Comparison Integration of Western and Eastern Medicine Jing

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Comparison & Integration of Western and Eastern Medicine Jing Liu, Ph. D, Lic. Ac

Comparison & Integration of Western and Eastern Medicine Jing Liu, Ph. D, Lic. Ac 2011

l A copy right is reserved for the materials in the following presentation

l A copy right is reserved for the materials in the following presentation

Integrated Medicine l Western Medicine + TCM + Natural Medicine ( Nutrition, diet, herbs,

Integrated Medicine l Western Medicine + TCM + Natural Medicine ( Nutrition, diet, herbs, natural therapies in the world) 11/10/10 Jing Liu 3

Content l Fatigue - Hormone Balance l Inflammation l Pain l Comments on acupuncture

Content l Fatigue - Hormone Balance l Inflammation l Pain l Comments on acupuncture clinical trails: l Placebo, Specificity of acupoints

Cause of Fatigue l Insomnia Heart - kidney disharmony l Hormone dysfunction Kidney deficiency

Cause of Fatigue l Insomnia Heart - kidney disharmony l Hormone dysfunction Kidney deficiency l Gut inflammatory status Spleen: Dampness / phlegm

Yin & Yang Insomnia treatment l WM ¡ Sedative-Hypnotics or antipsychotics ¡ Adverse reactions:

Yin & Yang Insomnia treatment l WM ¡ Sedative-Hypnotics or antipsychotics ¡ Adverse reactions: drowsiness, weakness, pseudodepression in the morning l EM ¡ Encouraging Yang energy in the morning and nourishing Ying in evening ¡ Yang encouraging : Yin nourishing: 11/10/10 Jing Liu

Yin & Yang Theory and Sleep l A general principle in traditional Chinese Medicine

Yin & Yang Theory and Sleep l A general principle in traditional Chinese Medicine (TCM) practice l Morning Yang Time: adrenal, thyroid hormone awake and rise to peak - energetic, active l Evening and Night Yin time: melatonin and serotonin dominant –calm and sound sleep l Higher Yang in the morning, Deeper Yin control in evening and night, better quality of sleep 11/10/10 Jing Liu 8

Sleep and Hormone Balance

Sleep and Hormone Balance

Insomnia - Cortisol Dysfunction Syndrome l l l l Fatigue Depression Insomnia Irritability/. Anxiety

Insomnia - Cortisol Dysfunction Syndrome l l l l Fatigue Depression Insomnia Irritability/. Anxiety Sweets craving Poor concentration Headache Allergy Elevated sympathetic nerve tone and decreased cortisol l = Heart Kidney Disharmony 心肾不交 ?

Insomnia Treatment Basic Formula (1) Kidney strengthening Mai Wei Di Huang Tang 麦味地黄 ¡Add:

Insomnia Treatment Basic Formula (1) Kidney strengthening Mai Wei Di Huang Tang 麦味地黄 ¡Add: Ginseng人参, Royal jelly蜂王浆, Adrenal hormone promoting: Shan Zhu Yu山茱萸, Shu Di Huang熟地黄 Estrogenic phytohormone: Shan Yao山药(tocopherol, Coenzyme Q 9, Cyloartenol, 1 - feruloyl glycerol, hydro-Q 9, chromene)

Insomnia Treatment Basic Formula (2) 酸枣仁汤 l 酸枣仁 l 川芎 Anti-inflammatory l 茯苓 Reduce

Insomnia Treatment Basic Formula (2) 酸枣仁汤 l 酸枣仁 l 川芎 Anti-inflammatory l 茯苓 Reduce edema l 知母 Anti-sympathetic, Anti-inflammatory l 甘草 Anti-inflammatory, Detox l Add: hehuanhua合欢花, lianzixin莲子芯,baishao 白芍

Causes of Fatigue l Heart: Insomnia l Kidney: Hormone Dysfunction ( HPTA Axis) l

Causes of Fatigue l Heart: Insomnia l Kidney: Hormone Dysfunction ( HPTA Axis) l Spleen: Gastrointestinal Dysfunction

Fatigue and Hormone HPA Axis l The current evidence supports the following factors of

Fatigue and Hormone HPA Axis l The current evidence supports the following factors of HPTA axis dysfunction in patients related with chronic fatigue syndrome (CFS): l l Mild hypocortisolism l Attenuated diurnal variation of cortisol l Blunted HPTA axis responsiveness to body need. l hypothyroid function l Imbalanced sexual hormones

Adrenal Hormone Synthesis l

Adrenal Hormone Synthesis l

Adrenal Hormone Synthesis

Adrenal Hormone Synthesis

Estrogen Family

Estrogen Family

Adrenal Dysfunction / Fatigue l Adrenal glands are unable to keep pace with the

Adrenal Dysfunction / Fatigue l Adrenal glands are unable to keep pace with the demands of perpetual stress. l Stress signals > cortex > limbic system > sympathetic nerve > adrenal gland > cortisol release/thyroid hormone l The gland can't produce quite enough of the hormones our mind-body need. l Existing blood tests, aren't sensitive enough to detect the decline in adrenal function: cortisol panel test

The Symptoms of Adrenal Fatigue l Qi & Yin Deficiency l l l l

The Symptoms of Adrenal Fatigue l Qi & Yin Deficiency l l l l l Fatigue, mostly Midday Fatigue Unexplained Weight loss Reduced tolerance for stress Insomnia Anxiety Craving for sweets and salty foods Body hair loss Body aches Depression l Low Cortisone Syndrome l Above symptoms plus: Increased susceptibility to infections Allergies to things you were never allergic to before Chemical sensitivities (Hyper Chemical Sensitivity)

Herbs for Adrenal Dysfunction l l l l l Panax Ginseng 人参 Elwutherococcus 西伯利亚人参

Herbs for Adrenal Dysfunction l l l l l Panax Ginseng 人参 Elwutherococcus 西伯利亚人参 Rhodiola 红景天 Yin Yang Huo 淫羊藿 Shan zhu yu 山茱萸 Ocimum sanctum ( holy basil) 圣罗勒 Withania 睡茄 Glycyrrhiza 甘草 (Hypotension) Other herbs for Kidney Yin/Yang deficiency

Treatment of Adrenal Fatigue l l l Progesterone cream Iodine / tyrosine Phosphorylated serine

Treatment of Adrenal Fatigue l l l Progesterone cream Iodine / tyrosine Phosphorylated serine / He Shou Wu 何首乌 Pregnenolone / Cortisol Melatonin at bed time

Hypothyroidism (1) Qi & Yang Deficiency l Fatigue l Shortness of breath with a

Hypothyroidism (1) Qi & Yang Deficiency l Fatigue l Shortness of breath with a shallow and slow respiratory pattern l Low basal body temperature, Cold intolerance l Thyroid-Related Depression l slow heart rate l Sluggish reflexes l Constipation l Poor muscle tone (muscle hypotonia) l Slow speech and a hoarse, breaking voice Depression Kidney deficiency l Decreased libido l Hair loss l Lower renal function with decreased glomerular filtration rate l Impaired memory l Abnormal menstrual cycles l Thin, brittle fingernails Female infertility

Hypothyroidism (2) Spleen deficiency l l l Weight gain and water retention Enlarged tongue

Hypothyroidism (2) Spleen deficiency l l l Weight gain and water retention Enlarged tongue Yellowing of skin due to impaired conversion of beta-carotene to vitamin A Impaired Puffy face, hands and feet (Non-specific Edema? ) Impaired cognitive function (brain fog) Yin & Blood deficiency l Dry, itchy skin l Decreased sweating l Others l Elevated serum cholesterol l Muscle cramps and joint pain l Hyperprolactinemia and galactorrhea

Wilson's Temperature Syndrome l Temperature lower than 98. 60 F l Hypothyroidism symptoms with

Wilson's Temperature Syndrome l Temperature lower than 98. 60 F l Hypothyroidism symptoms with normal T 3, T 4 l Typically brought on by stress l often exist with chronic fatigue syndrome, fibromyalgia’ l Improved by treatment of T 3 or herbs / supplements; not respond to T 4 treatment

Causes of Hypothyroid Syndrome l Iodine deficiency l Stress l Hushimoto disease ( chronic

Causes of Hypothyroid Syndrome l Iodine deficiency l Stress l Hushimoto disease ( chronic lymphocytic thyroiditis), 25% l lithium-based mood stabilizers, usually used to treat bipolar disorder (previously known as manic depression) l Congenital hypothyroidism is very rare accounting for approximately 0. 2‰

Thyroid Hormone l 90% T 3 (effects fast, short term) l 10% T 4

Thyroid Hormone l 90% T 3 (effects fast, short term) l 10% T 4 (effects slow, long term) l T 3 is only form of thyroid hormone to supply energy to heart from breaking down fat l Over dose of T 3 cause cardiac overloading

Conversion of T 3 or RT 3

Conversion of T 3 or RT 3

Conversion of T 4 to T 3 Promoters (1) l l l l Kelp

Conversion of T 4 to T 3 Promoters (1) l l l l Kelp (iodine, Iron), selenium Zinc, potassium, cupper High protein diet Vitamin A, E, C, B 2, B 3, B 6, B 12 Growth Hormone Testosterone Ashwaganda (India herb)

Inability to convert T 4 to T 3 l Excessive alcohol l Low protein/fat

Inability to convert T 4 to T 3 l Excessive alcohol l Low protein/fat diet l Too much cruciferous vegetables l Walnuts

Low T 3 / High reverse T 3 Promoters l l l l Stress

Low T 3 / High reverse T 3 Promoters l l l l Stress - epinephrine / NE, cortisol Free radicals Aging Fasting Diabetes Toxic metal exposure Inflammation-elevated inflammatory factors: IL-6, TNFalpha, IFN-2

Iodine Deficiency l 88% America women are in iodine deficiency. l Low iodine cause

Iodine Deficiency l 88% America women are in iodine deficiency. l Low iodine cause hyperestrogenic state and higher free estrogen level up to 80 to 90%, normal is 40 to 60%. l When Iodine is enriched, the estrogen receptor activity in the breast is reduced. l Iodine promote apoptosis and disrupt proliferation l Low iodine cause fibrocystic breast; Effective therapy (82%) in treating fibrocystic breast disease and prevent breast cancer l TCM: Hai Zao, Kun Bu 海藻,昆布

Iodine Deficiency

Iodine Deficiency

Causes of Iodine Deficiency l Diet in shortage of iodine l Iodine Taken Up:

Causes of Iodine Deficiency l Diet in shortage of iodine l Iodine Taken Up: Thyroid: 6 mg; breasts: 5 mg /day; other tissues: 2 mg/day l Japanese women: 13. 8 mg daily, lowest in breast cancer l Diet high in pasta/bread containing bromide (bind to iodine receptor) l Fluoride use (inhibiting iodine binding l Vegan and vegetarian diet

Drugs for T 3/T 4 replacement l T 3: Liothyronine, Triiodothyronine l T 4:

Drugs for T 3/T 4 replacement l T 3: Liothyronine, Triiodothyronine l T 4: Levothyroxine (Synthroid) Transfom to be T 3, but take up to 8 weeks to reach the required level of T 3. l Armour® a naturally derived from porcine thyroid glands. (T 3 liothyronine is 4 x as potent as T 4 levothyroxine; so 38 mcg T 4 and 9 mcg T 3 per grain of thyroid.

Thyroid Hormone Replacement Failure l After increase dosage still feel fatigue: l Magnesium deficiency

Thyroid Hormone Replacement Failure l After increase dosage still feel fatigue: l Magnesium deficiency l Adrenal deficiency l Overdose l Poor absorption from unhealthy gut

Side Effects of T 3 Therapy l l l l Fluid pretension Achiness Jitteriness

Side Effects of T 3 Therapy l l l l Fluid pretension Achiness Jitteriness Irritability Dull headache Increased heart rate Can not be used for severe Adrenal or cardiac deficiency

Herbs for Thyroid Function l Huang Qi黄芪 l Huang Qi Wu Wu Tang黄芪五物汤 l

Herbs for Thyroid Function l Huang Qi黄芪 l Huang Qi Wu Wu Tang黄芪五物汤 l Or add: Xiao Chai Hu Tang小柴胡汤, in case of autoimmune l Prolonged hypothyroidism cause adrenal fatigue l Adrenal: Ying Yang Huo 淫羊藿, Shan Zhu Yu山茱萸 l When the herbs not effective enough, add T 3, to reduce the dose of T 3 and reduce the side effect of T 3

Natural Supplements for Thyroid Function l Guggul (Commiphora mukul) increase iodine intake and thyroid

Natural Supplements for Thyroid Function l Guggul (Commiphora mukul) increase iodine intake and thyroid hormone production, enhance thyroid perocidase enzymes l Seaweed (algae) : Kelp (kun Bu) bladder wrack fucus vesiculosus (best antioxidant among seaweeds) l Seaweed contain diiodothyoinine (DIT), which may promote thyroid function l Zinc, Selenium l Blue Flag - potent detoxifier of thyroid l Improvement usually occurs within 3 to 4 weeks

Hushimoto’s Disease l Reduce autoimmune response and inflammation l l Xiao Chai Hu Tang

Hushimoto’s Disease l Reduce autoimmune response and inflammation l l Xiao Chai Hu Tang 小柴胡汤 Curcumin Boswellia Lycopus virginicus(lycopus lucidus 泽兰) l inhibit iodine metabolism, inhibits release of thyroxine from thyroid, binds with TSH, decrease pulse and BP l 95% improvement rate, officially recognized in Germany as prescription l Rosemary extract (迷 迭香 100: 1), reduce antibody

Hormone: Progesterone l Produced mainly in ovary, little in adrenal gland; Increase 100 x

Hormone: Progesterone l Produced mainly in ovary, little in adrenal gland; Increase 100 x during pregnancy l Enhance: thyroid function, apoptosis, estrogen sensitivity, brain cell growth in fetus l Decrease: breast cell growth, breast cancer, atherosclerosis, l Decrease Brain degeneration, neuro-blastoma, MS; antidepression l Burn fat for energy; hair growth; l Progestins are NOT equal to progesterone

Herbs for Progesterone l Juglans regia (England Walnut 核桃), progesterone detected l Progesterone-like steroids

Herbs for Progesterone l Juglans regia (England Walnut 核桃), progesterone detected l Progesterone-like steroids in Dioscorea mexicana of yam family native to Mexico, containing steroid diosgenin converting into progesterone. l Diosgenin and progesterone found in other Dioscorea species. l Dioscorea pseudojaponica from Taiwan, containing saponins —converted to diosgenin -> progesterone. l Other Dioscorea species: Dioscorea villosa and. Dioscorea polygonoides. l Dioscorea villosa contains 3. 5% diosgenin. l Dioscorea polygonoides contain 2. 64% l Dioscorea family: Shan Yao山药, Bi Xie, Chuan Shan Long穿山龙, Shan Ci Gu山慈姑 I l Sheng Ma 升麻 l Maca l Fu Pen Zi 覆盆子

Hormons: Estradiol(E 2) l Neuro-protective l Breast cancer promoting l Cell proliferation with alveoli

Hormons: Estradiol(E 2) l Neuro-protective l Breast cancer promoting l Cell proliferation with alveoli formation (hyperplasia) and even cyst formation

Effects of Estrogen Therapy l Prevent osteoporosis l Decrease LDL and increase HDL l

Effects of Estrogen Therapy l Prevent osteoporosis l Decrease LDL and increase HDL l l l Increase blood pressure, triglyceride Gallstone Elevated liver enzyme Increase carbohydrate craving Decrease thyroid function by increasing binding thyroid binding globulin

Estrogen Balance l l l In the 1960 s and 70 s Dr. Henry

Estrogen Balance l l l In the 1960 s and 70 s Dr. Henry Lemon concluded: Estrogen Quotient EQ=E 3/E 1+E 2 EQ<1: high risk for breast cancer EQ>1. 5: low risk for breast cancer

Hormone: Estriol l Anti-inflammation l Promote shift from T helper (Th) 1 to Th

Hormone: Estriol l Anti-inflammation l Promote shift from T helper (Th) 1 to Th 2 l Reduce autoimmune disease l Prevent osteoporosis l Breast caner protection l Menopause improvement 92 l Don't seem to increase risk of breast cancer Estriol binds to estrogen receptors with much weaker activity, competing stronger estradiol binding to receptors - protective against breast cancer

Estrogen Dominance Fatigue Hypothyroidism by decrease conversion of T 4 to T 3 l

Estrogen Dominance Fatigue Hypothyroidism by decrease conversion of T 4 to T 3 l Decreased sex drive l Depression / anxiety / Migraines / Insomnia l Memory loss or foggy thinking l Mood swings / Memory loss or foggy thinking l Weight gain secondary to insulin resistance / Fat gain l PMS / Menstrual disturbances--irregular and heavy bleeding. • Bone loss / Hair Loss l Breast cancer / Fibrocystic breasts / Uterine cancer / fibroids l Water retention, bloating. l Tendency of autoimmune disorder Correction: Progesterone therapy

Estrogen Dominance After menopause, Progesterone decreases by over 99% from its original youthful baseline

Estrogen Dominance After menopause, Progesterone decreases by over 99% from its original youthful baseline levels; while estrogen production only decreases by about 40%. l New research show that almost all the uncomfortable symptoms of PMS and of Menopause are actually caused by low progesterone levels in the body.

Breast Cancer prevention l Bio-identical Estrogen therapy l E 3: E 2 = 4:

Breast Cancer prevention l Bio-identical Estrogen therapy l E 3: E 2 = 4: 1 l l DIP D Vitamin D deficiency Iodine deficiency P Progesterone deficiency

Hormone: Testosterone l l l Testosterone Improve insulin resistance, belly fat Improve: sleep, vitality,

Hormone: Testosterone l l l Testosterone Improve insulin resistance, belly fat Improve: sleep, vitality, libido/orgasm/arousal Not necessary cause prostate cancer Herbs:Yin Yang Huo淫羊藿, Rou Cong Rong肉苁蓉, Lu Rong鹿茸, Ren Shen人参

Hormone: DHEA the first anti-aging hormone l l l l Improve motivation, well being,

Hormone: DHEA the first anti-aging hormone l l l l Improve motivation, well being, memory, libido/orgasm Anti-atherosclerosis Antidiabetic Anti-inflammatory Antiosteoporotic Anti-senility Reduce fat Protect thymus and immune function l 50 mg daily anti-age without significant side effects

Fatigue ¡Fatigue and GI dysfunctiion / Candida

Fatigue ¡Fatigue and GI dysfunctiion / Candida

Symptoms of Candia (1) l l l l fatigue concentration/focus memory problems painful joints,

Symptoms of Candia (1) l l l l fatigue concentration/focus memory problems painful joints, muscle aches unrefreshing sleep white coated tongue chronic sinusitis Diarrhea or chronic constipation headaches including migraines visual blurring, sensitivity to light, eye pain Depression, irritability, anxiety sensitivity to heat/cold alcohol intolerance gluten intolerance

Symptoms of Candia (2) l l l l Irritable bowel numbness/tingling in the face

Symptoms of Candia (2) l l l l Irritable bowel numbness/tingling in the face or extremities dryness of mouth and eyes menstrual problems (PMS/endometriosis) recurrent yeast infections skin rashes, dry/flaking skin Eczema, dermatitis, acne jock and rectal itching chronic athlete's foot, toenail and fingernail fungus ringing in the ears (tinnitus) allergies sensitivity to noise/sounds, foods, chemicals feeling in a fog muscle weakness jerky-leg syndrome low sex drive

Anti-Candida Herbs l Cinammon l Grapefruit seed extract l Olive leaf extract l Garlic

Anti-Candida Herbs l Cinammon l Grapefruit seed extract l Olive leaf extract l Garlic extract l Berbering, Goldenseal l Oregano leaf extract l Pau d’arco l Zinc l Coconut oil l Candex (cellulase enzymes)

Introduction: Inflammation l Normal inflammation is a necessary protective response to harmful stimuli to

Introduction: Inflammation l Normal inflammation is a necessary protective response to harmful stimuli to the body. l Prolonged or excessive inflammation is related pathological status including infection, autoimmune disorders, atherosclerosis, Alzheimer's, autism, arthritis and even cancer

Inflammation Process Eicosanoid Cyclooxygenase Pathway Pathogen IL-1, TNF-a, PDGF, IFNs, Tyrosine Kinase chemokines inflammation

Inflammation Process Eicosanoid Cyclooxygenase Pathway Pathogen IL-1, TNF-a, PDGF, IFNs, Tyrosine Kinase chemokines inflammation Adhesion proliferation penetration hypoxia, superoxide, NO, free radical cancer AA COX 2 PGE 2 inflammation

Eicosanoid Synthesis Prostaglandin/Inflammation Formation Pathway

Eicosanoid Synthesis Prostaglandin/Inflammation Formation Pathway

Eicosanoid Synthesis Prostaglandins and related compounds are collectively known as eicosanoids. Most are produced

Eicosanoid Synthesis Prostaglandins and related compounds are collectively known as eicosanoids. Most are produced from arachidonic acid (AA) l Step one: Release of AA from membrane phospholipids by phospholipase A 2(PLA 2). l Step Two: AA is metabolized by COX enzymes to be prostaglandin E 2 (PGE 2), or Thromboxin (TXA 2) or prostacyclin (PGI 2), l AA also metabolized by lipoxygenase or cytochrome P 450 to be l leukotrienes Ecosanoid considered "local hormones. " participating in intercellular signaling,

Role of Ecosanoid inflammation fever regulation of blood pressure blood clotting immune system modulation

Role of Ecosanoid inflammation fever regulation of blood pressure blood clotting immune system modulation control of reproductive processes & tissue growth regulation of sleep/wake cycle.

Ecosanoid Inhibitors Corticosteroids are anti-inflammatory from preventing PL A 2 expression, reducing AA release.

Ecosanoid Inhibitors Corticosteroids are anti-inflammatory from preventing PL A 2 expression, reducing AA release. Stress – adrenal fatigue – cortisol exhaustion - inflammation COX-2 is stimulated by growth factors, cytokines, and endotoxins. Attempts have been made to develop drugs that inhibit: Phospholipase A 2 / AA / COX for treating inflammatory diseases

Inflammation exist in many diseases: cancer, autoimmune disorders, infections, et al. l WM ¡

Inflammation exist in many diseases: cancer, autoimmune disorders, infections, et al. l WM ¡ COX-2 inhibitor (Vioxx, Celebrex) ¡ Adverse reactions: PGI 2 inhibition – inner membrane of blood vessel damage leading stomach ulcer, kidney failure, cardiac attack l EM ¡ Natural COX 2 inhibitor: Curcumin, turmeric姜黄, coptis黄连, berberine, Paeonia Latiflora芍药, Boswellia乳香 ¡ No obvious PG I 2 inhibition; Only benefit to heart 11/10/10 Jing Liu

COX-2 w COX-2 levels increase in inflammatory diseases such as arthritis. COX-2 expression is

COX-2 w COX-2 levels increase in inflammatory diseases such as arthritis. COX-2 expression is increased in some cancer cells. Angiogenesis, essential to tumor growth, requires COX -2. Over expression of COX-2 leads to expression of VEGF (vascular endothelial growth factor). Regular use of NSAIDs has been shown to decrease the risk of developing colorectal cancer.

Anti-inflammatory Therapy Side effects & Limitations of Chemical Drugs l Naproxen, trade name Alevea,

Anti-inflammatory Therapy Side effects & Limitations of Chemical Drugs l Naproxen, trade name Alevea, a nonsteroidal anti-inflammatory drugs (NSAID) l ibprofen, indomethacin and ketoprofen. l Common side effects l Constipation; diarrhea; dizziness; drowsiness; gas; headache; heartburn; nausea; stomach upset; stuffy nose. l Severe side effects l rash; hives; itching; swelling of the mouth, face, lips, or tongue; wheezing); bloody stools; change in the amount of urine produced; chest tightness or pain; confusion; dark urine; depression; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; loss of appetite; mental or mood changes; numbness of arm or leg; onesided weakness; pale stools; red, swollen, blistered, or peeling skin; ringing in ears; seizures; severe headache or dizziness; stomach pain, nausea, vomiting or bleeding; shortness of breath; weight gain; swelling of the hands, legs, or feet; bruising or bleeding; joint or muscle pain; tiredness or weakness; vision or speech changes; grounds; yellowing skin or eyes. l This is not a complete list of all side effects that may occur.

COX Inhibitors l Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and derivatives of ibuprofen:

COX Inhibitors l Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and derivatives of ibuprofen: a. Inhibit COX to form prostaglandins involved inflammation, pain. b. Inhibit blood clotting by blocking TXA 2 c. block AA enters COX active site. Most NSAIDs inhibit both COX I & COX II. Selective COX-2 inhibitors have been developed, e. g. , Celebrex and Vioxx. w COX-2 inhibitors are less likely to cause gastric toxicity compared with NSAIDs that block COX-1. l

Inflammation and Endothelial Dysfunction to Microvascular Dysfunction l Endothelial dysfunction is integral to the

Inflammation and Endothelial Dysfunction to Microvascular Dysfunction l Endothelial dysfunction is integral to the pathogenesis of many disorders: l l l Atherosclerosis Autoimmune disorders Inflammation Infection Trauma

Arterial Wall Anatomy

Arterial Wall Anatomy

Endothelium of Blood Vessels

Endothelium of Blood Vessels

Vascular Endothelial Mediators

Vascular Endothelial Mediators

Thromboxane A 2 - TXA 2 Stimulates blood platelet aggregation, essential to role of

Thromboxane A 2 - TXA 2 Stimulates blood platelet aggregation, essential to role of platelets in blood clotting. w Aspirin inhibit TXA 2 formation in blood platelets. w This effect of aspirin is long-lived, 7 days, because platelets lack a nucleus and do not make new enzyme.

Leukotrienes produce inflammation in: Blood vessel walls as part of the pathology of atherosclerosis.

Leukotrienes produce inflammation in: Blood vessel walls as part of the pathology of atherosclerosis. Bronchioles causing asthmatic constriction and asthma. Anti-asthma medications include: w Zyflo (zileuton): inhibitors of 5 -Lipoxygenase w Singulair (montelukast) & Accolate (zafirlukast): block leukotriene-receptor interactions.

Natural COX-2 Inhibitors l Huangqin黄芩 was found to have COX-2 inhibitory properties in China,

Natural COX-2 Inhibitors l Huangqin黄芩 was found to have COX-2 inhibitory properties in China, Spain, Korea, Canada and United States l Ginger姜 is a strong anti-inflammatory herb. Studies indicate that ginger is a safe COX- 2 and COX-1 modulator l Scientists in the USA, Sweden, Taiwan and Germany have confirmed that green tea is a high active COX-2 inhibitor. l The chemical ingredients, salicylic acid and polyphenols, including EGCG, in green tea are effective cancer antagonists.

Turmeric or curcuma longa l The anti-COX-2 effect of turmeric was discovered by Vanderbilt

Turmeric or curcuma longa l The anti-COX-2 effect of turmeric was discovered by Vanderbilt University researchers. Cornell University in New York and the University of Leicester in England. l The active anti-inflammation component curcumin is about 50% as effective as cortisone. l The purified form of 95% curcuminoids per dose is the best anti-inflammatory effects. l A number of publications have shown the anti-cancer effects of turmeric in in vitro and in vivo.

Natural COX-2 Inhibitors l Curcumin and capsaicin significantly lowered lysosomal enzymes from macrophages in

Natural COX-2 Inhibitors l Curcumin and capsaicin significantly lowered lysosomal enzymes from macrophages in animals l Macrophages from rats secreted less PG E 2, leukotrienes B 4 and C 4 and AA. l Curcumin and capsaicin lowered eicosanoids and AA in macrophage lipids. l Curcumin and capsaicin can lower secretary functions of macrophages in a beneficial manner.

Natural Anti-inflammation/COX-2 Agents Drynaria fortunei l Extracts of Drynaria fortunei (Gu Sui Bu): significant

Natural Anti-inflammation/COX-2 Agents Drynaria fortunei l Extracts of Drynaria fortunei (Gu Sui Bu): significant inhibition of carrageenan-induced paw oedema and granuloma formation in rats, almost comparable to that caused by indomethacin. Df significantly attenuated formalin-induced pain and acetic acid-induced writhing episodes in mice. l Clinical trial: significant effects for arthritis pain, joint function and osteoporosis without significant side effects l CONCLUSION: potent anti-inflammatory agent for alleviating painful inflammatory conditions of osteoarthritis. l The herbal formula for arthritis: Gu Sui Bu, Fang Feng, Cuan Duan, Zhi Mu, Jing Jie + Huang Qi Wu Wu Tang

Herbs with COX-2 Inhibitory Effects l green tea, ginger, grape seed, Holy basil, oregano,

Herbs with COX-2 Inhibitory Effects l green tea, ginger, grape seed, Holy basil, oregano, rosemary and willow bark l Giardina C褐茸藻, Stylopine from chelidonium majus白屈菜, Berbarine/Huanglian黄连, ginger, ginsenoside人参皂甙 Rh 1, grape seed葡萄, Salvia miltiorrhiza 丹参, fevervew, scutellaria黄 芩, phellodendron amurense黄柏, carthamus tinctorius红花, nettle leaf荨麻,willow bark柳树 皮

Anti COX Agents - Antioxidants l The oxygen burst in the inflammatory status generate

Anti COX Agents - Antioxidants l The oxygen burst in the inflammatory status generate excessive amount of reactive oxygen species (ROS). l Reactive neutrophil activity in the process is a principle source of ROS. l Inflammatory responses can be suppressed by the application of ROS scavenger, superoxide dismutase (SOD) and antioxidants. l Many antioxidants possess COX-2 inhibiting effects: Polyphenol and catechin in green tea Flavonoid and ursolic acid in many herbs linoleic acid, melatonin, IFN-βin our bodies physiologically inhibitory COX-2 effect

Omega-3: Role in Anti-inflammation l ω-3, mainly DHA and EPA, can effectively inhibit COX

Omega-3: Role in Anti-inflammation l ω-3, mainly DHA and EPA, can effectively inhibit COX mediated AA metabolism and PGE 2 -inflammation/cancer l Plant ω-3 shows inhibitory effect on inflammation and cancer

Acupuncture Mechanism: Pain / Inflammation / immune Pain Inflammatory Immune Cholinergic suppression: Sensory nerves

Acupuncture Mechanism: Pain / Inflammation / immune Pain Inflammatory Immune Cholinergic suppression: Sensory nerves Parasympathetic nerve endings release acetylcholine (ACh), Hypothalamus suppress release Anti-inflammatory output via CNS TNF-a, IL-1β in brain Neuroimmunology modulation

Inflammation Role of Arachidonic Acid l High arachidonic acid consumption (Omega-6) is not advised

Inflammation Role of Arachidonic Acid l High arachidonic acid consumption (Omega-6) is not advised for individuals with a history of inflammatory disease, it may counter the anti-inflammatory effects of omega-3 fatty acid supplementation.

Inflammation Omega-3 : Omega 6

Inflammation Omega-3 : Omega 6

Inflammation Omega-3 : Omega 6 l Patients with autism had significantly higher Omega 6

Inflammation Omega-3 : Omega 6 l Patients with autism had significantly higher Omega 6 in RBC membranes compared to higher Omega 3 in healthy people l Significantly reduced levels of ARA /EPA ratio in RBC polar lipids, when supplemented with EPA-rich fish oils l By taken EPA supplements, significantly reduced PLA 2 concentrations

Natural Anti-inflammation/COX-2 Agents Curcuma longa L l Positive effect on neurogenesis in hippocampus by

Natural Anti-inflammation/COX-2 Agents Curcuma longa L l Positive effect on neurogenesis in hippocampus by increasing brain-derived neurotrophic factor(BDNF) Improving stress, depression, a selective monoamine oxidase inhibitor (MAOI) Clinical trials: Alzheimer's disease.

Anti-inflammatary Supplements l Feverfew (菊蒿) l Holy basil (圣罗勒) l Nettle Leaf(荨麻) l Oregano

Anti-inflammatary Supplements l Feverfew (菊蒿) l Holy basil (圣罗勒) l Nettle Leaf(荨麻) l Oregano l Rosemay(迷迭香) l Boswellia

Natural Anti-inflammation Agents: Antioxidants l The oxygen burst in the inflammatory status generate excessive

Natural Anti-inflammation Agents: Antioxidants l The oxygen burst in the inflammatory status generate excessive amount of reactive oxygen species (ROS). Reactive neutrophil activity in the process is a principle source of ROS. l Inflammatory responses can be suppressed by the application of ROS scavenger, superoxide dismutase (SOD) and antioxidants.

Natural Anti-inflammation Agents: Antioxidants l Many antioxidants possess COX-2 inhibiting effects. l Phenol and

Natural Anti-inflammation Agents: Antioxidants l Many antioxidants possess COX-2 inhibiting effects. l Phenol and flavonoid compounds in many herbs: polyphenol and catechin in green tea, ginkgo biloba, soy, etc. l Some important antioxidants/anti-inflammation chemicals produced in the body: Glutathione, , melatonin, pyruvate, IFN-b, and SOD.

Natural Anti-inflammation Agents from diet: Berries l Berries Blueberries, raspberries, strawberries: antiinflammatory Blackberries and

Natural Anti-inflammation Agents from diet: Berries l Berries Blueberries, raspberries, strawberries: antiinflammatory Blackberries and blueberries are especially great.

Natural Anti-inflammation Agents from diet: Omega-3 l -3, mainly DHA and EPA, can effectively

Natural Anti-inflammation Agents from diet: Omega-3 l -3, mainly DHA and EPA, can effectively inhibit COX mediated AA metabolism and PGE-2 inducible inflammation/cancer. l High -6 low -3 diet favor inflammation l flax seed oil, walnut, pumpkin seed are rich in 3 but in shortage of DHA. l Botanical -3 may anti-inflammation by inhibiting -6 through competing delta desaturase 6.

Root of Inflammation l Broad-spectrum antibiotics kill good bacteria in gut, leading to leaky

Root of Inflammation l Broad-spectrum antibiotics kill good bacteria in gut, leading to leaky gut syndrome - large molecules get through. l l London’s Royal Free Hospital studied 60 autistic children: many more intestinal lesions than nonautistic children l In fact, over 90% of autistic children had chronically inflamed guts.

Root of Diseases - Inflammation Root of Inflammation - GI microflara l l l

Root of Diseases - Inflammation Root of Inflammation - GI microflara l l l Alzheimer, Autism Chronic lung/bronchus infection Arthrosclerosis Sinus infection/allergy Chronic Fatigue syndrome Fibromyagia l l l Autoimmune disorders: MS Lupus Colitis Arthritis

Acupuncture Pain 11/10/10 Jing Liu 90

Acupuncture Pain 11/10/10 Jing Liu 90

Acupuncture for pain Indication l A wide range of pain conditions, such as postoperative

Acupuncture for pain Indication l A wide range of pain conditions, such as postoperative pain, carpal tunnel syndrome, fibromyalgia, headache, low-back pain, menstrual cramps, myofascial pain, osteoarthritis, and tennis elbow. l Doctors from three medical schools published on New England Journal of Medicine l Conclusion: acupuncture is an effective means for treating lower back pain, based partly on a recent study of 6, 359 patients published 11/10/10 Jing Liu 91

Acupuncture Clinical Trail Osteoarthritis l 20 millions people with osteoarthritis l No satisfied pharmaceutical

Acupuncture Clinical Trail Osteoarthritis l 20 millions people with osteoarthritis l No satisfied pharmaceutical drugs l COX-2 inhibitor may cause heart, kidney stomach damage l Phase III radomized controlled clinical trail at Maryland School of Medicine in 2006 l 570 participants with moderate and severe pain l Results: significantly improve knee pain and function

Acupuncture for pain Significant, Mechanism New branch of therapy in clinical medicine: Trans-cutaneous Intervention

Acupuncture for pain Significant, Mechanism New branch of therapy in clinical medicine: Trans-cutaneous Intervention therapy l A lot of augments on the meridian theory At least, most parts of acupuncture theory and practice can be explained by the modern neurology or neurochemistry. ¡ CNS endorphin, serotonin, dopamine modulation, opioid receptor stimulation ¡ Neural segmental analgesia (spinal cord) ¡ Local anti-inflammatory cytokine, microcirculation promotion 11/10/10 Jing Liu 93

Specificity of Acupuncture points l Brain: Overlapped, relatively less specificity l Spinal cord: neural

Specificity of Acupuncture points l Brain: Overlapped, relatively less specificity l Spinal cord: neural segmentation distribution, relatively specificity, with connection l Local: chemicals, neuro-muscle-tendon effects, specific

Acupuncture Evidences in neurochemistry l In the mid 1970 s, Mayer and his colleagues

Acupuncture Evidences in neurochemistry l In the mid 1970 s, Mayer and his colleagues revealed that acupuncture led to a significant increase in the endogenous endorphin production and the effect of acupuncture can be blocked by the opioid receptor antagonist naloxone 11/10/10 Jing Liu 95

Acupuncture Evidences in neurochemistry l A large body of evidence indicates that acupuncture significantly

Acupuncture Evidences in neurochemistry l A large body of evidence indicates that acupuncture significantly affects the production and release of neurotransmitters including epinephrine, norepinephrine, dopamine, and 5 -hydroxytryptamine l Stress-induced increases in norepinephrine, dopamine, and corticosterone were inhibited after EA, l EA effects on the release of neurotransmitters are likely to be mediated through endogenous opioids. l EA at different frequencies (2, 10, or 100 Hz) elicited the analgesic effects and such effects could be at least partially blocked by a serotonin receptor antagonist 11/10/10 Jing Liu 96

Acupuncture Neural segmental analgesia 11/10/10 97

Acupuncture Neural segmental analgesia 11/10/10 97

Acupuncture Pain management and muscle relaxation l Acute pain l Muscle spasm l Chronic

Acupuncture Pain management and muscle relaxation l Acute pain l Muscle spasm l Chronic pain l Muscle spasm - shortening - fibrosis -hardening

Trigger Point – neural-muscle cycle l Pain signals from the muscles and joints cause

Trigger Point – neural-muscle cycle l Pain signals from the muscles and joints cause changes in the central nervous system (CNS) that in turn causes changes in the nerves affecting muscles and joints inducing perception of perpetuating pain. By needling into specific sites, such as hypersensitive skin or tight bands of muscle, this cycle is broken

Trigger Point – Muscle spasm l Chronic inflammation and pain results in muscle spasms

Trigger Point – Muscle spasm l Chronic inflammation and pain results in muscle spasms and lead to changes in the muscle structure. Long lasting muscle spasm causes accumulation of fibrotic tissue inside the muscle (can be palpated as taut band) with subsequent muscle shortening.

Trigger points - Location l Taut bands of muscle and are especially tender to

Trigger points - Location l Taut bands of muscle and are especially tender to palpate. l The muscle tendon junction and tendon attachment to bone provides a complete needling location for the tight muscle and mechanical distraction of fibrotic tissue, resulting in relaxation. l The treatment will increases circulation to the area and decreases pressure on joints.

Acupuncture for Pain Neuro-muscular mechanism ¡Needling by blocking the excessive release of acetylcholine from

Acupuncture for Pain Neuro-muscular mechanism ¡Needling by blocking the excessive release of acetylcholine from the peripheral nerve terminal at the neuromuscular junction (where the nerve transmits signals to the muscle); or muscle-tendon conjunction, where golgi receptor located, inducing muscle contraction inhibition, resulting in muscle relaxation and pain releasing.

Negative feedback regulation of muscle tension by Golgi tendon organs

Negative feedback regulation of muscle tension by Golgi tendon organs

Golgi Tendon Organ

Golgi Tendon Organ

“Golgi Points ? ” l ST 36 l GB 34, 37, Sp 6 l

“Golgi Points ? ” l ST 36 l GB 34, 37, Sp 6 l LI 3, 10 l BL 25 l Si 5

Acupuncture Back Pain- Piriformis Syndrome

Acupuncture Back Pain- Piriformis Syndrome

Role of natural anti-inflammatory Agents in Cancer Treatment l WM ¡ Chemo or Radiation:

Role of natural anti-inflammatory Agents in Cancer Treatment l WM ¡ Chemo or Radiation: limited effectiveness ¡ Side effects from cytotoxicity: immune, bone marrow, digestion, wellbeing l EM ¡ Supportive therapy: immune, bone marrow, digestion, gut bacteria, detoxification (free radicals) ¡ Enhance and reduce resistance of chemo: anti-inflammation ¡ Cause of cancer treatment: inflammation/detox 11/10/10 Jing Liu, MD, Ph. D 108

Cancer and COX-2 l A number of clinical investigations showed that high COX-2 activity

Cancer and COX-2 l A number of clinical investigations showed that high COX-2 activity was found in patients with a variety of cancers: Colorectal, gastric, breast, non-small cell lung, ovarian, hepatocellular, pancreatic, bladder, skin, and particularly, 80 -90% colon cancer

COX-2 Inhibitors for Chemo-resistance l Chemotherapeutic drug resistance is an unresolved challenge in clinical

COX-2 Inhibitors for Chemo-resistance l Chemotherapeutic drug resistance is an unresolved challenge in clinical cancer treatment, particularly for the metastasis carcinoma status. l The inflammation and pro-inflammatory cytokines are strong intrinsic factors for promoting multiple drug resistance (MDR). l Chemotherapy may induce the activities of COX-2 and inflammation. l COX-2 stimulates the P-Glycoprotein of the MDR, which rejects the drug out of the cancer cells. COX-2 inhibitors, celecoxib, aspirin, ibuprofen, and indomethacin may enhance chemotherapy

Synergistic Effect of Herbs with Chemo? l Multiple target model of cancer cell for

Synergistic Effect of Herbs with Chemo? l Multiple target model of cancer cell for Natural COX-2 Inhibitors l Multiple Signal Transduction systems (modulate the DNA/RNA and cell activities/growth, developed from evolution, primary cell to human being ) Growth factors Tyrosine Kinase EGFR/HER 2 IGFR

Pathway of Chemotherapy Resistance Breast Cancer

Pathway of Chemotherapy Resistance Breast Cancer

Natural Anti-inflammatory Agents Enhance Effects of Chemotherapy l Morphologic changes Fig 1. of MCF-7

Natural Anti-inflammatory Agents Enhance Effects of Chemotherapy l Morphologic changes Fig 1. of MCF-7 cells treated with COPE and TAX

Are Antioxidants counteract with Chemotherapy? l Meith I. Block analyzed the results of antioxidants

Are Antioxidants counteract with Chemotherapy? l Meith I. Block analyzed the results of antioxidants applications, including glutathione, melatonin, vitamin A, vitamin C, N-acetylcysteine, vitamin E, ellagic acid antioxidant mixture, from randomized and controlled clinical trials in 845 articles. l Conclusion: None of the trials reported evidence of significant decreases in efficacy from taking antioxidant supplements during chemotherapy.

Are Antioxidants counteract with Chemotherapy? l Instead, many of the studies suggested increased survival

Are Antioxidants counteract with Chemotherapy? l Instead, many of the studies suggested increased survival times, increased tumor responses, and less toxixity responses from taking antioxidants than controls[1] l [1] Block KI, etc. Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. l Int J Cancer. 2008

Are Antioxidants counteract with Chemotherapy? l The natural supplements may be taken after the

Are Antioxidants counteract with Chemotherapy? l The natural supplements may be taken after the chemotherapeutic agents are eliminated from plasma, which could be from a few hours to a few days. l The supplements should be stopped at least one day before the next chemotherapy session. l The information about the pharmacological dynamics of the chemotherapeutic agents should be researched before the natural supplements is administered.

11/10/10 Jing Liu, MD, Ph. D 118

11/10/10 Jing Liu, MD, Ph. D 118

l End

l End

Inflammation and Endothelial Dysfunction to Microvascular Dysfunction l Endothelial dysfunction is integral to the

Inflammation and Endothelial Dysfunction to Microvascular Dysfunction l Endothelial dysfunction is integral to the pathogenesis of many disorders: l l l Atherosclerosis Autoimmune disorders Inflammation Infection Trauma

Vascular Endothelial Mediators

Vascular Endothelial Mediators

Nitric Oxide/L-Arginine-Herbs l Nitric Oxide (NO) l anti-inflammatory and anti-proliferative effects l Endothelial function

Nitric Oxide/L-Arginine-Herbs l Nitric Oxide (NO) l anti-inflammatory and anti-proliferative effects l Endothelial function protection l Atherosclerosis protection

Nitric Oxide/L-Arginine-Herbs l L-arginine l Control blood pressure and improve heart function l Reducing

Nitric Oxide/L-Arginine-Herbs l L-arginine l Control blood pressure and improve heart function l Reducing cholesterol and plaque formation l Promote anti-aging growth hormone l Enhancing immune function and stop some cancer cell growth l Improving memory l Improve erectile dysfunction

Nitric Oxide/L-Arginine-Herbs l Herb l Dang Gui l Bai Shao l Bai Jili

Nitric Oxide/L-Arginine-Herbs l Herb l Dang Gui l Bai Shao l Bai Jili

The signal molecule ·NO (nitric oxide) may initiate prostaglandin synthesis by reacting with superoxide

The signal molecule ·NO (nitric oxide) may initiate prostaglandin synthesis by reacting with superoxide anion (O 2·-) to produce peroxynitrite, which oxidizes the heme iron enabling electron transfer from the active site tyrosine. Prostaglandin synthesis in response to some inflammatory stimuli is diminished by inhibitors of Nitric Oxide Synthase.

Autoimmune disorders l WM ¡ Prednisone, immune suppressor, T-cell inhibitor ¡ Adverse reaction: mal-metabolism

Autoimmune disorders l WM ¡ Prednisone, immune suppressor, T-cell inhibitor ¡ Adverse reaction: mal-metabolism cortisone withdrawal syndrome, immune dysfunction l EM ¡ Immune enhancing and Immune suppression together: astraglus vs. scutellaria, Bupleurum ¡ Stimulating adrenal –cortisone function for cortisone withdrawal syndrome (NIH fund supported project) ¡ Gentle but effective T-cell or TNF inhibitor: Olivenol, Rapamycin, Dichroa febrifuga黄常山, Principle: TNF is a dual side blade sword 11/10/10 132

Infection l WM ¡ Limitations of antibiotics in Chronic infection: immune function, beneficial bacteria

Infection l WM ¡ Limitations of antibiotics in Chronic infection: immune function, beneficial bacteria damage, drug resistance ¡ Co-existing inflammation, congested microcirculation l EM ¡ Detox - anti-pathogen ¡ De-congestion of circulation- open the microcirculation: antibiotic availability, flushing out toxins ¡ Promoting Qi – enhancing immune function ¡ Strengthen “spleen system” – protect digestion and prebiotic 11/10/10 Jing Liu 133

Natural therapy for autoimmune disorder David Fernandez (2010) discover: rapamycin can be an effective

Natural therapy for autoimmune disorder David Fernandez (2010) discover: rapamycin can be an effective treatment in human lupus, SLE. regulates interferon-α and T cell and promote Th 2 versus Th 1 immune responses suggest that the colitis, including crohn’s disease and ulcerative colitis, can be well controlled by natural therapy in many cases, and can be well integrated with cortisone or immune suppressor Probiotic + Enzymes + Herbs + Diet

Gastroesophageal reflux (GERD) l WM ¡ ¡ H 2 blocker – Zantac Proton pump

Gastroesophageal reflux (GERD) l WM ¡ ¡ H 2 blocker – Zantac Proton pump inhibitor – Prilosec Mucosal protectors – sucralfate Motility drugs - empty stomach, Reglan. l EM ¡ Mucosal protection: Gastric acid pseudo-overproduction, Deglycyrrhizinated licorice (DGL) Calming acid reflux and peptic ulcers by: ü Anti-inflammation and the pathogens ü Protect mucosal membrane by increasing the thick mucous production ü Free of the ingredients of increase fluid retention ¡ Anti-inflammation: Chamomile, slippery elm, coptis ¡ Motility promoting: Auklandia lappa Codonopsis 11/10/10¡ Digestive function promotion: Jing Liu, MD, Ph. D

针刺特异性的f. MRI 证据 1 l l (A) Both manual (MA) and electro-acupuncture (EA) but

针刺特异性的f. MRI 证据 1 l l (A) Both manual (MA) and electro-acupuncture (EA) but not tactile control stimulation at ST-36 induce f. MRI signal decrease in the amygdala as evidence by f. MRI signal time-courses during stimulation blocks (gray). l (B) The CTS patients demonstrated less hyperactivation and more focused SI finger representation to innocuous stimulation of the 3 rd finger. l (C) CTS patients demonstrated less separation of somatotopic representations. After acupuncture treatment, the 2 nd and 3 rd finger representations were more separated, approximating normal somatotopy in HC