Academic Journal
Discovery of Q-Markers of Mudan Granules by Chemical Profile, Pharmacokinetics, Neuroprotective Effect Evaluation, and Network Pharmacology.
| Title: | Discovery of Q-Markers of Mudan Granules by Chemical Profile, Pharmacokinetics, Neuroprotective Effect Evaluation, and Network Pharmacology. |
|---|---|
| Authors: | Wang Z; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.; Innovation Center of Translational Pharmacy, Jinhua Institute of Zhejiang University, Jinhua, China., Zhang S; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.; Innovation Center of Translational Pharmacy, Jinhua Institute of Zhejiang University, Jinhua, China., Hu C; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.; Innovation Center of Translational Pharmacy, Jinhua Institute of Zhejiang University, Jinhua, China., Wang S; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.; Innovation Center of Translational Pharmacy, Jinhua Institute of Zhejiang University, Jinhua, China. |
| Source: | Biomedical chromatography : BMC [Biomed Chromatogr] 2026 Jul; Vol. 40 (7), pp. e70494. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley Country of Publication: England NLM ID: 8610241 Publication Model: Print Cited Medium: Internet ISSN: 1099-0801 (Electronic) Linking ISSN: 02693879 NLM ISO Abbreviation: Biomed Chromatogr Subsets: MEDLINE |
| Imprint Name(s): | Publication: 1990- : Chichester : Wiley Original Publication: London : Heyden & Son, c1986-1990 |
| MeSH Terms: | Drugs, Chinese Herbal*/pharmacokinetics , Drugs, Chinese Herbal*/chemistry , Drugs, Chinese Herbal*/pharmacology , Drugs, Chinese Herbal*/analysis , Neuroprotective Agents*/pharmacokinetics , Neuroprotective Agents*/chemistry , Neuroprotective Agents*/pharmacology , Neuroprotective Agents*/analysis, Chromatography, High Pressure Liquid/methods ; Liquid Chromatography-Mass Spectrometry/methods ; Biomarkers/analysis ; Schwann Cells/drug effects ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Network Pharmacology |
| Abstract: | Mudan granules (MDs) are a widely used Chinese patent medicine for treating diabetic peripheral neuropathy (DPN). TCM quality is the basis to ensure its efficacy; however, the current quality standard for MD relies on the control of only two constituents derived from the minister drugs. Therefore, it is necessary to establish a more comprehensive quality evaluation system based on rational quality markers (Q-markers). In this study, Q-markers of MD were discovered through systematic evaluations. Thirty-seven compounds were newly characterized in MD by UPLC-QTOF-MS. Among all the 173 constituents in MD, 64 were found to be absorbed into the bloodstream and/or sciatic nerve of rats in prototype. The contents of 24 candidate Q-markers were determined, and the pharmacokinetics features of nine ones were analyzed by two developed UPLC-MS methods. Six candidate Q-markers were first found to exhibit protective effects on Schwann cells against the injury of high glucose/lipid. Finally, nine Q-markers were screened, and network pharmacology analysis showed that the enriched pathways for these nine Q-markers covered the major DPN-related pathways for the full set of 173 constituents. The results provide important evidence for improving the quality control system of MD and reference for discovering Q-markers of other TCM prescriptions. (© 2026 John Wiley & Sons Ltd.) |
| References: | An, J. H., X. Zhang, K. Q. Jia, et al. 2021. “Trichostatin a Increases BDNF Protein Expression by Improving XBP‐1s/ATF6/GRP78 Axis in Schwann Cells of Diabetic Peripheral Neuropathy.” Biomedicine & Pharmacotherapy 133: 111062. Bing, Y. F., X. L. Ji, F. J. Qiang, et al. 2026. “Antidepressant Efficacy and Q‐Markers Determination of Dachaihu Decoction: Combining Pharmacology, Correlation Analysis, and Network Pharmacology Approaches.” Journal of Pharmaceutical and Biomedical Analysis 267: 117169. Chen, H. X., J. P. Yang, M. M. Liang, et al. 2017. “Effect of Chinese Traditional Patent Medicine Mudan Particles on Sciatic Nerve in Diabetic Rats.” Zhongguo Tangniaobing Zazhi 25, no. 4: 359–362. Chen, Z. M., C. T. Vong, T. J. Zhang, et al. 2023. “Quality Evaluation Methods of Chinese Medicine Based on Scientific Supervision: Recent Research Progress and Prospects.” Chinese Medicine 18: 126. Gu, X., Z. Y. Li, Y. H. Feng, et al. 2025. “A Mathematical Multiple‐Dimensional Strategy for Q‐Markers Identification Based on “Five Principles”: Tianshu Capsule for Migraine Treatment as an Example.” Journal of Ethnopharmacology 337: 118848. Hernández‐Cáceres, M. P., K. Cereceda, S. Hernández, et al. 2020. “Palmitic Acid Reduces the Autophagic Flux in Hypothalamic Neurons by Impairing Autophagosome‐Lysosome Fusion and Endolysosomal Dynamics.” Molecular & Cellular Oncology 7, no. 5: 1789418. Hu, C., M. L. He, M. J. Chen, et al. 2022. “Amelioration of Neuropathic Pain and Attenuation of Neuroinflammation Responses by Tetrahydropalmatine Through the p38MAPK/NF‐κB/iNOS Signaling Pathways in Animal and Cellular Models.” Inflammation 45: 891–903. Liang, G., J. Y. Yang, T. T. Liu, et al. 2021. “A Multi‐Strategy Platform for Quality Control and Q‐Markers Screen of Chaiqin Chengqi Decoction.” Phytomedicine 85: 153525. Liu, C. X., S. L. Chen, X. H. Xiao, et al. 2016. “A New Concept on Quality Marker of Chinese Materia Medica: Quality Control for Chinese Medicinal Products.” Zhong Cao Yao = Chinese Traditional and Herbal Drugs 47, no. 9: 1443–1457. Liu, J. Q., J. Liu, X. L. Tong, et al. 2021. “Network Pharmacology Prediction and Molecular Docking‐Based Strategy to Discover the Potential Pharmacological Mechanism of Huai Hua San Against Ulcerative Colitis.” Drug Design, Development and Therapy 15: 3255–3276. Luo, T. F., G. Y. Liu, H. X. Ma, et al. 2014. “Inhibition of Autophagy via Activation of PI3K/Akt Pathway Contributes to the Protection of Ginsenoside Rb1 Against Neuronal Death Caused by Ischemic Insults.” International Journal of Molecular Sciences 15: 15426–15442. Lv, Y. N., Y. S. Qian, A. J. Ou‐Yang, et al. 2016. “Hydroxysafflor Yellow a Attenuates Neuron Damage by Suppressing the Lipopolysaccharide‐Induced TLR4 Pathway in Activated Microglial Cells.” Cellular and Molecular Neurobiology 36: 1241–1256. Naruse, K. 2019. “Schwann Cells as Crucial Players in Diabetic Neuropathy.” Advances in Experimental Medicine and Biology 1190: 345–356. Pathomthongtaweechai, N., and S. Chutipongtanate. 2020. “AGE/RAGE Signaling‐Mediated Endoplasmic Reticulum Stress and Future Prospects in Non‐Coding RNA Therapeutics for Diabetic Nephropathy.” Biomedicine & Pharmacotherapy 131: 110655. Sanajou, D., A. Ghorbani Haghjo, H. Argani, and S. Aslani. 2018. “AGE‐RAGE Axis Blockade in Diabetic Nephropathy: Current Status and Future Directions.” European Journal of Pharmacology 833: 158–164. Shi, Y. Q., H. R. Li, Y. G. Lin, et al. 2024. “Effective Constituents and Protective Effect of Mudan Granules Against Schwann Cell Injury.” Journal of Ethnopharmacology 323: 117692. Tang, X. Y., X. X. Wang, Z. X. Tan, et al. 2025. “Excavation of Q‐Markers From Ba‐Zi‐Bu‐Shen Capsule Through Efficacy Evaluation, Chemical Profile, Three‐Dimensions‐Overall Analysis and Anti‐Osteoporosis Bioactivity Based on Combinatorial Algorithm.” Journal of Ethnopharmacology 350: 120061. Wang, D. M., L. Liu, S. Q. Li, D. Wang, S. Li, and C. Wang. 2018. “Effects of Paeoniflorin on Neurobehavior, Oxidative Stress, Brain Insulin Signaling, and Synaptic Alterations in Intracerebroventricular Streptozotocin‐Induced Cognitive Impairment in Mice.” Physiology & Behavior 191: 12–20. Wang, S. F., H. R. Li, Y. G. Lin, et al. 2025. “A Novel Aptamer‐Based Fluorescent Biosensor for Imaging SIRT2 in Live Cells and Screening Its Modulators.” Analytical Chemistry 97: 8411–8418. Wang, X. Y., Y. J. Xie, A. Bayoude, et al. 2025. “Discovering the Q‐Marker of Scutellaria baicalensis Against Viral Pneumonia Integrated Chemical Profile Identification, Pharmacokinetic, Metabolomics and Network Pharmacology.” Journal of Ethnopharmacology 340: 119232. Wang, Z. W., C. Liu, A. H. Zhang, et al. 2022. “Discovery of Q‐Markers of Wenxin Formula Based on a Chinmedomics Strategy.” Journal of Ethnopharmacology 298: 115576. Yang, W. Z., Y. B. Zhang, W. Y. Wu, et al. 2017. “Approaches to Establish Q‐Markers for the Quality Standards of Traditional Chinese Medicines.” Acta Pharmaceutica Sinica B 7, no. 4: 439–446. Zhang, A. X., Q. Wang, M. Liu, et al. 2022. “Efficacy and Safety of Mudan Granules for Painful Diabetic Peripheral Neuropathy: A Protocol for a Double‐Blind Randomized Controlled Trial.” Medicine 101, no. 10: e28896. Zhang, L. D., X. Cui, F. M. Liu, Y. M. Xie, and Q. Zhang. 2021. “Clinical Comprehensive Evaluation of Mudan Granules in Treatment of Diabetic Peripheral Neuropathy With Qi‐Deficiency and Collateral Stagnation Syndrome.” Zhongguo Zhongyao Zazhi 46, no. 23: 6078–6086. Zhang, T. J., G. Bai, and C. X. Liu. 2019. “The Concept, Core Theory and Research Methods of Chinese Medicine Quality Markers.” Yaoxue Xuebao = Acta Pharmaceutica Sinica 54, no. 2: 187–196. Zhang, Y. H., D. Jin, Y. Y. Duan, et al. 2021. “Efficacy of Mudan Granule (Combined With Methylcobalamin) on Type 2 Diabetic Peripheral Neuropathy: Study Protocol for a Double‐Blind, Randomized, Placebo‐Controlled, Parallel‐Arm, Multi‐Center Trial.” Frontiers in Pharmacology 12: 676503. Zhou, Y., X. Wang, W. H. Ying, et al. 2019. “Cryptotanshinone Attenuates Inflammatory Response of Microglial Cells via the Nrf2/HO‐1 Pathway.” Frontiers in Neuroscience 13: 852. Zhu, X. Y., K. Li, X. Guo, X. Zhu, J. Wang, and Y. Xiang. 2016. “Schwann Cell Proliferation and Differentiation That is Induced by Ferulic Acid Through MEK1/ERK1/2 Signalling Promotes Peripheral Nerve Remyelination Following Crush Injury in Rats.” Experimental and Therapeutic Medicine 12, no. 3: 1915–1921. |
| Grant Information: | 82274088 National Natural Science Foundation of China; 2024-1-093 Jinhua Science and Technology Program |
| Contributed Indexing: | Keywords: Mudan granules; Q‐markers; network pharmacology; neuroprotective effect; pharmacokinetics |
| Substance Nomenclature: | 0 (Drugs, Chinese Herbal) 0 (Neuroprotective Agents) 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260526 Date Completed: 20260717 Latest Revision: 20260717 |
| Update Code: | 20260717 |
| DOI: | 10.1002/bmc.70494 |
| PMID: | 42187695 |
| Database: | MEDLINE |
Be the first to leave a comment!