Abstract
Lycium ruthenicum polysaccharides (LRP) are known to possess antioxidant effects. However, a systematic evaluation across chemical, cellular, and in vivo models have been lacking. The underlying metabolomic mechanisms also remain unexplored. This study systematically evaluated the antioxidant effects of LRP through in vitro assays, H₂O₂-induced AML12 hepatocytes, and liver tissue from mice, supplemented by untargeted metabolomic analysis of cell extracts to explore LRP’s antioxidant mechanisms. Results showed that LRP possessed significant oxygen radical absorbance capacity and potent scavenging activity against ABTS•+, DPPH•, and •OH radicals in vitro. In AML12 cells, LRP increased activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GSH-Px), while effectively reducing intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels (P<0.05). In mouse liver tissues, LRP may have slightly improved SOD and CAT levels while decreasing MDA levels (P>0.05). Furthermore, untargeted metabolomics revealed that LRP attenuated oxidative damage by modulating metabolic pathways, particularly glutathione metabolism, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. These findings confirm the significant antioxidant potential of LRP, supporting its promise as a functional food ingredient.
Download PDF
Full Article
A Preliminary Study on the Antioxidant Activity of Lycium ruthenicum Polysaccharides in vitro/vivo and its Protective Mechanism on Oxidized Damaged Cells
Jianhui Li,a Ruoyu Wu,a Li-e Liu,a,* Yujiao Li,a Lihua Ding,a Hongping Li,b,* and Fei Yu,a
Lycium ruthenicum polysaccharides (LRP) are known to possess antioxidant effects. However, a systematic evaluation across chemical, cellular, and in vivo models have been lacking. The underlying metabolomic mechanisms also remain unexplored. This study systematically evaluated the antioxidant effects of LRP through in vitro assays, H₂O₂-induced AML12 hepatocytes, and liver tissue from mice, supplemented by untargeted metabolomic analysis of cell extracts to explore LRP’s antioxidant mechanisms. Results showed that LRP possessed significant oxygen radical absorbance capacity and potent scavenging activity against ABTS•+, DPPH•, and •OH radicals in vitro. In AML12 cells, LRP increased activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GSH-Px), while effectively reducing intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels (P<0.05). In mouse liver tissues, LRP may have slightly improved SOD and CAT levels while decreasing MDA levels (P>0.05). Furthermore, untargeted metabolomics revealed that LRP attenuated oxidative damage by modulating metabolic pathways, particularly glutathione metabolism, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. These findings confirm the significant antioxidant potential of LRP, supporting its promise as a functional food ingredient.
DOI: 10.15376/biores.21.2.4720-4730
Keywords: Lycium ruthenicum Murray; Metabolomics; Bioactive compounds; Phytochemicals
Contact information: a: College of Public Health, Zhengzhou University, Zhengzhou 450001, China; b: School of Chemical Engineering, Zhengzhou University, Zhengzhou 450001, China;
* Corresponding author: lhpzdgw@zzu.edu.cn; zzdxlle66@zzu.edu.cn
Graphical Abstract
INTRODUCTION
Phytochemicals such as polysaccharides, polyphenols, and flavonoids have received extensive attention because of their beneficial biological effects, including antioxidant, hypoglycemic, anti-tumor, and other activities (Öz et al. 2023; Gogoi et al. 2025). Among these bioactive constituents, plant polysaccharides, which are macromolecules composed of numerous monosaccharides linked by glycosidic bonds (Huang et al. 2025). Moreover, polysaccharides have high thermal stability, excellent biocompatibility, and low toxicity, making them effective functional food ingredients for combating oxidative stress (Xue et al. 2024). Such compounds can exert exceptional antioxidative effects through three complementary mechanisms: (1) direct scavenging of reactive oxygen species (ROS) (Tang et al. 2025), (2) activation of the enzymatic antioxidant system (Song et al. 2025), (3) regulation of signaling pathways (Yang et al. 2025).
Lycium ruthenicum Murray, a medicinal and edible plant, is rich in anthocyanins, polyphenols, and essential amino acids (Dong et al. 2025). With expanding cultivation and growing research interest, this species has attracted increasing attention in recent studies. To date, most studies have focused on its salt stress tolerance and anthocyanin composition (Liu et al. 2025). Nevertheless, emerging evidence has begun to highlight the bioactive potential of L. ruthenicum polysaccharides (LRP) (Liu et al. 2024; Lu et al. 2025; Zhao et al. 2026). Despite these promising findings, two fundamental knowledge gaps persist: (1) lack of comprehensive antioxidant evaluation of LRP spanning chemical scavenging, cellular protection, and in vivo models; and (2) lack of exploration of LRP’s antioxidant mechanisms. These limit the development of LRP as a functional food ingredient for oxidative stress mitigation.
This study assessed the antioxidant capacity of LRP in vitro and in vivo, and elucidated the potential regulatory mechanisms of LRP in AML12 cells by non-targeted metabolomics. By integrating chemical, cellular, and in vivo models with metabolomic profiling, this work can provide evidence supporting the potential of LRP as a functional food against oxidative stress-related diseases.
EXPERIMENTAL
Materials
Lycium ruthenicum Murray was obtained from Beijing Tongrentang Health Pharmaceutical (Qinghai) Co., Ltd. (Bar Code: 6971315920533). Ascorbic acid and 2,2-diphenyl-1-picrylhydrazyl (DPPH) were purchased from Aladdin Reagent (Shanghai) Co., Ltd. 2,2′-Azobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was from Shanghai Yuanye Bio-Technology Co., Ltd. The assay kits for catalase (CAT), glutathione reductase (GSH-Px), malonaldehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD) were obtained from Nanjing Jiancheng Bioengineering Institute. The C57BL/6 mice were purchased from the Laboratory Animal Center of Zhengzhou University (SCXK (Yu) 2017-0001). The AML12 cells were from Procell Life Science & Technology Co., Ltd.
The LRP was extracted in the laboratory. Lycium ruthenicum Murray was dried, pulverized, and sieved. The powder was sequentially defatted, dealcoholized, and extracted with hot water. The extract was concentrated, deproteinized, and precipitated. The crude polysaccharide pellet was washed and lyophilized to obtain LRP, giving a yield of 1.921% ± 0.074%. The procedure and structural features refer to elsewhere (Li et al. 2025).
Free Radical Scavenging and Lipid Peroxidation Inhibition
The ORAC was measured in the same way with some modifications (Yuri et al. 2022). Briefly, LRP was mixed with 150 μL of 8.16×10-2 μmol/L fluorescein sodium and incubated at 37 °C for 10 min. After adding 25 μL of 153 mmol/L 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) solution, the area under the curve (AUC) of fluorescence intensity was recorded to establish a calibration curve, and Trolox solution was used as the control. The ORAC values were obtained as follows,
AUC = f0×0.5+(f0+f1+…+fn-1+fn)+fn×0.5 (1)
where f0, fn-1, fn is the relative fluorescence intensities of the 0, n-1, and n measuring points, respectively.
The corresponding radical scavenging activities were determined using ABTS, DPPH, and the Fenton reaction system. They were determined using modified methods (Alodaini et al. 2025). Scavenging activity (%) was calculated as follows,
(2)
where AS is the absorbance of sample group, AS0 is the absorbance of sample control group, A0 is the absorbance of blank control group, and A00 is the absorbance of blank group.
Lipid peroxidation inhibitory ability was evaluated using egg yolk homogenate and the thiobarbituric acid method (Deng et al. 2024). The lipid peroxidation inhibition rate (IR) was calculated as follows.
(3)
where AS is the absorbance of sample group, AS0 is the absorbance of sample control group, and A0 is the absorbance of black control group.
Assay of Antioxidant Activity In Vitro
The general steps of the cell experiment were shown in Graphical Abstract (b). The levels of SOD, CAT, GSH-Px, MDA, and ROS were analyzed using commercial kits.
Assay of Antioxidant Activity In Vivo
The steps of the animal experiment were shown in Graphical Abstract (c). After intervention, mice were fasted and anesthetized, and liver tissue was obtained. The levels of SOD, CAT, and MDA in mouse liver tissue were measured using commercial kits.
Untargeted Metabolomic Analysis of Cell Extracts
The steps of the experiment were shown in Graphical Abstract (d). Metabolites in cells from the MLRP and HLRP groups were measured by Beijing Biomarker Technologies Co., Ltd, with some modifications of the method from the previous study (Wang et al. 2016).
Statistical Analysis
Statistical analyses were performed using SPSS 25.0. The data that fitted a normal distribution were expressed as means ± SD. The Spearman correlation coefficient was used to judge the correlation between different metabolites and antioxidant indices. P<0.05 was considered statistically significant.
RESULTS AND DISCUSSION
Free Radical Scavenging and Lipid Peroxidation Inhibition
As shown in Figs. 1A and B, fluorescence decay rates decreased dose-dependently with increasing concentrations of both Trolox and LRP. The ORAC of LRP was 435.5 μmol TE/100 g DW. In radical scavenging assays (Fig. 1C to E), LRP demonstrated potent activity with 50% inhibition concentrations (IC50) of 0.080 mg/mL for ABTS•⁺, 0.084 mg/mL for DPPH•, and 0.343 mg/mL for •OH. Notably, LRP significantly inhibited lipid peroxidation with IC₅₀ of 0.88 mg/mL (Fig. 1F).
Antioxidant Activity In Vitro
As shown in Fig. 2A, cell viability exhibited clear improvement with increasing concentrations of LRP, reaching maximum recovery at the highest tested concentration (500 µg/mL). Although the LLRP group showed no statistically significant difference compared to the MD group (P>0.05), both MLRP and HLRP treatments significantly enhanced viability (P<0.01). In Fig. 2B to D, compared to the MD group, MLRP and HLRP treatments significantly increased the activities of key antioxidant enzymes. SOD activity rose 2.0-fold, CAT activity increased 5.7-fold, and GSH-Px activity was elevated by 1.9-fold (P<0.01). Simultaneously, these treatments markedly decreased oxidative damage biomarkers (P<0.01). MDA level decreased by 68% (Fig. 2E), and intracellular ROS production was reduced by 49% relative to the MD group (Fig. 2F). Overall, these results demonstrate that LRP protects against H₂O₂-induced damage by synergistically enhancing endogenous antioxidant defenses and mitigating oxidative damage.
Fig. 1. Free radical scavenging and lipid peroxidation inhibition capacity of Vc and LRP. A-B: The result of ORAC. C-E: ABTS•+, DPPH•, •OH scavenging ability of LRP; F: Effect of LRP on inhibition activity of lipid peroxidation.
Antioxidant Activity In Vivo
In T2DM mouse livers, LRP treatment showed modest effects on hepatic antioxidant markers. SOD and CAT activities showed non-significant increases, while MDA content decreased marginally compared with the MD group (P>0.05, Fig. 3).
Fig. 2. Antioxidant activity of LRP in vitro. A: The effect of LRP intervention dose (μg/mL) on the viability of H2O2-induced AML12 cells; B-D: Cellular SOD, CAT, and GSH-Px viability; E: Cellular MDA level. F: Fluorescence intensity of ROS in various cellular test solutions. NEG: AML12 cells + PBS. POS: AML12 cells + probe + ROS. The rest: different treatment groups + probe. Compared with NC group, * P<0.05, ** P<0.01, *** P<0.001. Compared with MD group, + P<0.05, ++ P<0.01, +++ P<0.001.
Fig. 3. Antioxidant activity of LRP in vivo. A-C: SOD, CAT, and MDA viability. Compared with the NC group, * P<0.05, ** P<0.01
Untargeted Metabolomic Analysis of Cell Extracts
Differential metabolites were defined based on thresholds of |fold change (FC)| > 1.0, P<0.05, and variable importance in projection (VIP) score>1.0. Detailed counts are provided in Fig. 1d. Pathway enrichment analysis revealed that the MLRP group exhibited significant enrichment in the purine metabolism pathway and the ABC transporters pathway compared to the MD group (Fig. 4A). Similarly, the HLRP group showed enrichment in the purine metabolism and the porphyrin metabolism pathways (Fig. 4B).
Figure 5 shows the correlation analysis between cellular oxidative stress-related indexes and DAMs. Based on FC magnitude and P-value, eight signature metabolites with notable correlations were identified. These included cytosine, P1, P4-Bis (5′-uridyl) tetraphosphate, adenosine tetraphosphate, hypoxanthine, coenzyme A (CoA), N2-succinyl-L-ornithine, angiotensin II, and CDP-4-dehydro-6-deoxy-D-glucose (Table 1). Figure 1e indicated that these metabolites are involved in key metabolic pathways such as arginine and proline metabolism, purine and pyrimidine metabolism, TCA cycle, glutathione metabolism, and cofactor/vitamin metabolism.
Fig. 4. Analyses of metabolic pathways. A-B: Volcano plot and KEGG pathway enrichment dotplot for MLRP vs MD; C-D: Volcano plot and KEGG pathway enrichment dotplot for HLRP vs MD. A high-resolution version is available upon request.
To understand how LRP influences cellular metabolism to exert antioxidant effects, differentially abundant metabolites (DAMs) in the treatment groups were examined. The analysis identified 47 DAMs in the MLRP group and 69 in the HLRP group, with 16 metabolites overlapping between the two groups (Graphical Abstract).
Fig. 5. Correlation analysis between cellular oxidative stress-related indexes and differentially abundant metabolites. * P<0.05, ** P<0.01, *** P<0.001.
Among these, 14 metabolites with consistent alterations were selected for correlation analysis with key oxidative stress markers (SOD, CAT, GSH-Px, MDA, and ROS).
Table 1. Consistently Altered Metabolites and Their Classification
In the case of LRP (Li et al. 2025), SEM showed a relatively smooth surface, indicating a uniform molecular arrangement that may help interact with oxidative species. The monosaccharide composition of LRP is characterized by high levels of galacturonic acid, arabinose, galactose, and rhamnose, all of which have been linked to antioxidant activity (Chen et al. 2025). Notably, galacturonic acid could contribute carboxyl groups that work together with hydroxyl groups, enhancing electron-donating ability. Besides monosaccharide composition, the pattern of glycosidic linkages also impacts antioxidant activity, with β-type links often associated with stronger effects (Ao et al. 2025). Additionally, polysaccharides with lower molecular weights generally exhibit higher antioxidant potential because of easier access to reductive hydroxyl groups (Chen et al. 2024). Collectively, the reducing properties of LRP can be attributed to its smooth surface, specific monosaccharide composition rich in acidic sugars and distinctive molecular structure.
LRP protects against H₂O₂-induced oxidative damage by modulating multiple metabolic pathways (Fig. 1e), which is consistent with previous reports (Karagiannis et al. 2024). Specifically, LRP influences amino acid metabolism—where arginine serves as a precursor for nitric oxide and modulates SIRT1-related pathways to reduce apoptosis, while proline helps maintain mitochondrial redox balance (Zhao et al. 2021; Feng et al. 2023). It also regulates nucleotide metabolism; uridine alleviates oxidative stress, whereas imbalances in purine and pyrimidine metabolism exacerbate it (Wu et al. 2025). Furthermore, LRP affects cofactor and vitamin metabolism, including pantothenic acid and CoA biosynthesis—pathways known to influence mitochondrial function and antioxidant capacity (Lee et al. 2023). Glutathione metabolism further underscores mitochondrial reliance on the ascorbate-glutathione cycle to neutralize ROS (Decros et al. 2023). However, as these findings are based on untargeted metabolomics, further validation of the identified differential metabolites and their specific roles is warranted.
CONCLUSIONS
- This study systematically demonstrated the antioxidant activity of Lycium ruthenicum polysaccharides (LRP) in vitro and in vivo. The key insight is that LRP was found to exert potent antioxidant effects through a dual mechanism: direct radical scavenging (ORAC: 435.5 μmol TE/100 g DW; IC50: 0.080 mg/mL for ABTS•⁺, 0.084 mg/mL for DPPH•, 0.343 mg/mL for •OH) and enhancement of endogenous antioxidant defenses (SOD: 2.0-fold, CAT: 5.7-fold, GSH-Px: 1.9-fold), while reducing oxidative damage markers in H₂O₂-induced AML12 cells.
- Untargeted metabolomics revealed that LRP attenuated oxidative damage by modulating key metabolic pathways including glutathione metabolism, TCA cycle, and amino acid metabolism. This provides the metabolomic-level insight into how LRP combats oxidative stress by regulating cellular metabolism.
- These findings establish that the polysaccharides from Lycium ruthenicum are potent natural antioxidants. The present work advances the field by providing a comprehensive evaluation spanning chemical, cellular, and in vivo, and by elucidating the metabolomic mechanisms underlying LRP’s protective effects. This positions LRP as a promising functional food ingredient for oxidative stress-related diseases, with a clearer mechanistic understanding than previously available.
ACKNOWLEDGMENTS
The authors are grateful for the support of the Science and Technology Project of Henan Province [242102311174, 262102311104], the Natural Science Foundation Project of Henan Province [252300421355] and the Youth Program of the National Natural Science Foundation of China [82304194].
REFERENCES CITED
Alodaini, H. A., Sheeja, R. R., Joselin, J., Hatamleh, A. A., Al-Dosary, M. A., Rani, S. A., Vijayaraghavan, P., and Arokiyaraj, S. (2025). “Agro-industrial residues: Low-cost biomass for the production of bioactive extracellular polysaccharides by Lactobacillus plantarum in solid state fermentation,” BioResources 20(3), 7358-7377. https://doi.org/10.15376/biores.20.3.7358-7377
Ao, J., Liu, Y., Wei, Y., Wang, D., Wang, C., Wei, L., and Wei, G. (2025). “Antibacterial and antioxidant activities of β-glucans derived from Aureobasidium pullulans,” Food Bioscience 70, article 107074. https://doi.org/10.1016/j.fbio.2025.107074
Chen, N., Jiang, T., Xu, J., Xi, W., Shang, E., Xiao, P., and Duan, J.-a. (2024). “The relationship between polysaccharide structure and its antioxidant activity needs to be systematically elucidated,” International Journal of Biological Macromolecules 270, article 132391. https://doi.org/10.1016/j.ijbiomac.2024.132391
Chen, Q., Li, M., Li, Z., Mei, M., Lin, Y., Shu, P., and Zhu, W. (2025). “Alhagi camelorum seed polysaccharide alleviates methylglyoxal-induced skin damage via antioxidant and anti-inflammatory actions,” International Journal of Biological Macromolecules 311(Part 3), article 143661. https://doi.org/10.1016/j.ijbiomac.2025.143661
Decros, G., Dussarrat, T., Baldet, P., Cassan, C., Cabasson, C., Dieuaide-Noubhani, M., Destailleur, A., Flandin, A., Prigent, S., Mori, K., et al. (2023). “Enzyme-based kinetic modelling of ASC–GSH cycle during tomato fruit development reveals the importance of reducing power and ROS availability,” New Phytologist 240(1), 242-257. https://doi.org/10.1111/nph.19160
Deng, N., Liu, Y., Cai, Y., Li, H., Li, C., Xiao, Z., Zhang, B., Liu, M., Fang, F., and Wang, J. (2024). “Characterization, antioxidant, and sausage preservation effects of ethanol extract from lotus seed peel powder,” Food Control 158, article 110202. https://doi.org/10.1016/j.foodcont.2023.110202
Dong, D., Wang, H., Bi, H., Li, Y., Gao, T., Feng, J., Li, G., Guo, S., Yuan, H., and Ni, W. (2025). “A pectic polysaccharide from Lycium ruthenicum Murray alleviates dextran sulfate sodium-induced colitis in mice,” Current Research in Food Science 10, article 100955. https://doi.org/10.1016/j.crfs.2024.100955
Feng, X., Wang, X., Zhou, L., Pang, S., and Tang, H. (2023). “The impact of glucose on mitochondria and life span is determined by the integrity of proline catabolism in Caenorhabditis elegans,” Journal of Biological Chemistry 299(2), article 102881. https://doi.org/10.1016/j.jbc.2023.102881
Gogoi, P., Sharma, P., Goudar, G., Mahajan, A., Kumar, D., Ananthan, R., and Longvah, T. (2025). “In-vitro gastrointestinal digestion impact on bioaccessibility and antioxidant activity of polyphenols from microwave-roasted and pressure-cooked pigmented rice,” Food Bioscience 71, article 107208. https://doi.org/10.1016/j.fbio.2025.107208
Huang, R., Li, R., Qin, M., Qian, N., Lai, K. P., Lu, H., and Li, R. (2025). “A review on anti-aging actions of plant polysaccharides,” Future Foods 12, article 100684. https://doi.org/10.1016/j.fufo.2025.100684
Karagiannis, D., Wu, W., Li, A., Hayashi, M., Chen, X., Yip, M., Mangipudy, V., Xu, X., Sánchez-Rivera, F. J., Soto-Feliciano, Y. M., et al. (2024). “Metabolic reprogramming by histone deacetylase inhibition preferentially targets NRF2-activated tumors,” Cell Reports 43(1), article 113629. https://doi.org/10.1016/j.celrep.2023.113629
Lee, Q., Han, X., Zheng, M., Lv, F., Liu, B., and Zeng, F. (2023). “Preparation of low molecular weight polysaccharides from Tremella fuciformis by ultrasonic-assisted H2O2-Vc method: Structural characteristics, in vivo antioxidant activity and stress resistance,” Ultrasonics Sonochemistry 99, article 106555. https://doi.org/10.1016/j.ultsonch.2023.106555
Li, Y., Wang, Y., Xu, X., Ding, L., Liu, and L.-e. (2025). “Characterization of polysaccharides from Lycium ruthenicum Murray and its regulatory effect on the intestinal flora of T2DM mice,” BioResources 20(4), 10568-10579. https://doi.org/10.15376/biores.20.4.10568-10579
Liu, B., Ma, J., Li, T., Li, P., Yan, D., Zhu, J., and Zhang, X. (2024). “Advances in the preparation, structure and bioactivity of polysaccharides from Lycium ruthenicum Murr.: A review,” Foods 13(13), article 1995. https://doi.org/10.3390/foods13131995
Liu, Z., Zhou, L., Yan, B., and Liu, Z. (2025). “Comprehensive assessment of climate-driven distribution dynamics and anthocyanin variation in Lycium ruthenicum using MaxEnt, HPLC, and chemometric approaches,” Industrial Crops and Products 233, article 121359. https://doi.org/10.1016/j.indcrop.2025.121359
Lu, N., Xu, S., Xiang, W., Mei, X., Hu, H., Tang, X., Gong, X., and Wang, X. (2025). “Lycium ruthenicum Murr. polysaccharide attenuated inflammatory response and intestinal flora dysbiosis in LPS-induced acute lung injury in mice,” Nutrients 17(18), article 2944. https://doi.org/10.3390/nu17182944
Öz, M., Baltaci, C., Fidan, M. S., and Karatas, S. M. (2023). “Antimicrobial, antioxidant, and phytochemical activities of Rhus coriaria L. and its phenolic compounds and volatile component analyses,” Bioresources 18(4), 6842-6861. https://doi.org/10.15376/biores.18.4.6842-6861
Song, J., Zhang, Z., Wang, H., Meng, Y., Sun, Y., and Yi, Y. (2025). “Study on the structure and lipid-lowering activity of different components of lotus root polysaccharides,” Food Research International 203, article 115801. https://doi.org/10.1016/j.foodres.2025.115801
Tang, D., Zhou, S., Wang, Z., Zhang, Y., Liu, K., Yang, J., Yang, X., Li, Y., and Zhang, X. (2025). “Efficiently radiation-induced degradation and extraction of Polygonatum sibiricum polysaccharides and its excellent ROS scavenging properties,” Chemical Engineering Journal 505, article 159717. https://doi.org/10.1016/j.cej.2025.159717
Wang, J., Zhang, T., Shen, X., Liu, J., Zhao, D., Sun, Y., Wang, L., Liu, Y., Gong, X., and Liu, Y. (2016). “Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC-QTOF/MS(Article),” Metabolomics 12(7), 1-10. https://doi.org/10.1007/s11306-016-1050-5
Wu, Y., Fan, F., Zhou, L., Shen, Y., Wang, A., Qin, Y., Wang, J., and Yao, W. (2025). “ADB-FUBINACA-induced developmental toxicity, neurotoxicity, and cardiotoxicity in embryonic zebrafish (Danio rerio),” Environmental Research 276, article 121517. https://doi.org/10.1016/j.envres.2025.121517
Xue, H., Du, X., Fang, S., Gao, H., Xie, K., Wang, Y., and Tan, J. (2024). “The interaction of polyphenols-polysaccharides and their applications: A review,” International Journal of Biological Macromolecules 278(1), article 134594. https://doi.org/10.1016/j.ijbiomac.2024.134594
Yang, M., Xiao, Y., Yan, Z., Duan, Y., Hu, K., Cai, M., and Zhang, H. (2025). “Poria cocos polysaccharide and lotus seedpod polyphenols synergistically inhibit CRFK cell damage induced by magnesium ammonium phosphate via activating Nrf2/HO-1 signaling pathway,” Food Bioscience 66, article 106184. https://doi.org/10.1016/j.fbio.2025.106184
Yuri, J. A., Neira, A., Fuentes, M., Sáez, B., and Razmilic, I. (2022). “Have the flowers, fruitlets, ripe fruit and leaves of apples cultivars similar compositions of phenolic and antioxidant capacity?,” Erwerbs-Obstbau 64(2), 201-209. https://doi.org/10.1007/s10341-022-00638-1
Zhao, Y., Jiang, Q., Zhang, X., Zhu, X., Dong, X., Shen, L., Zhang, S., Niu, L., Chen, L., Zhang, M., Jiang, J., Chen, D., and Zhu, L. (2021). “l-Arginine alleviates LPS-induced oxidative stress and apoptosis via activating SIRT1-AKT-Nrf2 and SIRT1-FOXO3a signaling pathways in C2C12 myotube cells,” Antioxidants (Basel, Switzerland) 10(12), article 1957. https://doi.org/10.3390/antiox10121957
Zhao, Y., Ma, C., Qiao, M., Hou, Q., Hu, J., Yang, J. (2026). “Integrated enzyme-ultrasound assisted aqueous two-phase extraction yields Lycium ruthenicum polysaccharides that attenuate hepatic and retinal aging via the gut-liver-retina axis,” Industrial Crops and Products 243, article 123117. https://doi.org/10.1016/j.indcrop.2026.123117
Article submitted: December 19, 2025; Peer review completed: March 21, 2026; Revised version received and accepted: March 30, 2026; Published: April 13, 2026.
DOI: 10.15376/biores.21.2.4720-4730