Currently, the number of diabetes patients and their corresponding treatment costs have increased year by year. Therefore, it is urgent to develop drugs with low cost, high efficacy and few side effects for the treatment of diabetes. As the first choice drug for type 2 diabetes, α-glucosidase inhibitors (AGIs) is widely used in the clinical treatment of diabetes. However, most of these drugs have been found to potentially cause various side effects. Natural AGIs derived from plants have gained widespread attention due to their mild, long-lasting, few side effects, high efficacy, and low complications. Microbial fermentation has always been one of the important auxiliary methods in the processing of Chinese herbal medicine. With the development of modern biotechnology, it has been widely applied in the discovery and improvement of natural AGIs. This article aims to review the research progresses of microbial fermentation technology in the development of natural AGIs from three aspects, including the types of microbial fermentation in plants, the effects of fermentation on plant AGIs, and the microorganisms used for AGIs fermentation. This article was expected to provide reference for future research and application development of green, efficient, and affordable AGIs drugs.

Ruoyou Ding, Shiya Niu. Review for the application of microbial fermentation technology in the study of natural α-glucosidase inhibitors. International Journal of Frontiers in Medicine(2025), Vol. 7, Issue 2: 97-102. https://doi.org/10.25236/IJFM.2025.070214.

[1] Nurkolis, F., et al., Food phytochemicals as epigenetic modulators in diabetes: A systematic review. Journal of Agriculture and Food Research, 2025. 21: p. 101873.

[2] Sun, H., et al., IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice, 2022. 183: p. 109119.

[3] Shahzad, N., et al., Therapeutic strategy of biological macromolecules based natural bioactive compounds of diabetes mellitus and future perspectives: A systematic review. Heliyon, 2024. 10(2): p. e24207.

[4] Zhang, J., et al., Research Progress in the Anti-Type 2 Diabetes Mellitus Mechanisms of Natural Products Dietary Polyphenols. Food Research and Development, 2025. 46(5): p. 218-224.

[5] Wang, T., et al., Antidiabetic mechanism of polysaccharides in traditional Chinese medicine and its development prospect. Chinese Traditional and Herbal Drugs, 2025. 56(6): p. 2184-2196.

[6] Rodríguez, I.A., et al. Natural Products as Outstanding Alternatives in Diabetes Mellitus: A Patent Review. Pharmaceutics, 2023. 15,  DOI: 10.3390/pharmaceutics15010085.

[7] Ye, W., Analysis of adverse reactions and combined use of antidiabetic drugs in type 2 diabetes mellitus. Chinese Journal of Modern Drug Application, 2023. 17(24): p. 152-154.

[8] Rangel-Galván, M., et al., Dietary natural products as inhibitors of α-amylase and α-glucosidase: An updated review of ligand-receptor correlations validated by docking studies. Food Bioscience, 2024. 62: p. 105456.

[9] Hafez Ghoran, S., et al., Insights into in vitro and in silico studies of α-glucosidase inhibitors isolated from the leaves of Grewia optiva (Malvaceae). International Journal of Biological Macromolecules, 2025. 287: p. 138590.

[10] Lu, W., et al., Activity-oriented isolation of nine α‑glucosidase inhibitors from the Rheum tanguticum waste and interaction mechanism analysis. Industrial Crops and Products, 2025. 226: p. 120697.

[11] Rehman, N.U., et al., Three new alkaloids from Haplophyllum tuberculatum as competitive type of in-vitro α-glucosidase inhibitors. Phytochemistry Letters, 2025. 65: p. 94-101.

[12] Yao, J., W. Sun, and M. Xie, Analysis and Suggestions on the Current Situation of Chinese Patent Medicines for Diabetes in China. Asia-Pacific Traditional Medicine, 2025. 21(4): p. 244-230.

[13] Luo, J., et al., Research progress in biotransformation of active ingredients in tratitional Chinese medicine by midicinal fungi. Chemicstry & Bioengineering, 2023. 40(6): p. 1-7.

[14] Zhao, Q., et al., Improved flavonoid content in mulberry leaves by solid-state fermentation: Metabolic profile, activity, and mechanism. Innovative Food Science & Emerging Technologies, 2023. 84: p. 103308.

[15] Liu, X., et al., Green tea fermented by Ganoderma lucidum presented anti-obesity properties via enhanced thermogenesis in vitro and on C57BL/6J mice. Food Research International, 2025. 207: p. 116092.

[16] Song, Q., et al., New progress in research on the fermentation of traditional Chinese medicine. . Journal of Shenyang Pharmaceutical University, 2024. 41(10): p. 1298-1305.

[17] Qu, Q., et al., Research progress on fermented traditional Chinese medicine and its theoreticalexploration of “fermentation compatibility”. Chinese Traditional and Herbal Drugs, 2023. 54(7): p. 2262-2273.

[18] Wang, B., et al., The effects of Monascus purpureus fermentation on metabolic profile, α-glucosidase inhibitory action, and in vitro digestion of mulberry leaves flavonoids. LWT, 2023. 188: p. 115449.

[19] Xiao, Y., et al., Characterization and discrimination of volatile organic compounds and α-glucosidase inhibitory activity of soybeans (Glycine max L.) during solid-state fermentation with Eurotium cristatum YL-1. Current Research in Food Science, 2024. 9: p. 100854.

[20] Magro, A.E.A., et al., Solid-state fermentation as an efficient strategy for the biotransformation of lentils: enhancing their antioxidant and antidiabetic potentials. Bioresources and Bioprocessing, 2019. 6(1): p. 38.

[21] Ye, M., et al., Screening, fermentation conditions optimization and enzymatic kinetics of α-glucosidase inhibitor-producing yeasts. Food science and technology, 2024. 49(3): p. 1-7.

[22] Hong, J., et al., The effects of Zygosaccharomyces rouxii fermentation on polyphenol profile, antioxidant properties, α-glucosidase inhibitory activity, and flavor compounds of Cynanchum auriculatum Royle ex Wight beverages. Food Bioscience, 2025. 67: p. 106363.

[23] ZHANG, M., et al., Research Progress on Solid-State Fermentation Promoting Release and Biotransformation of Bioactive Substances. China Condiment, 2025. 50(1): p. 233-240.

[24] Ren, Z. and J. Lü, Effects of Fermentation on Bioaccessibility of Polyphenols and Antioxidant Activities in Naked Oats. Journal of the Chinese Cereals and Oils Association, 2024. 39(7): p. 76-85.

[25] Zheng, Z., et al., Enhancement of anti-diabetic activity of pomelo peel by the fermentation of Aspergillus oryzae CGMCC23295: In vitro and in silico docking studies. Food Chemistry, 2024. 432: p. 137195.

[26] Wang, G., et al., Prevention and control effects of edible fungi and their active ingredients on obesity: An updated review of research and mechanism. Journal of Functional Foods, 2023. 107: p. 105621.

[27] Cai, G., et al., Synchronous reducing anti-nutritional factors and enhancing biological activity of soybean by the fermentation of edible fungus Auricularia auricula. Food Microbiology, 2024. 120: p. 104486.

[28] Kumari V B, C., et al., Fermented Ananas comosus and Carica papaya harbour putative probiotic Limosilactobacillus fermentum and Lacticaseibacillus paracasei strains with inhibitory activity against α-glucosidase and α-amylase. South African Journal of Botany, 2024. 172: p. 348-360.

[29] Yang, S., et al., Effects of Eurotium cristatum on chemical constituents and α-glucosidase activity of mulberry leaf tea. Food Bioscience, 2023. 53: p. 102557.

[30] Yu, G., et al., Multi-target anti-diabetic styrylpyrones from Phellinus igniarius: Inhibition of α-glucosidase, protein glycation, and oxidative stress. International Journal of Biological Macromolecules, 2024. 278: p. 134854.

[31] Zheng, M., et al., Extraction and identification of α-glucosidase-inhibitory components from Phellinus baumii. Acta Agriculturae Zhejiangensis, 2022. 34(5): p. 949-958.

[32] Chen, S., et al., Grifolamine A, a novel bis-γ-butyrolactone from Grifola frondosa exerted inhibitory effect on α-glucosidase and their binding interaction: Affinity and molecular dynamics simulation. Current Research in Food Science, 2022. 5: p. 2045-2052.

[33] Zhang, R., et al., Metabolite profiling, antioxidant and anti-glycemic activities of Tartary buckwheat processed by solid-state fermentation(SSF)with Ganoderma lucidum. Food Chemistry: X, 2024. 22: p. 101376.