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The Application of Rice Oil-derived Phytochemicals
Potential Effect of Rice-derived Compounds on Skin and Muscle
for Functional Foods and Cosmetics
Toru Takarada Ph.D.
Oryza Oil & Fat Chemical Co. Ltd.
ICRBO2018
Oryza Oil & Fat Chemical Co. LTD.
1939 Founded as manufactural rice bran oil company
1980 Began production of γ-Oryzanol
1996 Launched and sold GABA-enriched rice bran extract
1998 Developed rice-derived Tocotrienols
1999 Developed rice-derived Glucosylceramide
Part of corporate history
Office location in worldFounded April 1939
Tokyo
Aichi (HQ)
Kuala Lumpur
Bangkok
Head office
Aichi, JAPAN
Tokyo office
Tokyo, JAPAN
Thailand office
Bangkok, Thailand
Malaysia office
Kuala Lumpur, Malaysia
HO
HO
H3CO
C
H
CHCOOC30H49 HO
H3CO
C
H
CHCOOH
O
R1
HO
R2
R3
CH3
CH3
CH3 CH3 CH3
O
R1
HO
R2
R3
CH3
CH3
CH3 CH3 CH3
OH
OH
OH
HO
HO
OH
CH 3(CH 2)26 CH2 OH
NH2 CH2CH 2CH2COOH
O O
OH
OH
HO
CH2OH
CH2
R
CH CH
OH
CH (CH2)2 CH CH (CH2)8 CH3
C
O
CH
NH
Fattyacid
O
PO
OH
OH
O
PO
OH
OH
O P
O
OH
OH
OP
O
HO
HO
OP
O
HO
HO
O P
O
OH
OH
2. γ- oryzanol 3. Ferulic Acid
4. Tocotrienols 5. Tocopherols
1. Glycosphingolipid
7. Phytosterol 8. Phytic Acid
6. Inositol
9. Octacosanol
10. γ-amino butyric acid 11. Squalane
Health benefiting Ingredients of rice
12. polyamine
13. protein/peptide
Utilization of our extraction and purification technique
Kiwi seed Extract
Cacao Extract
b-Cryptoxanthine
Fucoxanthine
Green Coffee Bean
Extract
Lingonberry
Extract
Maquiberry Extract
Purple Rice
Extract
Sakura
Extract Resveratrol
Water shield Extract
Strawberry Seed
Extract
weight loss
bone care
eye care
anti-aging
skin care
joint care
muscle care
Black ginger
extract
Red ginger
extract
Gamma-Oryzanol
For the symptoms of menopause
Chapter 1
Description Content
Unsaturated Fatty
Acid
Oleic acid 40 ~ 50
Linoleic acid 29 ~ 39
Linolenic acid 0 ~ 1
Fatty Acid Myristic acid 0.4 ~ 1
Palmitic acid 13 ~ 18
Gamma - Oryzanol 1.2 ~ 1.5%
Tocopherols 0.2 ~ 0.4%
Tocotrienols 0.03~0.05%
Acid Value 0.35 max
Saponification Value 180 ~ 195
Iodine value 92 ~ 115
Unsaponification 5.0 max
Composition of Rice Bran Oil
“Rice Bran Oil” Oryza produces
as retail products.
6
Rice bran oil and Phytochemicals –gamma-oryzanol-
Post-menopausal syndrome,
Autonomic nerve disturbance,
Anti-stress
≪Brain≫
Lowering of cholesterol,
Lowering of blood sugar level,
Accumulation of glycogen,
Centrally acting intestinal
movement
Anti-colon cancer
Inhibition of IBS
≪Metabolism, Digestion≫
Elevation of surface temperature,
Activation of sebaceous glands,
Inhibition of melanin formation
≪Skin≫
Anti-ulcer,
Centrally acting stomach movement
≪Stomach≫
Anti-allergy, Anti-inflammation,
Anti-oxidation, Vitamin E-like effect
Pain relief of head, neck, eyes,
shoulder and hip.
≪Whole Body≫
Functional effects
7
Effect of gamma oryzanol on our whole body
Application Dose (mg/day) Treated term Effect
Menopausal
symptoms
5-10 10-38 days
Menopausal index
>50% reduction
90 14 days
Menopausal symptoms
76.6% improved
15-30 7-14 days
Autonomic dysfunction
70-90% improved
300 4-8 weeks
Subjective symptoms
>80% improved
Serum peroxylipid
Significantly improved
Improve menopausal symptoms
http://www.oryza.co.jp/html/english/pdf/ORYZAN
OL%203.1TK.pdf
8
Improvement of menopausal symptoms by γ-Oryzanol intake
OTC Drug in JapanEnd product
For Menopause in the overseas
For Athlete & Muscle builder in the overseas
For Cosmetics in the overseas
Tocotrienols
Lowering LDL cholesterol
Chapter 2
“Rice Bran Oil” Oryza produces
as retail products.
12
Rice bran oil and Phytochemicals –Tocotrienols-
Description Content
Unsaturated Fatty
Acid
Oleic acid 40 ~ 50
Linoleic acid 29 ~ 39
Linolenic acid 0 ~ 1
Fatty Acid Myristic acid 0.4 ~ 1
Palmitic acid 13 ~ 18
Gamma - Oryzanol 1.2 ~ 1.5%
Tocopherols 0.2 ~ 0.4%
Tocotrienols 0.03~0.05%
Acid Value 0.35 max
Saponification Value 180 ~ 195
Iodine value 92 ~ 115
Unsaponification 5.0 max
Composition of Rice Bran Oil
Tocotrienols
Benefits of Tocotrienols
Cholesterol
Lowering
Anti-Aging
Dipigmentation
Anti-Oxidation
Anti-Fatiuge
Anti-Cancer
Prevents
Atherosclerosis
Tocotrienol has various benefits for health
≪Method≫
Subjects; 18 subjects per group (90 hypercholesteremic patients)
Sample; the tocotrienol-rich fraction (TFR) of rice bran
Intake duration; 35 days
Qureshi A.A et al., Atherosclerosis, 161, 199-207 (2002)
0
20
40
60
80
100
Control 25mg/day 50mg/day 100mg/day 200mg/day
Total Cholestrol(mmol/L)
LDL-Cholesterol(mmol/L)
100mg/day group was highly effective against lowering of cholesterol
Cholesterol Lowering Effect
Total-Cholesterol (mmol/L)
LDL-Cholesterol (mmol/L)
Our Customer‘s Products (Food and Cosmetics: Japan)
Our Customer‘s Products (Food and Cosmetics: Overseas)
ORYZA CERAMIDE®
Pioneer of 1st Edible Ceramide
As Excellent Skin Rejuvenator
Chapter 3
ORYZA CERAMIDE®
Oryza Ceramide®
Appearance: Light yellowish powder
Contents of Glycosphingolipid: Min. 3.0%
Oryza ceramide-PT
Application of our ORYZA CERAMIDE®
Our Customer‘s Products (Food: Japan)
Our Customer‘s Products (Cosmetics: Japan)
Thailand
New Zealand
Taiwan
IndonesiaMalaysia
Vietnam
China
USA
Our Customer‘s Products (overseas)
Lipid Composition in Human Stratum Corneum
Imokawa G, J. Dermatol. Sci. 55, 1, (2009)
Ceramides (Cer)
Sphingomyerine Glucosylceramides (GlcCer)
Stratum
corneum
S. Granurosum
S. spinosum
Ceramides (Cer)
UV
dehydration
infection
Ceramides (Cer) and Glucosylceramides (GlcCer) in Epidermis
S. basal
Ceramide species in stratum corneum
TLC
Human stratum corneum
isolated by tape stripping
Std
CER1
EOS
CER2
NS
CER3
NP
CER4
EOH
CER5
AS
CER6
AP
CER7
AH
CER8
NH
CER9
EOP
9 types of ceramide species
Ceramidecontents/corneum(µg/mg)
0
1 0
2 0
3 0
4 0
5 0
6 0
9 07 05 03 01 0
●
●
●
●
●
●
● ●
●
●
●
●
●
●●
●
●●
●
●
●
●
●
●
●
●
●
●
●
●
●
●●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●●
●
●
●
●
Age
Senile xerosis
http://www.tonbyo.org/contents/series/2009_04.html
Atopic dermatitis
https://www.dermquest.com/image-library/
Depletion of skin ceramide causes skin dysfunctions
Age-related Decrease in Skin Ceramide
Imokawa G, J. Invest. Dermatol. 6, 523 (1991)
Effect of Rice–derived Glucosylceramide in Mouse Skin
Mice: Hos, HR-1, male,6 wks old
Sample: Rice-derived GlcCer (GCFr)
Skin irritant: Sodium dodecyl sulfate (SDS)
Mean with S.E. (n=5-6),
*: p<0.05, **: p<0.01 vs control
Protocol & Results
TEWL(Δg/m2/hr)
0
2
4
6
8
10
Norm Cont 3 10 (mg/kg/day)
GCFr
● ●
Sample p.o.
Day1 9 12 16
SDS treatment
TEWL (trans epidermal water loss)
Skin
evaluation
Rice-derived GlcCer improves skin function and increases ceramide production
■: Cer EOS ■: Cer NS, NDS
Shimoda H, et al. J. Med. Food 15, 1064-72 (2012)
β-Sitosterol-3-O-glucoside (BSG) in Oryza Ceramide®
Does BSG influence the ceramide
production?
This joint study with Dr. Imokawa (Chubu University) was supported by
the subsidies “Agricultural business subsidies” from Ogaki-Kyoritsu Bank in 2015.
stigmast-5-en-3-O-β-d-glucopyranoside
β-sitosterol-3-O-glucoside (BSG)
1 2
GlcCer
BSG
1 : GlcCer std
2 : Oryza Ceramide®
3 : rice ceramide (company A)
4 : rice ceramide (company B)
Oryza Ceramide®
3 4
We have identified the function of BSG
for the first time in the world
Oryza ceramide®︎ is
the largest amount of BSG
200
250
300
350
400
TotalCer
(μg/mgprotein)
*
Ceramide Contents in Stratum Corneum (in vitro)
Mean±SE (n=5-6)
* :P < 0.05
0
5
10
15
20
25
30
35
Cer
[EOS]
Cer
[NP]
Cer
[EOH]
Cer
[AS]
Cer
[NH]
Cer
[AP]
Cer
[AH]
CerspeciesinSC
(μg/mgprotein)
Control
1 μg/mL
3 μg/mL
10 μg/mL
BSG(µg/ml)
BSG enhances the production of total ceramide and Cer[EOS]
Total ceramide
Cer
[NDS, NS]
Ceramide spiecies
Cont 1 3 10
0
50
100
150
200
250
*
Design of clinical test; Double blind trial
Subjects: 33 (6 Male, 27 Female, average aged 25.1±7.8)
Dosage: Ceramide 40mg/day, Placebo 0mg/day
Duration: 6 weeks
Area of examination: whole body, left lower eye area, back area of neck, left upper arm inner area
Human Clinical Trials
•Collaboration with Dermatology Division, Medical Department, Osaka University & Medical Science Research Centre
水分量(%)
40
50
60
70
80
摂取前 3週間後 6週間後
Ceramide
Placebo
** p< 0.01
左眼下部水分量の推移 頚背部SEscの推移
皮膚剥離(+)
かさつき(+)
潤い(+)
なめらかさ( +)
摂取前 3週間後 6週間後
SEscIndex
50
40
45
Ceramide
Placebo
*P<0.05
オ リ ザ セ ラ ミ ド の 臨 床 効 果
Changes of Moisture content
on lower left eye area
Changes of SE sc value
at the back of neck area
Moisture(%)
Bef. T’ment 3- week 6-week Bef. T’ment 3- week 6-week
Dry scaly
skin (+)
Moisturised
skin (+)
Ceramide
Placebo
Ceramide
Placebo
SEscindex
Before After
3D Microscopic Illustration of skin surface before and after treatment of
Oryza Ceramide (oral) on the lower left eye area of a 23-yr old female
Effect of Oryza Ceramide : Clinical Trial
Summary -Oryza Ceramide®
ORYZA CERAIDE®
Glicosylceramide
Ceramide
Β-Sitosterol-O-glucoside
Sugar
epidermis
Stratum
corneum
Enhancement of
ceramide synthesis
Enhancement of
ceramide synthesis
Promotion of
ceramide transport
FERMENTED RICE GERM EXTRACT
Rice germ fermentation process
Potential effect of rice derived phytochemicals
Chapter 4
Rice Germ
endosperm
Active ingredients
• γ-Orizanol
• Ferulic acid
• Sterol
Fermented rice germ extract
Rice bran
Aspergillus oryzae
Fermentation of rice germ by
Aspergillus oryzae
• Tocotrienol
• Tocopherol
• GABA
Fermented rice germ extract (FRGE)
Appearance: slightly brown powder
Contents of polyphenols: Min. 3.0%
Fermented rice germ extract-P
(our product)
Immunostimulatory activity of fermented rice germ extract
• Prevention against infection
phagocytotic activity
of macrophages
• Anti-cancer effect
NK cells activities
(cytotoxic lymphocyte)
Effect of fermented rice germ extract on muscular function and performance
Next
Collaboration study with Sugiyama
Jogakuen University, Aichi, Japan .
Structure determination
Collaboration study with Osaka City
University, Aichi, Japan .
Bioactivity assay
0
0.25
0.5
0.75
1
1.25
1.5
0 1 3 10 30 100 1 3 10 30 100
Relativeab560
Effect of fermented rice germ extract on myotube maturation
Myoblast proliferation
Myotube differentiation
fermentation (+) fermentation (-)
**
** ** ** *
**
(μg / mL)
Mean ± S.E. (n=6)
* P < 0.05, ** P < 0.01,
0
1
10
FRGE(µg/mL)
fast-MHC slow-MHC DAPI
0 10
FRGE(µg/mL)
myotubesize
0
1
2
3
4
**
*
**
0
1
2
3
4
1
10
μg/mL
**
* *
RelativemRNAexpression
(Myh/GAPDH)
- 1 2 3 4 5
Compound
RelativemRNAexpression
(Myo/GAPDH)
- 1 2 3 4 5
Compound
N.D
N.D
Mean ± S.E. (n=4), * P < 0.05, ** P < 0.01.
HO
Stigmasterol (1, 0.18%)
HO
O
O
Ergosterol 5α,8α-epidioxide(2, 0.014%)
(R)
(R)
(Z)
(R)
(R)
(R)
(R)
O
(R)
(S)
HO
HO
OH
O
(S)
(S)
OH
β-sitosterol-3-O-glucoside(4, 0.005%) [GlcCer (d18:2)] (5, 0.005%)
Effect of fermented rice germ extract on myotube maturation
GlcCer(d18:2) enhances the expression of muscle maturation marker
0
1
2
3
4
5
Control 100 500
Score
(mg /kg, p.o.)
5 60 seconds and reach edge
4 46-60 seconds
3 31-45 seconds
2 16-30 seconds
1 5-15 seconds
Horizontal bar test
Means ± S.E.M. (n = 14-18).
0
20
40
60
80
100
120
140
Control 100 500
Gripstrength(g)
*
*
Means ± S.E.M.
*; p < 0.05 vs. Control (n = 6-9).
Grip strength test
0
50
100
150
200
Control 100 500
Muscleweight(mg)
*
Muscle weight
Means ± S.E.M.
*; p < 0.05 vs. Control (n = 8-10).
Control 100 500
FRGE
(mg /kg, p.o.)
Effect of FRGE on muscle strength and muscle mass
(mg /kg, p.o.) (mg /kg, p.o.)
Tanaka M, et al. J. Med. Food 20, 969-80 (2017)Collaboration study with Gifu Pharmaceutical University , Gifu, Japan .
Summary
moisture
Enzyme
production
Ceramide
amount
Skin Muscle
Cell proliferation
Muscle size
Muscle strength
ORYZA
CERAMIDE®️
Fermented
Rice germ extractGlucosylceramide
GlcCer derived from rice is a promising phytochemical
to exert skin and muscular health benefits.
Improvement of skin and muscular function by rice-derived glcosylceramide
#61K

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  • 1. The Application of Rice Oil-derived Phytochemicals Potential Effect of Rice-derived Compounds on Skin and Muscle for Functional Foods and Cosmetics Toru Takarada Ph.D. Oryza Oil & Fat Chemical Co. Ltd. ICRBO2018
  • 2. Oryza Oil & Fat Chemical Co. LTD. 1939 Founded as manufactural rice bran oil company 1980 Began production of γ-Oryzanol 1996 Launched and sold GABA-enriched rice bran extract 1998 Developed rice-derived Tocotrienols 1999 Developed rice-derived Glucosylceramide Part of corporate history Office location in worldFounded April 1939 Tokyo Aichi (HQ) Kuala Lumpur Bangkok Head office Aichi, JAPAN Tokyo office Tokyo, JAPAN Thailand office Bangkok, Thailand Malaysia office Kuala Lumpur, Malaysia
  • 3. HO HO H3CO C H CHCOOC30H49 HO H3CO C H CHCOOH O R1 HO R2 R3 CH3 CH3 CH3 CH3 CH3 O R1 HO R2 R3 CH3 CH3 CH3 CH3 CH3 OH OH OH HO HO OH CH 3(CH 2)26 CH2 OH NH2 CH2CH 2CH2COOH O O OH OH HO CH2OH CH2 R CH CH OH CH (CH2)2 CH CH (CH2)8 CH3 C O CH NH Fattyacid O PO OH OH O PO OH OH O P O OH OH OP O HO HO OP O HO HO O P O OH OH 2. γ- oryzanol 3. Ferulic Acid 4. Tocotrienols 5. Tocopherols 1. Glycosphingolipid 7. Phytosterol 8. Phytic Acid 6. Inositol 9. Octacosanol 10. γ-amino butyric acid 11. Squalane Health benefiting Ingredients of rice 12. polyamine 13. protein/peptide
  • 4. Utilization of our extraction and purification technique Kiwi seed Extract Cacao Extract b-Cryptoxanthine Fucoxanthine Green Coffee Bean Extract Lingonberry Extract Maquiberry Extract Purple Rice Extract Sakura Extract Resveratrol Water shield Extract Strawberry Seed Extract weight loss bone care eye care anti-aging skin care joint care muscle care Black ginger extract Red ginger extract
  • 5. Gamma-Oryzanol For the symptoms of menopause Chapter 1
  • 6. Description Content Unsaturated Fatty Acid Oleic acid 40 ~ 50 Linoleic acid 29 ~ 39 Linolenic acid 0 ~ 1 Fatty Acid Myristic acid 0.4 ~ 1 Palmitic acid 13 ~ 18 Gamma - Oryzanol 1.2 ~ 1.5% Tocopherols 0.2 ~ 0.4% Tocotrienols 0.03~0.05% Acid Value 0.35 max Saponification Value 180 ~ 195 Iodine value 92 ~ 115 Unsaponification 5.0 max Composition of Rice Bran Oil “Rice Bran Oil” Oryza produces as retail products. 6 Rice bran oil and Phytochemicals –gamma-oryzanol-
  • 7. Post-menopausal syndrome, Autonomic nerve disturbance, Anti-stress ≪Brain≫ Lowering of cholesterol, Lowering of blood sugar level, Accumulation of glycogen, Centrally acting intestinal movement Anti-colon cancer Inhibition of IBS ≪Metabolism, Digestion≫ Elevation of surface temperature, Activation of sebaceous glands, Inhibition of melanin formation ≪Skin≫ Anti-ulcer, Centrally acting stomach movement ≪Stomach≫ Anti-allergy, Anti-inflammation, Anti-oxidation, Vitamin E-like effect Pain relief of head, neck, eyes, shoulder and hip. ≪Whole Body≫ Functional effects 7 Effect of gamma oryzanol on our whole body
  • 8. Application Dose (mg/day) Treated term Effect Menopausal symptoms 5-10 10-38 days Menopausal index >50% reduction 90 14 days Menopausal symptoms 76.6% improved 15-30 7-14 days Autonomic dysfunction 70-90% improved 300 4-8 weeks Subjective symptoms >80% improved Serum peroxylipid Significantly improved Improve menopausal symptoms http://www.oryza.co.jp/html/english/pdf/ORYZAN OL%203.1TK.pdf 8 Improvement of menopausal symptoms by γ-Oryzanol intake
  • 9. OTC Drug in JapanEnd product For Menopause in the overseas
  • 10. For Athlete & Muscle builder in the overseas For Cosmetics in the overseas
  • 12. “Rice Bran Oil” Oryza produces as retail products. 12 Rice bran oil and Phytochemicals –Tocotrienols- Description Content Unsaturated Fatty Acid Oleic acid 40 ~ 50 Linoleic acid 29 ~ 39 Linolenic acid 0 ~ 1 Fatty Acid Myristic acid 0.4 ~ 1 Palmitic acid 13 ~ 18 Gamma - Oryzanol 1.2 ~ 1.5% Tocopherols 0.2 ~ 0.4% Tocotrienols 0.03~0.05% Acid Value 0.35 max Saponification Value 180 ~ 195 Iodine value 92 ~ 115 Unsaponification 5.0 max Composition of Rice Bran Oil
  • 14. ≪Method≫ Subjects; 18 subjects per group (90 hypercholesteremic patients) Sample; the tocotrienol-rich fraction (TFR) of rice bran Intake duration; 35 days Qureshi A.A et al., Atherosclerosis, 161, 199-207 (2002) 0 20 40 60 80 100 Control 25mg/day 50mg/day 100mg/day 200mg/day Total Cholestrol(mmol/L) LDL-Cholesterol(mmol/L) 100mg/day group was highly effective against lowering of cholesterol Cholesterol Lowering Effect Total-Cholesterol (mmol/L) LDL-Cholesterol (mmol/L)
  • 15. Our Customer‘s Products (Food and Cosmetics: Japan) Our Customer‘s Products (Food and Cosmetics: Overseas)
  • 16. ORYZA CERAMIDE® Pioneer of 1st Edible Ceramide As Excellent Skin Rejuvenator Chapter 3
  • 17. ORYZA CERAMIDE® Oryza Ceramide® Appearance: Light yellowish powder Contents of Glycosphingolipid: Min. 3.0% Oryza ceramide-PT Application of our ORYZA CERAMIDE®
  • 18. Our Customer‘s Products (Food: Japan) Our Customer‘s Products (Cosmetics: Japan)
  • 20. Lipid Composition in Human Stratum Corneum Imokawa G, J. Dermatol. Sci. 55, 1, (2009) Ceramides (Cer) Sphingomyerine Glucosylceramides (GlcCer) Stratum corneum S. Granurosum S. spinosum Ceramides (Cer) UV dehydration infection Ceramides (Cer) and Glucosylceramides (GlcCer) in Epidermis S. basal
  • 21. Ceramide species in stratum corneum TLC Human stratum corneum isolated by tape stripping Std CER1 EOS CER2 NS CER3 NP CER4 EOH CER5 AS CER6 AP CER7 AH CER8 NH CER9 EOP 9 types of ceramide species
  • 22. Ceramidecontents/corneum(µg/mg) 0 1 0 2 0 3 0 4 0 5 0 6 0 9 07 05 03 01 0 ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● Age Senile xerosis http://www.tonbyo.org/contents/series/2009_04.html Atopic dermatitis https://www.dermquest.com/image-library/ Depletion of skin ceramide causes skin dysfunctions Age-related Decrease in Skin Ceramide Imokawa G, J. Invest. Dermatol. 6, 523 (1991)
  • 23. Effect of Rice–derived Glucosylceramide in Mouse Skin Mice: Hos, HR-1, male,6 wks old Sample: Rice-derived GlcCer (GCFr) Skin irritant: Sodium dodecyl sulfate (SDS) Mean with S.E. (n=5-6), *: p<0.05, **: p<0.01 vs control Protocol & Results TEWL(Δg/m2/hr) 0 2 4 6 8 10 Norm Cont 3 10 (mg/kg/day) GCFr ● ● Sample p.o. Day1 9 12 16 SDS treatment TEWL (trans epidermal water loss) Skin evaluation Rice-derived GlcCer improves skin function and increases ceramide production ■: Cer EOS ■: Cer NS, NDS Shimoda H, et al. J. Med. Food 15, 1064-72 (2012)
  • 24. β-Sitosterol-3-O-glucoside (BSG) in Oryza Ceramide® Does BSG influence the ceramide production? This joint study with Dr. Imokawa (Chubu University) was supported by the subsidies “Agricultural business subsidies” from Ogaki-Kyoritsu Bank in 2015. stigmast-5-en-3-O-β-d-glucopyranoside β-sitosterol-3-O-glucoside (BSG) 1 2 GlcCer BSG 1 : GlcCer std 2 : Oryza Ceramide® 3 : rice ceramide (company A) 4 : rice ceramide (company B) Oryza Ceramide® 3 4 We have identified the function of BSG for the first time in the world Oryza ceramide®︎ is the largest amount of BSG
  • 25. 200 250 300 350 400 TotalCer (μg/mgprotein) * Ceramide Contents in Stratum Corneum (in vitro) Mean±SE (n=5-6) * :P < 0.05 0 5 10 15 20 25 30 35 Cer [EOS] Cer [NP] Cer [EOH] Cer [AS] Cer [NH] Cer [AP] Cer [AH] CerspeciesinSC (μg/mgprotein) Control 1 μg/mL 3 μg/mL 10 μg/mL BSG(µg/ml) BSG enhances the production of total ceramide and Cer[EOS] Total ceramide Cer [NDS, NS] Ceramide spiecies Cont 1 3 10 0 50 100 150 200 250 *
  • 26. Design of clinical test; Double blind trial Subjects: 33 (6 Male, 27 Female, average aged 25.1±7.8) Dosage: Ceramide 40mg/day, Placebo 0mg/day Duration: 6 weeks Area of examination: whole body, left lower eye area, back area of neck, left upper arm inner area Human Clinical Trials •Collaboration with Dermatology Division, Medical Department, Osaka University & Medical Science Research Centre 水分量(%) 40 50 60 70 80 摂取前 3週間後 6週間後 Ceramide Placebo ** p< 0.01 左眼下部水分量の推移 頚背部SEscの推移 皮膚剥離(+) かさつき(+) 潤い(+) なめらかさ( +) 摂取前 3週間後 6週間後 SEscIndex 50 40 45 Ceramide Placebo *P<0.05 オ リ ザ セ ラ ミ ド の 臨 床 効 果 Changes of Moisture content on lower left eye area Changes of SE sc value at the back of neck area Moisture(%) Bef. T’ment 3- week 6-week Bef. T’ment 3- week 6-week Dry scaly skin (+) Moisturised skin (+) Ceramide Placebo Ceramide Placebo SEscindex
  • 27. Before After 3D Microscopic Illustration of skin surface before and after treatment of Oryza Ceramide (oral) on the lower left eye area of a 23-yr old female Effect of Oryza Ceramide : Clinical Trial
  • 28. Summary -Oryza Ceramide® ORYZA CERAIDE® Glicosylceramide Ceramide Β-Sitosterol-O-glucoside Sugar epidermis Stratum corneum Enhancement of ceramide synthesis Enhancement of ceramide synthesis Promotion of ceramide transport
  • 29. FERMENTED RICE GERM EXTRACT Rice germ fermentation process Potential effect of rice derived phytochemicals Chapter 4
  • 30. Rice Germ endosperm Active ingredients • γ-Orizanol • Ferulic acid • Sterol Fermented rice germ extract Rice bran Aspergillus oryzae Fermentation of rice germ by Aspergillus oryzae • Tocotrienol • Tocopherol • GABA Fermented rice germ extract (FRGE) Appearance: slightly brown powder Contents of polyphenols: Min. 3.0% Fermented rice germ extract-P (our product)
  • 31. Immunostimulatory activity of fermented rice germ extract • Prevention against infection phagocytotic activity of macrophages • Anti-cancer effect NK cells activities (cytotoxic lymphocyte) Effect of fermented rice germ extract on muscular function and performance Next Collaboration study with Sugiyama Jogakuen University, Aichi, Japan . Structure determination Collaboration study with Osaka City University, Aichi, Japan . Bioactivity assay
  • 32. 0 0.25 0.5 0.75 1 1.25 1.5 0 1 3 10 30 100 1 3 10 30 100 Relativeab560 Effect of fermented rice germ extract on myotube maturation Myoblast proliferation Myotube differentiation fermentation (+) fermentation (-) ** ** ** ** * ** (μg / mL) Mean ± S.E. (n=6) * P < 0.05, ** P < 0.01, 0 1 10 FRGE(µg/mL) fast-MHC slow-MHC DAPI 0 10 FRGE(µg/mL) myotubesize
  • 33. 0 1 2 3 4 ** * ** 0 1 2 3 4 1 10 μg/mL ** * * RelativemRNAexpression (Myh/GAPDH) - 1 2 3 4 5 Compound RelativemRNAexpression (Myo/GAPDH) - 1 2 3 4 5 Compound N.D N.D Mean ± S.E. (n=4), * P < 0.05, ** P < 0.01. HO Stigmasterol (1, 0.18%) HO O O Ergosterol 5α,8α-epidioxide(2, 0.014%) (R) (R) (Z) (R) (R) (R) (R) O (R) (S) HO HO OH O (S) (S) OH β-sitosterol-3-O-glucoside(4, 0.005%) [GlcCer (d18:2)] (5, 0.005%) Effect of fermented rice germ extract on myotube maturation GlcCer(d18:2) enhances the expression of muscle maturation marker
  • 34. 0 1 2 3 4 5 Control 100 500 Score (mg /kg, p.o.) 5 60 seconds and reach edge 4 46-60 seconds 3 31-45 seconds 2 16-30 seconds 1 5-15 seconds Horizontal bar test Means ± S.E.M. (n = 14-18). 0 20 40 60 80 100 120 140 Control 100 500 Gripstrength(g) * * Means ± S.E.M. *; p < 0.05 vs. Control (n = 6-9). Grip strength test 0 50 100 150 200 Control 100 500 Muscleweight(mg) * Muscle weight Means ± S.E.M. *; p < 0.05 vs. Control (n = 8-10). Control 100 500 FRGE (mg /kg, p.o.) Effect of FRGE on muscle strength and muscle mass (mg /kg, p.o.) (mg /kg, p.o.) Tanaka M, et al. J. Med. Food 20, 969-80 (2017)Collaboration study with Gifu Pharmaceutical University , Gifu, Japan .
  • 35. Summary moisture Enzyme production Ceramide amount Skin Muscle Cell proliferation Muscle size Muscle strength ORYZA CERAMIDE®️ Fermented Rice germ extractGlucosylceramide GlcCer derived from rice is a promising phytochemical to exert skin and muscular health benefits. Improvement of skin and muscular function by rice-derived glcosylceramide