Dr Jianhui Rong’s research interests focus on the molecular characterization of anti-inflammatory, cardioprotective and neurotrophic activities of Chinese medicines against obesity, myocardial injury and neuroinflammation. Our strategy involves three major steps: 1) to profile the biological response fingerprints (BioReF) and proteomic response fingerprints (ProReF) of complex herbal medicine formulations for the discovery of the potential protein targets; 2) to identify the bioactive compounds for specific protein targets through a bioactivity-guided fractionation procedure; 3) to discover the covalent and non-covalent drug-protein interactions for drug discovery through chemical biology approaches. Our earlier effort was to use the selected signature genes for mechanistic studies and new quality control metrics. With the support of several previous GRF grants, we have successfully identified the active compounds for several representative gene products including heme oxygenase-1 (HO-1) and NADP-dependent leukotriene B4 12-hydroxydehydrogenase (LTB4DH) through bioactivity-guided fractionation procedure. We recently focused on the identification of covalent drug-protein conjugates for several active compounds including N-propargyl caffeamide, arachidonic acid metabolites and pentacyclic triterpene celastrol. We further employed molecular simulation and chemical biology techniques to develop specific drug candidates. We have established different cell models and animal models for pharmacological evaluation of the bioactive compounds.

Our recent research focus is well described by the following papers: 1) N-Propargyl caffeate amide (PACA) potentiates nerve growth factor (NGF)-induced neurite outgrowth and attenuates 6-hydroxydopamine (6-OHDA)-induced toxicity via activating the Nrf2/HO-1 pathway (ACS Chemical Neuroscience, 2015). This paper described the synthesis of small molecule probe PACA the discovery of covalent PACA-Keap1 conjugate; 2) Plant natural product puerarin ameliorates depressive behaviors and chronic pain in mice with spared nerve injury (SNI) (Molecular Neurobiology, 2017). This paper described the discovery of Chinese medicine puerarin as dual antidepressant and analgesic drug candidate; 3) ω-Alkynyl arachidonic acid promotes anti-inflammatory macrophage M2 polarization against acute myocardial infarction via regulating the cross-talk between PKM2, HIF-1α and iNOS (Biochim Biophys Acta- Molecular and Cell Biology of Lipids, 2017); 4) N-Propargyl caffeamide skews macrophages towards an M2-like phenotype against myocardial ischemic injury via activating Nrf2/HO-1 pathway and inhibiting NF-κB pathway (Cellular Physiology & Biochemistry, 2018). This paper called attention to the adverse interactions between the botanicals and endogenous neurotransmitters while effort is made to elucidate the pharmacological potential of various active compounds in herbal medicines.

Collectively, we have developed an integrative technology platform for better understanding on the basic mechanisms underlying the therapeutic potential of complex herbal medicines. We strived to dissect the interactions between the active compounds in complex herbal medicines and the protein targets for the development of new mechanism-specific medicines.

Selected Publications (* corresponding author)

1. Yuanyuan Cheng, Chuanbin Yang, Dan Luo, Xuechen Li, Chris X Le and Jianhui Rong^*, N-Propargyl caffeamide skews macrophages towards an M2-like phenotype against myocardial ischemic injury via activating Nrf2/HO-1 pathway and inhibiting NF-κB pathway, Cellular Physiology & Biochemistry, 2018;47(6):2544-2557.

2. Dan Luo, Yumeng Guo, Yuanyuan Cheng, Jia Zhao, Yu Wang*, Jianhui Rong *, Natural product celastrol suppressed macrophage M1 polarization against inflammation in diet-induced obese mice via regulating Nrf2/HO-1, MAP kinase and NF-κB pathways, Aging (Albany NY). 2017 Oct 16;9(10):2069-2082.

3. Yuanyuan Cheng, Yibin Feng, Zhengyuan Xia, Xuechen Li, Jianhui Rong*, ω-Alkynyl arachidonic acid promotes anti-inflammatory macrophage M2 polarization against acute myocardial infarction via regulating the cross-talk between PKM2, HIF-1α and iNOS, Biochim Biophys Acta- Molecular and Cell Biology of Lipids, 2017 Sep 28;1862(12):1595-1605.

4. Cheng Y, Xia Z, Han Y, Jianhui Rong^*. Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation. Oxidative Medicine and Cellular Longevity, 2016;2016:2060874.

5. Jia Zhao, Dan Luo, Zhaohui Liang, Lixing Lao, Jianhui Rong^*, Plant natural product puerarin ameliorates depressive behaviors and chronic pain in mice with spared nerve injury (SNI), Molecular Neurobiology, 2017 May, 54 (4), 2801–2812.

6. Chuanbin Yang, Jia Zhao, Yuanyuan Cheng, X Chris Le, Jianhui Rong*, N-Propargyl caffeate amide (PACA) potentiates nerve growth factor (NGF)-induced neurite outgrowth and attenuates 6-hydroxydopamine (6-OHDA)-induced toxicity via activating the Nrf2/HO-1 pathway, ACS Chemical Neuroscience, 2015 Sep 16;6(9):1560-9.

7. Yuanyuan Cheng, Chuanbin Yang, Jia Zhao, Hung-Fat Tse, Jianhui Rong*, Proteomic identification of calcium-binding chaperone calreticulin as a potential mediator for the neuroprotective and neuritogenic activities of botanical drug amygdalin, Journal of Nutritional Biochemistry, 2015, 26: 146–154.

8. Jia Zhao, Yuanyuan Cheng, Wen Fan, Chuanbin Yang, Shuifeng Ye, Wei Cui, Wei Wei, Lixing Lao, Jing Cai, Yifan Han, Jianhui Rong*, Botanical drug puerarin coordinates with nerve growth factor in the regulation of neuronal survival and neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the neurite extension process. CNS Neuroscience & Therapeutics. 2015 Jan;21(1):61-70.

9. Hongyi Qi, Yifan Han, Jianhui Rong*, Potential roles of PI3K/Akt and Nrf2-Keap1 pathways in regulating neurohormesis of Z-Ligustilide in neuronal PC12 cells against oxygen and glucose deprivation, Neuropharmacology, 62(4), 1659-1670, 2012.

10. Jianhui Rong*, Robert Tilton, Jiangang Shen, Ng KM, Chang Liu, Paul KH Tam, Allan SY Lau, Yung-Chi Cheng, Genome-wide biological response fingerprinting (BioReF) of the Chinese botanical formulation ISF-1 enables the selection of multiple marker genes as a potential metric for quality control. Journal of Ethnopharmacology, 113, 35-44, 2007.