Exploring the structure and function of metabolic networks in adverse drug reactions;

Developing AI tool for quality control of traditional Chinese medicine.

1. Research Projects

(1)Basic Research Fund of China Pharmaceutical University, Project No. 2632021ZD23, Research on a New Method for Evaluating Antitumor Drug Cardiotoxicity Based on Metabolic Phenotype, from January 2021 to December 2022, with a funding of 150,000 RMB, ongoing, as the principal investigator.

(2)National Natural Science Foundation of China, General Program, Project No. 81773861, Active Ingredient Group Discovery of Dachengqi Decoction for the Treatment of Intestinal Obstruction based on Tryptophan Metabolism Pathway Regulation: The Mechanism of Action and Network Pharmacology Bridge, from January 2018 to December 2021, with a funding of 570,000 RMB, completed, as a participant.

(3)National Natural Science Foundation of China, General Program, Project No. 81573626, Mechanism Research of Bupleurum's Dual Regulation Action on Liver Protection and Injury Based on Mitochondrial Functional Metabolomics, from January 2016 to December 2019, with a funding of 540,000 RMB, completed, as a participant.

(4)National Natural Science Foundation of China, Youth Program, Project No. 81403181, Study on the Mechanism of Nano-realgar Hepatotoxicity Based on Metabolic Network and Arsenic Species Analysis, from January 2015 to December 2017, with a funding of 230,000 RMB, completed, as the principal investigator.

(5)National Natural Science Foundation of China, General Program, Project No. 81473274, Establishment of a Metabolic Balance Model Based on Multiple Biomarker Methods to Study the Progression of Complex Cardiovascular Diseases, from January 2015 to December 2018, with a funding of 800,000 RMB, completed, as a participant.

(6)Jiangsu Natural Science Foundation, Youth Program, Project No. BK20140664, Research on the Toxicity and Mechanism of Nano-realgar Based on Metabolic Regulation Network Intervention, from July 2014 to June 2017, with a funding of 200,000 RMB, completed, as the principal investigator.

2. Academic Awards

(1)2018-07, Jiangsu Provincial Education Teaching and Research Achievement Award, 4/5.

3. Representative Research Achievements

(1) Mechanism research on the multi-organ toxicity of doxorubicin

Doxorubicin (DOX), an anthracycline antitumor drug, has a broad spectrum of antitumor effects and is a cornerstone drug in many chemotherapy regimens. However, DOX can cause many toxic side effects, such as cardiotoxicity, liver injury, and bone marrow suppression, which significantly limit its clinical application. Our research group systematically studied the toxic effects of DOX on the brain, heart, liver, spleen, and other organs in mice, related metabolic markers, and potential connections between organs using metabolomics and network medicine approaches. In particular, we found that inhibiting cardiac fatty acid metabolism leading to the reconstruction of energy metabolism might be one of the toxic mechanisms of DOX-induced heart failure.

(2) Mechanism research on the protective effects of Astragali Radix against doxorubicin-induced cardiotoxicity

Astragali Radix (AR) has been listed as a top-grade herb in the Shennong Bencao Jing. In clinical practice, various astragalus-containing prescriptions are used to supplement qi and tonify the heart depending on the specific symptoms of cancer patients. Our study found that the water extract of AR significantly improved the heart function and reduced the myocardial injury markers in mice treated with doxorubicin. By utilizing metabolic network analysis, we further found that two representative components of AR, astragaloside IV and formononetin, could work synergistically to maintain the homeostasis of heart fatty acid metabolism. They are the key components of AR that play a protective role on the heart.

1.  Han, Z.D.#; Guo, L.L.#; Yu, X.Y.; Guo, H.M.; Deng, X.Y.; Yu, J.Y; Deng, X.Y.; Xu, F.G.; Zhang, Z.J.*; Huang, Y.* Network-driven targeted analysis reveals that Astragali Radix alleviates doxorubicin-induced cardiotoxicity by maintaining fatty acid homeostasis. J Ethnopharmacol. 2022; 287:114967. (IF: 5.195)

2. Yu, X.Y.; Nai, J.X.; Guo, H.M.; Yang, X.P.; Deng, X.Y.; Yuan, X.; Hua, Y.F.; Tian, Y.; Xu, F.G.; Zhang, Z.J.*; Huang, Y.* Predicting the grades of Astragali radix using mass spectrometry-based metabolomics and machine learning. Journal of Pharmaceutical Analysis. 2021; 11(5):611-616. (IF: 14.026)

3. Yu, X.Y.#; Guo, L.L.#; Deng, X.Y.; Yang, F.; Tian, Y.; Liu, P.F.; Xu, F.G.; Zhang, Z.J.*; Huang, Y.* Attenuation of doxorubicin-induced oxidative damage in rat brain by regulating amino acid homeostasis with Astragali Radix. Amino Acids. 2021;53(6):893-901. (IF: 3.789)

4. Xu, J.L.#; Zhang, P.Y.#; Huang, Y.#; Zhou, Y.D.; Hou, Y.; Bekris, L. M.; Lathia, J.; Chiang, C. W.; Li, L.; Pieper, A. A.; Leverenz, J. B.; Cummings, J.; Cheng, F.X.* Multimodal single-cell/nucleus RNA sequencing data analysis uncovers molecular networks between disease-associated microglia and astrocytes with implications for drug repurposing in Alzheimer's disease. Genome Res. 2021;31(10):1900-1912. (IF: 9.438)

5. Guo, L.L.#; Li, L.R.#; Xu, Z.Y.; Meng, F.C.; Guo, H.M.; Liu, P.J.; Liu, P.F.; Tian, Y.; Xu, F.G.; Zhang, Z.J.; Zhang, S.*; Huang, Y.* . Anal Bioanal Chem. 2021;413(30):7421-7430. (IF: 4.478)

6. Yu, X.Y.; Guo, H.M.; He, H.; Deng, X.Y.; Yuan, X.; Han, Z.D.; Tian, Y.; Zhang, Z.J.*; Huang, Y.* Pharmacokinetics of T0901317 in mouse serum and tissues using a validated UFLC-IT-TOF/MS method. J Pharm Biomed Anal. 2020; 189:113420. (IF: 3.935)

7. Li, R.T.; He, H.; Fang, S.H.; Hua, Y.F.; Yang, X.P.; Yuan, Y.; Liang, S.; Liu, P.F.; Tian, Y.; Xu, F.G.; Zhang, Z.J.*; Huang, Y.* Time Series Characteristics of Serum Branched-Chain Amino Acids for Early Diagnosis of Chronic Heart Failure. J Proteome Res. 2019;18(5):2121-2128. (IF: 4.074)

8. Hua, Y.F.; Yang, X.P.; Li, R.T.; Liu, P.F.; Liu, P.J.; Li, L.R.; Yuan, X.; Hua, X.Y; Tian, Y.; Zhang, Z.J.*; Huang, Y.* Quantitative characterization of glutaminolysis in human plasma using liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2019;411(10):2045-2055. (IF: 3.637)

9. Liu, P.F.#; Li, R.T.#; Antonov, A. A.; Wang, L.H.; Li, W.; Hua, Y.F.; Guo, H.M.; Wang, L.J.; Liu, P.J.; Chen, L.X.; Tian, Y.; Xu, F.G.; Zhang, Z.J.; Zhu, Y.L.*; Huang, Y.* Discovery of Metabolite Biomarkers for Acute Ischemic Stroke Progression. J Proteome Res. 2017;16(2):773-779. (IF: 3.95)

10. Zhang, P.; Li, W.; Chen, J.Q.; Li, R.T.; Zhang, Z.J.; Huang, Y.*; Xu, F.G.* Amino Acids as Predictors for Individual Differences of Cisplatin Nephrotoxicity in Rats: A Pharmacometabonomics Study. J Proteome Res. 2017;16(4):1753-1762. (IF: 3.95)

Master's students

Yu Xinyue (2019)

Guo Linling (2020)

Xu Yan (2020)

Wang Lunan (2020)

Huang Hanhan (2020)

Wu Jing (2021)

Dong Jiamin (2022)