Key Research Areas
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blockquote HLscience’s Key Researchblockquote

Climacteria : Pomegranate concentrate [P-estro HL]
Skin health : Pomegranate concentrate [P-estro BL]

Research background

This is the background of the research on functional pomegranate concentrate (P-estro HL) used to improve menopausal symptoms

The need for menopausal care

Female hormones begin decreasing from age 35

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Short-&long-term consequences of menopause

years Menopausal symptoms Occurrence rate(%)
-2 Vasomotor disorders 60~70
1 Psychological/mental symptoms 20~30
5 Shrinkage of urogenital organs 20~30
7 Osteoporosis 25~35
10 Arteriosclerosis Increases with age
20 Alzheimer’s dementia Increases with age

Incidence of climacteric symptoms in Korean Women

Climacteric symptoms Frequency(%)
Flushing from heat 61
Forgetfulness 48
Heart acceleration 47
Muscle pains / joint pains 46
Perspiration 44
Depression 39
Dryness of skin 35
Frequent urination 28
Sleep disorder 28
Dyspareunia/discomfort 22
Urinary incontinence 16
Formication 12

The need for safe climacteric symptom materials

  • The long-term clinical trials of female hormone therapy by WHI (Women’s Health Initiative) in 2002 was halted due to severe side effects including breast cancer (26%), heart attacks (29%), strokes (41%), and cardiovascular diseases. It was recommended that long term administration be prohibited (Journal of the American Medical Association. 288(3):321-333)
  • Phytoestrogen: Does not combine with Estrogen receptor α, and it only gets involved with Estrogen receptor β. It does not have side effects such as increasing the incidence of breast cancer. A safe substance that can help in only improving climacteric symptoms needs to be developed.
phytoestrogen
hERα hERβ
17β-Estradiol 100 100
Coumestans Coumestrol 20 140
Isoflavonoids Genistein 4 87
Daidzein 0.1 0.5
Formononetin <0.1 <0.01
Biochanin A <0.1 <0.01
Flavonoids Apigenin 0.3 6
Naringenin 0.01 0.11

Evaluation of effectiveness and safety of improving climacteric and menopausal symptoms

HLscience’s core technology verified by clinical trials

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  • Clinical trials
  • 8 weeks oral administration
  • Targeted 62 local climacteric women
  • Random double-blind placebo–control group human application experiment
  • Functional pomegranate concentrate (ellagic acid 2.4mg/g) 10ml/day
  • Carried out human application experiments in local university hospitals
  • Improvements in the Kupperman Index (KI), menopause rating scale (MRS), and safety (Estradiol level in blood) verified

Experiment design

60 local climacteric women underwent 8 weeks of the human application experiment of functional pomegranate concentrate (P-estro HL) in local university hospitals (random double-blind placebo-control group human application experiment). This experiment verified improvements in the Kupperman Index, MRS, and safety (Estradiol level in blood).

Significant improvements in Kupperman Index verified after 4 weeks

Improvements in all 11 index items (facial flushing, perspiration, insomnia, ill temper, depression, vertigo, fatigue, joint/muscle pain, headache, heart palpitation, vaginal dryness)

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Improvement in menopause rating scale (MRS)

Significant improvements verified after 4 weeks

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Safety

No allergies or changes in concentration of estradiol level in blood after 8 weeks of the human application experiment.

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Climacteric symptoms improvement effects through climacterium induced animal subjects

Climacteric symptoms improvement effects were verified in the OVX-rat model through “weight change, abdominal fat, osteoporosis prevention (BMD, Osteocalcin, bALP), blood cholesterol improvement” according to 12 weeks of oral administration of functional pomegranate concentrate (P-estro HL).

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  • Climacteric symptoms improvement effects through climacterium induced animal subjects
  • OVX-rat model, 12 weeks of oral administration
  • Changes in weight and abdominal fat volume, Osteoporosis prevention(BMD, Osteocalcin, bALP), Improvement in blood cholesterol

Changes in weight and abdominal fat volume

Animal subjects induced with climacterium showed an increase in weight and abdominal fat. After 12 weeks of oral administration of functional pomegranate concentrate (P-estro HL), a significant reduction in weight and abdominal fat (by 57.56%) was verified.

Abdominal Fat Pad in Sham-operated or OVX ddY mice

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FIGURE 6. Representative Gross Images of Abdominal Fat Pads, Taken from Sham-operated or OVX ddY Mice Deposited in Abdominal Cavity

a. Sham, b.OVX, c.Estradiol, d.PCP 1ml, e.PCP 2ml, f. PCP 4ml

Osteoporosis prevention

BMD, femur strength improvement

As osteoporosis progresses in the climacterium induced subjects, minerals in the bones decrease and lower the BMD value. Oral administration of pomegranate concentrate resulted in significant improvements in BMD as well as femur strength.

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Improvement in blood osteocalcin and bALP concentration

The concentration of blood osteocalcin increases in the climacterium induced subjects as a result of the inducement while the concentration of bALP fell. After 12 weeks of oral administration of functional pomegranate concentrate, the concentration of blood osteocalcin was significantly reduced while the concentration of bALP was significantly increased.

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OVX = Bilateral ovariectomy
PCS = Pomegranate Concentrated Solution

a p < 0.01 as compared with sham control by MW test
b p < 0.01 as compared with OVX control by MW test

Improvement in blood cholesterol

Climacterium induced subjects showed a decrease in the concentration of blood estrogen, an increase in the concentration of TC, LDL, and TG in the blood, and a decrease in the concentration of HDL. This shows the same results as those in a recently published research paper: the content of blood cholesterol increases as climacterium progresses. After 12 weeks of oral administration of functional pomegranate concentrate to the climacterium induced subjects, the concentrations of TC, LDL, and TG decreased significantly while the concentration of HDL increased significantly.

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Values are expressed mean ± S.D. of eight mice

a p < 0.01 as compared with sham control by LSD test
b p < 0.01 and c p < 0.05 as compared with OVX control by LSDtest
d p < 0.01 as compared with sham control by MWtest
e p < 0.01andfp < 0.05 as compared with OVX control by MWtest

Research Results

The following are the research results of the functional pomegranate concentrate (P-estro HL) used for climacterium improvement.

Patent

Title Region Patent No.
Pomegranate extract with high ellagic acid content whose effects for alleviating climacteric symptoms have been improved Local No. 10-1272602
Pomegranate extract with high ellagic acid content whose effects for alleviating anxiety disorder, depression, or difficulty in concentrating have been improved Local No. 10-11432550000
Pomegranate extract having a high ellagic acid content, and use of Pomegranate extract China
Pomegranate extract having a high ellagic acid content, and use of the Pomegranate extract USA NO. 8986749

Research Background

This is the background of the research regarding the composite (P-estro BL) used for improving skin.

Aging skin

There are two causes of aging skin: endogenous and exogenous. Ultraviolet rays that cause photoaging are the main examples of exogenous aging: long hours under sunlight lead to pigmentation, dryness of skin, decreased elasticity, sagging skin, and fine/coarse wrinkles. Endogenous aging results in relatively minor fine wrinkles in areas not exposed to sunlight.

The skin is made up of the epidermis, dermis, and hypodermis, which consist of keratinocyte, fibroblast, melanocyte, collagen, elastin, and hyaluronic acid. Hyaluronic acid can collect more than 1,000 times its weight in water to supply moisture inside the skin, while collagen and elastin improves the wrinkles and elasticity of the skin.

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< Skin tissue >

Evaluation of effectiveness on skin health of functional pomegranate concentrate (P-estro BL) through cellular experiments

Increase in skin moisture through increase (by 400%) of hyaluronic acid synthesis

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Suppression of collagenase inhibitor (98%) verified

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Suppression of elastin inhibitor (35%) verified

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Suppression of melanin synthesis (38%) verified

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Ultraviolet irradiation

The degree of wrinkle improvement of skin wrinkle inducement and pomegranate concentrate was verified through the replica method.

Animal testing

Verified the effects of wrinkle improvement and moisture content after 10 weeks of orally administering pomegranate concentrate in animal subjects induced with photoaging with UVB

Wrinkle improvement effect

TThe effects of wrinkle improvement following the administration of pomegranate concentrate were verified as having significantly improved the depth of wrinkles.

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Comparison in skin replica of SKH-1 hairless mice. Images of replica were produced using Visioline VL-650. (A-I) Total wrinkle area, percentage of wrinkle area, number of wrinkle, total length, mean length, wrinkle depth, mean depth, max wrinkle depth, and mean form factorwere analyzed. UVB, ultraviolet B; PCS, Pomegranate Concentrated Solution. a p<0.001, b p<0.01, c p

Evaluation of skin moisturizing, elasticity, wrinkles, and whitening effects

healthlove-research-bg-03-text
  • Clinical experiments
  • 8 weeks of oral administration
  • Targeted 60 local women between the ages of 25~60 (moisture content index less than a factor of 49)
  • Random double-blind placebo-control human application experiment
  • Functional pomegranate concentrate (P-estro BL, ellagic acid 2.4mg/g) 10ml/day
  • Human application experiments carried out in local university hospitals
  • Skin elasticity, skin moisture content, and skin color verified

Changes in amount of dead skin cells (face)

Reduction in amount of dead skin cells verified: Reduced by 14.5%

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(Mean±SEM, *p < 0.05 vs. before application.)

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Changes in facial moisture content

Skin moisture verified: Facial moisture content increased by 13.13%

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(Mean±SEM, *p < 0.05 vs. before application.)

Changes in skin elasticity (overall elasticity)

Skin elasticity improvement: Significant elasticity improvement verified from 4 weeks

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(Mean±SEM, *p < 0.05 vs. before application.)

Changes in crow’s feet

Wrinkle improvement effect verified: Crow’s feet improvement verified

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(Mean±SEM, *p < 0.05 vs. before application.)

Changes in skin color (L*value)

Whitening effect verified through significant increase in L value from 4 weeks

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(Mean±SEM, *p < 0.05 vs. before application.)

Research results

Functional pomegranate concentrate (P-estro BL) exhibited effectiveness in increasing moisture content in skin and decreasing the amount of dead skin cells by increasing the hyaluronic acid synthesis of the skin. Increased elasticity has also been verified through the suppression of elastin inhibitors and wrinkle improvement through the suppression of collagen being broken down inside the skin. When wrinkles were increased, the elasticity also decreased due to ultraviolet rays. Skin whitening effects were also verified through the suppression of melanin synthesis.

Published research paper

Title Publishing organization Research paper no.
Effects of pomegranate concentrate on improving wrinkles caused by photoaging Korean Journal of Oriental Preventive Medicine 19(1).109-116(2015)
Inhibitory effects of pomegranate concentrated solution on the activities of hyaluronidase, tyrosinase, and metallopoteinase1. The journal of cosmetic science(2015)