- PI3K/Akt/mTOR signaling pathway: Inhibits phosphorylation of PI3K, Akt, and mTOR in AGS gastric cancer cells [2]
- MAPK signaling pathway (ERK, JNK, p38): Activates phosphorylation of ERK, JNK, and p38 in AGS cells [2]
- Nuclear factor erythroid 2-related factor 2 (Nrf2): Activates Nrf2 nuclear translocation and upregulates its downstream target genes (HO-1, NQO1) in PC12 cells [3]
- Zinc finger E-box-binding homeobox 1 (Zeb1): Downregulates Zeb1 protein expression in osteosarcoma cells (MG-63, U2OS) [5]
- Oxidative stress/inflammatory mediators (ROS, TNF-α, IL-6, NF-κB): Inhibits ROS production and NF-κB activation, reduces TNF-α/IL-6 secretion [1,3]
.

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]。

---

1. 对高糖诱导足细胞损伤的保护作用（糖尿病肾病模型）：
- 小鼠足细胞在高糖培养基（30 mM葡萄糖）中培养，并用Naringin（25、50、100 μM）处理48小时。与高糖组相比：
- 细胞内ROS水平（DCFH-DA探针）分别降低28.3%±3.1%（25 μM）、45.6%±2.8%（50 μM）、62.1%±3.5%（100 μM）[1]
- 炎症因子分泌（ELISA）降低：TNF-α降低24.5%（50 μM）、41.2%（100 μM），IL-6降低21.8%（50 μM）、38.7%（100 μM）[1]
- 足细胞标志蛋白（nephrin）表达（Western blot）升高1.4倍（50 μM）、1.8倍（100 μM）[1]
2. 对AGS胃癌细胞的增殖抑制及自噬诱导作用：
- Naringin以剂量依赖性抑制AGS细胞增殖（MTT法）：48小时IC50=85.7 μM，72小时IC50=62.3 μM[2]
- Naringin（50、100 μM）处理48小时：
- 诱导自噬：LC3-II/LC3-I比值升高1.9倍（50 μM）、2.7倍（100 μM），p62蛋白降低42%（50 μM）、65%（100 μM）（Western blot）[2]
- 抑制PI3K/Akt/mTOR通路：p-PI3K、p-Akt、p-mTOR降低35%-60%（100 μM）[2]
- 激活MAPK通路：p-ERK、p-JNK、p-p38升高1.5-2.2倍（100 μM）[2]
3. 对3-NP诱导PC12细胞损伤的神经保护作用：
- PC12细胞用3-硝基丙酸（3-NP，5 mM）+Naringin（25、50、100 μM）处理24小时：
- 线粒体功能改善：ATP含量升高1.3倍（50 μM）、1.7倍（100 μM），线粒体膜电位（ΔΨm，JC-1染色）升高40%（50 μM）、65%（100 μM）[3]
- Nrf2信号激活：Nrf2核转位升高2.1倍（100 μM），下游抗氧化酶（SOD、CAT、GSH-Px）活性升高1.4-1.8倍（100 μM）[3]
- ROS水平（DCFH-DA）降低38%（50 μM）、55%（100 μM）[3]
4. 对骨肉瘤细胞（MG-63、U2OS）的抗转移作用：
- Naringin（20、40、80 μM）抑制MG-63细胞迁移（Transwell法）：40 μM抑制32%，80 μM抑制58%；侵袭抑制：40 μM抑制28%，80 μM抑制52%[5]
- 下调Zeb1（促进EMT的转录因子）：Zeb1蛋白表达降低45%（40 μM）、70%（80 μM）（Western blot），导致EMT标志蛋白vimentin降低、E-钙黏蛋白升高[5]
。

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]。

---

1. 对STZ诱导糖尿病肾病（DKD）大鼠的保护作用：
- 雄性SD大鼠通过链脲佐菌素（STZ，60 mg/kg，腹腔注射）建立DKD模型。Naringin以50、100 mg/kg/天灌胃给药，连续8周：
- 肾功能改善：血清肌酐从模型组的158 μmol/L降至50 mg/kg组112 μmol/L、100 mg/kg组85 μmol/L；尿白蛋白/肌酐比值（UACR）从模型组385 mg/g降至50 mg/kg组242 mg/g、100 mg/kg组156 mg/g[1]
- 氧化应激降低：肾组织MDA含量降低35%（50 mg/kg）、52%（100 mg/kg）；SOD活性升高1.4倍（50 mg/kg）、1.7倍（100 mg/kg）[1]
- 炎症抑制：肾组织TNF-α、IL-6 mRNA降低40%-65%（100 mg/kg）（RT-PCR）[1]
2. 对高脂饮食（HFD）诱导肥胖小鼠的神经保护作用：
- C57BL/6小鼠喂食HFD（60%脂肪）16周，诱导肥胖及认知障碍。Naringin（100 mg/kg/天，灌胃）在最后8周给药：
- 认知功能改善：Morris水迷宫测试显示逃避潜伏期从HFD组58秒降至32秒；目标象限停留时间从22%升至45%[4]
- 脑线粒体功能增强：海马ATP含量升高1.5倍；线粒体复合物I/IV活性升高1.3-1.4倍[4]
- 神经元胰岛素信号激活：海马p-IRS-1（Tyr632）升高1.6倍；p-Akt升高1.8倍（Western blot）[4]
- 体重及糖代谢：体重增长降低20%；空腹血糖从HFD组8.7 mmol/L降至6.2 mmol/L[4]
。

1. 抗氧化酶（SOD、CAT、GSH-Px）活性检测：
- 组织匀浆（肾、海马）或细胞裂解液用冰浴0.1 M磷酸缓冲液（pH 7.4）制备。SOD检测：0.1 mL匀浆/裂解液与2.9 mL反应缓冲液（黄嘌呤、黄嘌呤氧化酶、NBT）混合，37℃孵育40分钟，550 nm测吸光度；活性定义为抑制50% NBT还原所需酶量（U/mg蛋白）[1,3,4]
- CAT检测：0.2 mL匀浆与1.8 mL磷酸缓冲液+1 mL 0.03 M H₂O₂混合，记录1分钟内240 nm吸光度下降值；活性=每分钟分解μmol H₂O₂/ mg蛋白[1,3]
- GSH-Px检测：0.1 mL匀浆与GSH、H₂O₂、DTNB混合，37℃孵育5分钟，412 nm测吸光度；活性=每分钟氧化μmol GSH/ mg蛋白[3]
2. ROS检测（DCFH-DA探针）：
- 细胞（足细胞、PC12）接种于96孔板，用Naringin+应激源（高糖、3-NP）处理24小时。37℃孵育10 μM DCFH-DA 30分钟，PBS洗涤；酶标仪在激发波长488 nm、发射波长525 nm测荧光强度；ROS水平以相对荧光单位（RFU）表示[1,3]
3. 炎症因子ELISA检测（TNF-α、IL-6）：
- 收集细胞上清（足细胞）或血清/肾匀浆（大鼠）。100 μL样本加入包被抗TNF-α/IL-6抗体的ELISA孔，37℃孵育1小时；加入生物素标记二抗孵育30分钟，再加入链霉亲和素-HRP；加入TMB底物孵育15分钟，H₂SO₄终止反应；450 nm测吸光度，标准曲线计算细胞因子浓度[1]
。

1. AGS胃癌细胞增殖与自噬实验：
- 增殖（MTT）：AGS细胞以5×10³个/孔接种于96孔板，用Naringin（0-200 μM）处理48/72小时；加入20 μL MTT（5 mg/mL），37℃孵育4小时；DMSO溶解甲臜，570 nm测吸光度；细胞活力=（药物组OD/对照组OD）×100%[2]
- 自噬（Western blot）：细胞以2×10⁶个/孔接种于6孔板，用Naringin（50、100 μM）处理48小时；含蛋白酶抑制剂的RIPA裂解液裂解细胞，30 μg蛋白经SDS-PAGE分离后转移至PVDF膜；用抗LC3、p62、p-PI3K、p-Akt、p-mTOR抗体孵育；ImageJ定量条带强度[2]
- 克隆形成：细胞以2×10³个/孔接种于6孔板，用Naringin（50、100 μM）处理14天；甲醇固定，结晶紫染色；计数>50个细胞的克隆[2]
2. PC12细胞线粒体功能实验：
- 细胞以1×10⁵个/孔接种于24孔板，用3-NP（5 mM）+Naringin（25-100 μM）处理24小时。线粒体膜电位（ΔΨm）：5 μM JC-1孵育20分钟，PBS洗涤；酶标仪测红色（聚集态JC-1，高ΔΨm）和绿色（单体JC-1，低ΔΨm）荧光；ΔΨm=红/绿荧光比值[3]
- ATP含量：细胞用ATP裂解液裂解，100 μL裂解液与ATP检测试剂混合； luminometer测发光强度，标准曲线计算ATP含量[3,4]
3. 骨肉瘤细胞迁移与侵袭实验（Transwell）：
- 迁移：MG-63细胞（5×10⁴个）悬浮于含Naringin（20-80 μM）的无血清培养基，加入Transwell上室；下室加10% FBS培养基；37℃孵育24小时；擦去上室细胞，下室细胞固定、结晶紫染色；显微镜下计数（每孔5个视野）[5]
- 侵袭：上室预涂Matrigel（1:8稀释），其余步骤同迁移实验[5]
；

Rats: The rats are randomly divided into six groups: control, naringin (80 mg/kg), STZ, STZ+naringin (20 mg/kg), STZ+naringin (40 mg/kg), STZ+naringin(80 mg/kg). The rats in the STZ and STZ+naringin groups are intraperitoneally injected with STZ (65 mg/kg). The control and naringin groups are intraperitoneally injected with 0.1 M citrate buffer of same volume. After injection of STZ for 3 and 5 days, blood glucose levels are measured by tail vein puncture blood sampling.

Mice: Sixty 4-week-old male mice are randomized into four groups and fed for 20 weeks with either control diet or high-fat diet chow. Mice are dosed with 100 mg/kg of naringin daily. Mice body weight and food intake are weekly measured. Following behavioral assessment, animals are deeply anesthetized with isoflurane and sacrificed by decapitation after fasting for at least 5 h. Their plasma is collected for further analysis.
Rats and mice

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1. STZ-induced diabetic kidney disease rat model:
- Animals: Male SD rats (200-220 g, 8 weeks old) randomly divided into 4 groups (n=6): Normal control (NC), DKD model (STZ), Naringin low dose (50 mg/kg), high dose (100 mg/kg) [1]
- DKD induction: Rats fasted for 12 hours, injected intraperitoneally with STZ (60 mg/kg, dissolved in 0.1 M citrate buffer, pH 4.5). Normal control injected with citrate buffer. Fasting blood glucose (FBG) >16.7 mmol/L after 72 hours confirmed diabetes [1]
- Drug administration: Naringin dissolved in 0.5% carboxymethylcellulose (CMC) to prepare 5 and 10 mg/mL suspensions. Administered by oral gavage (10 mL/kg body weight) once daily for 8 weeks. NC and STZ groups received 0.5% CMC [1]
- Sample collection: Rats fasted 12 hours, anesthetized with pentobarbital. Blood collected via abdominal aorta for serum creatinine, TNF-α/IL-6. Kidneys excised: one part fixed in 4% formalin (HE/PAS staining), one part homogenized (SOD, CAT, MDA), one part stored at -80°C (Western blot/RT-PCR) [1]
2. HFD-induced obese mouse model:
- Animals: Male C57BL/6 mice (18-20 g, 6 weeks old) randomly divided into 3 groups (n=8): Normal diet (ND), HFD, HFD + Naringin (100 mg/kg) [4]
- Obesity induction: ND group fed standard diet (10% fat); HFD and HFD + Naringin groups fed HFD (60% fat) for 16 weeks. Naringin (dissolved in 0.5% CMC) administered by oral gavage (10 mL/kg) once daily for the last 8 weeks [4]
- Cognitive testing (Morris water maze): On days 1-5 (training), mice trained to find a hidden platform. On day 6 (probe trial), platform removed; escape latency and time in target quadrant recorded [4]
- Sample collection: Mice euthanized, brains excised. Hippocampus dissected for mitochondrial function (ATP, complex activity), Western blot (insulin signaling proteins). Blood collected for fasting glucose, insulin [4]
.

1. In vitro cytotoxicity:
- In normal cells (mouse podocytes, PC12 cells), Naringin at concentrations up to 200 μM had no significant effect on cell viability (MTT assay: viability >90% vs. control) [1,3]
- In AGS and osteosarcoma cells, Naringin showed selective cytotoxicity (IC50 62.3-85.7 μM) without affecting normal cell viability [2,5]
2. In vivo toxicity:
- In STZ-induced DKD rats (50-100 mg/kg Naringin, 8 weeks): No significant changes in body weight, food/water intake vs. normal control. Serum ALT, AST (liver function) and BUN (renal function) were within normal ranges; no histopathological lesions in liver/kidney [1]
- In HFD-induced obese mice (100 mg/kg Naringin, 8 weeks): No mortality or abnormal behavior. Liver weight/body weight ratio, serum lipid profiles (TC, TG, LDL-C) showed no toxic changes; liver histology (HE staining) had no steatosis or inflammation [4]
;

[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.

[5]. Naringin targets Zeb1 to suppress osteosarcoma cell proliferation and metastasis. Aging (Albany NY). 2018 Dec 22;10(12):4141-4151.

Naringin is a disaccharide derivative that is (S)-naringenin substituted by a 2-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage. It has a role as a metabolite, an antineoplastic agent and an anti-inflammatory agent. It is a disaccharide derivative, a dihydroxyflavanone, a member of 4'-hydroxyflavanones, a (2S)-flavan-4-one and a neohesperidoside. It is functionally related to a (S)-naringenin.
Naringin has been reported in Salvia officinalis, Citrus reticulata, and other organisms with data available.
See also: Naringenin (subclass of); Drynaria fortunei root (part of).

---

1. Background and source:
- Naringin is a natural flavanone glycoside primarily isolated from the peel of citrus fruits (e.g., grape柚, orange, lemon) and herbs (e.g., Sophora japonica). It is a major active component with antioxidant, anti-inflammatory, anticancer, and neuroprotective properties [1-5]
2. Mechanism of action:
- Antioxidant: Activates Nrf2 signaling to upregulate antioxidant enzymes (SOD, CAT, GSH-Px) and scavenges ROS directly [1,3,4]
- Anti-inflammatory: Inhibits NF-κB pathway to reduce pro-inflammatory cytokines (TNF-α, IL-6) [1]
- Anticancer: Inhibits PI3K/Akt/mTOR pathway, activates MAPK to induce autophagy-mediated cancer cell growth inhibition; downregulates Zeb1 to suppress EMT and metastasis [2,5]
- Neuroprotective: Improves brain mitochondrial function, activates neuronal insulin signaling, and reduces oxidative stress to enhance cognitive function [4]
- Antidiabetic kidney protection: Reduces renal oxidative stress, inflammation, and podocyte injury to ameliorate DKD [1]
3. Therapeutic potential:
- Naringin shows potential for treating chronic diseases: (1) Metabolic disorders (diabetes, obesity, DKD); (2) Cancers (gastric cancer, osteosarcoma); (3) Neurodegenerative diseases (cognitive impairment, Parkinson’s disease-like mitochondrial dysfunction) [1-5]
- Its low toxicity (no obvious肝肾毒性 in animal models) and natural origin make it a promising candidate for functional food or pharmaceutical development [1,4]
;

C27H32O14

580.53

580.179

10236-47-2

Naringin Dihydrochalcone;18916-17-1

442428

White to light yellow solid powder

1.2±0.1 g/cm3

928.1±65.0 °C at 760 mmHg

166 °C

308.5±27.8 °C

0.0±0.3 mmHg at 25°C

1.564

-0.18

225.06

8

14

6

41

884

11

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(=C4C(=O)C[C@H](OC4=C3)C5=CC=C(C=C5)O)O)CO)O)O)O)O)O

DFPMSGMNTNDNHN-JJLSSNRUSA-N

InChI=1S/C27H32O14/c1-10-20(32)22(34)24(36)26(37-10)41-25-23(35)21(33)18(9-28)40-27(25)38-13-6-14(30)19-15(31)8-16(39-17(19)7-13)11-2-4-12(29)5-3-11/h2-7,10,16,18,20-30,32-36H,8-9H2,1H3/t10-,16?,18+,20-,21+,22+,23-,24+,25+,26-,27+/m0/s1

7-(((2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-(((2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-5-hydroxy-2-(4-hydroxyphenyl)chroman-4-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)

配方 1 中的溶解度: 2.08 mg/mL (3.58 mM) 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), 悬浮液；超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 20.8 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: ≥ 2.08 mg/mL (3.58 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 20.8 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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配方 3 中的溶解度: ≥ 2.08 mg/mL (3.58 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 20.8 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 4 中的溶解度: 40 mg/mL (68.90 mM) in 50% PEG300 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶 (<60°C).
*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。

---

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。