Industry Situationer and the Bioactive Components of Cosmeceuticals and Pharmaceuticals from Seaweeds : Pharmaceutics / Dr. Marco Nemesio E. Montaño

Pharmaceutical
• Connected with the science, preparation, and
production of drugs and medicines.

• Iodine is important for
normal thyroid function and
prevents the occurrence of
goiter
• Highest sources are
mollusks and crustaceans
but can also be found in
sea bass and seaweeds
(Halymenia spp.)
WHY IS SEAFOOD HEALTHY:
IODINE
3
IODINE
Photo courtesy of
Iodinefcsolutions.co.ukSource: Sioen et al, 2009

• Solieria robusta, a red macroalga belonging to the
Solieriaceae family of the order Gigartinales
• Its phycocolloid carrageenan extract predominantly
contains iota-carrageenan.
Carrageenan structure and gel properties of Solieria robusta (Greville) Kylin (Gigartinales, Rhodophyta)
from the Philippines
By Wilson G. Mendoza*, Edna T. Ganzon-Fortes and Marco Nemesio E. Montaño – UP MSI

Hypolipidaemic Activity of Seaweed
From the study:
Hypolipidaemic Activity of Seaweed from Karachi
Coast
Ara J., Sultana V., Qasim R., and Ahmad V.
Phytother. Res. 16, 479-483 (2002)

• Oligosaccharides derived from Porphyra were shown to have some physiological activities
including:
– desmutagenic
– anti-hypercholesterolemic
– anti-angiogenic
• Oligosaccharides prepared from agar and carrageenan were found to have very high
– antibrowning
– antimicrobial
– antihypertensive
– anticoagulant
– anticancer
Bioactive Product: Carrageenan

Halymenia durvillaei produces lambda-like
carrageenan and R-phycoerythrin.
This seaweed has important application in food
and cosmetics industry
Development of Post-Harvest Techniques for Halymenia durvillaei and Portieria
hornemannii and screening for their bioactive compounds
by Dr. Marco Nemesio Montaño and Dr. Gavino Trono - UPMSI

SiB Magallanes from http://www.sibmagallanes.cl/eng/ecosystems.php?section=aquatic-ecosystems,flora,macroalgae&pagenum=10
Flicker Hive Mind from http://flickrhivemind.net/Tags/agardhiella/Interesting
Glycomix from http://glycomix.co.uk
The Lancet from http://www.thelancet.com/journals/lancet/article/PIIS0140673608618243/fulltext?rss=yes
xylomannan sulfate from
Nothogenia fastigiata
ANTI-VIRAL against HIV, HSV, and RSV
galactan sulfate from
Agardhiella tenera
Carraguard,a vaginal microbicide

- found to have
antimicrobial activity and
enhanced the
effectiveness of some
antibiotics

• sulfated polysaccharide from brown algae
• sulfuric acid esterified L-fucose backbone with galactose,
xylose and glucuronic acid
Glycomix from http://glycomix.co.uk
Bioactive Product: Fucoidan

• ability to act as an anti-contraceptive
• reduce cholesterol levels
• anti-cancer
• anti-tumor agent
• anti-thrombotic
• against white spot syndrome virus
Source:The Biomedical Research Laboratories of Takara Shuzo and the Research Institute for
Glycotechnology Advancement
Bioactive Product: Fucoidan

Bioactive Product: Fucoxanthin
■ a pharmacologically active carotenoid commonly distributed in brown
algae
■ acts as an antioxidant and inhibits GOTO cells of neuroblastoma and
colon cancer cells (Mori et al., 2004)

• has beneficial effects on chemoprevention of cancer
• also inhibited the development of intestinal
carcinogenesis in animal experiments
• induced apoptosis of human leukemia HL-60 cells
• reduces viability of prostate cancer cells by inducing
apoptosis

0
50
100
150
200
250
25 45 65
United Kingdom
France
Spain
Japan
80
Breast Cancer Incidence 1968-1972
Cancersper100,000women
De Waard, F. JNCI, 1979
Age

• being developed into a slimming supplement or a
drug that targets harmful fat
• In obese animals, the compound appeared to
stimulate a protein called UCP1 which causes fat to
be broken down.
• The pigment, in the form of fucoxanthinol, also
caused the liver to produce DHA, which as have
mentioned earlier, can help cut levels of bad
cholesterol associated with obesity and heart
disease
(Dr. Kazuo Miyashita. Hokkaido University Research as presented in The American Society Meeting, September 11, 2006)
http://news.bbc.co.uk/2/hi/health/5335176.stm

• In a new human clinical trial, a patent-pending extract of fucoxanthin
called LipoxanThin, showed promising results for fat loss in humans.
• A proprietary concentrate of fucoxanthin from specially selected strains
of deep sea water cultivated brown marine vegetables grown under
closely controlled conditions in special photobioreactors in the pristine
Canary Islands, 1,000 miles from Europe.
Dr. Sergey Grachev and Dr. Musa Abidov. First Medical Academy and Institute of Immunopathology, Russian Academy of Natural
Sciences. September 18, 2006)
Brown seaweed is an ingredient of miso soup

LipoxanThin showed promising results for fat loss in humans.
This double-blind, placebo-controlled study of 140 obese females
demonstrated statistically significant reduction in liver fat, body fat, and
body weight versus placebo after 16 weeks.

• By stimulating the expression of UCP-1 gene in
white adipose tissue (WAT), fucoxanthin promotes
thermogenesis (fat burning) in white fat cells.
• No jitters, loss of sleep, or stimulation side effects
since the thermogenic effect is achieved without
stimulating the central nervous system.

• Quorum sensing disrupts bacterial communication
• Halymenia sp. - production of chemical
compounds such as furanones (Mclean, et al.,
2004)
• Ulva sp. - reliance on bacterium e.g.
Pseudoalteromonas tunicata that synthesize
inhibitory substances (Egan et al., 2002)
Quorum Sensing Inhibitory Activity

• Solieria robusta, a red macroalga belonging to the
Solieriaceae family of the order Gigartinales
• Its phycocolloid carrageenan extract
predominantly contains iota-carrageenan.
Soliera
Carrageenan structure and gel properties of
Solieria robusta (Greville) Kylin (Gigartinales,
Rhodophyta) from the Philippines
By Wilson G. Mendoza*, Edna T. Ganzon-Fortes
and Marco Nemesio E. Montaño – UP MSI

Wound healing
Toxicity Efficacy
Stimulates
wound
healing
Laminaria digtata in vitro Doyle JW, Roth TP, Smith RM, Li YQ, Dunn RM. Effect of
calcium alginate on cellular wound healing processes modeled in
vitro. J Biomed Mater Res (1996);32:561–568
Anti-
inflammatory
Undaria pinnatifida against
edema
Mice Khan MNA, Suk-Choi J, Lee MC, Kim E, Nam TJ, Fujii H, Hong YK. Anti-inflammatory
activities of methanol extracts from various seaweed species. J Environ Biol
(2008);29:465–469
ReferenceHealth
Claim
Seaweed species Evidence
(Lam, 2013)

Cardiovascular Health
Toxicity Efficacy
For 0.6g increase in seaweed
consumption associated with 2 pts
decrease in SBP and 3 pts decrease
in DBP.
533 Japanese school
children, cross
sectional
Wada K, Nakamura K, Tamai Y, Tsuji M, Sahashi Y, Watanabe K, Ohtsuchi
S, Yamamoto K, Ando K, and Nagata C. Seaweed intake and blood
pressure levels in healthy pre-school Japanese children. Nutrition
Journal (2011);10:83
5% dry wt (of feed) Hypnea charoides
reduced overall cholesterol
Sprague Dawley rats
Colpomenia sinuosa increased total
serum cholesterol
Sprague Dawley rats
24% dry wt Ulva fasciata reduces total
cholesterol
rats Carvalho AF, Portela MC, Sousa MB, Matins FS, Rocha FC, Farias DF,
Feitosa JP. Physiological and physico-chemical characterization
of dietary fibre from the green seaweed Ulva fasciata Delile.
Brazil J Biol (2009);69:969-977.
7% dry wt Nori, Konbu reduces total
cholesterol, and improved lipid profile
rats Bocanegra A, Bastida S, Benedi J, Nus M, Sanchez-Montero JM, Sanchez-
Muniz FJ. Effect of seaweed and cholesterol-enriched diets on
postprandial lipoproteinaemia in rats. Br J Nutri (2009);102:1728-
1739.
Seaweed consumption had no effect
on total serum cholesterol
7,000 Japanese cross
sectional study
Kondo I, Funahashi K, Nakamura M, Ojima T, Yoshita K, Nakamura Y;
NIPPON DATA 80/90 Research Group.
Association between food group intake and serum total
cholesterol in the Japanese population: NIPPON DATA 80/90. J
Epidemiol. 2010;20 Suppl 3:S576-81.
Seaweed consumption reduces risk of
cardiovascular mortality by 27%
40,547 Japanese over
7 years
Shimazu T, Kuriyama S, Hozaw a A, Ohmori K, Sato Y, Nakaya N, Nishino
Y, Tsubono Y, Tsuji I. Dietary patterns and cardiovascular diease
mortality in Japan: a prospective cohort study. Int J Epidemiol
(2007);36:600-609.
Carageenan in bread, corn pudding,
fish balls, and gruel lowered total
cholesterol
case control for 2
weeks
Panlasigui LN, Baello OQ, Dimatangal JM, Dumelod BD. Blood
cholesterol and lipid-lowering effects of carrageenan on human
volunteers. Asia Pac J Clin Nutr (2003);12:209-214.
Undaria pinnatifida delayed stroke
signs and moratality
Mice Ikeda K, Kitamura A, Machida H, Watanabe M, Negishi H, Hiraoka J,
Nakano T (2003) Effect of Undaria pinnatifida (wakame) on the
development of cerebrovascular diseases in stroke-prone
spontaneously hypertensive rats. Clin Exp Pharmacol Physiol
30:44–48
Wong KH, Sam SW, Cheung PCK, Ang Jr PO. Changes in lipid profiles
of rats fed with seaweed-based diets. Nutri Res (1999);19:1519.
Seaweed species Evidence Reference
(Lam, 2013)

Anti-arthritis
Toxicity Efficacy
Aquamin tables extends
range of motion for
patients with mild to
moderate Osteo arthritis
RCT Frestedt JL, Kuskow ski MA, Zenk JL. A natural seaweed derived
mineral supplement (Aquamin F) for knee osteoarthritis: A
randomised, placebo controlled pilot study. Nutrition Journal,
Open Access (2009);8:7
Ecklonia cava reduce OA
inflammation
In vitro Shin H, Hw ang HJ, Kang KJ, Lee BH. An antioxidative and
antiiflammatory agent for potential treatment of
osteoarthritis from Ecklonia cava. Arch Pharm Res
(2006);29:165.
ReferenceSeaweed species Evidence
(Lam, 2013)

Anti-obesity
Toxicity Efficacy
Alginates ehances satiety by 7% humans cross-
sectional
Paxman JR, Richardson JC, Dettmar PW, Corfe BM. Daily ingestion of
alginate reduces energy intake in free-living subjects . Appetite
(2008);51:713-719.
Alginate and guar-based
breakfast bar did not lower
macronutrient intake
over 5 days Mattes RD. Effects of a combination fiber system on appetite and
energy intake in overweight humans. Physiology and Behavior
(2007);90:705-711.
Seaweed consumption reduces
risk of obesity by 43%
3,760 Japanese
women, cross
sectional study
Okubo H, Sasaki S, Murakami K, Kim MK, Takahashi Y, Hosoi Y, Itabashi M;
Freshmen in Dietetic Courses Study II group. Three major dietary
patterns are all independently related to the risk of obesity
among 3760 Japanese women aged 18-20 years. Int J Obes
(Lam, 2013)

Anti-cancer
Toxicity Efficacy
Sargassum sp used as biosorbents (53
to 63%) of di(2-ethylhexyl)phthalate
(DEHP). DEHP released in PVC
processing in food packaging, IV line,
etc.
in vitro Chan HW, Lau TC, Ang PO, Wu M, Wong PK. Biosorption of di(2-
ethylhexyl)phthalate by seaweed biomass. Journal of Applied
Phycology (2004);16:263-274.
Seaweed consumption reduces risk of
breast cancer occurrence by 52%
724 South Korean
women, case
control study
Yang YJ, Nam S, Kong G, Kim MK. A case-control study on
seaweed consumption and the risk of breast cancer. Br J Nutr
(2010);103:1345-1353.
75mg/kg of body wt of Aaria esculenta
can lower serum oestradiol levels (anti-
breastcancer) by 58%
15 healthy females
RCT
Teas J, Hurley TG, Herbert JR, Franke AA, Sepkovic DW, Kurzer MS.
Dietary seaweed modiﬁes estrogen and phytoestrogen
metabolism in healthy postmenopausal women. J Nutr (2009);
139:939-944.
Fucus evanescens fucoidan as
possible Anti-tumor and Anti-metastatic
C57B1/6 mice with
Lewis lung
adenocarcinoma
(10 mg/kg for
antimetastatic, and
25mg/kg for anti-
tumor potentials of
cyclophosphamide)
Alekseyenko, T. V., Zhanayeva, S. Y., Venediktova, A. A., Zvyagintseva,
T. N., Kuznetsova, T. A., Besednova, N. N., & Korolenko, T. A. (2007).
Antitumor and antimetastatic activity of fucoidan, a sulfated
polysaccharide isolated from the Okhotsk sea Fucus
E cava phlorotannin
(dioxinodehydroeckol) as anticancer
human
breastcancer cell
line
Kong, C. S., Kim, J. A., Yoon, N. Y., & Kim, S. K. (2009). Induction of
apoptosis by phloroglucinol derivative from Ecklonia Cava in MCF-
7 human breast cancer cells. Food and Chemical Toxicology, 47, 1653-
1658.
Sargassum vulgare alginic acid as anti-
tumor
in vitro cancer cell
line, mice models
de Souza, A. P. A., Torres, M. R., Pessoa, C., de Moraes, M. O., Filho,
F.D. R., Alves, A. P. N. N., & Costa-Lotufo, L. V. (2007). In vivo growth-
inhibition of Sarcoma 180 tumor by alginates from brown
seaweed Sargassum vulgare. Carbohydrate Polymers, 69,
Saccharina latissima in vitro (HepG2,
A549, MGC 803
cells)
Murata M, Nakazoe J (2001) Production and use of marine algae in
Japan. Jpn Agr Res Q 35:281–290
Eucheuma cottonii suppresses breast
tumor
Rat Namvar F, Mohamed S, Fard SG, Behravan J, Mustapha NM, Alitheen
NBM, and Othman F. Polyphenol-rich seaweed (Eucheuma
cottonii) extract suppresses breast tumour via hormone
modulation and apoptosis induction. Food Chemistry (2012);
130:376-382.
(Lam, 2013)

Anti-diabetes
Toxicity Efficacy
Apostolidis E, Lee CM. In vitro potential of Ascophyllum nodosum
phenolic antioxidant-mediated alpha-glucosidase and alpha-
amylase inhibition. J Food Sci (2010);75:H97.
Zhang J, Tiller C, Shen J, Wang C, Gargouri GS, Dennis D. Antidiabetic
properties of polysaccharide- and polyphenolic-enriched
fractions from the brown seaweed Ascophyllum nodosum . Can
J Physiol Pharmacol (2007);85:1116.
5g sodium alginate added to food
reduced glycemic index among Type 2
diabetics by 31%
human Torsdottir I, Alpsten M, Holm G, Sandberg AS, Tolli J. A small dose of
soluble alginate-fiber affects postprandial glycemia and gastric
emptying in humans with diabetes. J Nutri (1991);121
5.5g guar gum plus 1.6g sodium alginate
reduced glycemic index by 33% among
healthy adults
human Williams JA, Lai C, Corw in H, Ma Y, Maki KC, Garleb KA, Wolf BW.
Inclusion of guar gum and alginate into a crispy bar improves
postprandial glycemia in humans. J Nutr (2004);134:886.
48g of seaweed (sea tangle, and sea
mustard) in pill form per day reduced
FBS levels and Glycemic index of Type
2 diabetics
20 Japanese
case control
study
Kim MS, Kim JY, Choi WH, Lee SS. Effects of seaweed
supplementation on blood glucose concentration, lipid profile,
and antioxidant enzyme activities in patients with type 2
diabetes mellitus. Nutr. Res. Practice (2008);2:62-67.
Seaweed consumption reduces risk for
Type II diabetes and pre-diabetes (34%
for men and 20% for women)
3,405 Koreans
in retrospective
study
Lee HJ, Kim HC, Vitek L, Nam MC. Algae consumption and risk of
type 2 diabetes, Korean National Health and Nutrition
Examination Survey in 2005. J Nutri Sci Vitaminol (2010);56:13-18.
3g of Nori in capsule form 15 minutes
before eating decreased glycemic index
of 50g starch bread
12 healthy
volunteers
Goni I, Valdivieso L, Garcia-Alonso A. A Nori seaweed
consumption modifies glycemic response in healthy
volunteers. Nutr Res (2000);20:1367.
Pelvetia siliquosa phlorotannin
(fucosterol) as anti-diabetic
Diabetic rat
model
Lee, Y. S., Shin, K. H., Kim, B. K., & Lee, S. (2004). Anti-diabetic
activities of fucosterol from Pelvetia siliquosa. Archives of
Pharmacal Research, 27, 1120-1122.
Ishige Okamurae phlorotannin
(diphlorecthohydroxycarmalol) as
whitener and anti-diabetic
Mouse model Heo, S. J., Hw ang, J. Y., Choi, J. I., Han, J. S., Kim, H. J., & Jeon, Y. J.
(2009). Diphlorethohydroxycarmalol isolated from Ishige
okamurae, a brown algae, a potent a-glucosidase and a-
amylase inhibitor, alleviates postprandial hyperglycemia in
diabetic
Reference
In vitroEcklonia stolonifera improved glycemic
index in diabetic mouse model
Seaweed species Evidence
(Lam, 2013)

Anti-osteoporosis
Toxicity Efficacy
Seaweed reduces risk of
osteoporosis by 78%
214 Japanese
longitudinal study over 5
years
Nakayama Y, Sakauchi F, Mori M. Risk factors for
osteoporosis in elderly people with a cohort study -
Using calcaneus stiffness as an index. Sapporo Medical
Journal (2008);76:33-40.
(Lam, 2013)

Anti-allergy
Toxicity Efficacy
Seaweed consumption reduces risk for
allergic rhinosinusitis among pregnant
women by 49%
1,002 pregnant
Japanese,
cross sectional
study
MiyakeY, Sasaki S, Ohya Y, Miyamoto S, Matsunaga I,
Yoshida . Dietary Intake of Seaweed and Minerals and
Prevalence of Allergic Rhinitis in Japanese Pregnant
Females: Baseline Data From the Osaka Maternal and
Child Health Study. Ann Epidemiol (2006);16:6
Eisenia arborea phlorotannin
(phlorofucofuroeckol-B) as anti allergy
in vitro (rat
basophile
leukemia (RBL-
2H3) cells
Sugiura, Y., Matsuda, K., Yamada, Y., Nishikaw a, M.,
Shioya, K., Katsuzaki, H., et al. (2007). Anti-Allergic
phlorotannins from the edible brown alga, Eisenia
Arborea. Food Science and Technology Research, 13, 54-
60.
(Lam, 2013)

With
a) Imported hydrocolloid
b) PVP-carrageenan
hydrogel
a
b
Split Thickness
Donor Site
Healing after 7 days
Clinical Testing of PVP-Carrageenan Hydrogel
for Burn/Wound Dressing

0.5% Carrageenan in Vanishing Cream as Treatment for Localized Eczemas
De Guzman, 2005
Dorsum of the left-foot of
54-year old male at baseline
After 1 week of
treatment

Third finger of a 71-year old female at baseline After 1 week of treatment
De Guzman, 2005
0.5% Carrageenan in Vanishing Cream as Treatment for Localized Eczemas

Conclusion
• The marine Environment is a rich source of raw
materials development of health and wellness
products
• Organismic behavior and ecology gives a clue to
product development
• By products of the fishery industryies have to be
developed . Biorefinery of products is key to
optimal utilization

Acknowledgements
• Seaweed Chemistry Staff
• The UP Marine Science Institute
• MSI Marine Plants Group
• DA-Biotech, DA-BFAR, DA-BAR
• BFAR - NFRDI
• DOST

50
They that go down to the sea in ships, that do
business in great work; these see the works
of the Lord, and his wonders in the deep.
Psalm 107:23-24

Industry Situationer and the Bioactive Components of Cosmeceuticals and Pharmaceuticals from Seaweeds : Pharmaceutics / Dr. Marco Nemesio E. Montaño

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Industry Situationer and the Bioactive Components of Cosmeceuticals and Pharmaceuticals from Seaweeds : Pharmaceutics / Dr. Marco Nemesio E. Montaño