TWI616203B - Use of bilberry extraction in preparing pharmaceutical composition for protecting and repairing mitochondria,improving an ability of the mitochondria to perform oxidative phosphorylation and synthesize adenosine triphosphate,increasing spare respiratory - Google Patents

Use of bilberry extraction in preparing pharmaceutical composition for protecting and repairing mitochondria,improving an ability of the mitochondria to perform oxidative phosphorylation and synthesize adenosine triphosphate,increasing spare respiratory Download PDF

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TWI616203B
TWI616203B TW105116251A TW105116251A TWI616203B TW I616203 B TWI616203 B TW I616203B TW 105116251 A TW105116251 A TW 105116251A TW 105116251 A TW105116251 A TW 105116251A TW I616203 B TWI616203 B TW I616203B
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mitochondria
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TW201740968A (en
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凃啟堂
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台灣粒線體應用技術股份有限公司
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K36/45Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction

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Abstract

一種山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途。山桑子萃取物含有花青素(Anthocyanidins)。當醫藥組合物被提供予細胞時,山桑子萃取物以山桑子萃取物水溶液的形式提供予細胞。山桑子萃取物水溶液的濃度為每毫升25至250微克(μg/ml)。 A mulberry extract is used for preparing protection and repairing mitochondria, improving the ability of mitochondria to undergo oxidative phosphorylation and ATP synthesis, improving the pre-existing oxygen consumption capacity of mitochondria, and improving mitochondria Use of a pharmaceutical composition for basal oxygen consumption of an oxidative phosphorylation reaction for synergistic efficiency of synthesizing triphosphates. Mangosteen extract contains Anthocyanidins. When the pharmaceutical composition is provided to the cells, the mulberry extract is provided to the cells as an aqueous solution of the mulberry extract. Bilberry extract concentration of the aqueous solution is from 25 to 250 micrograms per ml g / ml).

Description

山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷合成的能力、提高粒線體的預存耗氧能力以及提高粒線體的媒合效率之醫藥組合物的用途 Mulberry extract is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and triphosphate synthesis, increase the pre-existing oxygen consumption capacity of mitochondria, and improve the efficiency of mitochondria. Use of pharmaceutical composition

本發明係關於一種山桑子萃取物用於製備之醫藥組合物的用途,特別是一種山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷合成的能力、提高粒線體的預存耗氧能力以及提高粒線體的媒合效率之醫藥組合物的用途。 The invention relates to the use of a mulberry seed extract for preparing a pharmaceutical composition, in particular to a mulberry seed extract for preparing protection and repair of mitochondria, improving mitochondria for oxidative phosphorylation reaction and triphosphate glucoside. Use of a pharmaceutical composition capable of synthesizing, improving pre-stored oxygen consumption capacity of mitochondria, and improving mediation efficiency of mitochondria.

粒線體(Mitochondria)是細胞內進行氧化磷酸化和合成三磷酸腺苷(ATP)的主要場所。由於三磷酸腺苷為細胞活動的能量來源,所以粒線體又有「細胞能量工廠」之稱。除了為細胞提供能量外,粒線體還參與細胞分化、細胞資訊傳遞和細胞凋亡等過程,並擁有調控細胞生長周期的能力。 Mitochondria is the main site for oxidative phosphorylation and synthesis of adenosine triphosphate (ATP) in cells. Because adenosine triphosphate is the source of energy for cellular activities, mitochondria are also known as "cell energy factories". In addition to providing energy to cells, mitochondria are also involved in processes such as cell differentiation, cell information transmission, and apoptosis, and have the ability to regulate the cell growth cycle.

然而,粒線體在進行氧化磷酸化反應時產生的部份副產物對於粒線體的內膜是有害的。長期累積下來,嚴重受損的粒線體內膜將觸發粒線體崩解,進而觸發細胞凋亡。因此,如何修補與保護粒線體,藉此減緩粒線體崩解所觸發的細胞凋亡的速度已成為一個重要的課題。 However, some of the by-products produced by mitochondria during oxidative phosphorylation are harmful to the inner membrane of mitochondria. Over a long period of time, the severely damaged mitochondrial inner membrane will trigger mitochondrial disintegration, and then trigger apoptosis. Therefore, how to repair and protect mitochondria and thereby slow down the rate of apoptosis triggered by mitochondrial disintegration has become an important issue.

本發明係提供一種山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷合成的能力、提高粒線體的預存耗氧能力以及提高粒線體的媒合效率之醫藥組合物的用途,藉此延緩粒線體崩解所觸發細胞凋亡的速度。 The invention provides a mulberry seed extract for preparing protection and repairing mitochondria, improving the ability of mitochondria to undergo oxidative phosphorylation and synthesizing triphosphates, improving the pre-existing oxygen consumption capacity of mitochondria, and improving mitochondria. The use of the pharmaceutical composition of the mediating efficiency of the body, thereby delaying the rate of apoptosis triggered by mitochondrial disintegration.

本發明一實施例揭露一種山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途;其中,該山桑子萃取物含有花青素(Anthocyanidins);其中,當該醫藥組合物被提供予一細胞時,該山桑子萃取物以一山桑子萃取物水溶液的形式提供予該細胞,該山桑子萃取物水溶液的濃度為每毫升25至250微克(μg/ml)。 According to an embodiment of the present invention, a mulberry seed extract is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria. The use of a pharmaceutical composition for improving the efficiency of mediation of the oxidative phosphorylation of mitochondria for the oxidative phosphorylation of mitochondria for synthesizing the efficiency of synthesizing triphosphates; wherein the extract of the mulberry seed contains anthocyanidins; Wherein, when the medicinal composition is provided to a cell, the mulberry extract is provided to the cell in the form of an aqueous solution of mulberry extract, and the concentration of the aqueous solution of the mulberry extract is 25 to 250 micrograms per milliliter (μg / ml).

本發明另一實施例揭露一種山桑子萃取物用於製備保護與修復粒線體、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中該山桑子萃取物含有花青素,以及該山桑子萃取物的有效劑量為0.27克至2.7克。 According to another embodiment of the present invention, a mulberry seed extract is used for synthesis to protect and repair mitochondria, improve the pre-stored oxygen consumption capacity of mitochondria, and increase the basic oxygen consumption of oxidative phosphorylation of mitochondria. The use of a medicinal composition for the mediation efficiency of linosine triphosphate, wherein the extract of the mulberry seed contains anthocyanins, and the effective amount of the extract of the mulberry seed is 0.27 g to 2.7 g.

根據上述本發明所揭露的山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,提供山桑子萃取物予細胞可保護與修復粒線體的內膜以延緩粒線體發生崩解的時間。如此一來,可減緩粒線體崩解觸發細胞凋亡的速度。 The extract of mulberry seeds disclosed in the present invention is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria. Capability and use of a pharmaceutical composition for improving the efficiency of mitochondrial oxidative phosphorylation in the basic oxygen consumption of mitochondria for synthesizing triphosphate glycosides, providing mulberry seeds extract to cells to protect and repair mitochondria The inner membrane is used to delay the disintegration of mitochondria. In this way, the rate at which mitochondrial disintegration triggers apoptosis can be slowed.

以上之關於本揭露內容之說明及以下之實施方式之說明係用以示範與解釋本發明之精神與原理,並且提供本發明之專利申請範圍更 進一步之解釋。 The above description of the content of this disclosure and the description of the following embodiments are used to demonstrate and explain the spirit and principle of the present invention, and to provide more scope for the patent application of the present invention. Further explanation.

圖1為實施例一至實施例三與比較例一至比較例三之合成三磷酸線苷的耗氧量示意圖。 FIG. 1 is a schematic diagram of oxygen consumption of synthetic triphosphates in Examples 1 to 3 and Comparative Examples 1 to 3. FIG.

圖2為實施例一至實施例三與比較例一至比較例三之粒線體的基礎耗氧量示意圖。 FIG. 2 is a schematic diagram of the basic oxygen consumption of the mitochondria of Examples 1 to 3 and Comparative Examples 1 to 3. FIG.

圖3為實施例一至實施例三與比較例一至比較例三之克服氫離子洩漏的耗氧量示意圖。 FIG. 3 is a schematic diagram of oxygen consumption for overcoming hydrogen ion leakage in Examples 1 to 3 and Comparative Examples 1 to 3. FIG.

圖4為實施例一至實施例三與比較例一至比較例三之粒線體的最大耗氧能力示意圖。 FIG. 4 is a schematic diagram of the maximum oxygen consumption capacity of the mitochondria of Examples 1 to 3 and Comparative Examples 1 to 3. FIG.

圖5為實施例一至實施例三與比較例一至比較例三之粒線體的預存耗氧能力示意圖。 FIG. 5 is a schematic diagram of the pre-stored oxygen consumption capacity of the mitochondria of Examples 1 to 3 and Comparative Examples 1 to 3. FIG.

圖6為實施例一至實施例三與比較例一至比較例三之粒線體的三磷酸線苷媒合效率示意圖。 FIG. 6 is a schematic diagram of the mitochondrial triphosphate glycoside mediation efficiency of the mitochondria in Examples 1 to 3 and Comparative Examples 1 to 3. FIG.

以下在實施方式中詳細敘述本發明之詳細特徵以及優點,其內容足以使任何熟習相關技藝者了解本發明之技術內容並據以實施,且根據本說明書所揭露之內容、申請專利範圍及圖式,任何熟習相關技藝者可輕易地理解本發明相關之目的及優點。以下之實施例係進一步詳細說明本發明之觀點,但非以任何觀點限制本發明之範疇。 The detailed features and advantages of the present invention are described in detail in the following embodiments. The content is sufficient for any person skilled in the art to understand and implement the technical content of the present invention, and according to the content disclosed in this specification, the scope of patent applications and the drawings. Anyone skilled in the relevant art can easily understand the related objects and advantages of the present invention. The following examples further illustrate the viewpoints of the present invention in detail, but do not limit the scope of the present invention in any way.

山桑子(Bilberry),又稱越橘,為多種具有藍黑色或藍紫色漿果之杜鵑花科越橘屬(Vaccinium)矮生落葉灌木的統稱,主要分布於歐洲、北美(美國和加拿大)和亞洲北部。山桑子之漿果產於夏、秋兩季。山桑子富含各種生物類黃酮,包含花青素(Anthocyanidin)、翠雀花素(Delphinidin)、芍藥花素(Peonidin)、矮牽牛素(Petunidin)、天竺葵素 (Pelargonidin)、矢車菊素(Cyanidin)等及其糖苷類。 Bilberry, also known as bilberry, is a collective name for a variety of dwarf deciduous shrubs of the genus Vaccinium of the azalea family with blue-black or blue-purple berries, mainly distributed in Europe, North America (United States and Canada), and Asia North. Berries of mountain mulberry are produced in summer and autumn. Mulberry seeds are rich in various bioflavonoids, including anthocyanidin, delphinidin, peonydin, petunidin, pelargonidin, and cyanidin And its glycosides.

山桑子所含的生物類黃酮具有促進視網膜上的反式視黃醛(11-trans-Rentinal)與視蛋白(Opsin)合成視紫質(Rhodopsin)的功效。視網膜上的視紫質是視覺傳遞系統的受質。當視紫質受到光線照射時,視紫質內部的順式視黃醛(11-cis-Retinal)受到光的激發後轉變為反式視黃醛(11-trans-Rentinal),使得視紫質受到活化,進而透過一連串的連鎖反應而產生於視神經中傳遞的視覺訊號。活化的視紫質中的(11-trans-Rentinal)接著透過酵素的作用轉變為反式視黃醛(11-trans-Rentinal),並在生物類黃酮的作用下與視蛋白重新結合成視紫質。由於山桑子含有多種生物類黃酮,因此山桑子常被添加於視力保健產品中。 The bioflavonoids contained in mulberry seeds have the effect of promoting the synthesis of rhodopsin by 11-trans-Rentinal and Opsin on the retina. The rhodopsin on the retina is the subject of the visual transmission system. When rhodopsin is irradiated with light, 11-cis-Retinal inside rhodopsin is excited by light and transformed into 11-trans-Rentinal, making rhodopsin Activated, and then through a series of chain reactions to produce visual signals transmitted in the optic nerve. (11-trans-Rentinal) in activated rhodopsin is then transformed into 11-trans-Rentinal through the action of enzymes, and recombines with opsin to form rhodopsin under the action of bioflavonoids quality. Due to the variety of bioflavonoids contained in mulberry seeds, mulberry seeds are often added to vision health products.

本發明使用之山桑子的學名為Vaccinium uliginosum L.。山桑子萃取物之取得方式例如以二氧化碳作為超臨界流體萃取山桑子果實,或者是以甲醇、乙醇、丙酮、乙酸乙酯、重量百分濃度0.1至5%的氯化鈉水溶液、氯化鉀水溶液、氯化鈣水溶液、氯化鎂水溶液或重量百分濃度0.1至5%的氯化鈉乙醇溶液、氯化鉀乙醇溶液、氯化鈣乙醇溶液、氯化鎂乙醇溶液、乙醇溶液作為溶劑萃取山桑子而得到初萃液。接著,將初萃液過濾純化後得到本發明所使用的山桑子萃取物。 The scientific name of the mountain mulberry used in the present invention is Vaccinium uliginosum L. The way to obtain the mulberry extract is to extract the mulberry fruit with carbon dioxide as a supercritical fluid, or use methanol, ethanol, acetone, ethyl acetate, 0.1 to 5% by weight sodium chloride aqueous solution, and potassium chloride aqueous solution. , Sodium chloride aqueous solution, magnesium chloride aqueous solution or 0.1 to 5% by weight sodium chloride ethanol solution, potassium chloride ethanol solution, calcium chloride ethanol solution, magnesium chloride ethanol solution, ethanol solution as solvents Extraction. Next, the primary extract is filtered and purified to obtain the mulberry seed extract used in the present invention.

當提供濃度為每毫升25至250微克(μg/ml)之山桑子萃取物水溶液予細胞,進入細胞內的山桑子萃取物可保護與修復粒線體的內膜。如此一來,於粒線體內膜進行氧化磷酸化反應以合成三磷酸線苷之效率得到提升。詳細來說,經山桑子萃取物修復的粒線體進行氧化磷酸化反應合成的三磷酸線苷數量提高,粒線體的基礎耗氧量提高,粒線體內膜的氫離子洩漏量下降,粒線體的最大耗氧能力提高,粒線體的預存耗氧能力提高,粒線體的三磷酸線苷媒合效率提高。 When an aqueous solution of Mulberry seed extract is provided to cells at a concentration of 25 to 250 micrograms (μg / ml) per milliliter, the Mulberry seed extract entering the cells can protect and repair the inner membrane of mitochondria. In this way, the efficiency of oxidative phosphorylation reaction to synthesize glucosides of triphosphate is improved in the inner membrane of mitochondria. In detail, the amount of triphosphates synthesized by oxidative phosphorylation of mitochondria repaired with extract of mulberry seeds increased, the basic oxygen consumption of mitochondria increased, and the amount of hydrogen ion leakage in the inner membrane of mitochondria decreased, and The maximum oxygen consumption capacity of the mitochondria is increased, the pre-stored oxygen consumption capacity of the mitochondria is increased, and the mitochondrial triphosphate glycoside mediation efficiency is improved.

提供山桑子萃取物予細胞的方法例如為以食用的方式由口攝取山桑子萃取物。以食用的方式提供山桑子萃取物予細胞時,山桑 子萃取物的有效劑量為0.27克(g)至2.7克。此處之有效劑量係根據細胞實驗之有效劑量與人體公斤數之換算公式進行換算得到。換算公式如下:人體有效劑量=細胞實驗之有效劑量×小鼠體重×折算係數×人體公斤數。折算係數係由動物與人體的每公斤體重劑量折算係數表查表得到。當小鼠體重為20克以及人體公斤數為60公斤時,折算係數為9.01。 A method of providing a mangosteen extract to a cell is, for example, ingesting the mangosteen extract by mouth. When mulberry seeds are provided to cells in an edible manner, The effective dose of the sub-extract is 0.27 grams (g) to 2.7 grams. The effective dose here is calculated based on the conversion formula between the effective dose of the cell experiment and the kilogram of the human body. The conversion formula is as follows: effective dose for human body = effective dose for cell experiments × mouse weight × conversion factor × human kilograms. The conversion factor is obtained from a look-up table of dose conversion coefficients per kilogram of body weight of animals and humans. When the mouse weighs 20 grams and the human kilogram weighs 60 kilograms, the conversion factor is 9.01.

為方便以食用的方式由口攝取山桑子萃取物,山桑子萃取物可製成例如液體狀、固體狀、顆粒狀、粉體狀、糊狀或凝膠狀的山桑子萃取物加工品。山桑子萃取物加工品中可搭配作為添加劑的賦形劑或呈味劑,以提升風味與方便食用。 In order to facilitate the ingestion of the wild mulberry extract from the mouth, the wild mulberry extract can be made into, for example, a liquid, solid, granular, powdery, pasty, or gelled processed wild mulberry extract. The processed extract of mulberry seeds can be used as an excipient or flavoring agent as an additive to enhance the flavor and ease of consumption.

賦形劑例如為小麥澱粉、米澱粉、玉米澱粉、馬鈴薯澱粉、糊精、環糊精等澱粉類;結晶纖維素類;乳糖、葡萄糖、砂糖、還原麥芽糖、飴糖、果寡糖、乳化寡糖等糖類;山梨糖醇、赤藻糖醇、木糖醇、乳糖醇、甘露醇等糖醇類。 Excipients are, for example, starches such as wheat starch, rice starch, corn starch, potato starch, dextrin, and cyclodextrin; crystalline celluloses; lactose, glucose, granulated sugar, reduced maltose, caramel, fructooligosaccharides, and emulsified oligosaccharides And other sugars; sorbitol, erythritol, xylitol, lactitol, mannitol and other sugar alcohols.

呈味劑例如為龍眼萃取物、荔枝萃取物、柚子萃取物等各種果汁萃取物;蘋果汁、橘子汁、檸檬汁等各種果汁;桃子香料、梅子香料、酸乳酪香料等各種香料;乙醯磺胺酸鉀、蔗糖素、赤藻糖醇、寡糖類、甘露糖、木糖醇、異構化糖類等各種甜味劑;檸檬酸、蘋果酸、酒石酸、葡萄糖酸等各種酸味劑;綠茶、烏龍茶、巴拿巴茶(Banaba Tea)、杜仲茶、鐵觀音茶、薏苡茶、七葉膽茶、茭白茶、昆布茶等各種茶成分等。 Flavoring agents are, for example, various fruit extracts such as longan extract, lychee extract, grapefruit extract; various fruit juices such as apple juice, orange juice, and lemon juice; various spices such as peach flavor, plum flavor, and yogurt flavor; acesulfame Various sweeteners such as potassium acid, sucralose, erythritol, oligosaccharides, mannose, xylitol, isomerized sugars; various acidifiers such as citric acid, malic acid, tartaric acid, gluconic acid; green tea, oolong tea, Various tea ingredients such as Banaba Tea, Eucommia Tea, Tieguanyin Tea, 薏苡 Tea, Buckeye Tea, 胆 白茶, Kunbu Tea, etc.

再者,山桑子萃取物亦可包覆於膠囊中以方便由口攝取山桑子萃取物。山桑子萃取物可以乾燥粉末之形式被包覆於硬膠囊中,或者山桑子萃取物是以溶液狀、懸浮液狀、糊狀、粉末狀或顆粒狀的形式被包覆於軟膠囊中。 Furthermore, the extract of mulberry seeds can also be coated in capsules to facilitate the ingestion of mulberry seeds. The wild mulberry extract can be coated in hard capsules in the form of a dry powder, or the wild mulberry extract can be coated in soft capsules in the form of a solution, suspension, paste, powder or granule.

軟膠囊中用於溶解或分散山桑子萃取物之油脂類例如為萼梨油、杏仁油、亞麻仁油、小茴香油、白蘇油、橄欖油、橄欖角鯊烯、 甜橙油、胸棘鯛油(orange roughy oil)、芝麻油、蒜油、可可脂、南瓜子油、洋甘菊油、胡蘿蔔油、胡瓜油、牛油脂肪酸、夏威夷核果油、越橘子油、糙米胚芽油、大米油、小麥胚芽油、紅花油、牛油樹油脂、液狀牛油樹油脂、紫蘇油、大豆油、月見草油、山茶油、玉米油、菜子油、鋸葉棕萃取油(saw palmetto extract oil)、薏苡油、桃仁油、洋芹子油、蓖麻油、葵花子油、葡萄子油、琉璃苣油、澳洲胡桃油、繡線菊油(meadowfoam oil)、棉子油、花生油、龜油、貂油、蛋黃油、魚油、棕櫚油、棕櫚仁油、木蠟、椰子油、長鏈/中鏈/短鏈之脂肪酸三甘油酯、二酸甘油酯、牛油、豬油、角鯊烯、角鯊烷、姥鮫烷、以及該等油脂類之氫化物等。其中,琉璃苣油與月見草油含有大量伽瑪亞麻油酸(Gamma-Linolenic Acid,GLA),伽瑪亞麻油酸屬於人體必須脂肪酸,其具有保濕、促進細胞再生以及提升棕脂(Brown Fat)活躍度以促進脂肪燃燒的功能。 The oils and fats used in the soft capsules to dissolve or disperse the extract of mulberry seeds are, for example, argan oil, almond oil, linseed oil, cumin oil, white perilla oil, olive oil, olive squalene, Sweet orange oil, orange roughy oil, sesame oil, garlic oil, cocoa butter, pumpkin seed oil, chamomile oil, carrot oil, courgette oil, tallow fatty acids, Hawaiian stone oil, bilberry oil, brown rice germ oil , Rice oil, wheat germ oil, safflower oil, shea oil, liquid shea oil, perilla oil, soybean oil, evening primrose oil, camellia oil, corn oil, rapeseed oil, saw palmetto extract (saw palmetto extract oil), emu oil, peach kernel oil, parsley oil, castor oil, sunflower oil, grape seed oil, borage oil, Australian walnut oil, meadowfoam oil, cottonseed oil, peanut oil, turtle oil, Mink oil, egg butter, fish oil, palm oil, palm kernel oil, wood wax, coconut oil, long chain / medium chain / short chain fatty acid triglycerides, diglycerides, tallow, lard, squalene, Squalane, pinane, and hydrides of these oils and fats. Among them, borage oil and evening primrose oil contain a large amount of Gamma-Linolenic Acid (GLA). Gamma-linolenic acid is an essential fatty acid of the human body, which has moisturizing, promotes cell regeneration, and promotes brown fat activity. Degree to promote fat burning function.

此外,著色劑、防腐劑、增黏劑、結合劑、崩解劑、分散劑、穩定劑、膠化劑、抗氧化劑、界面活性劑、防腐劑、pH值調整劑等符合政府單位規定之添加物亦可依照政府單位規定之劑量標準與加工生產之需求添加於山桑子萃取物加工品中。 In addition, colorants, preservatives, tackifiers, binding agents, disintegrating agents, dispersants, stabilizers, gelling agents, antioxidants, surfactants, preservatives, pH adjusters, etc. are added in accordance with government regulations. It can also be added to the processed products of mulberry seed extract according to the dosage standard stipulated by the government unit and the requirements of processing production.

以下藉由本發明實施例一至實施例三與比較例一至比較例三說明本發明所揭露之保護與修復粒線體的方法,並且進行實驗測試以說明本發明所揭露之保護與修復粒線體的方法之功效。 In the following, the methods for protecting and repairing mitochondria disclosed by the present invention will be described by using examples 1 to 3 and comparative examples 1 to 3 of the present invention, and experimental tests will be performed to explain the protection and repair of mitochondria disclosed by the present invention. The efficacy of the method.

本發明之實驗使用的山桑子萃取物係將山桑子(Vaccinium uliginosum L.)的果實以乙醇水溶液進行萃取與乾燥後所得。乾燥後的山桑子萃取物型態為紫紅色粉末(Violet Red Powder),其密度為每毫升0.45至0.70公克(0.45~0.70g/ml),粉末可穿過80目(mesh)的篩網。山桑子萃取物中含有重量百分濃度25%以上的花青素(Anthocyanidins)。 The extract of mountain mulberry used in the experiment of the present invention is obtained by extracting and drying the fruit of mountain mulberry ( Vaccinium uliginosum L. ) with an aqueous ethanol solution. The dried mulberry extract is in the form of Violet Red Powder, with a density of 0.45 to 0.70 grams per milliliter (0.45 to 0.70 g / ml). The powder can pass through a mesh of 80 mesh. The extract of mountain mulberry contains anthocyanidins with an concentration of more than 25% by weight.

實驗使用的細胞為第六代(P6)的脂肪間葉幹細胞(ADSC)。實驗樣品準備方式為於孔盤的每一個孔中植入8000個脂肪間葉幹細胞後培養24個小時。 The cells used in the experiment were the sixth generation (P6) adipose mesenchymal stem cells (ADSC). The experimental sample was prepared by implanting 8000 adipose mesenchymal stem cells into each well of the well plate and culturing for 24 hours.

實驗中,模擬粒線體受損狀況的方式為將細胞暴露於濃度200mM的過氧化氫(H2O2)水溶液中30分鐘,接著再以磷酸緩衝生理食鹽水(Phosphate buffered saline,PBS)清洗細胞。由於過氧化氫的氧化力可對粒線體內膜造成傷害,因此在實驗中利用過氧化氫的氧化力對粒線體內膜之破壞,模擬體內自由基之氧化力對粒線體內膜所造成之破壞。 In the experiment, the mitochondrial damage was simulated by exposing the cells to a 200 mM aqueous solution of hydrogen peroxide (H 2 O 2 ) for 30 minutes, followed by washing with phosphate buffered saline (PBS). cell. Because the oxidizing power of hydrogen peroxide can cause damage to the inner membrane of the mitochondrial membrane, the oxidizing power of hydrogen peroxide is used to damage the inner membrane of the mitochondrial membrane in the experiment, and the oxidative power of free radicals in the body is caused to the inner membrane of the mitochondrial membrane damage.

於實驗過程中,首先將預定濃度的山桑子萃取物水溶液加入孔中並浸泡24小時。接著,將濃度為200mM的H2O2水溶液加入孔中,使細胞浸泡於濃度為200mM的H2O2水溶液中30分鐘。接著,以磷酸緩衝生理食鹽水(Phosphate buffered saline,PBS)清洗細胞。最後,以海馬生物能量測定儀量測孔中細胞的氧氣消耗量。 In the course of the experiment, an aqueous solution of a mulberry seed extract of a predetermined concentration was first added to the wells and soaked for 24 hours. Next, a 200 mM H 2 O 2 aqueous solution was added to the wells, and the cells were immersed in a 200 mM H 2 O 2 aqueous solution for 30 minutes. Next, the cells were washed with phosphate buffered saline (PBS). Finally, the hippocampal bioenergy meter was used to measure the oxygen consumption of cells in the wells.

於實施例一中,山桑子萃取物水溶液的濃度為每毫升25微克(μg/ml)。於實施例二中,山桑子萃取物水溶液的濃度為每毫升50微克(μg/ml)。於實施例三中,山桑子萃取物水溶液的濃度為每毫升250微克(μg/ml)。於比較例一中,孔盤的孔中未加入山桑子萃取物水溶液。於比較例二中,山桑子萃取物水溶液的濃度為每毫升12.5微克(μg/ml)。於比較例三中,山桑子萃取物水溶液的濃度為每毫升500微克(μg/ml)。 In Example 1, the concentration of the aqueous solution of Mulberry seed extract was 25 micrograms (μg / ml) per milliliter. In Example 2, the concentration of the aqueous solution of Mulberry seed extract was 50 micrograms (μg / ml) per milliliter. In Example 3, the concentration of the aqueous solution of Mulberry seed extract was 250 micrograms (μg / ml) per milliliter. In Comparative Example 1, an aqueous solution of mulberry seed extract was not added to the pores of the perforated disk. In Comparative Example 2, the concentration of the aqueous solution of Mulberry seed extract was 12.5 micrograms (μg / ml) per milliliter. In Comparative Example 3, the concentration of the aqueous solution of the mulberry extract was 500 micrograms (μg / ml) per milliliter.

海馬生物能量測定儀的測量原理與流程如下。首先,偵測孔中細胞的基礎耗氧量。接著,加入三磷酸線苷合成酶抑制劑以抑制粒線體產生三磷酸線苷,此時減少的耗氧量即為粒線體進行氧化磷酸化反應以合成三磷酸線苷的耗氧量,亦即是粒線體的基礎耗氧量(Basal Respiration)。三磷酸線苷合成酶抑制劑例如為寡黴素(Oligomycin)。接著,加入適當濃度的抗耦合劑,在不破壞粒線體內膜的電子傳遞鏈的情 況下,讓粒線體以極限狀況空轉以評估粒線體的最大耗氧能力(Maximal Respiration)。抗耦合劑例如為Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone(FCCP)。最後,加入電子傳遞鏈抑制劑已完全關閉粒線體的耗氧,藉此確認量測的背景值,亦即是非粒線體耗氧量(Non-mitochondrial Respiration)。電子傳遞鏈抑制劑例如為魚藤酮(Rotenone)與抗黴素A(Antimycin A)之組合。 The measurement principle and process of the hippocampal bioenergy meter are as follows. First, the basal oxygen consumption of the cells in the well is detected. Next, a triphosphate synthase inhibitor is added to inhibit mitochondria from producing triphosphate, and the reduced oxygen consumption at this time is the oxidative phosphorylation reaction of the mitochondria to synthesize the oxygen consumption of triphosphate. This is the basic oxygen consumption (Basal Respiration) of the mitochondria. An inhibitor of triphosphate glycoside synthase is, for example, Oligomycin. Next, add an appropriate concentration of anti-coupling agent to prevent the electron transport chain in the inner membrane of the mitochondria from breaking. In this case, the mitochondria were allowed to idle under extreme conditions to assess the maximum oxygen consumption capacity of the mitochondria (Maximal Respiration). The anti-coupling agent is, for example, Carbonyl cyanide-4- (trifluoromethoxy) phenylhydrazone (FCCP). Finally, the addition of an electron transfer chain inhibitor has completely turned off mitochondrial oxygen consumption, thereby confirming the measured background value, that is, non-mitochondrial oxygen consumption (Non-mitochondrial Respiration). The electron transport chain inhibitor is, for example, a combination of Rotenone and Antimycin A.

粒線體的基礎耗氧量等於細胞的基礎耗氧量減去非粒線體耗氧量。粒線體的基礎耗氧量減去合成三磷酸線苷消耗的氧氣量等於克服氫離子洩漏(Proton Leakage)的耗氧量。粒線體的最大耗氧能力減去粒線體的基礎耗氧量等於粒線體的預存耗氧能力(Spare Respiratory Capacity)。粒線體的三磷酸線苷媒合效率(Coupling Efficiency)等於合成三磷酸線苷耗氧量除以粒線體的基礎耗氧量。 The basal oxygen consumption of the mitochondria is equal to the basal oxygen consumption of the cells minus the non-mitochondrial oxygen consumption. The basic oxygen consumption of the mitochondria minus the amount of oxygen consumed by the synthesis of linear glucosides of triphosphate is equal to the oxygen consumption to overcome the hydrogen ion leakage (Proton Leakage). The maximum oxygen consumption capacity of mitochondria minus the basic oxygen consumption of mitochondria is equal to the Spare Respiratory Capacity of mitochondria. The mitochondrial triphosphate glycoside mediation efficiency (Coupling Efficiency) is equal to the oxygen consumption of the synthetic triphosphate glycoside divided by the mitochondrial base oxygen consumption.

實施例一至實施例三與比較例一至比較例三的山桑子萃取物水溶液濃度與實驗量測結果如表一與圖1至圖6所示。表一中呈現的每微克蛋白質每分鐘消耗的氧氣皮莫耳數(pmol/min/μg蛋白質)之實驗量測結果為已對細胞量進行標準化後之實驗量測結果。圖1為實施例一至實施例三與比較例一至比較例三之合成三磷酸線苷的耗氧量示意圖。圖2為實施例一至實施例三與比較例一至比較例三之粒線體的基礎耗氧量示意圖。圖3為實施例一至實施例三與比較例一至比較例三之克服氫離子洩漏的耗氧量示意圖。圖4為實施例一至實施例三與比較例一至比較例三之粒線體的最大耗氧能力示意圖。圖5為實施例一至實施例三與比較例一至比較例三之粒線體的預存耗氧能力示意圖。圖6為實施例一至實施例三與比較例一至比較例三之粒線體的三磷酸線苷媒合效率示意圖。 The concentration and experimental measurement results of the aqueous solution of the mulberry seed extract in Examples 1 to 3 and Comparative Examples 1 to 3 are shown in Table 1 and FIGS. 1 to 6. The experimental measurement results of the oxygen pmoles per microgram protein per minute (pmol / min / μg protein) presented in Table 1 are the experimental measurement results after the cell mass has been standardized. FIG. 1 is a schematic diagram of oxygen consumption of synthetic triphosphates in Examples 1 to 3 and Comparative Examples 1 to 3. FIG. FIG. 2 is a schematic diagram of the basic oxygen consumption of the mitochondria of Examples 1 to 3 and Comparative Examples 1 to 3. FIG. FIG. 3 is a schematic diagram of oxygen consumption for overcoming hydrogen ion leakage in Examples 1 to 3 and Comparative Examples 1 to 3. FIG. FIG. 4 is a schematic diagram of the maximum oxygen consumption capacity of the mitochondria of Examples 1 to 3 and Comparative Examples 1 to 3. FIG. FIG. 5 is a schematic diagram of the pre-stored oxygen consumption capacity of the mitochondria of Examples 1 to 3 and Comparative Examples 1 to 3. FIG. FIG. 6 is a schematic diagram of the mitochondrial triphosphate glycoside mediation efficiency of the mitochondria in Examples 1 to 3 and Comparative Examples 1 to 3. FIG.

表一 Table I

如圖1所示,實施例一至實施例三之合成三磷酸線苷的耗氧量高於比較例一至比較例三。如圖2所示,實施例一至實施例三之粒線體的基礎耗氧量高於比較例一至比較例三。如圖3所示,實施例二與實施例三之克服氫離子洩漏的耗氧量低於比較例一至比較例三。如圖4 所示,實施例一至實施例三之粒線體的最大耗氧能力高於比較例一至比較例三。如圖5所示,實施例一至實施例三之粒線體的預存耗氧能力高於比較例一至比較例三。如圖6所示,實施例一至實施例三之粒線體的三磷酸線苷媒合效率高於比較例一至比較例三。因此,由圖1至圖6可知實施例一至實施例三之粒線體增加的基礎耗氧量主要用作合成三磷酸線苷,使得三磷酸線苷的合成量增加,亦即是粒線體的三磷酸線苷媒合效率提高。同時,實施例二與實施例三之粒線體內膜的氫離子洩漏量下降,亦即是粒線體重新將氫離子輸送至膜間隙的所消耗氧氣量減少,代表的是粒線體內膜破損的情況受到山桑子萃取物的修復而改善。 As shown in FIG. 1, the oxygen consumption of the synthetic triphosphates in Examples 1 to 3 is higher than that in Comparative Examples 1 to 3. As shown in FIG. 2, the basic oxygen consumption of the mitochondria of Examples 1 to 3 is higher than that of Comparative Examples 1 to 3. As shown in FIG. 3, the oxygen consumption for overcoming hydrogen ion leakage in the second and third embodiments is lower than that of the first to the third comparative examples. Figure 4 As shown, the maximum oxygen consumption capacity of the mitochondria of Examples 1 to 3 is higher than that of Comparative Examples 1 to 3. As shown in FIG. 5, the pre-stored oxygen consumption capacity of the mitochondria of Examples 1 to 3 is higher than that of Comparative Examples 1 to 3. As shown in FIG. 6, the mitochondrial triphosphate glycoside mediation efficiency of the mitochondria of Examples 1 to 3 is higher than that of Comparative Examples 1 to 3. Therefore, it can be known from FIG. 1 to FIG. 6 that the increased basic oxygen consumption of the mitochondria in Examples 1 to 3 is mainly used for synthesizing triphosphates, which increases the synthesis amount of triphosphates, that is, mitochondria The efficiency of thioglycoside triphosphate is improved. At the same time, the leakage amount of hydrogen ions in the inner membrane of the mitochondria decreased in the second and third embodiments, that is, the amount of oxygen consumed by the mitochondria to retransmit hydrogen ions to the membrane space decreased, which represented the damage of the inner membrane of the mitochondria. The condition was improved by the repair of the extract of mulberry seeds.

根據上述實驗測試結果,以濃度為每毫升25微克至250微克(μg/ml)的山桑子萃取物水溶液處理後的粒線體受到山桑子萃取物的保護而降低粒線體內膜受到氧化劑的破壞。因此,濃度為每毫升25微克至250微克(μg/ml)的山桑子萃取物水溶液具有保護粒線體之功效。 According to the results of the above experimental test, the mitochondria treated with an aqueous solution of mulberry seeds at a concentration of 25 micrograms to 250 micrograms per milliliter (μg / ml) are protected by the berry extract to reduce the damage of the inner membrane of the mitochondria to oxidants. . Therefore, an aqueous solution of mulberry seed extract at a concentration of 25 micrograms to 250 micrograms (μg / ml) per milliliter has the effect of protecting mitochondria.

同時,以濃度為每毫升50微克至250微克(μg/ml)的山桑子萃取物水溶液處理後的粒線體之粒線體內膜也受到山桑子萃取物的修復,使得自膜間隙穿過破損的內膜洩漏至基質中的氫離子量下降,進而使得粒線體重新將氫離子輸送至膜間隙所消耗氧氣量減少。因此,濃度為每毫升50微克至250微克(μg/ml)的山桑子萃取物水溶液除了保護粒線體之功效外,更同時具有修補粒線體之功效。 At the same time, the mitochondrial inner membrane of the mitochondria treated with an aqueous solution of the mulberry extract at a concentration of 50 to 250 micrograms per milliliter (μg / ml) was also repaired by the mulberry extract, causing the self-membrane gap to break through The amount of hydrogen ions leaking from the inner membrane to the matrix decreases, which in turn reduces the amount of oxygen consumed by the mitochondria to retransmit hydrogen ions to the membrane space. Therefore, in addition to the effect of protecting mitochondria, the aqueous solution of extract of mulberry seeds at a concentration of 50 to 250 micrograms (μg / ml) per milliliter has the effect of repairing mitochondria.

然而,未以山桑子萃取物水溶液處理的粒線體未受到山桑子萃取物的保護,以及以濃度為每毫升12.5微克(μg/ml)的山桑子萃取物水溶液處理後的粒線體受到保護的程度不足,以至於粒線體內膜受到氧化劑的破壞。再者,以濃度為每毫升500微克(μg/ml)的山桑子萃取物水溶液處理後的粒線體,由於濃度過高的山桑子萃取物水溶液對粒線體內膜造成的傷害大於保護與修復粒線體能力,使得比較例三之粒線體之基礎耗氧量、最大耗氧能力、預存耗氧能力與三磷酸線苷媒合效率較實施 例一至實施例三之粒線體之基礎耗氧量、最大耗氧能力、預存耗氧能力與三磷酸線苷媒合效率下降,比較例三之粒線體之克服氫離子洩漏的耗氧量較實施例二與實施例三之粒線體之克服氫離子洩漏的耗氧量上升。 However, mitochondria that have not been treated with an aqueous solution of Japanese mulberry extract are not protected by an extract of Japanese mulberry seeds, and mitochondria treated with an aqueous solution of Japanese mulberry extract at a concentration of 12.5 micrograms (μg / ml) per milliliter are protected. It is not enough that the inner membrane of mitochondria is damaged by oxidants. Furthermore, the mitochondria treated with an aqueous solution of mulberry extract at a concentration of 500 micrograms (μg / ml) per milliliter, because the excessively concentrated aqueous solution of mulberry extract caused more damage to the inner membrane of the mitochondria than protection and repair. Mitochondrial capacity, the basic oxygen consumption, maximum oxygen consumption capacity, pre-stored oxygen consumption capacity, and the efficiency of mitochondrial triphosphate mediation in the mitochondria of Comparative Example 3 were implemented. The basic oxygen consumption, maximum oxygen consumption capacity, pre-existing oxygen consumption capacity, and the efficiency of mitochondrial triphosphate glycosides of the mitochondria of Examples 1 to 3 are reduced. The oxygen consumption of the mitochondria of Comparative Example 3 to overcome hydrogen ion leakage is reduced. Compared with the mitochondria of Examples 2 and 3, the oxygen consumption to overcome the leakage of hydrogen ions increases.

根據上述本發明所揭露的山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷合成的能力、提高粒線體的預存耗氧能力以及提高粒線體的媒合效率之醫藥組合物的用途,提供山桑子萃取物予細胞以保護與修復粒線體的內膜以延緩粒線體發生崩解的時間。如此一來,可減緩粒線體崩解觸發細胞凋亡的速度。 The extract of mulberry seeds disclosed in the present invention is used for preparing protection and repairing mitochondria, improving the ability of mitochondria to undergo oxidative phosphorylation and synthesizing triphosphates, improving the pre-existing oxygen consumption capacity of mitochondria, and improving The use of the pharmaceutical composition of the mitochondrial mediation efficiency, to provide the extract of the mulberry seed to the cells to protect and repair the inner membrane of the mitochondria to delay the time for the mitochondria to disintegrate. In this way, the rate at which mitochondrial disintegration triggers apoptosis can be slowed.

雖然本發明以前述之實施例揭露如上,然其並非用以限定本發明。在不脫離本發明之精神和範圍內,所為之更動與潤飾,均屬本發明之專利保護範圍。關於本發明所界定之保護範圍請參考所附之申請專利範圍。 Although the present invention is disclosed in the foregoing embodiments, it is not intended to limit the present invention. Changes and modifications made without departing from the spirit and scope of the present invention belong to the patent protection scope of the present invention. For the protection scope defined by the present invention, please refer to the attached patent application scope.

Claims (10)

一種山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中,該山桑子萃取物含有花青素(Anthocyanidins);其中,當該醫藥組合物被提供予一細胞時,該山桑子萃取物以一山桑子萃取物水溶液的形式提供予該細胞,該山桑子萃取物水溶液的濃度為每毫升25至250微克(μg/ml)。 A mulberry extract is used for preparing protection and repairing mitochondria, improving the ability of mitochondria to undergo oxidative phosphorylation and ATP synthesis, improving the pre-existing oxygen consumption capacity of mitochondria, and improving mitochondria Use of a medicinal composition for synthesizing the efficiency of synthesizing triphosphates in a basic oxygen consumption amount for performing an oxidative phosphorylation reaction, wherein the mulberry extract contains anthocyanidins; wherein, when the medicinal composition When an extract is provided to a cell, the extract of the mulberry seed is provided to the cell in the form of an aqueous solution of the berry extract, and the concentration of the aqueous solution of the berry extract is 25 to 250 micrograms per milliliter (μg / ml). 一種山桑子萃取物用於製備保護與修復粒線體、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中該山桑子萃取物含有花青素,以及該山桑子萃取物的有效劑量為0.27克至2.7克。 A berry extract used for the preparation and protection of mitochondria, improving the pre-existing oxygen consumption capacity of mitochondria and improving the basic oxygen consumption of oxidative phosphorylation reaction of mitochondria for synthesizing triphosphate glycosides The use of an efficient pharmaceutical composition, wherein the mulberry extract contains anthocyanins, and the effective amount of the mulberry extract is 0.27 g to 2.7 g. 如請求項1所述之山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中該山桑子萃取物含有重量百分濃度25%以上之花青素。 The Mulberry Seed Extract as described in claim 1 is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria. The use of the pharmaceutical composition for improving the efficiency of mitochondrial oxidative phosphorylation in the basic oxygen consumption of mitochondria for synthesizing the efficiency of synthesizing triphosphates, wherein the mulberry extract contains a concentration of 25% by weight or more. anthocyanin. 如請求項1所述之山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三 磷酸線苷的媒合效率之醫藥組合物的用途,其中該山桑子萃取物水溶液的濃度為每毫升50~250微克(μg/ml)。 The Mulberry Seed Extract as described in claim 1 is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria. Used in the synthesis of mitochondria to increase the basic oxygen consumption of oxidative phosphorylation The use of a pharmaceutical composition for the mediation efficiency of phosphinosides, wherein the concentration of the aqueous solution of the mulberry seed extract is 50-250 micrograms (μg / ml) per milliliter. 如請求項1所述之山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中提供該山桑子萃取物予該細胞的步驟包含食用該山桑子萃取物。 The Mulberry Seed Extract as described in claim 1 is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria. The use of a pharmaceutical composition for improving the efficiency of mitochondrial oxidative phosphorylation in basal oxygen consumption of mitochondria for synthesizing the efficiency of synthesizing triphosphates, wherein the step of providing the mulberry seed extract to the cells comprises eating the Mountain Mulberry Extract. 如請求項5所述之山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中食用的該山桑子萃取物的有效劑量為0.27克(g)至2.7克。 The mulberry extract as described in claim 5 is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria. The use of a pharmaceutical composition for improving the efficiency of mitochondrial oxidative phosphorylation in the basic oxygen consumption of mitochondria for synthesizing the efficiency of synthesizing triphosphates, wherein the effective amount of the edible mulberry extract is 0.27 g ( g) to 2.7 grams. 如請求項6所述之山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中該山桑子萃取物被包覆於軟膠囊或硬膠囊中。 The Mulberry Seed Extract as described in claim 6 is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria. Capability and use of a pharmaceutical composition for improving the efficiency of mitochondrial oxidative phosphorylation in the basic oxygen consumption of synthesizing triphosphates, wherein the mulberry extract is coated in soft or hard capsules in. 如請求項1所述之山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中該山桑子萃取物提高該些粒線體進行該氧化磷酸化反應的該基礎耗氧量。 The mulberry extract as described in claim 1 is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria The use of a pharmaceutical composition for improving the efficiency of mitochondrial oxidative phosphorylation in the basic oxygen consumption of mitochondria for synthesizing the efficiency of synthesizing triphosphates, wherein the mulberry extract enhances the mitochondria to perform the oxidation This basic oxygen consumption of the phosphorylation reaction. 如請求項1所述之山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中該山桑子萃取物提高該些粒線體的一三磷酸腺苷最大極限產量。 The Mulberry Seed Extract as described in claim 1 is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria. The use of a pharmaceutical composition for improving the efficiency of mitochondrial oxidative phosphorylation in the basic oxygen consumption of mitochondria for synthesizing the synergistic efficiency of triphosphates, wherein the extract of the mulberry seed enhances the adenosine monophosphates of the mitochondria Maximum limit production. 如請求項1所述之山桑子萃取物用於製備保護與修復粒線體、提高粒線體進行氧化磷酸化反應與三磷酸線苷(ATP)合成的能力、提高粒線體的預存耗氧能力以及提高粒線體進行氧化磷酸化反應的基礎耗氧量中使用於合成三磷酸線苷的媒合效率之醫藥組合物的用途,其中該山桑子萃取物以一山桑子萃取物水溶液的形式提供予該細胞,當該山桑子萃取物水溶液的濃度為每毫升50至250微克(μg/ml)時,該山桑子萃取物降低該些粒線體的一氫離子洩漏(Proton Leakage)。 The Mulberry Seed Extract as described in claim 1 is used to prepare and protect mitochondria, improve the ability of mitochondria to undergo oxidative phosphorylation and synthesize ATP, and increase the pre-existing oxygen consumption of mitochondria. Capability and use of a pharmaceutical composition for improving the efficiency of mediation of oxidative phosphorylation of mitochondria for oxidative phosphorylation of mitochondrial triphosphates, wherein the mulberry extract is in the form of an aqueous solution of the mulberry extract Provided to the cells, when the concentration of the aqueous solution of the wild mulberry extract was 50 to 250 micrograms (μg / ml) per milliliter, the wild mulberry extract reduced a hydrogen ion leakage of the mitochondria (Proton Leakage).
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