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R&D

Amber Biotechnology
The history of amber research and its results will be unraveled.

Keiji Kondo
琥珀バイオテクノロジー株式会社 非常勤取締役

Few in the world have been able to scientifically demonstrate what amber does and how it works."

Amber Biotechnology began its history of amber research as a challenge to the totally "unknown" and has now acquired a vast amount of research results and knowledge about amber. Our first efforts in basic amber research were the development of succinic powder. We developed a new amber pulverization technique to make the powder even finer than the powder used for amber therapy in Russia. We succeeded in creating a finer, smoother powder that could be used in cosmetics. In 2005, this powder was granted patents (Patent No. 3725848 and No. 3741429) as KOHAKU POWDER® (PD) for "prevention of fading of natural pigments in cosmetics. In addition, the start of joint research on amber with the (now) National Institute of Physical and Chemical Research (RIKEN) greatly accelerated our research on the extraction and purification of active ingredients.

We went through a lot of trial and error to figure out what to soak, at what temperature, for how long, and what ingredients to extract."

The "skin turnover promotion effect (2008)" and "hyaluronic acid production promotion effect (2009)," which contribute to the creation of beautiful skin, were first discovered through the painstaking extraction of extracts using fine amber powder particles and after a tremendous number of failures and modifications. For these effects, we obtained a patent in 2012 as Kohaku Extract® Repair (RE) (Patent No. 4953204, Patent No. 4953203). We also discovered "hair growth effect (2010)" and "whitening effect (2011)" from another extraction method, and succeeded in obtaining patents in 2015 as Kohaku Extract® Grow (GR) and Kohaku Extract® White (WH), respectively (Patent No. 5858561, Patent No. 5858562).

「新たな生理活性の可能性を秘めた素材として注目されています」

琥珀バイオテクノロジーは、琥珀の健康・美容効果など、琥珀が持つ未知なる可能性を引き続き探求すべく、2017年に筑波大学発ベンチャーとして、筑波大学内に中央研究所を設立しました。植物に含まれる物質には、多くの有用な生理活性が報告されています。琥珀には植物の樹脂が化石化する過程で生じる未知の成分が含まれており、様々な可能性を秘めた素材として期待されています。我々はこれまでに、発見した琥珀に関する研究成果を論文・出版物として数々発表しており、特に2013年、日本美容皮膚科学会誌に掲載された論文は、最優秀論文賞を受賞するに至りました。産学の協力による飽くなき研究の日々と、それを支える研究者たちの情熱は少しずつ、しかし確実に琥珀の神秘を解き明かすことにつながっているのです。

Researchers have unraveled
健康の為の食品用琥珀エキスと
Effects of Amber Extract for Beauty

Amber extract for food

  • Chapter.1

    Lipolysis promotion effect

    Inhibition of fat accumulation
    01

    Looks don't do it justice.
    Increase in "visceral fat

    Visceral fat is the storage of energy we need to carry out our daily activities. Therefore, if we do not use energy or take in excessive amounts of energy, the amount of fat will increase.

    As visceral fat increases, neutral fat in the blood also increases, and HDL (good) cholesterol tends to decrease while LDL (bad) cholesterol tends to increase. Visceral fat is mainly found around the intestines. Visceral fat tends to accumulate mainly around the intestines, but since it is not visible from the outside, it is important to prevent it in daily life.

    02

    脂肪分解のメカニズムと食品用琥珀エキスの働き

    Lipolysis Mechanism
    食品用琥珀エキスが
    when it works

    Fat in the body is broken down by lipolytic enzymes. The pieces of fat that are broken down are burned and act as energy.

    03

    in cellular experiments.
    食品用琥珀エキスの脂肪蓄積抑制効果

    test
    method

    マウス由来成熟脂肪細胞(分化させた3T3-L1細胞)に食品用琥珀エキスを与えて96時間培養した

    (A) MTT法で食品用琥珀エキスの細胞生存率を確認　

    result

    食品用琥珀エキス乾固物50μg/mLまでは細胞生存率に影響を与えないことがわかった

    (B) After fixation with paraformaldehyde, fat droplets in the cells are stained red using Oil Red O

    result

    食品用琥珀エキスを与える量が増えるほど、赤く染まる部分=脂肪滴が減っていることがわかった

    (C)(B)で染色した細胞をイソプロパノールで溶解し、
    脂肪滴中のトリアシルグリセロール(中性脂肪)を490nmで測定

    result

    食品用琥珀エキスを与える量が増えるほど、脂肪滴中のトリアシルグリセロールが減っていることがわかった

    成熟した培養脂肪細胞に食品用琥珀エキスを与えて培養すると、与えなかったものと比較して脂肪細胞中に蓄積される中性脂肪の量が抑えられるがわかりました。

    Sogoら　Molecules Vol.26, 4630, 2021より抜粋

  • Chapter.2

    Effect on glucose metabolism

    By amber extract for food
    Suppresses the absorption of sugar
    01

    What are the harmful effects of excessive sugar intake?

    We consume carbohydrates through our diet. When carbohydrates are digested in the body, they are broken down into glucose, which enters the bloodstream. The concentration of glucose in the blood is called "blood glucose level. Normally, the human body regulates blood glucose levels through the secretion of hormones. However, if a person's diet is unbalanced, with excessive intake of carbohydrates, alcohol, and sweets, the secretion of hormones cannot keep up, and a state called "hyperglycemia" occurs. The disease that results from chronic high blood sugar is diabetes, which can lead to a variety of other adverse effects on the body.

    02

    Sugar absorption mechanism and
    Function of Amber Extract for Food

    Sugar absorption mechanism
    食品用琥珀エキスの
    Absorption mechanism

    食品用琥珀エキスには、炭水化物がブドウ糖に分解される際に必要な糖質分解酵素を、必要以上に作らせない効果（ブロック1）があります。また、ブドウ糖に分解されても、そのブドウ糖が小腸の壁を通過するのを防ぐ効果（ブロック2）があります。２段階の抑制がかかった結果、血液中に入って体内に吸収されるブドウ糖の量は減少します。そして吸収されなかったブドウ糖は、体の外へと排泄されます。

    食品用琥珀エキスには、炭水化物がブドウ糖に分解される際に必要な糖質分解酵素を、必要以上に作らせない効果（ブロック1）があります。また、ブドウ糖に分解されても、そのブドウ糖が小腸の壁を通過するのを防ぐ効果（ブロック2）があります。２段階の抑制がかかった結果、血液中に入って体内に吸収されるブドウ糖の量は減少します。そして吸収されなかったブドウ糖は、体の外へと排泄されます。

    03

    Amber Extract for Food in Cell Experiments
    double-blocking effect

    A

    Inhibition of sugar degradation

    test
    method

    ヒト結腸癌由来細胞(Caco-2細胞に食品用琥珀エキスを与えて8日間培養する
    ⇒Dissolves cells and is a carbohydrate-degrading enzyme

    Proteins of the sucrase-isomaltase complex (hereafter referred to as SI proteins) were detected by Western blotting. Similarly, β-actin protein was detected as an internal standard.

    result

    食事として摂取した糖質は、小腸内でSIタンパク質よりブドウ糖となり、血中に吸収されます。食品用琥珀エキスを与えたものはそうでないものと比べて、SIタンパク質の発現が抑制されていました。このことから食品用琥珀エキスには、糖質分解酵素が働くのを抑えることにより、糖の吸収を抑える効果があることが期待されました。Excerpt from Patent No. 6599592

    B

    Inhibition of sugar absorption

    test
    method

    Cultured human colon cancer-derived cells (Caco-2 cells) on Transwell membrane filters for 3 weeks.(*Normally, 0.4-μm pore size membrane filters allow glucose to pass through)

    Intercellular electrical resistance is confirmed to be 350 Ω-cm2 or higher. *

    上層にブドウ糖と食品用琥珀エキスを添加して2時間培養。その後下層に移ったブドウ糖量を測定。
    Reconfirmation that intercellular electrical resistance is greater than 350 Ω-cm2.

    result

    腸管にはブドウ糖を選択的に透過させる膜タンパク質が存在していることが分かっています。食品用琥珀エキスを多く添加した細胞ほどブドウ糖を透過させないことがわかりました。Drawing based on the example of patent No. 6601860*The intercellular electrical resistance value is a guide to confirm whether or not Caco-2 cells are tightly bound together. 50 Ω-cm2 or higher is considered to indicate that they are tightly bound together and form a barrier.

  • Chapter.3

    Effect on blood pressure regulation

    By amber extract for food
    Normal blood pressure" effect
    01

    Common among the Japanese.
    Mechanism of "hypertension

    Blood pressure is controlled by the autonomic nervous system (sympathetic and parasympathetic nerves). The autonomic nervous system (sympathetic nerves), which responds to "emergency reactions" to protect oneself from external enemies, puts the body in a state that is suitable for movements such as fighting or fleeing, and the same reaction occurs when the body experiences strong stress.

    The greater the mental and physical stress, the more active the autonomic (sympathetic) nervous system becomes, resulting in an increase in heart rate. This means that the heart has to pump more blood, resulting in "high blood pressure. In addition, excessive salt intake and excessive alcohol consumption can also cause blood pressure to rise.

    02

    The mechanism of elevated blood pressure and
    Function of Amber Extract for Food

    Mechanism of blood pressure elevation
    食品用琥珀エキスの
    mechanism of action

    When exposed to mental or physical stress, angiotensin converting enzyme (ACE) is activated and blood pressure rises*1 in an attempt to shrink blood vessels. Amber extract for food can act on this ACE and inhibit its activation, thereby reducing the increase in blood pressure.

    1 In fact, substances generated by ACE activation constrict blood vessels.

    03

    Amber Extract for Food in Cell Experiments
    Inhibition of blood pressure elevation

    test
    method

    アンギオテンシンⅠ変換酵素(ACE)阻害活性測定キット(同仁化学)を用いて測定。食品用琥珀エキス(乾固物)10mgをジメチルスルホキシド1mLで溶解し遠心後の上清を原液としました。この液を純水で5倍希釈していきました。これらサンプルに、基質と酵素を加えて反応させて生成した物質を定量しました。

    Conclusion.

    食品用琥珀エキスの濃度が高くなるほど、酵素ACE(アンギオテンシン変換酵素)活性の阻害率が上昇することがわかりました。食品用琥珀エキスは血圧上昇を抑える食品等に応用できる可能性を有していると考えられました。Excerpt from an example from Patent No. 6548797

Amber extract

  • Chapter.1

    by Kohaku Extract® Repair (RE)
    Aging care of epidermis and stratum corneum

    Skin turnover promotion effect (Patent No. 4953204)Kohaku Extract® Repair (RE) is
    Leads to normal skin renewal,
    By smoothing out rough skin,
    It produces a beautiful skin effect.

    Amount of genes that promote turnover

    test
    method

    After 24 hours of culture of normal human epidermal keratinocytes (NHEK) with Kohaku Extract Repair (RE), total RNA was collected and the amount of gene (HB-EGF)*) that promotes turnover was measured by RT reaction → real-time PCR method.What is HB-EGF?
    Heparin-Binding EGF-like Growth Factor stands for heparin-binding epidermal growth factor. It is a growth factor involved in skin wound healing.

    result

    For smooth skin
    Promotes skin renewal

    Compared to cells without Kohaku Extract Repair (RE), the amount of HB-EGF gene was increased in cells given Kohaku Extract Repair (RE). This indicates that Kohaku Extract is expected to be effective in normalizing the turnover rate, which tends to be delayed due to aging.Excerpted from Ohara et al. Journal of Cosmetic Chemistry 34. 89-101, 2010

    Hyaluronic acid production promoting effect (Patent No. 4953203)Kohaku Extract® Repair (RE) is
    Increased skin moisture content,
    It leads to fresh and plump skin.

    Amount of hyaluronic acid producing enzyme gene

    test
    method

    Human immortalized epidermal keratinocytes (HaCaT cells) were cultured with Kohaku Extract Repair (RE) cells for 24 hours, and total RNA was collected and the amount of hyaluronic acid producing enzyme 3 (HAS3) gene was determined by RT reaction → real-time PCR method.

    result

    For fresh skin
    Increased skin moisture

    Compared to cells without Kohaku Extract Repair (RE), cells treated with Kohaku Extract Repair (RE) had increased levels of hyaluronic acid-producing enzyme 3 genes, which are involved in the production of hyaluronic acid by epidermal keratinocytes. This indicates that Kohaku Extract is expected to enhance the skin's ability to produce hyaluronic acid and retain its own moisture.Based on Ohara et al.

    Stained image of hyaluronic acid

    test
    method

    Human skin reconstruction culture model*) (hereafter referred to as "skin model") was incubated with succinic extract repair (RE) at a final concentration of 25 μg/mL for 40 hours. The tissues were then fixed using paraformaldehyde and glutaraldehyde, and hyaluronic acid was stained brown.*Human skin reconstruction model
    The skin consists of three layers from the top: stratum corneum, epidermis, and dermis, and this structure is reproduced by cultured cells. The function of human skin tissue is reproduced, albeit to a limited extent.

    Stained image of hyaluronic acid

    result

    Compared to the skin model without Kohaku Extract Repair (RE), the skin model treated with Kohaku Extract Repair (RE) showed a darker brown color, especially in the epidermis, indicating that more hyaluronic acid was produced.Based on Ohara et al.

  • Chapter.2

    Kohaku Extract® Grow (GR)
    hair growth spurt

    Effect of increasing VEGF gene (Patent No. 5858561)With KOHAKU EXTRAX® GROW(GR)
    By processing
    VEGF遺伝子が増加しました。
    test
    method

    Human immortalized epidermal keratinocytes (HaCaT cells) were cultured with succinic extract grow (GR) cells for 24 hours, total RNA was collected, and the amount of growth factor (VEGFA) genes that promote angiogenesis was measured by RT reaction → real-time PCR method.

    result

    Treatment with Kohaku Extract Grow (GR) was found to increase the VEGFA gene. This is expected to increase blood circulation around hair follicles, resulting in thicker, more vibrant hair.Sato et al. (Basic research in collaboration with the National Institute of Physical and Chemical Research).

  • Chapter.3

    Kohaku Extract® White (WH)
    Beauty Skin Effect

    Inhibition of melanin production (Patent No. 5858562)For KOHAKU EXTract® White (WH),
    Suppresses melanin production,
    It is effective in leading to blemish-free skin.

    Cultured human epidermal keratinocytes
    Endothelin-1 gene

    test
    method

    Cultured human immortalized epidermal keratinocytes (HaCaT cells) were irradiated with UV light and then given succinic extract white and further cultured for 24 hours, after which total RNA was collected and gene expression of endothelin-1 was measured using the RT reaction → real-time PCR method.

    result

    Clear, blemish-free skin

    It was found that gene expression of endothelin-1, an inflammatory peptide, was suppressed in those fed Kohaku Extract White compared to those that were not. This indicates that Kohaku Extract White is expected to be effective in preventing blemishes by suppressing endothelin-1, which transmits inflammation, the source of blemishes, to melanocytes.Patent No. 5656582, Drawing based on in-house data

PATENT / TREATISE

  • 2023

    JP 2022-10503, "Amber-containing compositions useful for prevention or improvement of periodontal pockets and their use."

  • 2023

    Patent Application 2022-10502, "Amber-containing compositions useful for the prevention or improvement of osteoporosis and their use."

  • 2023

    Behavioral and Biochemical Evaluation of Anti-Depressive and Oxidative Stress-Ameliorating Effects of Amber Extract in Adult Male ICR Mice

    For more information on the paper, click here.

  • 2023

    Amber (Succinite) Extract Enhances Glucose Uptake through the Up-Regulation of ATP and Down-Regulation of ROS in Mouse C2C12 Cells

    For more information on the paper, click here.

  • 2023

    Amber Extract Suppressed Mast Cell-Mediated Allergic Inflammation via the Regulation of Allergic Mediators-An In Vitro Study

    For more information on the paper, click here.

  • 2022

    Anti-inflammatory activities of amber extract in lipopolysaccharide-induced RAW 264.7 macrophages

    For more information on the paper, click here.

  • 2022

    Protective Effect of Amber Extract on Human Dopaminergic Cells against 6-Hydroxydopamine-Induced Neurotoxicity

    For more information on the paper, click here.

  • 2021

    Amber Extract Reduces Lipid Content in Mature 3T3-L1 Adipocytes by Activating the Lipolysis Pathway

    For more information on the paper, click here.

  • 2021

    Role of amber extract in protecting SHSY5Y cells against amyloid beta1-42-induced neurotoxicity

    For more information on the paper, click here.

  • 2019

    Patent No. 6601860, "Glucose Absorption Inhibitor."

  • 2019

    Patent No. 6599592, "Alpha Glucosidase Activity Inhibitor."

  • 2019

    Patent No. 6548797, "Angiotensin I Converting Enzyme Activity Inhibitor."

  • 2019

    Patent No. 6534500, "Glycerol Release Accelerator."

  • 2019

    Patent No. 6534500, "Glycerol Release Accelerator."

  • 2015

    Patent No. 5858561, "Amber-derived VEGF production stimulating agent and preparations or cosmetics containing amber-derived VEGF production stimulating agent or cosmetics for head and scalp."

  • 2015

    Patent No. 5858562 "Endothelin-1 production inhibitor, SCF production inhibitor, and melanin production inhibitor obtained from amber and their uses."

  • 2013

    Enhancement of VEGF expression and promotion of hair growth by ethanol extract of amber

    For more information on the paper, click here.

  • 2012

    Patent No. 4953204 "Compositions containing skin turnover promoting factors obtained from amber and their use."

  • 2012

    Patent No. 4953203 "Compositions containing hyaluronic acid production promoting factors obtained from amber and their use."

  • 2010

    Effects of Amber Alcohol Extract Fraction on Promoting Skin Turnover and Hyaluronic Acid Production

    For more information on the paper, click here.

  • 2006

    Patent No. 3741429, "Cosmetics Colored with Natural Pigments and Method for Preventing Discoloration and Fading Thereof."

  • 2005

    Patent No. 3741429, "Cosmetics."

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