This document discusses current trends in natural health products and research on natural products from garlic and perilla. It provides background on the history of using natural products for medicine beginning with Hippocrates prescribing garlic. Developments are discussed such as the discovery of antibiotics from microorganisms in the 1970s and shift to laboratory drug discovery in the 1980s. The presentation will cover organic chemistry, biochemistry, pharmacology and synthetic analogs related to natural product research and development. Studies on garlic are summarized showing that consuming garlic may help lower blood glucose, cholesterol, and triglycerides.

1. Current Trends in Natural
Health Products
1
School of Medical Sciences,
University of Phayao, Phayao,
Thailand
About my presentation
• Background and history of
natural products.
• Research and development
of natural products from the
past to the present.
•Our research on natural
products: Garlic and perilla
(Nga-mon).

2. “Let food be thy
medicine, and medicine
be thy food.
• Said by Hippocrates,
460 BC, the father of
Western medicine.
• Hippocrates used to
prescribe garlic to
treat a variety of
medical conditions.

3. History of Natural Products
3
Natural product : a chemical compound or
substance produced by a living organism –
found in nature including any substance
produced by life.
The products are drugs, cosmetics, dietary
supplements, and foods .
Nature has been long known as a source of
medicinal products with many useful drugs
developed from plant sources.
In the 1970s Discovery of the antibiotics
from microbial sources:Penicillins.
In late 1980s, combinatorial chemistry
shifted the focus of drug discovery efforts
from Nature to the laboratory.

4. Chemistry and Pharmacology are Essential for Research
and Development of Natural Products
4
Organic chemistry- natural products is usually restricted to mean
purified organic compounds isolated from natural sources.
Bio-chemistry- These compounds are produced by the pathways
of primary or secondary metabolism.
Medicinal chemistry- secondary metabolites which are essential for
survival of plants or microorganisms. They may be cytotoxic and have
been selected and optimized agents against prey, predators, and
competing organisms.
Pharmacology - biological activity that can be of therapeutic benefit in
treating diseases. Some agents are the active components of
many traditional medicines.
Synthetic analogs of natural products with improved potency and safety
are often used as starting points for drug discovery.
Sofar, natural products are approximately one half of U.S. Food and
Drug Administration-approved drugs.
Natural products can also be prepared by total synthesis which have
played a central role in the development of the field of organic chemistry
by providing challenging synthetic active compounds for health benefits.

5. 5
Natural products
drug discovery of
microorganisms,
outlining important
drugs from natural
sources that
revolutionized
treatment of
serious diseases.
Nature will continue
to be a major
source of new
structural leads,
and effective drug
development
depends on
multidisciplinary
collaborations.

6. Penicillin can kill streptococcus,
meningococcus and the diphtheria
bacillus.
Discovery of penicillin drug from Penicillium notatum
by Alexander Fleming (1928)

7. The former research
director of the US
National Cancer
Institute (NCI)
Chief of the NCI’s Natural
Products Branch (NPB) in
1989-2004.
He was involved in the NCI’s
search for new cancer
medicines from plants
and other natural
sources
And successfully discovered
anticancer drug Taxol
and related derivative
compounds
7
Gordon M. Cragg:
A Man for All
Natural Products
http://www.researchgate.net/publication/221797061_Gordon_M._Cragg_D.Phil._D.Sc
._(h.c.)_a_man_for_all_natural_products

8. Taxol: The first novel anticancer drug from plant
8
The Yew bark is peeled and processed to provide paclitaxel (Taxol and
Abraxane) : a mitotic inhibitor used in cancer chemotherapy

9. Biodiversity of Natural Sources and Bioactive Compounds
• Plants have always been a rich source of pharmacologically
active nature products
e.g. Alkaloids, morphine, cocaine, digitalis,quinine, tubocurari
ne, nicotine, and muscarine.
• Microorganisms- such as bacteria and fungi have been
invaluable for discovering pharmacologically active natural
products.
• Other sources- herbal plants, marine products, mushroom ,
venoms, local foods,
9

10. Biodiversity as a source of anticancer drugs.
• Gordon Cragg, D. Phil., chief of the NPB, notes that the quest
for therapeutic natural products can be akin to “looking for a
needle in a haystack.” “In the first group of extracts studied
from 1960 to 1982 that gave us two anti-cancer agents, Taxol
and camptothecin, over 114,000 extracts were investigated.”
• Cragg says part of the problem with plant collections is that
the sources for many of these natural products reside in
developing countries, where, historically, cancer has not been
a health issue.
• “If we were looking for an anti-malarial agent or treatments
for other diseases affecting the local populations, we could
use the knowledge of local healers to guide the collections,
but for cancer we pretty much just grab any species we can
find, and cover a broad taxonomic range.” 10

11. Genetic Information and Drug Discovery from Natural
Products
• The genetic techniques permitted the implementation of
combinatorial biosynthetic technology and genome mining.
..unknown molecules to be identified.
• These novel bioactive structures can be optimized by using
combinatorial chemistry generating new drug candidates for
many diseases.
• The advent of genetic techniques that permitted the isolation
/ expression of biosynthetic cassettes from microbes may well
be the new frontier for natural products lead discovery.
• It is now apparent that biodiversity may be much greater in
those organisms. The numbers of potential species involved in
the microbial world are many orders of magnitude greater
than those of plants and multi-celled animals.
• Coupling these numbers to the number of currently
unexpressed biosynthetic clusters now identified (>10 per
species) the potential of microbial diversity remains essentially
untapped. 11

12. •Phytochemicals usually have biological and
pharmacological activities that greatly affect and
influence human and animal health.
•They have been commonly used in different ways as
health products, dietary supplements, nutraceuticals,
medical foods, pharmaceutical drugs and cosmetics.
•To understand how these natural compounds work, the
study of chemistry and biochemistry of active
compounds and their biological mechanisms or
interactions in vitro and in vivo should be experimented
and clearly described.
•In the past decades, scientific research about
biological active phytocompounds have been increasingly
carrying on by chemists, biochemists, biotechnologists in
well known governmental and private laboratories and
industrially developed into commercial health products
and designed drugs by pharmacologists and
pharmacists.
12
Plants and foods are the main source of phytochemicals

13. R & D of Natural products are the chemical compounds
Currently, most of reports mainly involve secondary plant
metabolites such as polyphenols, bioflavonoids,
carotenoids, curcuminoids, tocopherols, tocotrienols and
others which are powerful antioxidants, anti-
inflammatory agents and other health promoting activities
against cancer, cardiovascular diseases, diabetes ,
obesity, impotence, aging, etc..Recently omega-3 fatty
acid, coenzyme Q10, ginseng products, resveratrol and
other polyphenols consumed regularly were shown to have
the most notable cardiovascular protective properties.
Several natural products such as flavonoids, sesamin,
essential oils, omega 3 fatty acids, cordycepin and which
were extracted and isolated from local Thai native plants,
studied in laboratories and finally developed to
commercial health products for international markets
will presented and discussed.
13

14. Nutraceutical and Functional Food R&D Center (NFF) in PSU
14
http://nff.psu.ac.th/en/index.php

15. PHYTOCHEMICALS FROM GARLIC

16. I.About Garlic
• Allium sativum , Family Alliaceae
• Are native of Africa, Asia, South
Amecia , Europe including Egypt,
Greece, China and cultivated in all
over the world
• Popular for use as food flavoring
and taste
• Reports has shown that garlic is one
of the best medicinal plant

17. “Let food be thy medicine,
and medicine be thy food.
• Said by Hippocrates,
460 BC, the father of
Western medicine.
• Hippocrates used to
prescribe garlic to
treat a variety of
medical conditions.

18. Eastern and Western Medical Uses
• Traditionally
– Antibiotic for colds, sore throat, phlegm in
respiratory tract, asthma, bronchitis,
abscesses and tuberculosis
• Reduce high blood pressure and
cholesterol
– Heart disease and hypertension
• Prevention and treatment of certain
cancers (stomach and colon cancer)

19. Ancient uses of Garlic
• Ancient Egyptians used garlic to cure
– Headaches
– Tumors
– Heart disorders and intestinal worms
• Ancient Olympic athletes ate garlic to
increase their energy
• First century A.D. it was prescribed to
the Roman army as an anthelmintic
(intestinal worms)

20. Enzymatic Formation of Allicin
in Crushed Garlic
Odorless
, not
volatile,
stable
Pungent
odor,
corosive,vol
atile,
unstable

21. How Garlic is Consumed
• Eaten
– Raw or cooked
• Chopped, minced, whole, and crushed
• Raw cloves use to make oils and liquid extracts
• Dried or powdered
• Tablets
• Capsules containing oil or liquid extract

22. Garlic and Health

23. Preparation of Garlic Oil from Raw Garlic

24. Note: No allicin was found in steamed garlic oil
due to its oxidation.

25. Carbohydra
te contains
inulin, a
prebiotic
which is an
health
compound.
Antioxidativ
e activity
comes from
volatile
organosulfu

26. Including Garlic in the Diet May Help Lower Blood
Glucose, Cholesterol, and Triglycerides
• The goal was to study the efficiency of an aqueous
extract of raw garlic in controlling levels of sugar,
cholesterol and triglycerides in the blood of normal
rats.
• Materials and Methods
– Female Sprague-Dawley rats weight 200-250g
– Maintained on a normal diet and tap water
– Divided into 5 groups
• Group 1: normal saline (control)
• Group 2: orally force-fed garlic by stomach gavages using a ball
tipped needle
• Group 3: garlic by intrapertioneal injection
• Group 4: orally forced-fed boiled garlic using the same methods
as group 2
• Group 5: intraperitoneal injections of boiled garlic
Journal of Nutrition (2003) 136:3S

27. Garlic in Diet May Help Lower Blood Glucose,
Cholesterol, and Triglycerides.
• Both oral garlic and garlic IP showed a significant difference from the control
group for lowering triglycerides
• Only raw garlic IP showed a significant difference from the control for lowering
cholesterol
• Boiled garlic showed no significant difference

28. Conclusions:
• Aqueous extract of raw garlic taken in
small amounts has an effect in lowering
cholesterol and triglyceride levels
• “Raw garlic is more beneficial than
cooked in reducing blood lipid and
glucose levels and could potentially play
an important role in preventing
atherosclerosis.”

29. Effect of garlic supplementation on oxidized
low density lipoproteins and lipid peroxidation in
patients of essential hypertension.
0
50
100
150
200
250
TotoalC
holesterol
Triglycerides
LD
L-C
H
D
L-C
mg/dl
Hypertensive Baseline
Hypertensive after 8 weeks
Control Baseline
Control after 8 weeks
Ref. Molecular and Cellular Biochemistry (2004)
Results

30. Effect of garlic supplementation on oxidized
low density lipoproteins and lipid
peroxidation in patients of essential
hypertension
Conclusion: “Including garlic as a daily
supplement in our diet is a useful and an
attractive proposition for counteracting
high blood pressure and oxidative stress
and various other factors associated
with cardiovascular risk”
Molecular and Cellular Biochemistry (2004)

31. Effect of garlic on cardiovascular
disorders: a review
• An overall review of the efficiency of garlic in
cardiovascular disease conditions both in humans and
animals.
• Reviewed Animal Studies and human studies in
– lipid metabolism
– Fibrinolytic activity
– platelet aggregation
– blood pressure lowering effect
– Diabetes mellitus
– other cardio protective properties of garlic
– adverse effects of garlic.
. Nutrition Journal (2002)

32. Effect of garlic on cardiovascular
disorders: a review.
• Scientific literature supports the proposal of garlic
consumption and it’s cardio protective effect.
• However, there are still issues on the type of garlic
preparations that have been used in the studies
• Suggest further research to identify specific compounds
from garlic and garlic product that are responsible for
the biological effects.
Nutrition Journal (2002)

33. Possible Side Affects
• Bad Breath and Body Odor
• Heart burn, upset stomach, and allergic
reaction
– Most only occur with raw garlic
• Blood thinner (like aspirin)
– Inability to clot, can become a more concern
during and after surgery
• Avoid for at least 1 week before surgery or dental
work
• Interferes with the effectiveness of
Saquinavir, a drug used to treat HIV
• No known effects on other drugs

34. How much garlic may be useful for cancer prevention?
• The National Cancer Institute, National Institutes of
Health, does not recommend any dietary supplement for
the prevention of cancer, but recognizes garlic as one of
several vegetables with potential anticancer properties.
• Because all garlic preparations are not the same, it is
difficult to determine the exact amount of garlic that
may be needed to reduce cancer risk. he active compounds
present in garlic may lose their effectiveness with time,
handling, and processing.
• WHO guidelines for general health promotion for adults is
a daily dose of 2 to 5 g of fresh garlic (approximately one
clove), 0.4 to 1.2 g of dried garlic powder, 2 to 5 mg of
garlic oil, 300 to 1,000 mg of garlic extract, or other
formulations that are equal to 2 to 5 mg of allicin.

35. Conclusions
 Most studies have shown some improvement
of cholesterol levels by using garlic alone.
 The types of garlic used can influence the
affect the garlic has on cholesterol.
 Raw has a higher effect than boiled and tablets.
 Those who wish to reduce their cholesterol
using garlic should consult their physician for
possible side affects of using garlic and their
current medications to lower their
cholesterol.

36. II. Phytochemicals from Nga-mon (Perilla)
• What is Nga-mon (periila)?
• Polyunsaturated fatty acids in Nga-mon seeds
• Rosmarinic acid in Nga-mon leaves
• What are health benefits of Nga-mon oil
compared to fish oil?
• Our research activities of Nga-mon in
University of Phayao

37. Nga Mon Farm in Nan, North Thailand
Nga-mon is Perilla frutescens (L.) Britt. (syn. Perilla
nankinensis (Lour.) Decne.) of the mint
family, Lamiaceae.
 It is the species with identified two distinct varieties.
Traditional crop in East Asia: Northern Thailand.
What is Nga Mon?

38. Thai: Nga Kee Mon , Nga Mon(งาขี้ม ้อน งาม ้อน)
Laos: Ma Nga Chan (มะงาเจียง งามน)
Vietnam:Hojiso(Tía tô, Lá tía tô, Rau tía tô)
Bengali: ban tulsi
Hindi: bhanjira
Chinese: tzu ssu, yeh-ssu, chi-ssu, hung-
sha-yao, ts'ao-t'ou, tsu-shih ts'ao,
Japanese: shiso, Akaijiso (red), Aojiso
(green), egoma, shisonoha, umeboshi (in plum
pickle)
Korean: Deulggae, Tulkkae, Soyeob, Soyop,
Kkaennip, Ggaesip
English: perilla, beefsteak plant, Chinese
basil, purple mint
German: Schwarznessel, Chinesische Melisse,
Wilder Sesam, Perilla
38
Different names of perilla which is not sesame.

39. Uses of Nga Mon as functional foods
• Thai native foods: mixed with sticky rice, salt,
honey; in bread and bamboo rice (ข ้าวหนุกงา ข ้าว
หลาม)
• ผลิตภัณฑ์เสริมอาหารเพื่อสุขภาพ

40. Plant seeds containing omega-3 fatty acids:
Perilla, Chia, flax, hemp, nuts (walnut, pecan, peanut, etc.)
40

41. 41

42. Oamega-3 fatty acids in different kinds of seed oil
Omega-3 fatty acids (% of total lipid )

43. Total Oil Content in Nga-mon seeds cultivated in Different
Provinces

44. Polyunsaturated Fatty Acids (n-3, n-6, n-9)

45. Unsaturated fatty acids in Nga-mon seeds:
Oleic acid (OA)14–23%, linoleic acid (LA) 11–16%,
and alpha-linolenic acid (ALA) 54–64%
LA
ALA
OA
GLC analysis

46. Fatty Acids in Nga-mon Seed Oil from Thai Northern
Provinces

47. Almond, walnuts
and other nuts
.
47
Omega-6 Content in Nuts(1/4 cup)
Walnuts – 9.5 g
Almonds – 4.36 g
Cashews – 2.6 g
Macadamias – 0.5 g
Brazil nuts – 7.2 g
Hazelnuts – 2.7 g
Pistachio – 4.1 g
Pine nuts – 11.6 g
Pecans – 5.8 g
Omega-6s, though essential, tend to work opposite to omega-3s in
some ways, promoting inflammation and platelet stickiness.
However, since the ratio of omega-3 to omega-6 in the modern diet
has drastically changed over the last century —favoring omega-6s,
which are cheap and abundant in our food supply, so nutritionists
recommend increasing dietary omega-3s by eating more foods such
as perilla, flax, walnuts and especially fish oils.
The goal is to get closer to a ratio of 2:1 or 3:1 of omega-6 /omega-3
from the current 10:1 to 20:1.

48. Common Name Alternative Name Linnaean Name
% N-3
(ALA)
Perilla Shiso Perilla frutescens 61
Chia Chia sage Salvia hispanica 58
Flax Linseed Linum usitatissimum 55
Lingonberry Cowberry Vaccinium vitis-idaea 49
Camelina Gold-of-pleasure Camelina sativa 36
Purslane Portulaca Portulaca oleracea 35
Black Raspberry Rubus occidentalis 33
Hemp Cannabis sativa 19
ALA = Alpha-linolenic acid (OMEGA 3 )
Ref.: Wikipedia : Omega 3 Fatty Acids
Alpha Linolenic Acid (ALA, Omega-3) in Plant
Seed Oil

49. Alpha-linolenic acid (ALA)
49

50. Fish oil V.S plant seed oils (nga-mon, flax and sesame)
Omega 3 fats in Fish and Plant Seeds
(of total lipid by wt.)
Salmon, sardine, etc. =1.3 2%
Nga-mon =55%
Flax =53%
Sesame =1 %

51. Toxic Contamination in Fish and Fish 0il
•Heavy metal poisoning by the body's accumulation of
traces of heavy metals, in particular mercury, lead,
nickel, arsenic, and cadmium, is a possible risk from
consuming fish oil supplements.
•Also, other toxin contaminants (PCBs, furans, dioxins,
and PBDEs) might be found, especially in less-refined
fish oil supplements.
•An independent test in 2005 of 44 fish oils on the US
market found all of the products passed safety
standards for potential contaminants.80
Bent S, Bertoglio K, Hendren RL (August 2009). "Omega-3 fatty acids for autistic
spectrum disorder: a systematic review". J Autism Dev Disord 39 (8): 1145–54

52. Health Benefits of Omega-3 Fats
Alzheimer’s disease
Asthma
Attention deficit
hyperactivity disorder
(ADHD)
Bipolar disorder
Cancer
Cardiovascular disease
Depression
Diabetes
Eczema
High blood pressure
Huntington’s disease
Lupus
Migraine headaches Multiple
sclerosis
Obesity
Osteoarthritis
Osteoporosis
Psoriasis
Rheumatoid arthritis

53. 53
Metabolism of omega 3 fatty acids (ALA, EPA, DHA)

54. 54
Requirement of omega 3 fatty acids (ALA, EPA, DHA)
The daily intake of six 1,000-mg capsules of stabilized
perilla oil capsules provides 3.3 grams of the essential
omega-3 oil, alpha-linolenic acid.

55. ALA, EPA and DHA and Their Health Benefits
• The three types of omega-3 fatty acids involved in
human physiology are ALA (found in plant oils), EPA,
and DHA (both commonly found in marine oils).
• Marine algae and phytoplankton are primary sources of
omega-3 fatty acids. Common sources of plant oils
containing the omega 3 ALA fatty acid include walnut,
edible seeds, clary sage seed oil, algal oil, flaxseed oil,
Sacha Inchi oil, Echium oil, and hemp oil, while sources
of animal omega-3 EPA and DHA fatty acids include fish
oils, egg oil, squid oils, and krill oil.
• Supplementation with omega-3 fatty acids does not
appear to affect the risk of death, cancer or heart
disease.[3][4]
55
Ref: Omega-3 fatty acid - Wikipedia, the free encyclopedia.html#cite_note-
CL2005-80

57. Omega-3 Fatty Acids and Health of Brain and
Nerves
- Significant changes structure and functions of hippocampus could
increase memory and learning capability.

58. EPA (eicosapentaenoic acid) & DHA
(docosahexaenoic acid)
• Omega-3 fatty acids linked to a number of major
health benefits, including:
• Decreased triglycerides and blood pressure;
• Prevention of inflammatory diseases (arthritis) ,
atherosclerosis, heart attack and stroke
• Increased HDL (good) cholesterol levels
• improved cognitive function;
• shunted breast cancer development
• potentially enhanced muscle protein synthesis.

59. Comparative effects of perilla and fish oils on the activity and
gene expression of fatty acid oxidation enzymes in rat liver.
Biochim Biophys Acta. 2000 May 6;1485(1):23-35.
59
Among rats fed polyunsaturated fats…Safflower and fish oils but
not perilla oil, compared to palm oil, also decreased malic enzyme
activity and mRNA level.
Examination of the fatty acid composition of hepatic phospholipid
indicated that dietary alpha-linolenic acid is effectively
desaturated and elongated to form EPA and DHA.
Dietary perilla oil and fish oil therefore exert similar
physiological activity in modulating hepatic fatty acid
oxidation, but these dietary fats considerably differ in affecting
fatty acid synthesis.

60. Dietary sources of alpha-linolenic acid, perilla seed oil,,may have
the capacity to inhibit the generation of leukotrienes (LTs) by
leucocytes in patients with asthma,
• METHODS:
• The factors affecting the suppression of leukotriene (LT) C4 generation by
leucocytes were examined by comparing the clinical features of patients
with asthma who had been given dietary perilla seed oil (n-3 fatty acids).
Group A consisted of patients in whom the leucocyte generation of LTC4
was suppressed by dietary perilla seed oil. Group B consisted of those in
whom LTC4 generation was not suppressed.
• Serum levels of total cholesterol, triglyceride, high-density lipoprotein
cholesterol, LDL cholesterol and phospholipid differed significantly
between the two study groups prior to dietary supplementation. Serum
levels of triglyceride and LDL cholesterol differed significantly between
the two study groups after 4 weeks of dietary supplementation.
• CONCLUSIONS:
• Dietary supplementation with perilla seed oil in selected patients with
asthma suppresses the generation of LTC4 and is associated with clinical
features such as respiratory function and fat metabolism.
Okamoto M, Mitsunobu F, Ashida K, Mifune T, Hosaki Y, Tsugeno H, Harada S, Tanizaki Y, Kataoka M, Niiya
K, Harada M. Effects of perilla seed oil supplementation on leukotriene generation by leucocytes in patients
with asthma associated with lipometabolism. Int Arch Allergy Immunol. 2000 Jun;122(2):137-42.

61. Research Project of ARDA 2013-2016
Development of Nga-mon products and dietary supplements rich in omega-3
fatty acids & antioxidants for clinical trials of dementia and allergy
University of Phayao, Thailand
Seed Oil
Omega-3 fatty acids
Nga-mon leaves extract
Antioxidants, etc.
Nga-mon health products
and dietary supplements
Clinical trials of
dementia & allergy
Nga-mon cosmetics
Nga-mon
Animal
experiments
Nga-mon oil capsules

62. Thank you for your attention
Thanks to all the research team members:
Verapol Chandeying, Busabong Jamroendararasame, Pramote
Wanittanakom, Maroot Kaewwongse, Komsak Pintha, Jukkrit
Wungrath , Payungsak Tantipaiboonwong, Puksiri Sinchaikij,
Kanakokarn Phromnoi and Jukkrit Khanaree

63. University of Phayao, Thailand