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Herbal Medicine in Endocrinology
and Metabolic Disease
CONTENTS
Introduction
Presented by Lee Mina
Gout
October 22 2007
Obesity
College of Pharmacy, Seoul National University
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Hyperlipidemia
Thyroid Disorder
Menopause
Toxicity
Conclusion
Introduction
Target of Study
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Gout – Primary problem
Herbal options in treating metabolic and endocrine disease
Not, excessive intake of purine –containing food
Diabetes Mellitus and Gout – wide range of natural treatment
Heart disease → cholesterol-lowering plant
→ no tradition of usage
Obesity → Increasing problem
But, enzyme defect in urate metabolism
→buildup of uric acid
→when it crystallizes in joint, acute inflammation
; Gout
Simple solution is the most important challenge in treating
metabolic disease and herbal options are being explored
No uricase in human
Uric acid
Side effect of hormone replacement therapy during menopause
→ traditional plant therapy
However, long-term plant usage may also be associated with side effects
uricase
allantoin
CONTENTS
Diabetes Mellitus
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Study of Gout
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Prevalence of Gout
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▪
Study of Gout
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Gout → 3~5 people /100
The frequency increases with age
More than 1% of the over-30 population are troubled with attacks
Many traditional remedies are found in different parts of the world
Figure 1 Prevalence of gout in US men, 1990−1999
(adapted, with permission, from Wallace et al. 2004)3
Treatment of Gout
Study of gout
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Culpepper
▪ listed more than 40 different herbal treatments, 4C ago
Figure 2 Prevalence of gout in men in New Zealand
Treatment
▪ plants → mild diuretics ( remove excess water)
▪ theory → toxic substance(uric acid) remove through the kidney
But, orthodox diuretics therapy and removal of fluid
▪ in fact, uric acid↑ → gout ↑
Mild diuretics
▪ Dandelion (Taraxacum officinale)
▪ Celery (Apium graveolens)
▪ Parsley (Petroselinium crispum)
▪ Nettle (Urtica dioica)
▪ Carrot (Daucus carota)
Roddy E et al. (2007) The changing epidemiology
of gout Nat Clin Pract Rheumatol 3: 443–449
doi:10.1038/ncprheum0556
Roddy E et al. (2007) The changing epidemiology
of gout Nat Clin Pract Rheumatol 3: 443–449
doi:10.1038/ncprheum0556
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Gout – Orthodox medicine
Study of gout
Xanthine oxidase inhibitor
Allopurinol
Interfere with purine metabolism
stop the buildup of uric aicd
Indomethacin
Medicine
No reliable clinical study
NSAIDS in Gout
NSAIDS except aspirin,salicylate
Probenecid
Uricosuric Agents
Sulfinpyrazone
Gout – Orthodox medicine
Study of gout
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Gout – plant threapy
Study of gout
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In nature, some fruits
→ weak xathine-oxidase-inhibitoring property
Gout
Study of gout
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Colchicine
▪ The most rapidly effective conventional treatment for acute attack.
▪ Alkaloid, first isolate from the meadow saffron (Colchicum autumnale)
Flavonoid content
▪ Prevent tublin polymerization into microtubules
▪ Chiso (Perilla frutescens)
preventative
treatment
▪ Skullcap (Scutellaria baicalensis)
▪ Yarrow (Achillea millefolium)
▪ Suppress the release of inflammation-causing
chemicals from WBC
▪ Inhibit the formation
of leukotriene B4
▪ But, GI side effect↑
colchicine
Cyanidin content
▪ therapeutic option
Gout weed (Aegopodium podagraria)
▪ traditional European treatment
▪ but, no effect
red yarrow
→ eating half a pound of cherries per day
cherry
Gout
Study of gout
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Plant (natural aspirin-like substance)
Willowbark (Salix alba)
Meadowsweet (Spirea ulmaria)
Poplar (Populus spp.)
Turmeric (Curcuma longa)
Boswellia (Boswellia serata)
Ginger (Zingiber officinale)
Black cohosh (Cicimifuga racemosa)
Study of DM
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Prevalence of Diabetes Mellitus
▪ treat inflamed joints
▪ their effect is much slower than orthodox therapy
1.
2.
3.
4.
5.
6.
7.
Prevalence of Diabetes Mellitus
Component
▪ Bromelain
▪ Boswellia serata
▪ With the increasing age and obesity,
an epidemic of non-insulin-requiring diabetes is developing
▪ in western population 2/3male, 1/3 female – overweight
▪ 100million diabetics worldwide, expected to grow 350million by 2025
▪ about half of these people →without orthodox medicine
Herbal alternative are widely used
▪ Turmeric root
Devil`s claw(Harpagophytum procumbens)
▪ analgesic effect
▪ little anti-inflammatory potential
No clinical trials have adequately demonstrated the effectiveness of these
Age
Residence
Physical activity
Ethnicity
Obesity
Study of DM
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World wide epidemic
Diabetes Mellitus
Study of DM
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Prevalence of India
▪ In the indian subcontinent, genetic factors → high incidence of diabetes
▪ many traditional ayurvedic medicines are used
▪ Plant metabolism is based on carbohydrates
Sugar-lowering potential of plants
1. Madagascar periwinkle (Catharanthus roseus)
2. Bitter gourd (Mormordica charantia)
No satisfactory
clinical study
3. Fenugreek (Trigonella feonumgraecum)
India:
2000:32 mill
2020: 81 mill
4. Jambul (Sygyium cumini)
5. Gymnema (Gymnema sylvestre)
Extensive animal study
No good human study
Madagascar periwinkle (Catharanthus roseus)
Zimmet, Nature 2001
Diabetes mellitus – Orthodox medicine
Study of DM
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Study of DM
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Diabetes mellitus
Table 18.1 herbal plants and diabetes proposed mode of action
Biguanide Metformin
▪ most useful medication for treating diabetes in the obese
▪ developed from a commmonly used herbal remedy
→ goat`s rue (Galega officinale)
Reduce/slow
sugar
absorption
▪ makes insulin more effective
Stimulate
Insulin
production
Stimulate
Liver
function
both liver and muscle receptor
▪ cause weight loss
▪ used in the 1500s to treat the plague
▪ found to lower blood sugar in 1927
▪ carried out extensive research
in the 1930s to produce a synthetic compound
Title
Unknown
▪ Aloe
Aloe vera
▪ Guar
goat`s rue (Galega officinale)
Reduce
Insulin
resistance
Cyamopsis
tetragonoloba
▪ Wild oats
Avena sativa
▪ Barley
Hordeum disticum
▪ Indianipecac
Gymnena sylvestre
▪ Fenugreek
Trigonella
foenum-graecum
▪ Chicory
▪ Periwinkle
Cichorium intybus
▪ Ginseng
Panax ginseng
▪ goat`s rue
Catharnthus roseus
Galega officinale
▪ Chinese
-foxglove
Rehmannia glutinosa
Diabetes Mellitus
Target of Study
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Plant – containing high levels of Chromium
Target of Study
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Diabetes is another condition in which antioxidants have been suggested
beneficial, US Physician Study showed no reduction in incidence of
Type II DM With long term B-carotene supplementation
▪ reduce insulin resistance
▪ Human study → lipid lowering
▪ Animal study → hypertension
◎ Barley (Hordeum disticum)
▪ slow sugar absorption
▪ high Cr → lowering blood sugar in rat
Other herbs
Sulphur-containing herbs
◎ garlic (Allium sativum), onion → insulin ↑
Improve liver function & hepatic glucose utilization in the liver
◎ chicory (Cichorium intybus)
ginseng (Panax ginseng) → effective hypoglyceimic agent
Diabetes Mellitus
Diabetes Mellitus
Study of DM
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More than 1200 hypoglycemic plant
(Half traditional and half experimental evidence)
→ future treatment
Herbal treatment of diabetic complication
◎ Evening primrose (Oenothera biennis)
◎ Baical skullcap (Scutellaria baicalensis)
→ treat diabetic complication involving the nerve and eye
→ reduce toxic metabolite buildup in nerves
by aldose reductase inhibition
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▪
▪
▪
▪
▪
▪
▪
carrot
Nettle
Dandelion
Sunflower (Helianthus annuus)
Life root (Senecio neurorensis)
Bilberry (Vaccinium myrtillus)
St. Mary`s thistle (Silybum marianum)
Licorice (Glycyrrhiza glabra)
Andrographis (Andrographis paniculata)
Introduction of
Overweight and Obesity
What are Overweight and Obesity?
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Overweight and Obesity
▪ Abnormal or excessive fat accumulation that may impair health
Body mass index (BMI)
▪ A simple index of weight-for-height that is commonly used
in classifying overweight and obesity
▪ The same for both sexes and for all ages of adults
◎ BMI (kg/m2) = Weight / (Height)2 = 52/1.632 = 19.57 kg/m2
◎Topical cayenne (Capsicum)
→ reduce pain in diabetic peripheral neuropathy
Extensive overview by Ernst in 1997
→ lack of adequate studies of hypoglycemic plant remedies
makes their use difficult to support
Classification
BMI
(kg/m2)
Principal
cut-off
point
Underweight
<18.50
Obese
Normal
range
Overweight
class I
class II
18.50 -
25.00-
30.00 -
35.00 -
24.99
29.99
34.99
39.99
class III
≥40.00
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Introduction of
Overweight and Obesity
Facts about Overweight and Obesity
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Country comparison - BMI Obese Adults (%), Most recent
Introduction of
Overweight and Obesity
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Overweight and Obesity are a major risk factor for chronic diseases
USA
32.2
U.K.
24.2
Germany
Musculoskeletal
disorders – arthritis
of spine & legs
Cardiovascular
disease
19.4
Australia
16.4
Canada
15.3
Japan
Korea
Heath Consequences of Overweight and Obesity
3.1
2.4
Overweight
Diabetes
Hypertension
& Obesity
BMI Overweight and Obese Adults in the world (million), by 2015
Obesity
1600
2005
Over
weight
2300
2015
Breathing difficulty
- Sleep apnea
Cancers
400
2005
2015
700
Reported by
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What causes obesity and overweight?
Introduction of
Overweight and Obesity
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The fundamental cause of obesity and overweight is an energy
imbalance between calories consumed and expended
5 / 37
Targets of Anti-Obesity Treatment
Neurobiological
mechanism
Tendencies of
ethnic groups
Living habits
Overweight
& Obesity
Poverty link
Additional
factors
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Orthodox medicine → short-term treatments
Targets
Management of obesity → restrict calorie intake
→ ”wonder cures”
Overeating
Introduction of
Overweight and Obesity
Mode
of action
CNS
adrenergic
stimulants
Reducing
food intake
Increasing
energy
expenditure
Altering
metabolism
Regulation
of hormone
Selective
serotonin
reuptake
inhibitor
Adrenergic
β3-agonist
List of drugs
Remarks and Side effect
Bensphetamine (Ergoset,Bromidine)
High chance of misuse
Dietylpropion (Amfepramone,Tenuate)
Primary pulmonary
High chance of Hypertension
Fenfluramine (Pondimin,Ponderal)
Dexfenfluramine (Redux)
Damage of valves of the heart
Withdrawn an approval by FDA
Fluoxetin (Prozac,Proctin)
Disapproved by FDA
Silbutramine (Meridia)
Approved by FDA in ‘97
Ephedrine/caffeine combination
BRL 26830, BRL 35135, CL 316243, RO 40-2148, RO 16-8714,
ZD 7114
Lipase inhibitor
Orlistat (Xenical)
Fat substitutes
Olestra
Pseudoleptin, Neuropeptide Y restrainer
Approved by FDA in ‘99
Introduction of
Overweight and Obesity
Targets of Anti-Obesity Treatment
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Domestic consumption drugs for reducing food intake and obesity
Name of drugs
Ingredient
Green tea, orthosiphoris
OTC
Narmin Cap.
Green tea, orthosiphoris
OTC
Diaen Cap.
Green tea, orthosiphoris
OTC
Diva Cap.
Green tea, orthosiphoris
OTC
Rosecana Cap
Green tea, orthosiphoris
OTC
Reductil Cap.
Sibutramine
Prescription
Maront Cap.
Norpseudophedrine
Prescription
Exollise Cap.
Green tea
Xenical Cap.
Orlistat
Prescription
Furimin Tab.
Phendimetrazine tartate
Prescription
Freesel Cap.
Calcium gluconate
Free-L Cap.
Arsobic acid , phenylpropanolamine
Study of obesity
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Garcinia cambogia
▪ Hydroxy citric acid from Indian plant
Class
Greenphon Cap.
Obesity
▪ it is incorporated into many
weight-reducing products
▪ in vitro
→ beneficial effect on the fat metabolism,
appetite suppression, weight reduction
Garcinia Cambogia Extract (Citrimax)
→ 50% HCA - 500 mg
▪ in human → no benefit
OTC
Gymnema
▪ ayurvedic medicine,
reducing appetite, losing weight
OTC
⇒some animal experiments suggest benefit,
no human studies have been conducted
Prescription
8 / 37
Obesity
Study of obesity
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Hyperlipidemia
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Study of hyperlipidemia
Cholesterol →cause of disease in heart and circulation
South African catus, Hoodia annilata
▪ used by the Kalahari bushman
to suppress appetite
No historical basis for lipid-lowering herbal therapy
▪ clinical trial as a weight loss aid
▪ Need closer scientific evaluation
Orthodox treatment
Non proven herbal remedy
1.Guarana (Paullinia cupana) – high caffeine
Hoodia annilata
▪ a group of drugs called the statins
ex)simvastatin, pravastatin → produced by fungi
2.Bladderwrack (Fucus vesiculosus) – high iodine
3.Chili (Capsicum annuum)
4.Mahuang (Ephedra sinica) – ephedrine
Side effect
▪ nervous system, cardiovascular system, psychosis, seizure,
strokes, heart attacks
lovastatin
simvastatin
Hyperlipidemia
Study of
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hyperlipidemia
Hyperlipidemia
Study of
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Hyperlipidemia
Psyllium (Plantago isphagula)
Plant sitosterol, sitostanol
▪ small effect
▪ High-fiber diet → cholesterol absorption↓
▪ reduce cholesterol absorption
▪ vegetarian ≫ omnivorous
Soya bean (Glycine soja)
Soy product
Psyllium (Plantago isphagula)
▪ effective dietary remedy
▪ meta-analysis of 38 controlled clinical trials confirmed benefit
▪ soy – 1960s, first clinical study trial prior to lipid-lowering agents
▪ available in a variety of spreads
▪ regular use products significant improvement in the lipid profile
▪ recommended by the AHF
Garlic acid
Pine tree-derived sterol
▪ lowering cholesterol
▪ cardiovascular benefits → antiplatelet action
→ reducing blood viscosity
→ improving endothelial function
▪ controversy but, modest benefit on the meta-analysis
▪ Become available as additives to spread
▪ have confirmed low-density lipoprotein cholesterol-lowering property
Hyperlipidemia
Another approach
▪ walnut, olive oil, fish oil, evening primrose
Study of
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Hyperlipidemia
Thyroid disorder
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Study of Thyroid disorder
Globe artichoke (Cynara scolymus)
▪ reduce hepatic cholesterol production
Thyroid Overactivity
(Thyrotoxicosis)
Red clover (Trifolium pratense)
Uncommon condition affecting
mainly women
▪ treatment of menopausal symptom
▪ isoflavone (genistein, daidzein, biochamin A)
polyphenol
Red clover (Trifolium pratense)
Thyroid
disorder
▪ no cholesterol-lowering effect in post-menopausal women
Thyroid Underactivity
(Myxoedema)
▪ but, HDL↑
Common, particulary(2~3%)
in older women, and is often
undiagnosed
Herbal remedy
▪ Rhubarb (Rheum palmatum)
▪ Turmeric (Curcuma longa)
▪ Devil’s claw (Harpagophytum procumbens)
▪ Gulgul (Commiphora mukul)
Lipid-lowering potential
But, no confirm in humans
Click to add text
Thyroid disorder - thyrotoxicosis
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Study of Thyroid disorder
Thyroid Disorder – thyroid underactivity
Bugleweed (Lycopus virginicus), Gypsy (Lycopus europaeus)
Underactive thyroid gland
▪ European plants, traditional use
▪ treating palpitations, goiter (thyroid swelling), Grave`s disease
▪ Caused by Iodine deficiency
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Study of Thyroid disorder
▪ This can be corrected by increasing iodine intake
►Experimental work
▪ Addition of iodine to salt → option in iodine-deficient areas
▪ An effect on output of various pituitary hormone
→ TSH, gonadotropins, Prolactin
▪ kelp (Fucus vesiculosys) – iodine↑
►Work in humans
Natural therapy
▪ effect iodine metabolism and thyroxine hormone
▪ but, clinical effect – mild
▪ radish (Raphanus sativus) – Russian folk medicine
▪ walnuts (Juglans spp.) – Turkish folk medicine
Lithospermum officinale, lemon balm (Melissa officinale)
▪ mustard (Brassica nigra) - Europe
►Laboratory work
▪ motherwort (Leonurus cardiaca) – supported by German Commission E
- treat thyroid overactivity
- controlling the resulting palpitations
though its direct effect of the heart
▪ react with the antibody produced in thyrotoxicosis
▪ no clinical study
Prevalence of Menopause
Study of Menopause
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Many women suffer from menopausal symptoms in middle age
▪ 70% → estiamted to experience flushes
▪ 40% → mood swings
Menopause
Study of Menopause
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Plant estrogen
▪ fruits, vegetable, cereal
▪ soy diet : promoted as an alternative, but need large amounts
▪ benefit → treating high cholesterol, osteoporosis and
→reducing the risk of cancers
Side effects of Hormone Replacement Therapy (HRT) ↑
Side effect of high levels of phytoestrogens
Natural alternatives are commonly used
Scandinavian survey
▪ 21% → hormone replacement therapy
▪ 45% → alternative therapy
▪ eipdemiological evidence → adverse effect on
male sexual development in pregnancy
Menopause
Study of Menopause
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Menopause
Black cohosh (Cimicifuga racemosa)
Ginseng, evening primrose oil, angelica
▪ used by Algonqium Indians of North America
▪ no proven benefit
Target of Study
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to treat premenstrual problems
▪ approved by the GCE for premenstrual
syndrome, dysmenorrhea, Menopausal symptoms
▪ safe and effective alternative to estrogen therapy
Wild yam (Dioscorea villosa)
▪ alternative approach to hormone therapy
▪ but, no effect
▪ diosin (progesterone precursor – not convert in body)
Conclusion
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Conclusion of Study
▪ Our diet has changed VS Our metabolism has not
▪ People are reluctant to change eating habits.
▪ Herbal supplement reduce the metabolic disorder.
▪ This change should not be based on laboratory experimentation,
pseudoscience, testimonials.
▪ Until such time as medical benefit is proven in clinical trial, we should use
orthodox treatment.
▪ In the long time, traditional plants therapies will be proven effective and
incorporated into orthodox treatment regimes.
A recent Australian study of a traditional Chinese formula
containing 12 Herbs showed no symptom improvement
over three months.