WO2022134332A1 - 芦荟苦素在制备预防或治疗肥胖产品中的应用 - Google Patents

芦荟苦素在制备预防或治疗肥胖产品中的应用 Download PDF

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WO2022134332A1
WO2022134332A1 PCT/CN2021/082124 CN2021082124W WO2022134332A1 WO 2022134332 A1 WO2022134332 A1 WO 2022134332A1 CN 2021082124 W CN2021082124 W CN 2021082124W WO 2022134332 A1 WO2022134332 A1 WO 2022134332A1
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aloin
preparation
preventing
aloe
treating obesity
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French (fr)
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王燕
李友宾
谭银丰
王雪松
徐俊裕
曾婷婷
崔雪
陈煜�
张雪映
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海南医学院
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents

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  • the invention relates to the technical field of botanical medicines, in particular to the application of aloe verain in the preparation of products for preventing or treating obesity.
  • Obesity refers to excess fat accumulation caused by calorie intake greater than consumption, and it is one of the major health problems facing the world today. In 2015, an estimated 609 million adults worldwide were obese, twice as many as in 1980. Obesity is a serious risk factor for insulin resistance, diabetes, atherosclerosis and cardiovascular disease. Changing eating habits and increasing physical activity are traditional methods of treating obesity. However, after controlling diet and increasing exercise, the effect of reducing fat is temporary, and weight will rebound. In addition, other methods such as bariatric surgery and medication have their own risks and side effects such as alcoholism and acute kidney injury.
  • Aloe vera is a commonly used medicine in several traditional countries including Greece, Egypt, India, Mexico, Japan and China. In my country, it is commonly used as a laxative to treat constipation.
  • Aloe vera is the application of aloe vera extracted from aloe vera in the preparation of products for preventing or treating obesity.
  • Aromatic C-glycosylated 5-methylchromones are widely distributed in most aloe vera species and have a wide range of pharmacological effects. It is generally believed that it can directly inhibit melanin production and tyrosinase activity, and aloe verain can promote wound healing and improve diabetic syndrome by inhibiting oxidation and interfering with MAPK/Rho and Smad signaling pathways.
  • aloin has been continuously reported, such as improving insulin resistance, inhibiting the exacerbation of colitis in rats, inhibiting the cell growth and metastasis of ovarian cancer SKOV3 cells, and inhibiting colorectal cancer by interfering with Wnt/ ⁇ -catenin and Notch signaling pathways. cell growth.
  • aloe verain has anti-obesity effects remains unclear.
  • the present invention provides the application of aloin in the preparation of anti-obesity agents, obesity treatment agents and related products.
  • aloin in the preparation of an anti-obesity agent for preventing obesity.
  • aloin in the preparation of an obesity therapeutic agent for treating obesity.
  • aloin in the preparation of a UCP1 gene expression promoter for preventing or treating obesity.
  • aloin in the preparation of PDRM16 gene expression promoter for preventing or treating obesity.
  • aloin in the preparation of UCP-1 and PDRM16 gene expression promoters for preventing or treating obesity.
  • aloin in the preparation of a transcription factor C-EBP ⁇ expression promoter for preventing or treating obesity.
  • aloin in the preparation of an adiponectin promoter for preventing or treating obesity.
  • aloin in the preparation of IL-1 ⁇ inhibitor for preventing or treating obesity.
  • the beneficial effects of the present invention are: the present invention finds that aloe verain can inhibit lipid accumulation, increase the expression of the browning genes UCP1 and PRDM16 and the transcription factor C-EBP ⁇ , and improve the specificity factor adiponectin.
  • the expression and release of IL-1 ⁇ inhibited the release of non-specific factor IL-1 ⁇ , indicating that aloin can mediate the browning of 3T3-L1 adipocytes, and aloin can be used to prepare products for preventing or treating obesity.
  • aloe verain is derived from plants, with high safety, providing a better choice for obese patients, and at the same time, making aloe verain exert a higher value.
  • Figure 2 The effect of aloe verain on preadipocyte differentiation.
  • Oil red O staining image (A) lipid accumulation after pretreatment with aloin for 24 h
  • B lipid accumulation after pretreatment with aloin for 48 h
  • FIG. 3 Effects of aloe verain on lipid accumulation in adipocytes.
  • 3T3-L1 preadipocytes were originally derived from Swiss mouse embryonic tissue. Because of its potential to differentiate from fibroblasts to mature adipocytes, this cell line has been widely used in mechanistic studies of obesity, diabetes and related diseases. Therefore, in this experiment, we will select 3T3-L1 preadipocytes and adipocytes to explore the effect of aloe verain on adipocytes.
  • Mouse 3T3-L1 preadipocytes were seeded at a density of 1 x 10 4 /mL in high glucose medium containing 10% fetal bovine serum (Gibco) and antibiotics (100 U/mL penicillin G and 100 mg/mL, streptomycin) (H-DMEM, Hyclon) for 72 hours in an incubator at 37°C and 5% CO 2 .
  • 10% fetal bovine serum, 10 ⁇ g/mL insulin (sigma), 1 ⁇ M dexamethasone (sigma), 0.5 mM isobutyl group were added at 80% cell confluency, that is, on day 0.
  • GM 1-methylxanthine
  • Cell viability was measured by MTT, 3T3-L1 preadipocytes were seeded in 96-well plates at a density of 1 ⁇ 10 4 /mL, cultured in an incubator for 24 h, and then replaced with media containing 10, 15, 30 and 60 ⁇ M aloe verain. Continue to cultivate for 24h or 48h. 0.5% MTT was added to the cells, and after incubation at 37°C for 1 h, the MTT solution was removed and DMSO was added to dissolve. Absorbance at 570 nm was measured using a microplate reader (Molecular Devices, CA, USA). Cell viability (%) is expressed as a percentage relative to untreated control cells.
  • Differentiated adipocytes were washed 3 times with PBS, fixed with 10% formaldehyde for 1 h, then washed with PBS for 3 times, dried for 15 to 30 min, and stained with Oil Red O working solution for 2 h. Washed 2 and 3 times with 60% isopropanol (IPA) and double distilled water, respectively. Images were acquired using a Zeiss fluorescence microscope (Tokyo, Japan). Oil red O was extracted with 100% IPA, and the absorbance at 490 nm was measured.
  • IPA isopropanol
  • RNA from 3T3-L1 adipocytes was extracted using total RNA extraction reagent (TIANGEN, China). Reverse transcription to cDNA was performed using the 1 st strand cDNA kit (Vazyme biotechnology). Adipocyte browning genes (Ucp-1 and PRDM16) and transcription factors (Fabp, Ppar- ⁇ and C-EBP ⁇ ) were detected by SYBR Green PCR Master Mix Kit (Monad, China) and CFX-1000Touch instrument (Applied Biosystems, USA). ) mRNA levels. Reverse transcription was performed using the following conditions: 5 min at 25°C, 15 min at 50°C and 5 min at 85°C.
  • 3T3-L1 adipocytes were treated with aloe verain for 48 h and the supernatant was collected, and the levels of adiponectin and IL-1 ⁇ in the supernatant were detected by ELISA kit (Proteintech, China). The ELISA reagent operation was carried out according to the manufacturer's instructions.
  • 3T3-L1 preadipocytes were pretreated with 15 and 30 ⁇ M aloin for 24h and 48h and then differentiated for 10 days.
  • the induced differentiated adipocytes were detected by oil red staining.
  • the results showed that pretreatment with 15 and 30 ⁇ M aloin for 24 h (Fig. 2A and Fig. 2B) and 48 h (Fig. 2A and Fig. 2C) had no effect on the differentiation of 3T3-L1 preadipocytes.
  • adipocyte-specific cytokines adiponectin
  • IL-1 ⁇ non-specific cytokines
  • aloe verain could reduce lipid accumulation by activating the browning of white adipocytes and improve the specific and non-specific pro-inflammatory effects of adipocytes.
  • Aloin can reduce lipid accumulation in 3T3-L1 adipocytes and increase the mRNA expressions of UCP1 and PRDM16, indicating that aloin may inhibit lipid accumulation by inducing browning of adipocytes.
  • Aloin can increase the expression and secretion of adiponectin mRNA, reduce the secretion of non-specific cytokine IL-1 ⁇ , and further consolidate the effect of aloe in inducing the browning of 3T3-L1 adipocytes.
  • Aloe verain can enhance the mRNA expression of adipogenic transcription factor C-EBP ⁇ , but not FABP and PPAR- ⁇ , indicating that the mechanism of aloe verain-induced browning is related to its enhanced expression of transcription factor C-EBP ⁇ .
  • aloin can inhibit lipid accumulation, increase the expression of browning genes UCP1 and PRDM16 and transcription factor C-EBP ⁇ , improve the expression and release of specific factor adiponectin, and inhibit non-specific factor IL-1 ⁇ . , indicating that aloe verain can mediate the browning of 3T3-L1 adipocytes.
  • Aloe verain can be used to prepare products for preventing or treating obesity, and can be used to prepare anti-obesity agents for preventing obesity or obesity therapeutic agents for treating obesity, and the like.

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Abstract

芦荟苦素在制备预防或治疗肥胖产品中的应用。芦荟苦素能够抑制脂质堆积，增加褐化基因UCP1和PRDM16及转录因子C-EBPα的表达，提高特异性因子脂联素的表达和释放，抑制非特异性因子IL-1β的释放，表明芦荟苦素能够介导3T3-L1脂肪细胞的褐化，可将芦荟苦素应用于制备预防或治疗肥胖产品。

Description

芦荟苦素在制备预防或治疗肥胖产品中的应用 技术领域
本发明涉及植物药物技术领域，特别涉及芦荟苦素在制备预防或治疗肥胖产品中的应用。
背景技术
肥胖指因热量摄入大于消耗导致的过剩脂肪堆积，是目前全球面临的主要健康问题之一。2015年，全球估计有6.09亿成年人肥胖，相当于1980年的两倍。肥胖是导致胰岛素抵抗、糖尿病、动脉粥样硬化和心血管疾病的严重风险因素。改变饮食习惯和增加体育锻炼是传统治疗肥胖的方法，然而在控制饮食和增加运动后，脂肪的减少效应是暂时性的，体重会出现反弹情况。此外，减肥手术和药物治疗等其他方法也有其本身的风险和副作用如酗酒和急性肾损伤等。
芦荟是希腊、埃及、印度、墨西哥、日本和中国等几个传统国家常用的药物。在我国常用作通便剂治疗便秘。芦荟苦素是从芦荟中提取的芦荟苦素在制备预防或治疗肥胖产品中的应用芳香族C-糖基化5-甲基色酮类化合物，广泛分布于大多数芦荟物种中，具有广泛的药理作用。通常认为它能够直接抑制黑色素的生成和酪氨酸酶活性，此外芦荟苦素能够通过抑制氧化和干扰MAPK/Rho和Smad信号通路促进伤口愈合，并改善糖尿病综合征。近来芦荟苦素的新药理作用不断被报道，如改善胰岛素抵抗，抑制大鼠结肠炎加重，抑制卵巢癌SKOV3细胞的细胞生长和转移，通过干扰Wnt/β-catenin和Notch信号通路抑制结直肠癌细胞的生长。然而，芦荟苦素是否具有抗肥胖作用仍不清楚。
发明内容
鉴于此，本发明提供芦荟苦素在制备抗肥胖剂、肥胖治疗剂以及相关产品中的应用。
本发明的技术方案是这样实现的：
芦荟苦素在制备用于预防肥胖症的抗肥胖剂中的应用。
芦荟苦素在制备用于治疗肥胖症的肥胖治疗剂中的应用。
芦荟苦素在制备用于预防或治疗肥胖症的UCP1基因表达促进剂中的应用。
芦荟苦素在制备用于预防或治疗肥胖症的PDRM16基因表达促进剂中的应用。
芦荟苦素在制备用于预防或治疗肥胖症的UCP-1和PDRM16基因表达促进剂中的应用。
芦荟苦素在制备用于预防或治疗肥胖症的转录因子C-EBPα表达促进剂中的应用。
芦荟苦素在制备用于预防或治疗肥胖症的脂联素促进剂中的应用。
芦荟苦素在制备用于预防或治疗肥胖症的IL-1β抑制剂中的应用。
与现有技术相比，本发明的有益效果是：本发明研究发现芦荟苦素能够抑制脂质堆积，增加褐化基因UCP1和PRDM16及转录因子C-EBPα的表达，提高特异性因子脂联素的表达和释放，抑制非特异性因子IL-1β的释放，表明芦荟苦素能够介导3T3-L1脂肪细胞的褐化，可将芦荟苦素应用于制备预防或治疗肥胖产品。而且芦荟苦素来源于植物，安全性较高，为肥胖症患者提供更优选择，同时，使得芦荟苦素发挥更高的价值。
附图说明
图1芦荟苦素的化学结构(A)和实验设计(B)。芦荟苦素预处理24h(C)和48h(D)后对细胞活力的影响。n＝6-12。
图2芦荟苦素对前脂肪细胞分化的影响。油红O染色图像(A)，芦荟苦素预处理24h的脂质蓄积情况(B)，芦荟苦素预处理48h后的脂质蓄积情况，n＝6(C)。
图3芦荟苦素对脂肪细胞脂质蓄积的影响。油红O染色图像(A)。芦荟苦素处理脂肪细胞24h的脂质蓄积情况(B)。芦荟苦素处理脂肪细胞48h的脂质蓄积情况，n＝6(C)。
图4芦荟苦素对3T3-L1脂肪细胞中UCP-1、PRDM16、PPAR-γ、C-EBPα和FABP的mRNA表达的影响。n＝4-8。
图5芦荟苦素对3T3-L1脂肪细胞中脂联素和IL-1β的mRNA表达和释放的影响。n＝3-8。
具体实施方式
为了更好理解本发明技术内容，下面提供具体实施例，对本发明做进一步的说明。
本发明实施例所用的实验方法如无特殊说明，均为常规方法。
本发明实施例所用的材料、试剂等，如无特殊说明，均可从商业途径得到。
3T3-L1前脂肪细胞最初来源于瑞士小鼠胚胎组织。因其具有从成纤维细胞分化为成熟脂肪细胞的潜力，该细胞系已被广泛用于肥胖、糖尿病及其相关疾病的机制研究中。因此，在本实验，我们将选择3T3-L1前脂肪细胞和脂肪细胞，探索芦荟苦素对脂肪细胞的影响。
1.材料和方法
1.1细胞培养
小鼠3T3-L1前脂肪细胞以1×10 4/mL的密度接种于含10％胎牛血清(Gibco)和抗生素(100U/mL青霉素G和100mg/mL，链霉素)的高糖培养基(H-DMEM，Hyclon)中，于37℃和5％CO 2的培养箱中培养72小时。为诱导3T3-L1前脂肪细胞分化，在80％细胞融合时，即第0天加入含10％胎牛血清、10μg/mL胰岛素(sigma)、1μM***(sigma)、0.5mM异丁基-1-甲基黄嘌呤(sigma)的生长培养基(GM)。第2天，更换为含10％小牛血清和10μg/mL胰岛素的高糖培养基中，直至第10天，前脂肪细胞分化出现大量脂滴积累。
1.2 MTT法
通过MTT测定细胞活力，将3T3-L1前脂肪细胞以1×10 4/mL密度接种于96孔板中，于培养箱培养24h，随后置换含10，15，30和60μM芦荟苦素的培养基继续培养24h或48h。将0.5％MTT加入到细胞中，37℃下孵育1h后，移除MTT溶液，加入DMSO溶解。使用酶标仪(Molecular Devices,CA,USA)测定570nm处的吸光度。细胞活力(％)表示为相对于未处理对照细胞的百分比。
1.3油红染色
将分化的脂肪细胞用PBS洗涤3次，10％甲醛固定1h，然后再用PBS洗涤3次，干燥15至30分钟后应用油红O工作溶液染色2h。分别用60％异丙醇(IPA)和双蒸水洗涤2次和3次。应用蔡司荧光显微镜(日本东京)采集图像。100％IPA提取油红O，测定490nm的吸光度。
1.4实时定量PCR分析
采用总RNA提取试剂(TIANGEN，China)提取3T3-L1脂肪细胞中的总RNA。使用1 ststrand cDNA试剂盒(Vazyme biotechnology)进行反转录为cDNA。应用SYBR Green PCR Master Mix Kit(Monad,China)试剂和CFX-1000Touch仪器(Applied Biosystems,USA)检测脂肪细胞褐化基因(Ucp-1和PRDM16)和转录因子(Fabp、Ppar-γ和C-EBPα)的mRNA水平。使用以下条件进行逆转录：25℃下5min、50℃下15min和85℃下5min。扩增：95℃下初始变性30秒，随后95℃变性5秒和59℃变性30秒(40个循环)。将β-肌动蛋白作为参考基因以标准化qPCR反应。基于样品之间的平均Ct值计算基因的相对表达。相对表达量＝2^{[Ct 目的基因–Ct(β-actin)] 芦荟苦素处理组-[Ct 目的基因–Ct(β-actin)]3T3-L1 脂肪细胞]}.
表1.引物序列
Figure PCTCN2021082124-appb-000001
Figure PCTCN2021082124-appb-000002
1.5酶联免疫吸附试验(ELISA)
3T3-L1脂肪细胞经芦荟苦素处理48h后收集上清液，应用ELISA试剂盒(Proteintech,China)检测上清液中脂联素和IL-1β的水平。ELISA试剂操作按厂家说明书进行。
1.6统计分析
结果值表示为均值±标准误。使用GraphPad Prism 8软件通过单因素方差分析或双侧T检验分析统计学显著性，P<0.05认为具有统计学差异。
2.结果
2.1芦荟苦素对3T3-L1前脂肪细胞活力的影响
通过MTT法评价芦荟苦素对3T3-L1前脂肪细胞活力的影响。15和30μM芦荟苦素预处理前脂肪细胞24h对前脂肪细胞活力无影响。10-60μM浓度芦荟苦素预处理48h，亦对前脂肪细胞活力无影响。因此，我们选择了15μM和30μM浓度的芦荟苦素用于进一步研究(图1C和1D)。
如图1所示，芦荟苦素的化学结构(A)和实验设计(B)。芦荟苦素预处理24h(C)和48h(D)后对细胞活力的影响。n＝6-12。
2.2芦荟苦素不影响前脂肪细胞的分化
应用15和30μM的芦荟苦素预处理3T3-L1前脂肪细胞培养24h和48h后将前脂肪细胞分化10天，应用油红染色检测诱导分化的脂肪细胞。结果显示，15和30μM芦荟苦素预处理24h(图2A和图2B)和48h(图2A和图2C)后对3T3-L1前脂肪细胞的分化并无影响。
2.3芦荟苦素减少3T3-L1脂肪细胞的脂质堆积
将3T3-L1前脂肪细胞诱导分化为脂肪细胞后，在脂肪细胞中分别加入芦荟苦素(15和30μM)培养24h和48h。结果显示，芦荟苦素(15和30μM)处理24h不影响3T3-L1脂肪细胞中的脂质堆积(图3A和图3B)。然而，与对照组相比，用15和30μM芦荟苦素处理48h能够显著降低脂肪细胞的脂质堆积(图3A和图3C)。
2.4芦荟苦素通过诱导褐变降低脂肪细胞内脂质堆积
为深入探索芦荟苦素对脂质堆积的影响机制，我们通过实时荧光定量PCR分析了与脂肪细胞褐变相关关键基因的mRNA表达。结果发现，芦荟苦素能够提高褐变基因(UCP-1和PDRM16)的表达。进一步的结果显示，15和30μM的芦荟苦素均能提高转录因子C-EBPα的表达，但对FABP和PPAR-γ并无影响，提示芦荟苦素对UCP-1和PDRM16转录的影响可能受到C-EBPα的调节，但与FABP和PPAR-γ不相关(图4)。
2.5芦荟苦素增加脂肪细胞特异性细胞因子(脂联素)的释放，降低非特异性细胞因子(IL-1β)的表达
15μM芦荟苦素能够增强脂肪细胞中脂联素的mRNA表达和释放，而15和30μM芦荟苦素处理后能够降低脂肪细胞中IL-1β的释放(图5)。
在本研究中发现，(1)芦荟苦素能够通过激活白色脂肪细胞的褐化减少脂质蓄积，改善脂肪细胞的特异性和非特异性促炎作用。
(2)芦荟苦素能够降低3T3-L1脂肪细胞的脂质蓄积，增加UCP1和PRDM16的mRNA表达，说明芦荟苦素可能通过诱导脂肪细胞褐变来抑制脂质蓄积。
(3)芦荟苦素能够增加脂联素mRNA的表达和分泌，减少非特异性细胞因子IL-1β的分泌，更加夯实芦荟苦素诱导3T3-L1脂肪细胞褐化的作用。
(4)芦荟苦素能够增强脂肪形成转录因子C-EBPα，而不是FABP和PPAR-γ的mRNA表达，说明芦荟苦素诱导褐化的机制与其增强转录因子C-EBPα的表达相关。
综上，本发明发现芦荟苦素能够抑制脂质堆积，增加褐化基因UCP1和PRDM16及转录因子C-EBPα的表达，提高特异性因子脂联素的表达和释放，抑制非特异性因子IL-1β的释放，说明芦荟苦素能够介导3T3-L1脂肪细胞的褐化。芦荟苦素可应用于制备预防或治疗肥胖产品，可应用于制备预防肥胖的抗肥胖剂或者治疗肥胖的肥胖治疗剂等。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所做的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (8)

  1. 芦荟苦素在制备用于预防肥胖的抗肥胖剂中的应用。
  2. 芦荟苦素在制备用于治疗肥胖的肥胖治疗剂中的应用。
  3. 芦荟苦素在制备用于预防或治疗肥胖的UCP1基因表达促进剂中的应用。
  4. 芦荟苦素在制备用于预防或治疗肥胖的PDRM16基因表达促进剂中的应用。
  5. 芦荟苦素在制备用于预防或治疗肥胖的UCP-1和PDRM16基因表达促进剂中的应用。
  6. 芦荟苦素在制备用于预防或治疗肥胖的转录因子C-EBPα表达促进剂中的应用。
  7. 芦荟苦素在制备用于预防或治疗肥胖的脂联素促进剂中的应用。
  8. 芦荟苦素在制备用于预防或治疗肥胖的IL-1β抑制剂中的应用。
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