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Pharmacological Basis of ‘Yang-Invigoration’ in Chinese Medicine

Pharmacological Basis of ‘Yang-Invigoration’ in Chinese Medicine. Kam Ming Ko, PhD Department of Biochemistry The Hong Kong University of Science and Technology. Treasure. 寶. Supplement. 補. Yin. Qi. Yang. Blood. Genetic Factors. Acquired, Environmental. Neuro-, Endocrino-modulation.

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Pharmacological Basis of ‘Yang-Invigoration’ in Chinese Medicine

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  1. Pharmacological Basis of ‘Yang-Invigoration’ in Chinese Medicine Kam Ming Ko, PhD Department of Biochemistry The Hong Kong University of Science and Technology

  2. Treasure

  3. Supplement

  4. Yin Qi Yang Blood Genetic Factors Acquired, Environmental Neuro-, Endocrino-modulation Metabolism Nutrients Bioenergy Production Blood function Immune function Circulatory System Immunomodulation Antioxidant Hormone-like Action (Enhance Physiological Function) Supplementation (Sub-healthy Status) Deficiency

  5. Modernization of Chinese Medicine Experience + Theory  Language of Modern Medicine

  6. Qi Blood

  7. 5 4 3 2 1 0 Free Radical Scavenging Activity of Chinese Tonifying Herbs (in vitro) IC50 (mg/ml) Radix Fici Fructus Mori Fructus Ziziphi Radix Oryzae Fructus Lycii Herba Ecliptae Radix Asparagi Semen Sesami Radix Ginseng Radix Dipsaci Radix Morindae Ramulus Visci Rhizoma Cibotii Radix Codonopsis Testa Dolichoris Radix Astragali Herba Epimedii Herba Dendrobii Radix Polygoni Fructus Ligustri Radix Angelicae Semen Cuscutae Cortex Eucommiae Fructus Psoraleae Herba Cistanches Semen Prinsepiae Rhizoma Dioscoreae Radix Quinquefolii Radix Ophiopogonis Rhizoma Atractylodis Radix Glycyrrhizae Rhizoma Polygonati Rhizoma Drynariae Rhizoma Polygonati Radix Pseudostellariae Radix Rehmanniae Paraparata Yang-promoting Qi-invigorating Yin-nourishing Blood-enriching

  8. 2.0 1.5 1.0 0.5 0.0 Immunomodulatory Action of Chinese Tonifying Herbs (Ex Vivo) Immunomodulatory Index * * * * * * * * * * * * * * * * * * Radix Fici Fructus Mori Radix Oryzae Fructus Lycii Herba Ecliptae Radix Asparagi Semen Sesami Radix Ginseng Radix Dipsaci Radix Morindae Ramulus Visci Rhizoma Cibotii Fructus Ziziphi Testa Dolichoris Radix Astragali Herba Epimedii Herba Dendrobii Radix Polygoni Fructus Ligustri Radix Angelicae Semen Cuscutae Cortex Eucommiae Radix Codonopsis Fructus Psoraleae Herba Cistanches Semen Prinsepiae Radix Quinquefolii Radix Ophiopogonis Radix Glycyrrhizae Rhizoma Polygonati Rhizoma Drynariae Rhizoma Polygonati Rhizoma Dioscoreae Rhizoma Atractylodis Radix Pseudostellariae Radix Rehmanniae Paraparata Yang-promoting Qi-invigorating Yin-nourishing Blood-enriching

  9. Yang vs. Yin Yang herbs  Antioxidant Yin herbs  Immunostimulatory Pharmaceutical Biology 2002

  10. Yang-Invigoration • Yang = manifestation of body function • Bioenergy – ATP

  11. Can Yang-invigorating herbs enhance ATP production?

  12. 300 200 100 0 Myocardial ATP Generation Capacity of Chinese Tonifying Herbs Ex Vivo % control ** ** ** * * * * * * * * * Radix Fici Fructus Mori Radix Oryzae Radix Asparagi Herba Ecliptae Fructus Ligustri Semen Allii Radix Dipsaci Fructus Lycii Radix Astragali Radix Polygoni Semen Sesami Fructus Ziziphi Radix Angelicae Semen Prinsepiae Ramulus Visci Herba Epimedii Radix Quinquefolii Radix Morindae Testa Dolichoris Herba Dendrobii Radix Codonopsis Herba Cynomorii Semen Cuscutae Cortex Eucommiae Rhizoma Polygonati Radix Glycyrrhizae Fructus Psoraleae Radix Rehmanniae Rhizoma Drynariae Rhizoma Polygonati Rhizoma Dioscoreae Herba Cistanches Radix Ophiopogonis Rhizoma Atractylodis RhizomaCurculiginis Radix Pseudostellariae Yang-promoting Qi-invigorating Yin-nourishing Blood-enriching Phytomedicine 2006

  13. 140 120 100 80 60 40 20 0 Effect of Chinese Tonifying Herbs on Myocardial Mitochondrial Electron Transport **** * % control **** **** *** *** * Herba Ecliptae Fructus Mori Radix Oryzae Radix Polygoni Fructus Ligustri Radix Angelicae Semen Cuscutae Radix Glycyrrhizae Herba Cynomorii Radix Codonopsis Fructus Psoraleae Radix Pseudostellariae Yang-promoting Qi-invigorating Yin-nourishing Blood-enriching

  14. 250 200 *a a 150 100 50 0 Effect of Herba Cistanche treatment on Mitochondrial ATP Generation Capacity in Rat Hearts * % Control % Control Control 0.031 0.125 0.5 Dose (g/kg)

  15. 160 * 140 * 120 100 80 60 40 20 0 Effect of Herba Cistanche Treatment on Mitochondrial Respiratory Complex in Rat Hearts % Control Complex I Complex II Complex IV Complex III Citrate Synthase

  16. 220 50mg/ml 200 150mg/ml 180 160 * 140 a * 120 a a a 100 a 80 60 0 2 4 6 8 10 12 14 16 18 Incubation Time (h) Effects of Herba Cistanche Treatment on Mitochondrial ATP Generation Capacity in Cultured H9c2 cells * * a * a % Control * a * a * a

  17. Studies on a ‘Yang-Invigorating’ Chinese Medicine Formula –VI-28

  18. Male Female 250 # 250 VI-28 80mg/kg VI-28 240mg/kg 200 200 150 150 100 100 50 0 50 Cu-Zn SOD 0 Cu-Zn SOD Effect of VI-28 treatment on RBC – CuZn-SOD in rats % Control % Control * # * * Rejuven Res 2005

  19. VI-28 80mg/kg 300 * # 300 VI-28 240mg/kg * # Brain * # * # * 200 * * # 200 * * # * * * # * * * 100 100 0 0 300 300 * # * # Heart * * * # 200 200 * # * * * * * * * * 100 100 0 0 * * 300 300 * * # Liver * # * # 200 200 * * * * * # * * * * * 100 100 0 0 * # 300 300 Skeletal muscle * * # 200 200 * # * * * # * # * # * * * * * 100 100 * 0 0 Effects of VI-28 Treatment on Mitochondrial functional and Antioxidant Status in Various Rat Tissues Male Female % Control % Control ATP-GC GSH a-TOC Mn-SOD ATP-GC GSH a-TOC Mn-SOD % Control % Control ATP-GC GSH a-TOC Mn-SOD ATP-GC GSH a-TOC Mn-SOD % Control % Control ATP-GC GSH a-TOC Mn-SOD ATP-GC GSH a-TOC Mn-SOD % Control % Control ATP-GC GSH a-TOC Mn-SOD ATP-GC GSH a-TOC Mn-SOD

  20. 120 VI-28 80mg/kg VI-28 240mg/kg 100 * * * * * 80 * % Control 60 40 20 0 Liver Brain Heart Skeletal Muscle Effects of VI-28 Treatment on Mitochondrial ROS Generation in Various Rat Tissues

  21. Cordyceps Yang-invigorating and Yin-nourishing

  22. Wild Cordyceps Cultured Cordyceps Herba Cynomorii 90 Fructus Ligustri 80 70 * # 60 50 * # * # 40 * # 30 * * * # * 20 10 0 0 25 50 75 100 125 150 175 200 225 Effects of Herbal Extracts on ConA-Stimulated Proliferation of Mouse Splenocytes in vitro (Arbitrary Unit) The Extent of Con A-stimulated Proliferation (AUC-1) Concentration (mg/ml)

  23. (a) (b) 160 300 ** 140 * *** 250 *** 120 200 100 # ** # ** 80 150 60 100 40 50 20 0 0 Control Wild Cultured Fructus Herba Control Wild Cultured Fructus Herba Cordyceps Cordyceps Ligustri Cynomorii Cordyceps Cordyceps Ligustri Cynomorii Effects of Herbal Extracts on Myocardial ATP Generation Capacity and Mitochondrial Electron Transport in Mice Ex Vivo (nmol/mg protein) (% Control) ATP Generation Capacity Mitochondrial Electron Transport

  24. Cordyceps • Stimulate ATP production (Yang) • Enhance immune response (Yin)

  25. Yang vs. Yin • Yang but not Yin herbs stimulate ATP production • Pharmacological basis of Yang-invigoration in Chinese medicine Trends in Pharmacological Sciences (2004)

  26. Yang-Invigorating Herbs Yang - oxidation  Yin - antioxidation Why Yang herbs contain high antioxidant activity?

  27. Mitochondrial Electron Transport Chain

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