ABSTRACT This study demonstrates the antioxidative stress potential of Shanyao–Fuling–Yiyiren (SFY) decoction—a Chinese polyherbal formulation derived from Si Fang decoction—by establishing a systematic framework that integrates network pharmacology, molecular docking, in vitro synergy assays, cellular experiments, and 3D printing. Despite its long traditional use, the molecular and cellular mechanisms underlying its antioxidative effects remain unclear, and its formulations are based more on empirical methods than on systematic design. To fill this gap, a fuzzy mathematical model was used to select the optimal polyherbal combination. A central composite circumscribed design determined that a Shanyao:Fuling:Yiyiren ratio of 2:2:1 maximized radical scavenging, with a strong correlation (R ^2 = 0.9665) between antioxidant activity and the combination index. Furthermore, network pharmacology, molecular docking, and cell‐based assays jointly confirm the AKT1/GSK3β/HIF1α pathway plays a crucial role in preventing the antioxidant effects of SFY. Finally, the development of 3D printing SFY‐inks with the optimized shape fidelity suggests promising applications for both nutraceuticals and hepatocellular carcinoma diagnosis. Overall, the results prove that 3D printing SFY‐based polyherbal formulation with promising antioxidant potential and maximum synergism may indeed be a potential source of preventing oxidant damages in pharmaceutical and food industries. Keywords: 3D printing food, AKT1/GSK3β/HIF1α pathway, fuzzy mathematical model, network pharmacology, Shanyao–Fuling–Yiyiren (SFY)‐based polyherbal formulation __________________________________________________________________ SFY‐based polyherbal formulation was selected based on fuzzy mathematical model. The best combinations with synergistic effect were optimized and identified by central composite circumscribed design. Network pharmacology and molecular docking‐based approach revealed that the potential mechanisms of decoction against oxidant damage via multicomponent, multitarget, and multipathway. Decoction presented ideal antioxidative protection activity against H[2]O[2] damage. Decoction‐based inks have great practical printability and 3D printing performance for potential application in functional food production. graphic file with name FSN3-13-e70349-g005.jpg 1. Introduction About 95% of humans worldwide stay up late at night, but handling jet lag can disrupt circadian rhythms, which is considered a stress state related to many diseases, including metabolic disorders and liver cancer. As a vital organ in charge of detoxification, the liver is very sensitive to damages from physiological stress, resulting in life‐threatening conditions (e.g., liver injury) with a high mortality rate and poor prognosis. Among the many causes of liver injury, uninterrupted production of reactive oxygen species (ROS) from both endogenous and exogenous origins has received much attention, including hydroxyl radical (OH˙), hydrogen peroxide (H[2]O[2]), hydroxyl ion (OH^−), singlet oxygen (^1O[2]), superoxide anion (O[2]˙^−), and ozone (O[3]) (Chen et al. [44]2020). Studies have demonstrated a connection between prolonged exposure to ROS and liver diseases (Prieto and Monsalve [45]2017). The elevated levels of ROS are intracellular signaling factors that remarkably enhance hepatic stellate cell activation and extracellular matrix generation amid liver injuries. Additionally, ROS activates significant oncogenic pathways leading to hepatocarcinogenesis, such as extracellular signal‐regulated kinase, protein kinase B, c‐Jun N‐terminal kinase, hypoxia‐inducible factor (HIF), microtubule‐related protein kinase, and intensified cellular DNA mutations (Hammouda et al. [46]2020). Concurrently, concerns about the adverse effects of synthetic antioxidants in foods have diverted more attention to novel sources of natural antioxidants from the safety aspect. Given the critical role of oxidative stress in liver disease occurrence, the role of phospholipid peroxidation in liver injuries shall be urgently explored. Against this backdrop, we hypothesize that phospholipid peroxidation represents a key mechanistic link between circadian disruption and stress‐related liver injuries. Emerging evidence has described that traditional medicinal herbs potentially contribute to preventing oxidative stress‐related chronic diseases (Allison et al. [47]2025; Ashraf et al. [48]^2024). These herbs have been applied conventionally for millennia by many cultures as medicine, flavoring reagents, and even food preservatives, and are basically cheap and available for poor populations. Researchers have tested their antioxidant abilities and potential replacements of synthetic additives in protecting food and cosmetic products from oxidative damages. Specifically, Shanyao (Rhizoma Dioscoreae), Fuling (Poria cocos (Schw.) Wolf.), and Yiyiren (Coicis Semen) are widely used in traditional medicine, owing to their potent antioxidant properties. Shanyao in the crude form has long been used as a spice, dietary supplement, and a constituent of many traditional Asian medicines (Luo et al. [49]2024). Shanyao contains curcumin, which has these pharmacological abilities owing to its basic beneficial antioxidant, anti‐inflammatory, antibacterial, and anticancer abilities (Alam et al. [50]2024). Fuling has diverse pharmacological activities against rheumatoid arthritis, type II diabetes, multiple sclerosis, atherosclerosis, Alzheimer's disease, and other chronic diseases (Guo et al. [51]2025). Free radicals, which are key stimuli for carcinogenesis, can be inhibited by Fuling from modulating lipid peroxidation of membranes or oxidative DNA harms. As for the antioxidant role, Yiyiren is proved to effectively scavenge diverse risky free radicals, including ROS, NO[2] radicals, O[2]˙^−, and OH˙ (Zhang et al. [52]2024). Regardless of the abundant research, observations about the antioxidant synergism in mixtures are still deficient. Moreover, recent studies have raised significant controversy regarding the standardization of such evaluations, reflecting a wider gap in understanding the underlying mechanisms of antioxidant synergism (Cnudde et al. [53]2024; Eawsakul and Bunluepuech [54]^2024; Shen et al. [55]^2025). This lack of consensus has led to speculation and explanations in the literature, many of which lack empirical verification. In view of antioxidant synergism effects, the mixing of antioxidant extracts may induce a synergism to generate a better antioxidant effect than the sum produced by single extracts (additives) (Eawsakul and Bunluepuech [56]2024; Kurnia et al. [57]^2025). Moreover, the ratio and type of individual herb extracts are pivotal in deciding the chemo‐preventive potential or antioxidant capacity in a health‐benefiting herb combination. Thus, the regulation of antioxidant properties shall be investigated according to the proportions of herbs in a mixture that can be used to develop functional foods and pharmaceutical products at different contents. For instance, the combination of Osmanthus fragrans flower extract with four types of tea (Longjing, Tieguanyin, black, or Pu'er Tea) can synergistically scavenge 2,2‐diphenyl‐1‐picrylhydrazyl free radicals (Mao et al. [58]2017), demonstrating how specific combinations can enhance antioxidant performance beyond individual components. To our knowledge, though the antioxidant activities of Shanyao, Fuling, and Yiyiren have been extensively reported, there is little research on the bio‐effects of extracts combined with bioactive compounds, which are believed to improve the antioxidant benefit of free radical scavenging. Therefore, this study was aimed primarily to explore the antioxidant interaction among Shanyao, Fuling, and Yiyiren at various proportions using response surface methodology (RSM) and the combination index. On the basis of synergism and optimization of the decoction process, we simultaneously conducted network pharmacology and molecular docking experiments to elucidate the mechanisms of the Shanyao, Fuling, and Yiyiren compound (SFY) binding with AKT1, GSK3B, TP53, HIF1A, and PTGS2‐related targets. Then whether SFY can mitigate oxidative stress via the AKT1/GSK3β/HIF1α antioxidant system was evaluated, aiming to provide insight into the intervention of H[2]O[2]‐induced oxidative injuries. Finally, a decoction‐based broad spectrum of edible inks was selected and developed for a 3D printing ink in a balanced diet. Collectively, the present study provides a molecular basis for using SFY as a promising antioxidant in the future. 2. Materials and Methods 2.1. Reagents and Materials Shanyao, Fuling, and Yiyiren were obtained from a local market of Yangzhou. 2,2′‐Azino‐bis (3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS) and 2,4,6‐tris (2‐pyridyl)‐1,3,5‐triazine (TPTZ) were made in Aldrich‐Sigma (St. Louis, MO, USA). H[2]O[2] (30%), chloroform, anhydrous ethanol, and isopropanol were bought from Sinopharm Chemical Reagent Co. Ltd. (China). TRIzol was obtained from Thermo Fisher Scientific (USA). A real‐time fluorescence quantitative PCR system (qRT‐PCR) and a reverse transcriptional kit were purchased from TransGen Biotech (China). Superoxide dismutase (SOD) and catalase (CAT) activity detection kits were obtained from Beyotime Biotechnology and Grace Biotechnology (both China), respectively. Dimethyl sulfoxide (DMSO), ethylene diamine tetraacetic acid (EDTA), phosphate buffer solution (PBS) phosphate dry powder, and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) were offered by Beijing Solarbio (China). All other agents were analytically pure. 2.2. Optimization and Preparation of Formulations of Decoction The preparations of medicinal and edible herbals were determined according to the method from Guan et al. ([59]2021). Based on a modified classic folk recipe, Sifang Tang, Shanyao, Fuling, and Yiyiren were selected, cleaned, and air‐dried at 60°C overnight. Then the dried materials were filtrated through an 80‐mesh sieve and kept in an airtight container at ambient temperature until used. With the solid/liquid ratio at 1:20, the three types of herbal powders were randomly combined and thoroughly mixed in an RK103H ultrasonic bath (BANDE‐LIN SONOREX, Germany) at 80 kHz. After 4 h of extraction, the extracts were centrifuged at 4500 rpm for 10 min. The final sensory test samples were obtained by mixing the three extracts. 2.3. Fuzzy Mathematical‐Based Sensory Evaluation Sensory evaluation was carried out according to the procedure from Jaya and Das ([60]2003). Briefly, 10 reportedly healthy, nonsmoking potential evaluators from the staff and students of the College of Tourism and Culinary Science, Yangzhou University were selected at a 60% success rate in triangle tests and enrolled to evaluate the color, odor, taste, and texture of sensory test samples. The testing was finished in the laboratory as per regulations in ASTM MNL‐26 (1996). The panelists each sensorily analyzed 10 samples. The tested samples were categorized into four distinct grades: excellent, good, fair, and poor, which reflected their distinctiveness. The criteria for sensory evaluation were listed in Table [61]S1, and the voting outcomes for each criterion were recorded in Table [62]1. TABLE 1. Sensory evaluation indexes of polyherbal formulations. Num. Sample Color Odor Taste Texture V[1] V[2] V[3] V[4] V[1] V[2] V[3] V[4] V[1] V[2] V[3] V[4] V[1] V[2] V[3] V[4] T [1] Euryale ferox ; Lotus seed; Shanyao 4 2 4 0 3 4 2 1 3 5 1 1 2 6 2 0 T [2] Euryale ferox ; Lotus seed; Yiyiren 3 3 4 0 2 4 4 0 6 6 1 0 1 3 5 1 T [3] Euryale ferox ; Lotus seed; Fuling 0 4 3 3 0 1 4 5 1 5 3 1 5 3 2 0 T [4] Lotus seed; Shanyao; Yiyiren 5 2 2 1 4 2 2 2 2 4 4 0 3 4 2 1 T [5] Lotus seed; Shanyao; Fuling 4 5 1 0 5 3 1 1 5 5 0 0 4 4 2 0 T [6] Shanyao; Yiyiren; Fuling 6 4 0 0 7 2 1 0 7 3 0 0 3 4 1 2 T [7] Euryale ferox ; Shanyao; Yiyiren 4 4 2 0 6 3 1 0 5 4 1 0 2 8 0 0 T [8] Euryale ferox ; Shanyao; Fuling 2 1 4 3 3 4 2 1 3 7 0 0 0 6 4 0 T [9] Euryale ferox ; Yiyiren; Fuling 3 5 1 1 2 8 0 0 7 1 1 1 5 3 1 1 T [10] Lotus seed; Yiyiren; Fuling 1 6 1 2 5 3 2 0 4 4 2 0 2 5 2 1 [63]Open in a new tab Fuzzy mathematical sensory evaluation was integrated into food sensory assessment to quantify evaluation factors, substantially mitigate the influence of personal bias, and produce more accurate and scientific scoring results (Ranneh et al. [64]2021). In detail, a set of sensory factors for the prepared solutions was defined as U, and a set of grades as V. U comprises color (U[1]), odor (U[2]), taste (U[3]), and texture (U[4]), and V includes excellent (V[1]), good (V[2]), average (V[3]), and poor (V[4]). The relative weight of each sensory factor in the overall flavor profile was determined using the fuzzy binary comparative decision method. Ten sensory evaluators compared these factors pairwise. A factor deemed important was given 1 point, whereas those considered less important were assigned 0 point. The total score of each sensory factor divided by the maximum score of 100 was used as the weight of this sensory factor (Table [65]S2). Based on the evaluators' scoring on the importance of color, odor, taste, and texture in the overall sensory evaluation, the distribution of weights among these factors is X = {color, odor, taste, texture} = {0.24, 0.28, 0.33, 0.15}. 2.4. Determination of ABTS Radical (ABTS^+) Scavenging Capacity The ABTS^+ scavenging ability was tested following the method from Guan, Li, et al. ([66]2024) with modifications. Briefly, an ABTS^+ stock solution was prepared by mixing 5 mL of 7 mM ABTS and 5 mL of 2.45 mM potassium persulfate and put for 12–16 h at room temperature (RT) without light. Then the mixture was diluted using ultrapure water until the absorbance at 405 nm was 1.4, forming an ABTS working solution. Gradient diluted extracts or ascorbic acid (0.5 mL) were blended with 0.5 mL of the ABTS working solution and stood for 30 min in the dark at RT. Then the absorbance at 734 nm was recorded. The percent of ABTS^+ scavenging activity of the extracts was computed using Equation ([67]1): [MATH: ABTS%=1A1A2/A0×100% :MATH] (1) where A [1], A [2], and A [0] are the absorbance of the mixture of ABTS^+ and the sample solution, the mixture of ABTS^+ and the control sample, and the mixture of ABTS^+ and deionized water, respectively. 2.5. Experiment Design and Mixture Optimization Mixture design, a special type of RSM, was used to optimize the composition of herbal mixtures and test the interactive effect between components. Based on Section [68]2.3, the polyherbal formulations for further optimization consisted of Shanyao, Fuling, and Yiyiren. In total, 16 formulations were formed and the responses were analyzed using DesignExpert 13 (Minitab Inc., State College, PA, USA). The layout of the herbal formulations is shown in Table [69]2. The dependent variable was in vitro ABTS antioxidant ability. The canonical model of was used for each response after adjustment based on the testing data. Linear, quadratic, and special cubic models were tested to determine regression coefficients, which were kept only at the significant level. Data were refitted to obtain the final model for each index. The adequacy and goodness of fitting for each model were statistically analyzed and fitted to a second‐order polynomial regression model involving the coefficients of linear, quadratic, and interactive terms. For validation, the optimal formulation was examined in triplicate and expressed as mean ± standard deviation. Analysis of variance (ANOVA) was conducted to calculate the model significance and suitability of the factors and interactions. The formulations with highly desirable functions were chosen for further analysis. TABLE 2. Mixture design experimental arrangement and results. Standard order Factor A (Fuling, g) Factor B (Shanyao, g) Factor C (Yiyiren, g) Response ABTS^+ radical scavenging capacity (%) 1 0.75 0.55 0.40 41.30 ± 0.73 2 0.65 0.75 0.30 56.98 ± 0.41 3 0.65 0.65 0.40 54.35 ± 0.98 4 0.75 0.62 0.33 50.76 ± 0.47 5 0.65 0.65 0.40 61.18 ± 0.63 6 0.75 0.65 0.30 55.61 ± 0.24 7 0.65 0.75 0.30 53.13 ± 0.30 8 0.72 0.62 0.37 61.32 ± 1.09 9 0.65 0.75 0.30 54.63 ± 0.38 10 0.75 0.75 0.20 46.27 ± 0.29 11 0.55 0.75 0.40 61.15 ± 0.66 12 0.62 0.72 0.37 67.47 ± 0.68 13 0.55 0.75 0.40 57.46 ± 0.34 14 0.75 0.68 0.27 53.50 ± 0.64 15 0.68 0.68 0.33 67.60 ± 0.60 16 0.65 0.65 0.40 54.94 ± 0.21 [70]Open in a new tab 2.6. Determination of Antioxidant Synergism Based on the Chou–Talalay combined drug theory, the synergistic antioxidant effects of different combinations were explored (Chou [71]2018). Specifically, antioxidant synergism was determined as per the sum of IC[50] from seven concentrations based on RSM to generate a total of 16 solution combinations. The absorbance of the solution combination was then detected to determine the percent of ABTS^+ scavenging capacity. To quantify the synergistic, additive, or antagonistic impact of the combinations of decoction, the testing data were converted to the combination index (CI): [MATH: CI=MCa/SCa+MCb/SCb :MATH] where MCa and MCb are the concentrations of compounds A and B in the mixture to achieve 50% antioxidant activity respectively; SCa and SCb are the EC[50] of the single compounds A and B, respectively. CI < 1, = 1, or > 1 implies a synergistic, additive, or antagonistic effect, respectively. 2.7. Identification of Core Ingredients, Potential Targets of Decoction, and Network Construction The active constituents and related targets in SFY‐based polyherbal formulations were cited from Chinese Medicine System Pharmacology Database ([72]https://old.tcmsp‐e.com/tcmsp.php) with pharmacokinetic parameters (oral bioavailability [OB] ≥ 30% and drug‐like activity [DL] ≥ 0.18). Then the target names of the corresponding core active ingredients were turned into a unified format with Homo sapiens via Unified Protein Database ([73]https://www.uniprot.org/). In addition, the potential antioxidant associated targets were gathered from GeneCards ([74]http://www.genecards.org/), Herb 2.0 ([75]http://www.disgenet.org/search), and OMIM ([76]https://omim.org/). Then duplicates were removed after the targets were merged from the databases above. The targets of antioxidants and SFY‐based polyherbal formulations and their common targets were acquired via Venny 2.1.0. To systematically examine the network, the “herb‐compound‐common target” network was imported and constructed via Cytoscape 3.9.1. 2.8. Protein–Protein Interaction (PPI) Network Construction, Topology Analysis, and GO/KEGG Enrichment Analysis of Core Targets To investigate the core targets and their interactions against oxidant damages, the overlapping targets between SFY‐based polyherbal formulations and oxidant damages were examined using the STRING network platform ([77]https://stringdb.org/). Furthermore, a PPI network was created at a confidence level > 0.4 and with the “ Homo sapiens ” filter (Ren et al. [78]2024). The network was further analyzed in Cytoscape 3.9.1 using MCODE to identify the associations between hub genes and network clusters with specific parameters. Core clusters were then identified based on degree centrality. GO and KEGG pathway enrichment analyses of the core targets were done using David 6.8 ([79]https://david.ncifcrf.gov/) to explore specific mechanisms and signaling pathways. Enrichment results with p and q < 0.05 were visualized using bar and bubble charts on the online tool imageGP. 2.9. Molecular Docking Molecular docking, an increasingly important computational tool for exploring the behaviors of biomacromolecule complexes, was conducted as per the approach of Guan et al. ([80]2023) with modifications. Based on the degrees from Section [81]2.8, the top targets and core ingredients from the SFY‐based polyherbal formulations were chosen for affinity calculations. The 3D structures of AKT1, GSK3B, TP53, HIF1A, and PTGS2 were cited and constructed via AutoDockTools 1.5.6. Polar hydrogens were added to demand charges after water was removed. The smallest binding energy was computed on AutoDock Vina. Finally, the binding details were illustrated on PyMOL and Discovery Studio 2018. 2.10. Cytotoxicity Evaluation and Antioxidant Enzyme Activity Analysis The BNLCL.2 mouse embryonic liver cell line from Meilun Biotechnology Co. Ltd. (Dalian, China) was cultured in high‐glucose DMEM added with 10% FBS and 1% P/S at 37°C with 5% CO[2]. Trypsin was used for cell passage. For H[2]O[2] cytotoxicity assessment, the BNLCL.2 cells (1 × 10^4 cells/well) were planted in 96‐well plates and processed with 0, 200, 400, 600, 800, or 1000 μmol/L H[2]O[2] for 24 h. To evaluate the protective effect of SFY, the cells were pretreated with 600 μM H[2]O[2] for 4 h, and co‐cultured with 0.5, 1, 2, 4, or 8 mg/mL SFY for 24 h. In MTT assays, each well was added with 100 μL of 5 mg/mL MTT, incubated for 4 h, and then the formazan crystals were solubilized with DMSO. The absorbance at 490 nm was recorded using a microplate reader (Flefel et al. [82]2019). Additionally, BNLCL.2 cells were pretreated with H[2]O[2] or SFY at specific concentrations. Then CAT and SOD activities were assessed using commercial kits (Cat. no. S0101S, G0105W48) as instructed by the manufacturer, and were detected with colorimetry and the xanthine oxidase method, respectively (Ding et al. [83]2020). 2.11. RNA Extraction and qRT‐PCR Analysis The BNLCL.2 cells were incubated in 6‐well plates for 24 h, pretreated with 600 μM H[2]O[2] for 4 h, and exposed to SFY seeds (0, 2, 4, and 8 mg/mL) for 24 h. The treated BNLCL.2 cells were collected. Total RNA was extracted from the BNLCL.2 cells using a TRIzol reagent, and reverse transcribed to cDNA using a first‐strand cDNA synthesis SuperMix kit for qPCR (gDNA digester plus) from TransGen Biotech (China). Real‐time PCR was conducted with fast SYBR green master mix (Wang et al. [84]2023). The quantities of transcripts were standardized to that of GAPDH. The primers (Sangon Biotech, China) were presented in Table [85]S3. 2.12. 3D Printing Ink Preparation and Printability Assessment 3D printing inks were prepared and assessed in terms of printability by forming different structures and printing them using an in‐house 3D printing system. The SFY decoction‐based 3D‐printed gels were prepared following a modified version of a previous method. Specifically, 2% and 2.7% high acyl gellan gum (HAG) and gelatin (GL) hydrogels were made by dissolving the powder in a solution at about 50°C under continuous stirring. These hydrocolloids were then mixed with 1%, 2%, 3%, or 4% glycerin to form the final testing gels. An extrusion‐based 3D printer (Luckybot One, Wiiboox Technology Co. Ltd., Nanjing, China) with a syringe and a retractable plunger was operated at around 26°C. A 0.25 mm inner diameter nozzle was used for printing, and images were captured from the top side on a food‐grade glass plate using a mobile phone. Uniform lighting was achieved with a white mini‐studio light box (Rui Teng Digital, Zhejiang, China) containing 144 LED aerial lights above the inks. 2.13. Statistical Analysis All assays were conducted in biological triplicate unless specified otherwise. The means of two independent groups were compared with an unpaired two‐tailed Student's t‐test. The normally distributed data among more than two groups were compared via one‐way ANOVA with Tukey's post hoc test. Data were expressed as mean ± standard deviation (SD) and analyzed on GraphPad Prism 9.5.0 (San Diego, CA, USA). The significance levels were *p < 0.05, **p < 0.01, and ***p < 0.001. 3. Results and Discussion 3.1. Sensory and Fuzzy Comprehensive Evaluation of Optimized Compatibility Components To enhance the medicinal value and reduce production costs of Sifang Tang, sensory evaluation and fuzzy mathematical methods were utilized to optimize the active ingredients and compositions. The compatibility of the five components (Qianshi, Shanyao, Fuling, Lianzi, and Yiyiren) in Sifang Tang was analyzed through sensory evaluation (Table [86]1) and radar plotting (Figure [87]1A–D). In detail, after the individual sensory attribute for each polyherbal formulation was calculated, the highest color was found on sample 6 (V[1] = 6), followed by sample 4 (V[1] = 5), and samples 1, 5, and 7 (V[1] = 4). As for odor, the highest polyherbal formulation on the response scale was found in sample 6, which linguistically means “Good.” The highest SI on taste, flavor, and mouthfeel was found all on the response scale F4, which linguistically implies “Good.” The SI of color was on the response scale F3, which linguistically refers to “Satisfactory.” For sample 6, the frequency of odor under “Excellent,” “Good,” “Average,” and “Poor” is 7, 2, 1, and 0, and the frequency of odor is 7, 3, 0, and 0 respectively. From the above ranking, in the EFSSE fortified bread sample, sample 6 (Shanyao, Fuling, and Yiyiren) showed better sensory evaluation compatibility. FIGURE 1. FIGURE 1 [88]Open in a new tab Optimized compound formula compatibility: sensory evaluation (A–D), antioxidant effect (E–G), and component quantification analysis (H–J). Sums of sensory scores for quality attributes of tested samples: T [1] ( Euryale ferox , Lotus seed, Shanyao), T [2] ( Euryale ferox , Lotus seed, Yiyiren), T [3] ( Euryale ferox , Lotus seed, Fuling), T [4] (Lotus seed, Shanyao, Yiyiren), T [5] (Lotus seed, Shanyao, Fuling), T [6] (Shanyao, Yiyiren, Fuling), T [7] ( Euryale ferox , Shanyao, Yiyiren), T [8] ( Euryale ferox , Shanyao, Fuling), T [9] ( Euryale ferox , Yiyiren, Fuling), T [10] (Lotus seed, Yiyiren, Fuling). Traditional sensory evaluation methods are frequently hard to achieve consensus, owing to personal subjective perceptions, environmental variations, and psychological fluctuations. In comparison, membership function theory‐based fuzzy mathematical sensory evaluation can enhance the reliability of sensory evaluations, and thus has been innovatively integrated into food sensory assessment (Pallavi [89]2025). The sensory evaluation data from the 10 evaluators (Table [90]1) were aggregated into matrix R by dividing the number of votes received for each grade by 10. The weight set X was then integrated with matrix R to form an evaluation matrix Y = X × R. Then matrix Y was processed using a comprehensive scoring matrix T. The set of evaluation grades K = {90, 70, 50, 30} was utilized, and each grade was multiplied by its corresponding weight and summed to compute the total fuzzy comprehensive evaluation score for each sample. For instance, when the colors of medicinal solutions in the first group were evaluated: four evaluators rated it as excellent, two as good, four4 as average, and none as poor, resulting in R [color] = (0.4, 0.2, 0.4, 0), R [odor] = (0.3, 0.4, 0.2, 0.1), R [taste] = (0.3, 0.5, 0.1, 0.1), and R [texture] = (0.2, 0.6, 0.2, 0). Then we have [MATH: Y1=R1×X=0.40.30.20.40.4 0.200.1 0.30.2< /mtable>0.50.60.10.2< mtd>0.10×0.24,0.28,0.33,0.15=0.309,0.415,0.21 5,0.061 :MATH] Similarly, we have Y [2] = (0.341, 0.33, 0.427, 0.015), Y [3] = (0.108, 0.446, 0.313, 0.133), Y [4] = (0.343, 0.296, 0.266, 0.095), Y [5] = (0.461, 0.429, 0.082, 0.028), Y [6] = (0.616, 0.311, 0.043, 0.03), Y [7] = (0.459, 0.432, 0.109, 0), Y [8] = (0.231, 0.457, 0.212, 0.1), Y [9] = (0.434, 0.422, 0.072, 0.072), and Y [10] = (0.326, 0.435, 0.176, 0.072). Then, we get T [1] = 0.309 × 90 + 0.415 × 70 + 0.215 × 50 + 0.061 × 30 = 69.44, T [2] = 75.59, T [3] = 60.58, T [4] = 65.74, T [5] = 72.41, T [6] = 80.26, T [7] = 77, T [8] = 66.38, T [9] = 74.36, and T [10] = 70.75. With sensory evaluation of fuzzy mathematical models considered, the polyherbal formulations can be ranked as follows: T [6] > T [7] > T [2] > T [9] > T [5] > T [10] > T [1] > T [8] > T [4] > T [3]. After quantitative analysis of sensory evaluation using fuzzy mathematics, the group members/consumers believed sample T [6] (Shanyao, Fuling, and Yiyiren) had higher overall sensory acceptability than the average. Moreover, the overall acceptability parameter was mainly dependent on quantitative analysis of personalized sensory attributes of the samples, including taste, flavor, and texture. These findings indicate the sensory characteristics of the SFY decoction are closely linked to the proportions of Shanyao, Fuling, and Yiyiren, which could be explained by the different molecular profiles of each herb that contribute uniquely to taste and texture. However, the sample scope of the current study was limited to school‐based participants and thus may not fully reflect broader market preferences. Future work will focus on