Abstract
Pyracantha fortuneana fruit (PF), a traditional edible-medicinal resource, holds promising potential for functional food and nutraceutical applications. In this study, we evaluated the preventive effects of PF on T2DM in Sprague-Dawley (SD) rats using a high-fat and high-sugar diet combined with streptozotocin (STZ)-induced diabetes model. Forty male SD rats were randomly divided into four groups: normal control (NC), model control (MC), low-dose PF (PF-L, 450 mg/kg/d), and high-dose PF (PF-H, 900 mg/kg/d). The rats were administered PF or vehicle for six weeks before STZ injection, followed by assessments of body weight, glucose tolerance, insulin sensitivity, and serum lipid profiles. UHPLC-MS/MS analysis identified 15 PF-derived compounds in the bloodstream, including flavonoids and phenolic acids. 16S rDNA sequencing revealed that PF pre-intervention restored gut microbiota balance by reducing pathogenic bacteria (e.g., Prevotella 9) and increasing beneficial taxa (e.g., Blautia). Serum metabolomics demonstrated PF’s regulatory effects on 269 metabolites, particularly in glycerophospholipid metabolism and bile acid pathways. Correlation analysis linked six key PF components to improved metabolic and microbial profiles, suggesting a multi-target mechanism for its anti-diabetic effects. These findings highlight PF as a promising natural intervention for T2DM, with potential applications in functional foods or nutraceuticals. These findings highlight PF as a valuable natural resource for developing functional foods or nutraceuticals to manage T2DM, supporting its further industrial exploitation.
Highlights
- Pyracantha fortuneana (Maxim.) H. L. Li fruit (PF) deserves to be new natural cash crops and health products.
- The key functional components of PF benefit to T2DM were identified.
- The role of PF-regulated metabolic pathway and intestinal flora in alleviating the progression of T2DM were discovered.
Introduction
Diabetes is an endocrine and metabolic disorder characterized by hyperglycemia caused by insufficient insulin secretion or insulin resistance (Khunti et al., 2023). Recent global estimates indicate that 537 million adults have diabetes, of whom 80 % live in low-income and middle-income countries (Gregg et al., 2023). Especially, the number of diabetics in China has exceeded 140 million, accounting for 40 % of the world, and is still increasing (Fralick et al., 2022). Rising economic level, the change of diet structure, obesity and aging are the main reasons for the prevalence of diabetes in our country (Chu et al., 2023). Chronic hyperglycemia can lead to diabetic nephropathy, diabetic retinopathy, neuropathy and other complications (Dhanapalaratnam et al., 2024, Hu et al., 2024, Ma et al., 2022). Both diabetes and its complications are serious threats to human health that need to be contained urgently (Khosla et al., 2021). Among them, type 2 diabetes mellitus (T2DM) accounts for more than 90 % of all diabetic patients, and the treatment rate and treatment compliance rate of patients diagnosed with T2DM are less than 50 %(Bielka et al., 2024; Li Zhen et al., 2025). Up to now, there is no effective cure for diabetes treatment, and blood sugar of patients can only be controlled through oral drugs, insulin injection therapy, exercise and dietary intervention (Ahmad et al., 2022). Even worse are the side effects produced by oral hypoglycemic drugs such as biguanides, thiazolidinediones and glucosidase inhibitors and their inability to prevent diabetes and improve its complications (Rossing et al., 2023, Yao et al., 2024). These therapeutic challenges have spurred interest in medicinal-edible plants as complementary interventions(Valabhji and Kar, 2023). The use of them in diabetes intervention offers multiple benefits, including natural and mild effects that reduce side effects, holistic regulation of blood sugar and metabolism, long-term safety for chronic management, multi-target actions such as improving insulin sensitivity and reducing inflammation, and potential synergy with conventional treatments to lower medication dependence(Rana et al., 2022; Shahidi and Ambigaipalan, 2018).
Among many promising candidates, PF emerges as a particularly compelling subject for diabetes research due to its unique phytochemical profile and traditional use history. PF belongs to Rosaceae family, is a thorny and evergreen shrub that densely distributes from Southeast Europe to South-East Asia(Li et al., 2024). The PF has been taken for food source more than 1700 years in China and the Western Himalayas. Countries such as Germany, England, China and France also have been listed PF fruits as herbal drugs (Chauhan and Banerjee, 2024). The PF taste slightly astringent and actually fragrant with sweet taste. PF is rich in nutrients, containing 18 amino acids, various vitamins, trace elements, and unsaturated fatty acids. It also possesses abundant bioactive compounds, including phenolic acids, flavonoids, polysaccharides, fatty acids, as well as volatile components such as aldehydes, ketones, alcohols, alkanes, alkenes, esters, and terpenes. To date, researchers have isolated and identified over 100 different compounds from Pyracantha fruits (Yao et al., 2021). Belwal et al. and Wang et al. successfully isolated multiple phenolic acids from PF, including ellagic acid, chlorogenic acid, gallic acid, m-coumaric acid, p-coumaric acid, caffeic acid, sinapoylglucose, and veratric acid (Belwal et al., 2019, Wang et al., 2019). Modern research indicates that PF exhibits significant bioactive effects, primarily including antioxidant, immunomodulatory, anti-inflammatory, antimicrobial, antitumor, skin-whitening, anti-aging, and regulation of glucose and lipid metabolism(Li et al., 2022; Xu et al., 2019). A molecular docking study employed computational techniques, including molecular docking, ADMET analysis, and pharmacokinetic prediction, to systematically investigate the active constituents of PF and their potential anti-diabetic mechanisms. The research identified several bioactive compounds, such as phenolic acids (e.g., chlorogenic acid, caffeic acid), flavonoids (e.g., rutin, quercetin, kaempferol), and triterpenoids (e.g., ursolic acid, oleanolic acid), which exhibit therapeutic effects by targeting multiple diabetes-related pathways. Furthermore, these compounds demonstrated favorable pharmacokinetic properties and low toxicity, suggesting a potential multi-target synergistic mechanism for anti-diabetic activity(Arya, 2024). However, despite these promising indications, rigorous experimental validation of PF’s anti-diabetic potential remains lacking. Therefore, in this paper, the preventive effect of PF was evaluated through a high-fat and high-sugar SD rat type 2 diabetes model. The results of the study will provide evidence of PF in the prevention of type 2 diabetes, and lay a foundation for its development and utilization and subsequent in-depth research.
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Xiaoshuang Wang, Xuanlin Wu, Qingwen Ouyang, Fusong Liu, Sha Liu, Jia Qiu, Delin Zhang, Wenping He, Qian Tian, Bingjing Li, Shuang Ren, Yanju Li, Ting Pan, Faming Wu, Unlocking the anti-diabetic potential of Pyracantha fortuneana fruit: A natural remedy to combat type 2 diabetes in SD rats, Industrial Crops and Products, Volume 237, 2025, 122170, ISSN 0926-6690, https://doi.org/10.1016/j.indcrop.2025.122170.
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