Dr Rong, Jianhui 榮建輝
- Molecular characterization of the cellular responses to complex herbal medicines by integrative genomic, proteomic, cell signaling and chemical biology approaches
- Basic mechanisms underlying the neuroprotective, neurorestorative and cardioprotective activities of the bioactive botanicals
- Structure-activity relationship of the bioactive botanicals
Dr Jianhui Rong’s research interests focus on the molecular characterization of anti-inflammatory, neuroprotective and neurotrophic activities of Chinese medicines towards the development of novel therapies for neurological and cardiovascular diseases. Our strategy involves two major steps: 1) to investigate the biological response fingerprints (BioReF) and proteomic response fingerprints (ProReF) of complex herbal medicine formulations in human cells. The potential protein targets are selected from the transcriptomic or proteomic profiles in a bias-free manner; 2) to isolate the corresponding active compounds from the complex herbal medicine formulations through a bioactivity-guided fractionation procedure for the regulation of the disease-relevant protein targets. In fact, these signature genes may not only lead to new therapeutic interventions but also help the development of new quality control metrics. With the support of previous GRF grants, we have applied such new strategy to define 145 genes as the gene signature for a classic post-stroke rehabilitation formulation ISF-1, also known as Bu-Yang-Huan-Wu-Tang (in Chinese). By targeting two representative gene products, namely, heme oxygenase-1 (HO-1) and NADP-dependent leukotriene B4 12-hydroxydehydrogenase (LTB4DH), we successfully identified the active herbal ingredients and isolated the active compounds from specific herbal extracts through bioactivity-guided fractionation procedure. We further examined how the bioactive botanical compounds regulated different protein targets as well as the intracellular signalling pathways in cell models and animal models. In addition, we implemented chemical biology measures to verify and further characterize our findings resulted from genomics proteomics and cell signalling technologies.
Our research focus could be well presented by the following four papers: 1) 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. This is probably the first paper describing the use of a set of signature genes as quality control metric for complex herbal medicines; 2) Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1. Heme oxygenase-1 was selected as a key anti-oxidant and cytoprotective protein target for the formulation ISF-1 by genome-wide biological response fingerprinting; 3) Potential roles of PI3K/Akt and Nrf2-Keap1 pathways in regulating neurohormesis of Z-Ligustilide in neuronal PC12 cells against oxygen and glucose deprivation; This paper represented our effort to integrate the cell signaling technologies with the cell model of ischemic stroke for characterizing the pharmacological basis of botanical z-ligustilide in the treatment of post-stroke disorders; 4) (Z)-Ligustilide potentiates the neurotoxicity of dopamine in rat dopaminergic neuronal PC12 cells. 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 the understanding of 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 in human cells for the development of new chemically-defined and mechanism-specific medicines. I invite you to join our effort to introduce new Chinese medicines to the entire world.
Selected Publications (* corresponding author)
Cui W, Zhang ZJ, Hu SQ, Mak SH, Xu DP, Choi CL, Wang YQ, Tsim WK, Lee MY*, Rong JH*, Han YF*, Sunitinib Produces Neuroprotective Effect Via Inhibiting Nitric Oxide Overproduction, CNS Neurosci Ther. 2014 Jan 7.[Epub ahead of print]
Yang CB, Pei WJ, Zhao J, Cheng YY, Zheng XH, Rong JH*, Bornyl caffeate induces apoptosis in human breast cancer MCF-7 cells via the ROS- and JNK-mediated pathways, Acta Pharmacol Sin. 2014 Jan;35(1):113-23
Cui W, Zhang Z, Li W, Hu S, Mak S, Zhang H, Han R, Yuan S, Li S, Sa F, Xu D, Lin Z, Zuo Z, Rong J, Ma ED, Choi TC, Lee SM, Han Y. The anti-cancer agent SU4312 unexpectedly protects against MPP(+) -induced neurotoxicity via selective and direct inhibition of neuronal NOS. Br J Pharmacol. 2013 Mar;168(5):1201-14.
Qi H, Han Y, Lau ASY, Rong J*, (Z)-Ligustilide potentiates the neurotoxicity of dopamine in rat dopaminergic neuronal PC12 cells, Neurotoxicity Research, 22(4):345-354, 2012
Qi H, Chen B, Le X Chris, Rong J*, Concomitant induction of heme oxygenase-1 attenuates the cytotoxicity of arsenic species from Lumbricus extract in human liver HepG2 cells, Chemistry and Biodiversity, 2012 Apr;9(4):739-54
Cui W, Zhang Z, Li W, Mak S, Hu S, Zhang H, Yuan S, Rong J, Choi TC, Lee SM, Han Y. Unexpected neuronal protection of SU5416 against 1-Methyl-4-phenylpyridinium ion-induced toxicity via inhibiting neuronal nitric oxide synthase, PLoS One. 2012;7(9):e46253.
Qi H, Han Y, Rong J*, 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
Wei L, Liu J, Le X Chris, Han Y, Tong Y, Lau, ASY, Rong, J*, Pharmacological induction of LTB4 12-hydroxydehydrogenase (LTB4DH) suppresses the oncogenic transformation of human hepatoma HepG2 cells, International Journal of Oncology, 39(3):735-45, 2011
Qi H, Siu SO, Chen Y, Han Y, Chu IK, Tong Y, Lau ASY, Rong J*. Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1, Chem Biol Interact. 183(3):380-9, 2010
Qi HY, Wei L, Han YF, Zhang QL, Lau ASY, Rong J*, Proteomic characterization of the cellular response to chemopreventive triterpenoid astragaloside IV in human hepatocellular carcinoma cell line HepG2, International Journal of Oncology, 36(3):725-35, 2010
Rong J*, Cheung CYH, Lau ASY, Shen JG, Tam PKH, Cheng YC, Induction of heme oxygenase-1 by traditional Chinese medicine formulation ISF-1 and its ingredients as a cytoprotective mechanism against oxidative stress, International Journal of Molecular Medicine, 21: 405-411, 2008
Rong J*, Tilton R., Shen J, Ng KM, Liu C, Tam Paul KH, Lau Allan SY, Cheng YC, 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
|Awardees||Award Date||Honours / Awards / Prizes||Category|
|2010-02-01||補陽還五湯對缺血性中風後神經元保護及增殖作用的相關機制研究: 2009年度中華中醫藥學會科學技術獎三等獎, 補陽還五湯對缺血性中風後神經元保護及增殖作用的相關機制研究, 2009年度中華中醫藥學會科學技術獎三等獎||Research Achievement|
|2009-09-01||补阳还五汤对缺血性中风后神经元保护及增殖作用的相关机制研究: 2009年广东省科学技术奖, 补阳还五汤对缺血性中风后神经元保护及增殖作用的相关机制研究, 2009年广东省科学技术奖||Research Achievement|
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