Comparison & Integration

of Western and Eastern Medicine

Jing Liu, PhD, Lic.Ac

2011

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

Integrated Medicine

Western Medicine + TCM + Natural

Medicine ( Nutrition, diet, herbs, natural

therapies in the world)

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Natural Medicine

从学科分类学的角度审视，一门学科不应是有地区属性的医学科学不应分属于西、东方，应该统一于现代医学范畴内。中医药学应属于现代医学的一个分支学科 .

从科学的定义上考虑，在中医药学最终能够被现代医学接受之前，将中医纳入到自然医学体系。

自然医学将逐步取代替代医学 / 中西医结合等名称而成为现代医学家族的 ( 而非西方医学）中的一个重要学术分支。

在自然医学的范畴中，国家的属性将被医学体系的自然性和科学性逐渐取代，成为世界医学界都容易被接受的一门医学

Content

Fatigue - Hormone BalanceInflammation Pain

Comments on acupuncture clinical trails: Placebo, Specificity of acupoints

Cause of Fatigue

Insomnia Heart - kidney disharmony

Hormone dysfunction Kidney deficiency

Gut inflammatory status Spleen: Dampness / phlegm

Yin & YangInsomnia treatment

WMSedative-Hypnotics or antipsychotics

Adverse reactions: drowsiness, weakness, pseudo-depression in the morning

EMEncouraging Yang energy in the morning and

nourishing Ying in evening

Yang encouraging : Yin nourishing:

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Yin & Yang Theory and Sleep

A general principle in traditional Chinese Medicine (TCM) practice

Morning Yang Time: adrenal, thyroid hormone awake and rise to peak -

energetic, active

Evening and Night

Yin time: melatonin and serotonin dominant –calm and sound sleep

Higher Yang in the morning, Deeper Yin control in evening and night, better quality of sleep

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Sleep and Hormone Balance

Insomnia - Cortisol Dysfunction Syndrome

Fatigue Depression Insomnia Irritability/. Anxiety Sweets craving Poor concentration Headache Allergy

Elevated sympathetic nerve tone and decreased cortisol= Heart Kidney Disharmony 心肾不交 ?

Insomnia TreatmentBasic Formula (1)

Kidney strengtheningMai 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 Q9, Cyloartenol, 1- feruloyl glycerol, hydro-Q9, chromene)

Insomnia TreatmentBasic Formula (2)

酸枣仁汤酸枣仁川芎 Anti-inflammatory茯苓 Reduce edema知母 Anti-sympathetic, Anti-inflammatory甘草 Anti-inflammatory, Detox

Add:

hehuanhua 合欢花， lianzixin 莲子芯， baishao 白芍

Causes of Fatigue

Heart: Insomnia Kidney: Hormone Dysfunction ( HPTA Axis)Spleen: Gastrointestinal Dysfunction

Fatigue and Hormone HPA Axis

The current evidence supports the following factors of The current evidence supports the following factors of HPTA axis dysfunction in patients related with chronic HPTA axis dysfunction in patients related with chronic fatigue syndrome (CFS):fatigue syndrome (CFS):

Mild hypocortisolismMild hypocortisolism Attenuated diurnal variation of cortisol Attenuated diurnal variation of cortisol Blunted HPTA axis responsiveness to body need.Blunted HPTA axis responsiveness to body need. hypothyroid function Imbalanced sexual hormones

Adrenal Hormone Synthesis

Adrenal Hormone Synthesis

Estrogen Family

Adrenal Dysfunction / Fatigue

Adrenal glands are unable to keep pace with the demands of perpetual stress.

Stress signals > cortex > limbic system > sympathetic nerve > adrenal gland > cortisol release/thyroid hormone

The gland can't produce quite enough of the hormones our mind-body need.

Existing blood tests, aren't sensitive enough to detect the decline in adrenal function: cortisol panel test

The Symptoms of Adrenal Fatigue

Qi & Yin Deficiency 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

Low Cortisone Syndrome 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

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

Progesterone cream Iodine / tyrosinePhosphorylated serine / He Shou Wu 何首乌Pregnenolone / Cortisol Melatonin at bed time

Hypothyroidism (1)

Qi & Yang Deficiency Fatigue Shortness of breath with a shallow and slow respiratory pattern Low basal body temperature, Cold intolerance Thyroid-Related Depression slow heart rate  Sluggish reflexes Constipation Poor muscle tone (muscle hypotonia) Slow speech and a hoarse, breaking voice Depression

Kidney deficiency Decreased libido  Hair loss Lower renal function with decreased glomerular filtration rate Impaired memory Abnormal menstrual cycles Thin, brittle fingernails

Female infertility

Hypothyroidism (2)

Spleen deficiency 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 Dry, itchy skin Decreased sweating

Others Elevated serum cholesterol Muscle cramps and joint pain Hyperprolactinemia and galactorrhea

Wilson's Temperature Syndrome

Temperature lower than 98.60F

Hypothyroidism symptoms with normal T3, T4

Typically brought on by stress

often exist with chronic fatigue syndrome, fibromyalgia’

Improved by treatment of T3 or herbs / supplements; not respond to T4 treatment

Causes of Hypothyroid Syndrome

Iodine deficiency

Stress

Hushimoto disease ( chronic lymphocytic thyroiditis), 25%

lithium-based mood stabilizers, usually used to treat bipolar disorder (previously known as manic depression)

Congenital hypothyroidism is very rare accounting for approximately 0.2‰

Thyroid Hormone

90% T3 (effects fast, short term)10% T4 (effects slow, long term)

T3 is only form of thyroid hormone to supply energy to heart from breaking down fat

Over dose of T3 cause cardiac overloading

Conversion of T3 or RT3

Conversion of T4 to T3 Promoters (1)

Kelp (iodine, Iron), seleniumZinc, potassium, cupperHigh protein dietVitamin A, E, C, B2, B3, B6, B12Growth HormoneTestosteroneAshwaganda (India herb)

Inability to convert T4 to T3

Excessive alcoholLow protein/fat dietToo much cruciferous vegetablesWalnuts

Low T3 / High reverse T3 Promoters

Stress - epinephrine / NE, cortisolFree radicalsAgingFastingDiabetesToxic metal exposure Inflammation-elevated inflammatory factors: IL-6, TNF-

alpha, IFN-2

Iodine Deficiency

88% America women are in iodine deficiency. Low iodine cause hyperestrogenic state and higher free estrogen level up

to 80 to 90%, normal is 40 to 60%.

When Iodine is enriched, the estrogen receptor activity in the breast is reduced.

Iodine promote apoptosis and disrupt proliferation

Low iodine cause fibrocystic breast; Effective therapy (82%) in treating fibrocystic breast disease and prevent breast cancer

TCM: Hai Zao, Kun Bu 海藻，昆布

Iodine Deficiency

Causes of Iodine Deficiency

Diet in shortage of iodine Iodine Taken Up: Thyroid: 6mg; breasts: 5mg /day; other

tissues: 2mg/dayJapanese women: 13.8mg daily, lowest in breast cancer

Diet high in pasta/bread containing bromide (bind to iodine receptor)

Fluoride use (inhibiting iodine bindingVegan and vegetarian diet

Drugs for T3/T4 replacement

T3: Liothyronine, Triiodothyronine

T4: Levothyroxine (Synthroid)

Transfom to be T3, but take up to 8 weeks to reach the required level of T3.

Armour® a naturally derived from porcine thyroid glands. (T3 liothyronine is 4x as potent as T4 levothyroxine; so 38 mcg T4and 9 mcg T3 per grain of thyroid.

Thyroid Hormone Replacement Failure

After increase dosage still feel fatigue:Magnesium deficiencyAdrenal deficiencyOverdosePoor absorption from unhealthy gut

Side Effects of T3 Therapy

Fluid pretensionAchinessJitteriness IrritabilityDull headache Increased heart rateCan not be used for severe Adrenal or cardiac deficiency

Herbs for Thyroid Function

Huang Qi 黄芪Huang Qi Wu Wu Tang 黄芪五物汤 Or add: Xiao Chai Hu Tang 小柴胡汤 , in case of

autoimmune

Prolonged hypothyroidism cause adrenal fatigueAdrenal: Ying Yang Huo 淫羊藿 , Shan Zhu Yu 山茱萸

When the herbs not effective enough, add T3, to reduce the dose of T3 and reduce the side effect of T3

Natural Supplements for Thyroid Function

Guggul (Commiphora mukul) increase iodine intake and thyroid hormone production, enhance

thyroid perocidase enzymes

Seaweed (algae) : Kelp (kun Bu) bladder wrack fucus vesiculosus (best antioxidant among seaweeds) Seaweed contain diiodothyoinine (DIT), which may promote thyroid

function

Zinc, Selenium Blue Flag - potent detoxifier of thyroid

Improvement usually occurs within 3 to 4 weeks

Hushimoto’s Disease

Reduce autoimmune response and inflammationXiao Chai Hu Tang 小柴胡汤CurcuminBoswelliaLycopus virginicus （ lycopus lucidus 泽兰 ) inhibit iodine metabolism, inhibits release of thyroxine from thyroid, binds

with TSH, decrease pulse and BP 95% improvement rate, officially recognized in Germany as prescription

Rosemary extract ( 迷 迭香 100:1), reduce antibody

Hormone: Progesterone

Produced mainly in ovary, little in adrenal gland; Increase 100x during pregnancy

Enhance: thyroid function, apoptosis, estrogen sensitivity, brain cell growth in fetus

Decrease: breast cell growth, breast cancer, atherosclerosis,

Decrease Brain degeneration, neuro-blastoma, MS; anti-depression

Burn fat for energy; hair growth;Progestins are NOT equal to progesterone

Herbs for Progesterone

 Juglans regia (England Walnut 核桃 ), progesterone detected

Progesterone-like steroids in Dioscorea mexicana of yam family native to Mexico, containing steroid  diosgenin converting into progesterone.

 Diosgenin and progesterone found in other Dioscorea species.  Dioscorea pseudojaponica from Taiwan, containing saponins —converted to

diosgenin -> progesterone.

Other Dioscorea species:  Dioscorea villosa andDioscorea polygonoides. Dioscorea villosa contains 3.5% diosgenin. Dioscorea polygonoides contain 2.64%

Dioscorea family: Shan Yao 山药 , Bi Xie, Chuan Shan Long 穿山龙 , Shan Ci Gu 山慈姑 I

Sheng Ma 升麻 Maca Fu Pen Zi 覆盆子

Hormons: Estradiol(E2)

Neuro-protectiveBreast cancer promotingCell proliferation with alveoli formation

(hyperplasia) and even cyst formation

Effects of Estrogen Therapy

Prevent osteoporosis Decrease LDL and increase HDL

Increase blood pressure, triglycerideGallstoneElevated liver enzyme Increase carbohydrate cravingDecrease thyroid function by increasing binding thyroid

binding globulin

Estrogen Balance

In the 1960s and 70s Dr. Henry Lemon concluded:Estrogen QuotientEQ=E3/E1+E2EQ<1: high risk for breast cancerEQ>1.5: low risk for breast cancer

Hormone: Estriol

Anti-inflammationPromote shift from T helper (Th) 1 to Th2Reduce autoimmune diseasePrevent osteoporosisBreast caner protectionMenopause improvement 92Don'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 T4 to T3 Decreased sex drive Depression / anxiety / Migraines / Insomnia Memory loss or foggy thinking Mood swings / Memory loss or foggy thinking Weight gain secondary to insulin resistance / Fat gain PMS / Menstrual disturbances--irregular and heavy bleeding. Bone loss / Hair Loss Breast cancer / Fibrocystic breasts / Uterine cancer / fibroids Water retention, bloating. Tendency of autoimmune disorder

Correction: Progesterone therapy

Estrogen Dominance

After menopause, Progesterone decreases by over 99% from its original youthful baseline levels; while estrogen production only decreases by about 40%. 

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

Bio-identical Estrogen therapyE3:E2 = 4:1

DIPD Vitamin D deficiency Iodine deficiencyP Progesterone deficiency

Hormone: Testosterone

Testosterone Improve insulin resistance, belly fat Improve: sleep, vitality, libido/orgasm/arousalNot necessary cause prostate cancerHerbs ： Yin Yang Huo 淫羊藿 , Rou Cong Rong 肉苁蓉

， Lu Rong 鹿茸 , Ren Shen 人参

Hormone: DHEAthe first anti-aging hormone

Improve motivation, well being, memory, libido/orgasmAnti-atherosclerosisAntidiabeticAnti-inflammatoryAntiosteoporoticAnti-senilityReduce fatProtect thymus and immune function

50mg daily anti-age without significant side effects

Fatigue

Fatigue and GI dysfunctiion / Candida

Symptoms of Candia (1)

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)

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

CinammonGrapefruit seed extractOlive leaf extractGarlic extractBerbering, GoldensealOregano leaf extractPau d’arcoZincCoconut oilCandex (cellulase enzymes)

Introduction: Inflammation

Normal inflammation is a necessary protective response to harmful stimuli to the body.

Prolonged or excessive inflammation is related pathological status including infection, autoimmune disorders, atherosclerosis, Alzheimer's, autism, arthritis and even cancer

Inflammation ProcessEicosanoid Cyclooxygenase Pathway 

Pathogen IL-1, TNF-, PDGF, IFNs, Tyrosine Kinase

Adhesion penetration

inflammation proliferation

hypoxia, superoxide, NO, free radical

AA COX2 PGE2

inflammation

cancer

chemokines

Eicosanoid SynthesisProstaglandin/Inflammation Formation Pathway

Eicosanoid Synthesis

Prostaglandins and related compounds are collectively known as eicosanoids. Most are produced from arachidonic acid (AA)

Step one: Release of AA from membrane phospholipids by phospholipase A2(PLA2).

Step Two: AA is metabolized by COX enzymes to be prostaglandin E2 (PGE2),or Thromboxin (TXA2)or prostacyclin (PGI2),

AA also metabolized by lipoxygenase or cytochrome P450 to be leukotrienes

Ecosanoid considered "local hormones." participating in intercellular signaling,

Role of Ecosanoid

inflammationfeverregulation of blood pressureblood clottingimmune system modulationcontrol of reproductive processes & tissue growthregulation of sleep/wake cycle.

Ecosanoid Inhibitors

Corticosteroids are anti-inflammatory from preventing PL A2

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 A2 / AA / COX

for treating inflammatory diseases

Inflammation

WM COX-2 inhibitor (Vioxx, Celebrex) Adverse reactions: PGI2 inhibition – inner membrane of blood

vessel damage leading stomach ulcer, kidney failure, cardiac attack

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

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

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COX-2

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 TherapySide effects & Limitations of Chemical Drugs

Naproxen Naproxen, trade name Alevea, a nonsteroidal anti-inflammatory drugs (NSAID) ibprofen, indomethacin and ketoprofen.

Common side effects Constipation; diarrhea; dizziness; drowsiness; gas; headache; heartburn; nausea;

stomach upset; stuffy nose.

Severe side effects 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; one-sided 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.

This is not a complete list of all side effects that may occur.

COX Inhibitors

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 TXA2 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.

COX-2 inhibitors are less likely to cause gastric toxicity compared with NSAIDs that block COX-1. 

Inflammation and Endothelial Dysfunction to Microvascular Dysfunction

Endothelial dysfunction is integral to the pathogenesis of many disorders:

AtherosclerosisAutoimmune disorders Inflammation InfectionTrauma

Arterial Wall Anatomy

Endothelium of Blood Vessels

Vascular Endothelial Mediators

Thromboxane A2 - TXA2

Stimulates blood platelet aggregation, essential to role of platelets in blood clotting.

Aspirin inhibit TXA2 formation in blood platelets.

This effect of aspirin is long-lived, 7 days, because platelets lack a nucleus and do not make new enzyme.

Leukotrienes

Leukotrienes produce inflammation in:

Blood vessel walls as part of the pathology of atherosclerosis.

Bronchioles causing asthmatic constriction and asthma.

Anti-asthma medications include:

Zyflo (zileuton): inhibitors of 5-Lipoxygenase Singulair (montelukast) & Accolate (zafirlukast):

block leukotriene-receptor interactions.

Natural COX-2 Inhibitors

Huangqin 黄芩 was found to have COX-2 inhibitory properties in China, Spain, Korea, Canada and United States

Ginger 姜 is a strong anti-inflammatory herb. Studies indicate that ginger is a safe COX- 2 and COX-1 modulator

Scientists in the USA, Sweden, Taiwan and Germany have confirmed that green tea is a high active COX-2 inhibitor.

The chemical ingredients, salicylic acid and polyphenols, including EGCG, in green tea are effective cancer antagonists.

Turmeric or curcuma longa

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.

The active anti-inflammation component curcumin is about 50% as effective as cortisone.

The purified form of 95% curcuminoids per dose is the best anti-inflammatory effects.

A number of publications have shown the anti-cancer effects of turmeric in in vitro and in vivo.

Natural COX-2 Inhibitors

Curcumin and capsaicin significantly lowered lysosomal enzymes from macrophages in animals

Macrophages from rats secreted less PG E2, leukotrienes B4 and C4 and AA.

Curcumin and capsaicin lowered eicosanoids and AA in macrophage lipids.

Curcumin and capsaicin can lower secretary functions of macrophages in a beneficial manner.

Natural Anti-inflammation/COX-2 Agents

Drynaria fortunei

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.

Clinical trial: significant effects for arthritis pain, joint function and osteoporosis without significant side effects

CONCLUSION: potent anti-inflammatory agent for alleviating painful inflammatory conditions of osteoarthritis.

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

green tea, ginger, grape seed, Holy basil, oregano, rosemary and willow bark

Giardina C 褐茸藻 , Stylopine from chelidonium majus 白屈菜 , Berbarine/Huanglian 黄连 , ginger, ginsenoside 人参皂甙 Rh1, 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

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.

Inflammatory responses can be suppressed by the application of ROS scavenger, superoxide dismutase (SOD) and antioxidants.

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

ω-3, mainly DHA and EPA, can effectively inhibit COX mediated AA metabolism and PGE2-inflammation/cancer

Plant ω-3 shows inhibitory effect on inflammation and cancer

Pain Inflammatory Immune

Sensory nerves

Hypothalamus

Anti-inflammatory output via CNS

TNF-, IL-1β in brain

Neuroimmunologymodulation

Cholinergic suppression:

Parasympathetic nerve endings

release acetylcholine (ACh),

suppress release

AcupunctureMechanism: Pain / Inflammation / immune

InflammationRole of Arachidonic Acid

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.

InflammationOmega-3 : Omega6

InflammationOmega-3 : Omega6 Patients with autism had significantly higher Omega 6 in RBC membranes compared to higher Omega 3 in healthy people Significantly reduced levels of ARA /EPA ratio in RBC polar lipids, when supplemented with EPA-rich fish oils

By taken EPA supplements, significantly reduced PLA2 concentrations

Natural Anti-inflammation/COX-2 Agents Curcuma longa 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

Feverfew ( 菊蒿）Holy basil ( 圣罗勒）Nettle Leaf （荨麻）OreganoRosemay （迷迭香）Boswellia

Natural Anti-inflammation Agents:Antioxidants

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.

Inflammatory responses can be suppressed by the application of ROS scavenger, superoxide dismutase (SOD) and antioxidants.

Natural Anti-inflammation Agents:Antioxidants

Many antioxidants possess COX-2 inhibiting effects. Phenol and flavonoid compounds in many herbs:

polyphenol and catechin in green tea, ginkgo biloba, soy, etc.

Some important antioxidants/anti-inflammation chemicals produced in the body: Glutathione,, melatonin, pyruvate, IFN-b, and SOD.

Natural Anti-inflammation Agentsfrom diet: Berries

BerriesBlueberries, raspberries, strawberries: anti-inflammatory

Blackberries and blueberries are especially great.

Natural Anti-inflammation Agentsfrom diet: Omega-3

-3, mainly DHA and EPA, can effectively inhibit COX mediated AA metabolism and PGE-2 inducible inflammation/cancer.

High -6 low -3 diet favor inflammationflax seed oil, walnut, pumpkin seed are rich in -

3 but in shortage of DHA. Botanical -3 may anti-inflammation by inhibiting

-6 through competing delta desaturase 6.

Root of Inflammation

Broad-spectrum antibiotics kill good bacteria in gut, leading to leaky gut syndrome - large molecules get through. 

 London’s Royal Free Hospital studied 60 autistic

children: many more intestinal lesions than non-autistic children

In fact, over 90% of autistic children had chronically inflamed guts.

Root of Diseases - InflammationRoot of Inflammation - GI microflara

Alzheimer, AutismChronic lung/bronchus infectionArthrosclerosisSinus infection/allergyChronic Fatigue syndromeFibromyagia

Autoimmune disorders:MSLupusColitisArthritis

AcupuncturePain

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Acupuncture for painIndication

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.

Doctors from three medical schools published on New England

Journal of Medicine

Conclusion: acupuncture is an effective means for treating lower

back pain, based partly on a recent study of 6,359 patients

published

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Acupuncture Clinical TrailOsteoarthritis

20millions people with osteoarthritisNo satisfied pharmaceutical drugsCOX-2 inhibitor may cause heart, kidney stomach

damagePhase III radomized controlled clinical trail at Maryland

School of Medicine in 2006570 participants with moderate and severe painResults: significantly improve knee pain and function

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

Acupuncture for painSignificant, Mechanism

New branch of therapy in clinical medicine:

Trans-cutaneous Intervention therapy

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Specificity of Acupuncture points

Brain: Overlapped, relatively less specificity

Spinal cord: neural segmentation distribution, relatively specificity, with connection

Local: chemicals, neuro-muscle-tendon effects, specific

AcupunctureEvidences in neurochemistry

In the mid 1970s, 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

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AcupunctureEvidences in neurochemistry A large body of evidence indicates that acupuncture significantly

affects the production and release of neurotransmitters including epinephrine, norepinephrine, dopamine, and 5-hydroxytryptamine

Stress-induced increases in norepinephrine, dopamine, and corticosterone were inhibited after EA,

EA effects on the release of neurotransmitters are likely to be mediated through endogenous opioids.

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

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11/10/10

AcupunctureNeural segmental analgesia

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穴位特异性与神经阶段内脏与体表相连：白交通支

AcupuncturePain management and muscle relaxation

Acute painMuscle spasm

Chronic pain Muscle spasm - shortening - fibrosis -hardening

Trigger Point – neural-muscle cycle

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

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

Taut bands of muscle and are especially tender to palpate.

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.

The treatment will increases circulation to the area and decreases pressure on joints.

Acupuncture for PainNeuro-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 

Golgi Tendon Organ

“Golgi Points ?”

ST36GB34, 37, Sp6LI3, 10BL25Si5

AcupunctureBack Pain- Piriformis Syndrome

Role of natural anti-inflammatory Agents in Cancer Treatment

WM Chemo or Radiation: limited effectiveness

Side effects from cytotoxicity: immune, bone marrow, digestion, wellbeing

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

108Jing Liu, MD, PhD11/10/10

Cancer and COX-2

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

Chemotherapeutic drug resistance is an unresolved challenge in clinical cancer treatment, particularly for the metastasis carcinoma status.

The inflammation and pro-inflammatory cytokines are strong intrinsic factors for promoting multiple drug resistance (MDR).

Chemotherapy may induce the activities of COX-2 and inflammation.

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?

Multiple target model of cancer cell for Natural COX-2 Inhibitors

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/HER2

IGFR

Pathway of Chemotherapy Resistance Breast Cancer

Natural Anti-inflammatory Agents Enhance Effects of Chemotherapy

Morphologic changes Fig 1. of MCF-7 cells treated with COPE and TAX

Are Antioxidants counteract with Chemotherapy?

Meith I. Block analyzed the results of antioxidants applications, including glutathione, melatonin, vitamin A, vitamin C, N-acetylcysteine, vitamin E, ellagic acid and antioxidant mixture, from randomized and controlled clinical trials in 845 articles.

Conclusion: None of the trials reported evidence of significant decreases in efficacy from taking antioxidant supplements during chemotherapy.

Are Antioxidants counteract with Chemotherapy?

Instead, many of the studies suggested increased survival times, increased tumor responses, and less toxixity responses from taking antioxidants than

controls[1] 

[1] Block KI, etc.Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials.

Int J Cancer. 2008

Are Antioxidants counteract with Chemotherapy?

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.

The supplements should be stopped at least one day before the next chemotherapy session.

The information about the pharmacological dynamics of the chemotherapeutic agents should be researched before the natural supplements is administered.

Natural Medicine 自然医学Definition

1 、基于自然界整体观发展的医学理论体系，强调人体的生理、疾病与自然界的紧密联系。

2 、强调人体内部整体间的相互关联。

3 、承认个体之间的差异性，因而诊治体现个性化差异。

4 、治疗手段，特别是药物，直接来源于自然界，强调其自然属性。

5 、治疗、预防与调养相结合的、符合人体生理特征的治疗方针。

6 、植根于悠久的民族、民间医学，具备丰富的临床实践经验。自然医学应融 合和吸收世界各国民族医学和自然疗法的精华，用现代医学的技术手段加以证实和发展。

7. 中医药学应以其悠久的历史，博大系统的理论、丰富的实践以及可信的疗效，在自然医学的形成和发展中占有重要地位。

118Jing Liu, MD, PhD11/10/10

End

Inflammation and Endothelial Dysfunction to Microvascular Dysfunction

Endothelial dysfunction is integral to the pathogenesis of many disorders:

AtherosclerosisAutoimmune disorders Inflammation InfectionTrauma

Vascular Endothelial Mediators

Nitric Oxide/L-Arginine-Herbs

Nitric Oxide (NO) anti-inflammatory and anti-proliferative

effectsEndothelial function protectionAtherosclerosis protection

Nitric Oxide/L-Arginine-Herbs

L-arginineControl blood pressure and improve heart

functionReducing cholesterol and plaque formationPromote anti-aging growth hormoneEnhancing immune function and stop some

cancer cell growthImproving memoryImprove erectile dysfunction

Nitric Oxide/L-Arginine-Herbs

HerbDang GuiBai ShaoBai Jili

The signal molecule ·NO (nitric oxide) may initiate prostaglandin synthesis by reacting with superoxide anion (O2·) 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

WM Prednisone, immune suppressor, T-cell inhibitor Adverse reaction: mal-metabolism cortisone withdrawal syndrome,

immune dysfunction

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

13211/10/10

Infection

WM Limitations of antibiotics in Chronic infection: immune

function, beneficial bacteria damage, drug resistance

Co-existing inflammation, congested microcirculation

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

133Jing Liu11/10/10

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 Th2 versus Th1 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)WM

H2 blocker – Zantac Proton pump inhibitor – Prilosec Mucosal protectors – sucralfate Motility drugs - empty stomach, Reglan.

EM Mucosal protection: Gastric acid pseudo-overproduction, Deglycyrrhizinated

licorice (DGL)

Calming acid reflux and peptic ulcers by: Anti-inflammation and the pathogens Protect mucosal membrane by increasing the thick mucous production Free of the ingredients of increase fluid retention

Anti-inflammation: Chamomile, slippery elm, coptis Motility promoting: Auklandia lappa Digestive function promotion: Codonopsis 135Jing Liu, MD, PhD11/10/10

穴位特异性 -安慰

针灸穴位特异性的质疑一直与针灸是否为安慰治疗的争论并存。对穴位的特异性的解释经常困扰临床研究的设计和结论。

穴位无特异性 = 安慰穴位部分特异 = 部分安慰穴位全部特异 = ？

安慰针对照原则

目的：排除术者与病人的“期望” 和暗示效应要求：安慰刺激方式没有特定治疗作用

方法： a. 针刺或其他刺激方式选在没有特定治疗作用的部 位， sham？

b. 受试者不能察觉安慰针与治疗针在外观和操作和 感觉上的差别

针刺部位选择的质疑

采用非传统中医穴位作为疗效安慰对照，针刺穴位数目增加的历史。 “安慰穴位”可能是明日公认

的治疗穴位

采用近经络刺激点作为经络论证或疗效对照不能排除经与络的连接。只适用于证明经络的特异程度，不适于疗效判定。

1 ，验证疗效：

应符合如下全部条件：

a. 非经络非传统穴位。

b. 与治疗穴位保持一定距离，以回避“经与络”相关联的嫌疑

c. 二组穴位非处于同一神经节段分布

d. 二组穴位非同一解剖组织相关。例如，二穴不能位于同一肌肉上。 穴位的特异性与肌体组织结构相关。如肌肉、肌腱、骨膜，间质组织。

安慰针刺部位选择原则

安慰针刺部位选择原则

2 ，验证传统针灸经络理论

不同穴位或非穴位点：穴位特异性离开经络的针点：经络特异性

安慰方式质疑

浅刺穴位点或非穴位点的方式作为安慰对照并不完全合理 .

假针具欺骗性的可靠性值得怀疑： a. 钝针头压迫到表皮，不能排除“假针“的治疗作用 ; b. 反复使用； c. 有针灸体验或知识者， 尤其是从签署同意书时获知是受试者

模拟皮表电刺激 ：没有任何刺激的感觉所引起的心理反应

症结

理想安慰方法：外观、感觉上与治疗组针灸没有区别，但无特定疗效。即无暗示和期望效应。

为何目前的安慰对照设计很难完全达到标准？针灸未被纳

入西方主流医学的障碍之一。

问题的症结在于传统的安慰剂的概念和使用，不完全适用于针灸？

药物： Placebo效应

对临床疗效具有重要影响：与疼痛相关的治疗中 Placebo作用可达 50% 。焦虑明显影响 Placebo效应。

临床药物：单分子化学结构药物，有明确的特异受体或靶点。其引起的生理或病理变化有明确的表现和体征。

如果表述出与药物作用或毒副作用无关的反应，特别是心理、精神方面的反应，也可能被认为安慰效应。

针刺 -介入疗法？

针刺应与外科手术同属介入疗法，在介入性治疗的临床研究中不适于用安慰对照， 但这一理由很难被西方医学界认同。

主要原因：手术的危险性和伤害程度要远甚于针刺？

合理对照的选择（ 1 ）

2000年世界医学大会修订的《进行人体生物医学研究的伦理道德原则》指明，测试一种新疗法时，应以当时最有效的方法作对照，虽然并不排除使用安慰剂治疗对照，但仅用于未有有效治疗方法对照时。

合理对照的选择（ 2 ）

Placebo 或 Sham 针刺的结果不应是作为结论的绝对依据。此外，没有 Placebo 但有相应对照的研究论文也不应再被一概视为“不科学、不可靠“的依据。

重视针灸临床方法学整体与细节上与国际化标准的接轨。除了对照组设计外，随机原则的使用，样本量的考虑，受试者同意书的措辞以及严格的管理执行体系。

1. 德国 2005年在一份临床针灸方法学的研究报告中回顾总结了 1000 例头痛，腰痛的治疗，结论是针灸完全可以按照严格的标准来完成临床实验研究

的差别

合理对照设计的建议

最大限度的减少期望与暗示效应。为此，建立严格独立的随机分组，诊断，治疗，资料收集，资料处理，统计处理系统。

按照病因，病理详细针灸适应症，例如高血压，头痛，腰痛的病例选择或结果分析

用国际认可的标准量表，如疼痛，背功能量表

组成基础，临床，统计，管理专家体系的针灸临床研究队伍，特别是加强对安慰效应的基础研究如 fMRI

穴位特异性 Hypothesis

不同穴位刺激在大脑水平有相当的重叠反应，但强度不同

穴位刺激 在脊髓阶段的反应有相应的特异性，但在一定刺激强度下有各脊髓阶段之间的重叠

穴位刺激， 特别是 trigger 穴位的局部反应是相对特异的

针刺通过三级反应共同完成效应机制

针刺特异性：大脑效应：多系统、多靶点

fMRI 研究的证据：针刺多个不同体表穴位后会在大脑神经网络的躯体感觉区，边缘系统，扣带回前区，下丘脑，海马回，大脑皮层前回，小脑蚓区 等不同神经元区域产生广泛影响。

边缘系统，扣带回前区，大脑皮层前回，小脑蚓区等对精神、情绪、心理状态有控制，调节作用。

针刺的反应过程有脑啡呔，单胺，多巴胺， 5-羟色胺、等神经介质的广泛参与。

针刺安慰效应 acupuncture placebo response

针刺的安慰效应 (opioid placebo response) 主要集中在 Posterior midcingulate cortex, pMCC 的尾部。 这一区域对躯体疼痛有最高密度的反应。

吗啡的安慰效应 (opioid placebo response) 主要集中在与内脏相关的 subgeneral anterior cingulated cortex 区域

fMRI 的研究显示， placebo 麻醉效应区，主要是在导水管周围灰质（ PAG ） , 扣带回前区啄部（ rostroil ACC ） , 岛区（ insula ） , 杏仁核，下丘脑， 与针刺的作用靶点有重叠

结果推测： Placebo 效应可能是针刺的一个必然结果。 针灸适用于心身（ Mind-Body ）疾病治疗的机制之一。

假设：激发启动效应burst – firing mechanism

“得气”刺激信号激发了神经介质参与的神经网络通路信号系统的调整。其中包括了支配精神、情绪的神经元的整合。

推论：与作用于神经、精神系统的化学药物仅作用于单一脑内受体不同。针刺对大脑系统的作用是多方面的，不是单一的对某一受体的抑制或增强，而是调整或重新整合式的，这一过程必然有控制情绪、精神的神经元的被调整。

举例：针灸可以减轻焦虑、紧张的状态，而情绪的紧张程度与痛觉感受的程度相关。

学说：针刺改变疼痛感受而不是疼痛本身

针刺安慰效应

Placebo效应，也就是说 Placebo可以通过心理暗示获得，也可能通过物理、化学刺激获得，仅是效应强度和治疗可能带来的副作用可能是不同的 .

针刺治疗的最常见适应症之一疼痛症与情绪状态有直接相关。大脑前区在反应疼痛与情绪的过程中由扣带回区参与了两者之间的整合 .

情绪，精神心理的控制

3

针刺特异性的 fMRI 证据 1

(A) Both manual (MA) and electro-acupuncture (EA) but not tactile

control stimulation at ST-36 induce fMRI signal decrease in the amygdala as evidence by fMRI signal time-courses during stimulation blocks (gray).

(B) The CTS patients demonstrated less hyperactivation and more focused SI finger representation to innocuous stimulation of the 3rd finger.

(C) CTS patients demonstrated less separation of somatotopic representations. After acupuncture treatment, the 2nd and 3rd finger representations were more separated, approximating normal somatotopy in HC

fMRI 证据 : 穴位的特异性是相对的

尚没有确立针刺的特异反应区

针刺穴位与 sham点似有不同的反应区

不同穴位 , 不同刺激方法引起的信号有相当的重叠

针刺穴位较之钝针对边缘系统和边缘旁系统有更强烈的调整作用

Insula cortex 可能是针刺的特异反应区，而针刺在 Dosolateral PFC, rostral ACC, 和 midbrain PAG 的反应可能与安慰期望程度有关

穴位特异性Trigger point (扳机点）

Trigger point 可以在传统穴位或非穴位位置上

潜伏期：无疼痛。在病理刺激下转化（寒冷、疲劳、损伤、肌肉紧张）

被动期：可触摸到的疼痛活动期：清楚感觉的疼痛，穴位面积增大。最早多出现在

神经干、体表浅层、肌门，数目随疼痛迁延增多

穴位特异性穴位的局部反应

改善（微）循环调节免疫功能、减少炎症缓解肌紧张 调节神经（眩晕、哮喘、呕吐）