-fed mice. Food Biosci. 52, 102371 (2023).
Kim, M. J. et al. Hypolipogenic effect of shikimic acid via inhibition of MID1IP1 and phosphorylation of AMPK/ACC. Int. J. Mol. Sci. 20, 582 (2019).
Rives, C. et al. Oxidative stress in NAFLD: role of nutrients and food contaminants. Biomolecules 10, 1702 (2020).
Wang, J. et al. Alleviating effect of quercetin on cadmium-induced oxidative damage and apoptosis by activating the Nrf2-keap1 pathway in BRL-3A cells. Front. Pharmacol. 13, 969892 (2022).
Qi, Y. et al. Luteolin attenuated cisplatin-induced cardiac dysfunction and oxidative stress via modulation of Keap1/Nrf2 signaling pathway. Free Radic. Res. 56, 209–221 (2022).
Zhang, J. et al. Apigenin protects against renal tubular epithelial cell injury and oxidative stress by high glucose via regulation of NF-E2-related factor 2 (Nrf2) pathway. Med. Sci. Monit. 25, 5280 (2019).
Shwartz, A., Goessling, W. & Yin, C. Macrophages in zebrafish models of liver diseases. Front. Immunol. 10, 2840 (2019).
Phung, T. D., Le, T. N. & Phung, A. T. Naringin extracted from vietnamese citrus maxima peels: extraction and optimization. Agric. Rev. 46, 1–8 (2025).
Lozada, D. N., Pulicherla, S. R. & Holguin, F. O. Widely targeted metabolomics reveals metabolite diversity in jalapeno and serrano chile peppers (Capsicum annuum L.). Metabolites 13, 288 (2023).
Fang, X. et al. Puerarin induces macrophage M2 polarization to exert antinonalcoholic steatohepatitis pharmacological activity via the activation of autophagy. J. Agric. Food Chem. 72, 7187–7202 (2024).
Cheng, J. et al. Investigation of anti-inflammatory effect of essential oil extracted from Achillea alpina L. through multi-omics analysis in zebrafish tail fin amputation model. J. Ethnopharmacol. 344, 119519 (2025).
Acknowledgements
This research was supported by the University-College Joint Scientific and Technological Innovation Fund of Guangzhou University of Chinese Medicine (GZYDG2024G07); the Jilin Provincial Development and Reform Commission (No. 2023C028-1); the Pilotscale Selection Project of Colleges and Universities in Changchun City (No.24GXYSZZ10); the Ministry of Human Resources and Social Security of the People's Republic of China high-level talent project (No.030102070; No.030102071). The authors would like to thank Mr. Zhongfeng Chen, Ms. Mengyu Jiang and Guanshu Biotechnology Services (Changchun) Co., Ltd for providing the technical guidance.
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Min He, Mengmeng Sun and Dong Li designed the study. Yuliang Liu, Qizhong Lian, Jianan Wang and Mengmeng Sun conducted experimental work and data analysis. Xianghe Meng provided zebrafish resource. Yuliang Liu and Mengmeng Sun drafted the manuscript. Davron Dekhkonov, Hilola Ahunova and Komiljon Tojibaev contributed to revisions of the manuscript. All authors read and approved the final manuscript.
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Liu, Y., Sun, M., Lian, Q. et al. Valorizing common pomelo peel by-product via a multi-dimensional framework: a functionally equivalent alternative to a rare botanical for liver health. npj Sci Food (2026). https://doi.org/10.1038/s41538-026-00813-8
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DOI: https://doi.org/10.1038/s41538-026-00813-8


