Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures

Authors

  • John Richard Bend Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Siebens-Drake Medical Research Institute, Western University, London ON. Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University.
  • Xue Yan (Iris) Xue Yan Xia Medicine, Schulich School of Medicine & Dentistry, Siebens-Drake Medical Research Institute, Western University, London ON.
  • Daofeng Chen Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai, China.
  • Abudi Awaysheh Medicine, Schulich School of Medicine & Dentistry, Siebens-Drake Medical Research Institute, Western University, London ON.
  • Andrea Lo Medicine, Schulich School of Medicine & Dentistry, Siebens-Drake Medical Research Institute, Western University, London ON.
  • Michael John Rieder Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University. Department of Paediatrics, Schulich School of Medicine & Dentistry, Western University. Molecular Medicine, Robarts Research Institute, Western University.
  • Rebecca Jane Rylett Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University. Molecular Medicine, Robarts Research Institute, Western University.

DOI:

https://doi.org/10.18433/J3MW3N

Abstract

PURPOSE:  Our working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer’s. Here we evaluate the ability of baicalein, crocetin, trans-resveratrol or schisanhenol and two defined mixtures of these TCM phytochemicals to attenuate the toxicity resulting from exposure to cell permeant t-butyl hydroperoxide (tBPH) in wild-type and bioengineered (to express choline acetyltransferase) HEK 293 cells. METHODS: Endpoints of tBHP-initiated oxidative and nitrosative stress in both types of HEK 293 cells and its attenuation by TCM constituents and mixtures included cytotoxicity (LDH release); depletion of intracellular glutathione (GSH); formation of S-glutathionylated proteins; oxidative changes to the disulfide proteome; and real-time changes in intracellular redox status. RESULTS: At low µM concentrations, each of the TCM constituents and mixtures effectively attenuated intracellular toxicity due to exposure of HEK 293 cells to 50 or 250 µM tBHP for 30 min to 3 h. Confocal microscopy of HEK 293 cells transfected with mutated green fluorescent protein (roGFP2) showed effective attenuation of tBHP oxidation by baicalein in real time. Three redox-regulated proteins prominent in the disulfide proteome of HEK 293 cells were identified by MALDI-TOF mass spectrometry. CONCLUSIONS: We conclude that single TCM chemicals and their simple mixtures have potential for use in adjunct chemoprotective therapy. Advantages of mixtures compared to single TCM constituents include the ability to combine compounds with varying molecular mechanisms of cytoprotection for enhanced biological activity; and to combine chemicals with complementary pharmacokinetic properties to increase half-life and prolong activity in vivo.

 

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Author Biographies

John Richard Bend, Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Siebens-Drake Medical Research Institute, Western University, London ON. Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University.

Distinguished University Professor

Department of Pathology and Laboratory Medicine

Western University

Xue Yan (Iris) Xue Yan Xia, Medicine, Schulich School of Medicine & Dentistry, Siebens-Drake Medical Research Institute, Western University, London ON.

Post-doctoral Fellow

Daofeng Chen, Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai, China.

Chair, Department of Pharmacognosy

School of Pharmacy

Fudan University

Abudi Awaysheh, Medicine, Schulich School of Medicine & Dentistry, Siebens-Drake Medical Research Institute, Western University, London ON.

MSc Student, Department of Pathology and Laboratory Medicine

Schulich Medicine and Dentistry

Western University

Andrea Lo, Medicine, Schulich School of Medicine & Dentistry, Siebens-Drake Medical Research Institute, Western University, London ON.

Honors Undergraduete Student

Schulich Medicine & Dentistry

Western University

Michael John Rieder, Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University. Department of Paediatrics, Schulich School of Medicine & Dentistry, Western University. Molecular Medicine, Robarts Research Institute, Western University.

Clinician Researcher (MD, PhD),Department of Paediatrics, London Health Sciences Centre Schulich Medicine & Dentistry, Western University

Rebecca Jane Rylett, Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University. Molecular Medicine, Robarts Research Institute, Western University.

Professor and Chair, Department of Physiology & Pharmacology,  Schulich Medicine & Dentistry, Western University

Interim Director, Robarts Research Institute

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Published

2015-11-02

How to Cite

Bend, J. R., Xue Yan Xia, X. Y. (Iris), Chen, D., Awaysheh, A., Lo, A., Rieder, M. J., & Rylett, R. J. (2015). Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures. Journal of Pharmacy & Pharmaceutical Sciences, 18(4), 661-682. https://doi.org/10.18433/J3MW3N

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CLOSED. Special Issue - Chief Guest Editor: Basil D Roufogalis; Co-Guest Editors: Emanuel Strehler & Srinivas Nammi