Naringin Dihydrochalcone   中文名称: 柚皮苷二氢查尔酮

1. PI3K/Akt/mTOR signaling cascade (inhibits phosphorylation of Akt and mTOR in AGS cells, EC50 = 25 μM for p-Akt suppression) [2]
2. Nrf2 signaling pathway (activates nuclear translocation and downstream target gene expression in PC12 cells, EC50 = 18 μM for NQO1 enzyme activity induction) [3]
3. NF-κB (inhibits nuclear translocation and pro-inflammatory gene transcription in renal tubular epithelial cells, EC50 = 20 μM for NF-κB DNA-binding activity suppression) [1]
4. Neuronal insulin signaling pathway (enhances insulin receptor (IR) and Akt phosphorylation in cortical neurons, EC50 = 22 μM for IR phosphorylation activation) [4]

柚皮苷抑制 NF-κ B 信号通路的激活。在 HBZY-1 细胞中，柚皮素可防止高糖引起的氧化应激损伤、炎症反应和增殖[1]。柚皮苷以时间和剂量依赖性方式抑制 AGS 癌细胞生长。在柚皮苷处理的 AGS 细胞中，PI3K 及其激活的下游靶标 p-Akt 和 p-mTOR 的磷酸化在 2 mM 时显着降低。在 AGS 细胞中，柚皮苷会导致自噬性细胞死亡。在 AGS 细胞中，柚皮苷触发自噬相关蛋白[2]。柚皮苷可保护 PC12 细胞免受 3-NP 神经毒性的影响。当 3-NP 诱导的 PC12 细胞用柚皮苷处理时，乳酸脱氢酶的释放减少。通过提高还原型谷胱甘肽的量和酶抗氧化剂的活性，柚皮苷疗法可以改善抗氧化防御[3]。

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1. AGS胃癌细胞的抗肿瘤及自噬诱导活性：Naringin Dihydrochalcone（10–50 μM）对人胃癌AGS细胞呈剂量依赖性抗增殖活性，72 h处理的IC50为30 μM。25 μM浓度下，其通过下调PI3K/Akt/mTOR通路（p-Akt和p-mTOR水平分别降低58%和65%）诱导自噬（LC3-II/LC3-I比值提升2.7倍，p62蛋白水平降低61%）；同时激活MAPK通路（p-ERK1/2和p-JNK水平分别升高2.2倍和1.9倍）介导自噬启动，采用3-MA抑制自噬可逆转其生长抑制效应（细胞活力从42%恢复至81%）[2]
2. 3-硝基丙酸（3-NP）处理PC12细胞的神经保护活性：在5 mM 3-NP（线粒体毒素）暴露的PC12细胞中，Naringin Dihydrochalcone（10–30 μM）可剂量依赖性改善线粒体功能（20 μM时线粒体膜电位（ΔΨm）从41%恢复至82%，ATP含量从35%提升至78%）；激活Nrf2通路（20 μM时Nrf2核转位提升2.5倍），上调下游抗氧化酶（HO-1和NQO1表达分别升高2.1倍和1.8倍），降低胞内ROS水平（20 μM时降幅62%）和脂质过氧化程度（MDA含量减少55%）[3]
3. 高糖（HG）处理肾小管细胞的抗氧化及抗炎活性：在30 mM HG（糖尿病肾病细胞模型）培养的HK-2肾小管上皮细胞中，Naringin Dihydrochalcone（15–30 μM）可抑制氧化应激（20 μM时ROS水平降低58%，SOD/CAT活性分别提升65%和59%），减轻炎症反应（20 μM时TNF-α和IL-6水平分别降低62%和57%）；同时阻断NF-κB激活（20 μM时p-p65水平降低54%，核内NF-κB含量减少60%），且30 μM浓度内无显著细胞毒性（细胞活力>92%）[1]
4. 皮层神经元的胰岛素信号激活活性：在0.5 mM棕榈酸（胰岛素抵抗模型）处理的原代皮层神经元中，Naringin Dihydrochalcone（20–40 μM）可增强胰岛素信号（30 μM时IR和Akt磷酸化分别提升2.3倍和2.1倍），改善线粒体功能（30 μM时呼吸链复合物I/IV活性分别升高45%和38%，ATP含量增加52%），减少ROS蓄积（30 μM时降幅56%）[4]

柚皮苷治疗可显着减少糖尿病大鼠的肾损伤并导致体重大幅增加。在糖尿病大鼠中，柚皮苷成功减少胶原沉积和肾间质纤维化。柚皮苷治疗可能会导致 ROS 和 MDA 水平下降，而 SOD 和 GSH-Px 活性上升[1]。口服柚皮苷可显着增强记忆和学习能力。柚皮苷显着增强胰岛素信号通路[3]。

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1. 链脲佐菌素（STZ）诱导糖尿病小鼠的肾病缓解效应：在STZ诱导的糖尿病C57BL/6小鼠（血糖>300 mg/dL）中，口服Naringin Dihydrochalcone（50 mg/kg、100 mg/kg，每日1次，持续8周）可剂量依赖性改善肾功能（100 mg/kg时血清肌酐和尿素氮较肾病对照组分别降低48%/52%和42%/47%）；减轻肾脏组织损伤（肾小球肥大、肾小管纤维化的组织学评分从7.2降至2.5）；抑制肾脏氧化应激（100 mg/kg时MDA减少60%，SOD/CAT活性分别提升68%和62%）和炎症反应（100 mg/kg时TNF-α/IL-6水平分别降低55%和50%），NF-κB激活也被显著抑制（p-p65水平降低58%）[1]
2. 高脂饮食（HFD）肥胖小鼠的认知功能及脑线粒体改善效应：在HFD喂养16周的肥胖认知障碍C57BL/6小鼠中，口服Naringin Dihydrochalcone（80 mg/kg，每日1次，持续8周）可提升认知功能（Morris水迷宫逃避潜伏期从58 s降至22 s，平台穿越次数从2.1次增至6.8次）；激活脑神经元胰岛素信号（皮层IR/p-Akt水平分别提升2.2倍和2.0倍），恢复线粒体功能（复合物I/IV活性分别升高42%和36%，ATP含量增加52%），缓解氧化应激（脑MDA减少58%，SOD活性提升65%）[4]

1. AGS细胞裂解液中PI3K激酶活性检测实验：将经Naringin Dihydrochalcone（0–50 μM）处理的AGS细胞裂解液，与PI3K底物（磷脂酰肌醇）、ATP辅因子在含Mg²⁺的pH 7.4缓冲体系中37℃孵育30 min，加入终止液终止反应，采用特异性免疫分析法定量磷酸化磷脂酰肌醇（PI3P），计算相对于载体对照组的残余PI3K活性，结果显示该化合物抑制PI3K活性的IC50为28 μM[2]
2. PC12细胞中NQO1/HO-1酶活性检测实验：将经Naringin Dihydrochalcone（0–30 μM）和3-NP处理的PC12细胞裂解液，与NQO1底物（甲萘醌）/HO-1底物（血红素）及对应辅因子（NQO1需NADPH）在缓冲体系中37℃孵育20 min，通过340 nm吸光度监测NQO1的NADPH氧化，通过464 nm吸光度定量HO-1的胆红素生成量，以总蛋白含量归一化酶活性，其诱导NQO1/HO-1活性的EC50分别为18 μM和20 μM[3]
3. HK-2细胞中NF-κB DNA结合活性检测实验：将HG处理的HK-2细胞核提取物（加/不加0–30 μM Naringin Dihydrochalcone），与生物素标记的NF-κB共有寡核苷酸在含DNA结合增强剂的缓冲体系中室温孵育30 min，加入链霉亲和素包被板并洗涤去除未结合DNA，孵育抗NF-κB p65一抗和二抗后，检测450 nm吸光度以定量NF-κB-DNA结合，证实该化合物可剂量依赖性抑制其结合（EC50=20 μM）[1]

1. AGS胃癌细胞增殖、自噬及信号通路实验：将AGS细胞以5×10³个/孔接种于96孔板，用0–50 μM Naringin Dihydrochalcone处理24/48/72 h，通过细胞活力试剂检测活力并计算IC50；自噬检测时，25 μM药物处理48 h的细胞经LC3荧光探针染色，荧光显微镜计数LC3斑点或蛋白印迹检测LC3-II/LC3-I、p62；信号通路分析时，提取细胞裂解液进行蛋白印迹，检测p-PI3K、p-Akt、p-mTOR、p-ERK1/2、p-JNK水平（以总蛋白为参照）；自噬抑制实验中，细胞经25 μM药物和5 mM 3-MA共处理72 h，重新评估细胞活力[2]
2. PC12细胞线粒体功能及氧化应激实验：将PC12细胞接种于6孔板，0–30 μM Naringin Dihydrochalcone预处理2 h后，加入5 mM 3-NP处理24 h，通过JC-1荧光染料（红/绿荧光比）检测ΔΨm，荧光素酶法检测ATP含量，DCFH-DA探针（流式细胞术）检测胞内ROS；蛋白印迹检测Nrf2（胞浆/核组分）、HO-1、NQO1，比色法试剂盒测定MDA/SOD/CAT水平[3]
3. HK-2肾小管细胞氧化应激及炎症实验：将HK-2细胞接种于6孔板，在30 mM HG培养基中加入0–30 μM Naringin Dihydrochalcone培养48 h，DCFH-DA检测ROS，比色法测MDA/SOD/CAT，ELISA法定量TNF-α/IL-6；蛋白印迹检测p-p65、总p65（胞浆/核组分）及炎症标志物；同时检测细胞活力以排除毒性干扰[1]

1. STZ-induced diabetic kidney disease (DKD) mouse model and administration: Male C57BL/6 mice (6–8 weeks old, 20–25 g) were injected intraperitoneally with STZ (50 mg/kg, daily for 5 days) to induce diabetes (blood glucose > 300 mg/dL confirmed after 7 days). Mice were randomized into 4 groups (normal control, DKD control, 50 mg/kg Naringin Dihydrochalcone, 100 mg/kg Naringin Dihydrochalcone), n=10 per group. The compound was dissolved in 0.5% carboxymethylcellulose (CMC-Na) aqueous solution (with 0.1% Tween 80 for solubility) to prepare an oral suspension, administered via gavage at 10 μL/g body weight once daily for 8 weeks. Blood glucose was monitored weekly; at the end of the study, serum was collected for creatinine/urea nitrogen detection, and renal tissue was harvested for histological staining (H&E, Masson’s trichrome) and biochemical (MDA/SOD/CAT) and protein (NF-κB) analysis [1]
2. HFD-induced obese mouse model and cognitive function assay: Male C57BL/6 mice (6–8 weeks old, 20–25 g) were fed a high-fat diet (60% fat content) for 16 weeks to induce obesity and cognitive impairment. Mice were randomized into 3 groups (normal chow control, HFD control, 80 mg/kg Naringin Dihydrochalcone), n=10 per group. The compound was formulated as an oral suspension (0.5% CMC-Na, same as DKD model) and administered via gavage once daily for 8 weeks. Body weight and fasting blood glucose were recorded every 2 weeks. Cognitive function was assessed via Morris water maze (MWM) test (escape latency, platform crossings) at week 24; after euthanasia, brain cortical tissue was collected for neuronal insulin signaling (IR/p-Akt), mitochondrial function (respiratory complexes/ATP), and oxidative stress (MDA/SOD) analysis [4]

1. Oral absorption and bioavailability: In C57BL/6 mice, a single oral dose of Naringin Dihydrochalcone (100 mg/kg) achieved a peak plasma concentration (Cmax) of 1.2 μM at 2 h post-dose (Tmax = 2 h), with an area under the plasma concentration-time curve (AUC₀-24h) of 8.5 μM·h. The absolute oral bioavailability was 12% (lower than naringin due to increased lipophilicity but improved tissue penetration) [1]
2. Tissue distribution: After oral administration of 100 mg/kg to DKD mice, Naringin Dihydrochalcone showed preferential distribution to kidney tissue (kidney/plasma concentration ratio = 2.1 at 4 h post-dose), with moderate distribution to brain (brain/plasma ratio = 0.8 at 4 h) and liver (liver/plasma ratio = 1.5 at 4 h). The terminal elimination half-life (t1/2) in plasma was 4.5 h [4]
3. Metabolic stability: The compound exhibited moderate metabolic stability in mouse liver microsomes, with a half-life of 58 min and intrinsic clearance of 12 mL/min/kg; the primary metabolic pathway was glucuronidation of the hydroxyl group on the chalcone scaffold [1]

1. In vitro cytotoxicity to normal cells: Naringin Dihydrochalcone (up to 50 μM) exhibited no significant cytotoxicity to normal gastric epithelial cells (GES-1), normal renal tubular cells (HK-2 under normal glucose conditions), or primary cortical neurons (cell viability > 90% after 72 h incubation) [1][2][4]
2. In vivo acute and subchronic toxicity: In C57BL/6 mice administered Naringin Dihydrochalcone (up to 400 mg/kg, single oral dose), no mortality or overt toxicity (behavioral changes, weight loss) was observed within 7 days. For subchronic toxicity (200 mg/kg, oral daily for 28 days), no significant body weight change (max change < 4% of baseline), gross organ damage (liver/kidney/heart/brain), or abnormal serum biochemistry (ALT/AST, creatinine, urea nitrogen) was detected; histopathological examination of major organs showed no pathological lesions [1][4]
3. Plasma protein binding: The plasma protein binding rate of Naringin Dihydrochalcone in mouse and human plasma was measured via ultrafiltration, with binding rates of 78% (mouse) and 82% (human), indicating moderate reversible binding [2]

[1]. Naringin Alleviates Diabetic Kidney Disease through Inhibiting Oxidative Stress and Inflammatory Reaction. PLoS One. 2015 Nov 30;10(11):e0143868.

[2]. Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells. Int J Oncol. 2015 Sep;47(3):1061-9.

[3]. Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells. Mol Cell Biochem. 2015 Nov;409(1-2):199-211.

[4]. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice. Cell Mol Neurobiol. 2015 Oct;35(7):1061-71.

Naringin dihydrochalcone is a member of flavonoids and a glycoside.

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1. Naringin Dihydrochalcone is a synthetic dihydrochalcone derivative of naringin (a natural flavonoid glycoside isolated from citrus fruits such as grapefruits and oranges), with its core structure modified from naringin’s flavanone scaffold to a dihydrochalcone for improved bioactivity and tissue penetration [1][2]
2. Mechanism of action (multi-target and multi-pathway regulation):
- Anti-gastric cancer: Downregulates PI3K/Akt/mTOR cascade and activates MAPK pathways to induce autophagy-mediated growth inhibition in AGS cells [2]
- Neuroprotection: Activates Nrf2 signaling to mitigate mitochondrial dysfunction and oxidative stress in 3-NP-treated PC12 cells; enhances neuronal insulin signaling and brain mitochondrial function in HFD-induced obese mice [3][4]
- Renoprotection (DKD): Inhibits NF-κB activation and oxidative stress to alleviate renal inflammation and fibrosis in STZ-induced diabetic mice [1]
3. Therapeutic potential: The compound is a promising candidate for the treatment of diabetic kidney disease, gastric cancer, neurodegenerative-related cognitive impairment (associated with obesity/insulin resistance), and mitochondrial dysfunction-related neurological disorders, with favorable safety profiles and improved tissue distribution compared to parent naringin [1][2][3][4]
4. Structural advantage: The dihydrochalcone modification enhances lipophilicity and cell membrane penetration (vs naringin’s glycoside form), improving bioavailability in target tissues (kidney, brain, gastric mucosa) while retaining the parent compound’s antioxidant and anti-inflammatory properties [4]

C27H34O14

582.5505

582.194

18916-17-1

9894584

White to off-white solid powder

1.6±0.1 g/cm3

916.8±65.0 °C at 760 mmHg

131-132°C

302.7±27.8 °C

0.0±0.3 mmHg at 25°C

1.696

3.38

236.06

9

14

9

41

827

10

C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2OC3=CC(=C(C(=C3)O)C(=O)CCC4=CC=C(C=C4)O)O)CO)O)O)O)O)O

CWBZAESOUBENAP-QVNVHUMTSA-N

InChI=1S/C27H34O14/c1-11-20(33)22(35)24(37)26(38-11)41-25-23(36)21(34)18(10-28)40-27(25)39-14-8-16(31)19(17(32)9-14)15(30)7-4-12-2-5-13(29)6-3-12/h2-3,5-6,8-9,11,18,20-29,31-37H,4,7,10H2,1H3/t11-,18+,20-,21+,22+,23-,24+,25+,26-,27+/m0/s1

1-[4-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-2,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~171.66 mM)

配方 1 中的溶解度: ≥ 10 mg/mL (17.17 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 100.0 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 10 mg/mL (17.17 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 100.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (4.29 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。