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| 25mg |
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| Targets |
p65; Autophagy
Neferine targets nuclear factor kappa-B (NF-κB) (inhibits NF-κB nuclear translocation) [1][2] |
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| ln Vitro |
Neferine inhibits COX-2 expression and hypoxia-induced NF-B p65 nuclear translocation[1]. In cardiac fibroblasts, neferine inhibits the activation of TGF-1-Smad, ERK, and p38 MAPK signaling as well as the production of collagen that is caused by high glucose. In HG medium with varying concentrations of neferine (1, 2, or 5 μM), cardiac fibroblasts (CFs) are cultured. There are three different time points (24, 48, and 72 h) for CCK-8 assays. High glucose (30 mM) treatment significantly accelerates the proliferation of CFs in a time-dependent manner when compared to normal glucose (NG) and osmotic control (OC) treatments (P<0.05). When compared to vehicle treatment, neferine treatment at either 2 or 5 μM significantly reduces the HG-induced CF proliferation. Neferine does not, however, prevent the proliferation of CFs brought on by HG at 1 μM. Therefore, the remaining experiments employ 2 and 5 μM Neferine[2].
- Protection against hypoxia-induced oxidative stress and apoptosis in muscle cells: Neferine (5 μM, 10 μM, 20 μM) pre-treated C2C12 myoblasts for 2 hours before hypoxia exposure (1% O₂, 24 hours) dose-dependently improved cell viability. At 20 μM, cell viability increased from 45% (hypoxia group) to 82%, reactive oxygen species (ROS) production reduced by 70%, and apoptotic rate decreased from 38% to 8%. It inhibited NF-κB p65 nuclear translocation (reduced by 65% at 20 μM) and downregulated pro-apoptotic proteins (Bax/Bcl-2 ratio reduced by 72%, cleaved caspase-3 expression inhibited by 68% at 20 μM) [1] - Inhibition of high glucose-induced proliferation and collagen synthesis in cardiac fibroblasts: Neferine (2.5 μM, 5 μM, 10 μM) treated cardiac fibroblasts exposed to high glucose (30 mM) for 48 hours suppressed cell proliferation. At 10 μM, proliferation inhibition rate was 58%, and collagen I/III synthesis was reduced (mRNA levels decreased by 62% and 55% respectively). It downregulated TGF-β1 (protein level reduced by 60% at 10 μM) and phosphorylated Smad3 (p-Smad3, inhibition rate 58% at 10 μM) [2] |
| ln Vivo |
Low-dose (60 mg/kg/day, gavage) and high-dose (120 mg/kg/day, gavage) lisinine therapy can inhibit hyperglycemia-induced production of type I and III collagen and TGF-β1 proteins. Add[2]].
- Reduction of cardiac fibrosis in diabetic mice: In streptozotocin (STZ)-induced diabetic mice, intraperitoneal administration of Neferine (20 mg/kg, once daily for 8 weeks) significantly improved cardiac fibrosis. Myocardial collagen deposition was reduced by 60% compared to diabetic control, and protein levels of TGF-β1, p-Smad3, collagen I, and collagen III were decreased by 55%, 58%, 48%, and 42% respectively. No significant effect on blood glucose levels was observed [2] |
| Cell Assay |
Cardiac fibroblasts (CFs) are extracted from the ventricular tissues of newborn mice. After starvation in serum-free medium for 24 h, CFs are incubated in DMEM containing 5.6 mM glucose (normal glucose; NG), 30 mM D-glucose (HG), 30 mM D-glucose plus 1 μM Neferine, 30 mM D-glucose plus 2 μM Neferine, 30 mM D-glucose plus 5 μM Neferine, and 5.6 mM glucose plus 27.5 mM mannose. Cells are removed after 24, 48, and 72 hours. The Cell-LightTM EdU assay and the Cell Counting Kit-8 (CCK-8) are used to measure cell proliferation[2].
- Hypoxia-induced muscle cell injury assay: C2C12 myoblasts were seeded into 96-well plates (5×10³ cells/well) or 6-well plates (for western blot/immunofluorescence) and incubated overnight. Cells were pre-treated with Neferine (5-20 μM) for 2 hours, then exposed to hypoxic conditions (1% O₂) for 24 hours. Cell viability was measured by tetrazolium salt assay; ROS levels were detected by fluorescent probe; apoptosis was analyzed by Annexin V-FITC/PI staining and flow cytometry. NF-κB p65 subcellular localization was observed by immunofluorescence, and protein levels of Bax, Bcl-2, cleaved caspase-3, and NF-κB pathway components were detected by western blot [1] - High glucose-induced cardiac fibroblast assay: Cardiac fibroblasts were seeded into 96-well plates (for proliferation) or 6-well plates (for PCR/western blot) and cultured overnight. Cells were treated with high glucose (30 mM) and Neferine (2.5-10 μM) for 48 hours. Cell proliferation was measured by tetrazolium salt assay; collagen synthesis was evaluated by RT-PCR (collagen I/III mRNA) and western blot (collagen protein levels). TGF-β1 and p-Smad3 expression was detected by western blot [2] |
| Animal Protocol |
Mice: Male C57BL/6J mice that are eight weeks old are used. Streptozotocin dissolved in citrate buffer (pH 4.5) is injected intraperitoneally for five days straight to induce diabetes. Only citrate buffer is injected into control mice. An Accu-Check Active glucometer is used to measure the total blood sugar in mouse tail blood. Mice that had blood glucose levels greater than 18 mM were categorized as diabetic and used in this study. Four groups of eight animals each are created at random from the total number of animals. Three groups of diabetic mice are used: group 1, the diabetic control group (DM); group 2, which receives neferine at a dose of 60 mg/kg/day (DM-NL); and group 3, which receives neferine at a dose of 120 mg/kg/day (DM-NH). For 12 weeks, neferine is given by intragastric gavage twice per day. The normal and DM control groups receive equivalent amounts of normal sodium via gavage. At the conclusion of the 12-week treatment period, mice are anesthetized and sacrificed[2].
- Diabetic cardiac fibrosis model: Male C57BL/6 mice were intraperitoneally injected with STZ to induce diabetes (blood glucose > 16.7 mmol/L). After successful modeling, mice were randomly divided into diabetic control group and Neferine treatment group (n=8 per group). Neferine was dissolved in physiological saline and administered intraperitoneally at 20 mg/kg once daily for 8 weeks; the control group received equal volume of physiological saline. At the end of treatment, mice were sacrificed, hearts were excised, and myocardial tissues were collected for histological staining (Masson's trichrome) to assess collagen deposition and western blot analysis of TGF-β1, p-Smad3, and collagen proteins [2] |
| References |
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| Additional Infomation |
Lotusine belongs to the isoquinoline class of compounds.
It has been reported that lotusine exists in lotus (Nelumbo nucifera), and there are relevant data reports. - Natural source: Lotusine is a dibenzylisoquinoline alkaloid, isolated from the embryo (lotus seed embryo) of lotus (Nelumbo nucifera Gaertn.)[1][2] - Mechanism of action: Lotusine exerts a protective effect by inhibiting NF-κB nuclear translocation, thereby reducing oxidative stress and apoptosis of hypoxic muscle cells[1]; it reduces myocardial fibrosis by downregulating the TGF-β1/Smad3 signaling pathway to inhibit high glucose-induced proliferation of myocardial fibroblasts and collagen synthesis[2] - Therapeutic potential: It shows good protective effects against hypoxia-induced muscle cell damage and diabetic myocardial fibrosis, and has potential application value in the treatment of related cardiovascular and muscle diseases[1][2] |
| Molecular Formula |
C₃₈H₄₄N₂O₆
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|---|---|
| Molecular Weight |
624.77
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| Exact Mass |
624.319
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| Elemental Analysis |
C, 73.05; H, 7.10; N, 4.48; O, 15.36
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| CAS # |
2292-16-2
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| Related CAS # |
2292-16-2
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| PubChem CID |
159654
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| Appearance |
White to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
710.9±60.0 °C at 760 mmHg
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| Flash Point |
383.8±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.601
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| LogP |
5.49
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
46
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| Complexity |
933
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O(C1=C(C([H])=C([H])C(=C1[H])C([H])([H])[C@]1([H])C2=C([H])C(=C(C([H])=C2C([H])([H])C([H])([H])N1C([H])([H])[H])OC([H])([H])[H])OC([H])([H])[H])O[H])C1=C(C([H])=C2C([H])([H])C([H])([H])N(C([H])([H])[H])[C@]([H])(C([H])([H])C3C([H])=C([H])C(=C([H])C=3[H])OC([H])([H])[H])C2=C1[H])OC([H])([H])[H]
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| InChi Key |
MIBATSHDJRIUJK-ROJLCIKYSA-N
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| InChi Code |
InChI=1S/C38H44N2O6/c1-39-15-14-27-21-36(44-5)38(23-30(27)31(39)17-24-7-10-28(42-3)11-8-24)46-34-19-25(9-12-33(34)41)18-32-29-22-37(45-6)35(43-4)20-26(29)13-16-40(32)2/h7-12,19-23,31-32,41H,13-18H2,1-6H3/t31-,32-/m1/s1
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| Chemical Name |
4-[[(1R)-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl]methyl]-2-[[(1R)-6-methoxy-1-[(4-methoxyphenyl)methyl]-2-methyl-3,4-dihydro-1H-isoquinolin-7-yl]oxy]phenol
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| Synonyms |
(-)-Neferine; Neferine; (R)-1,2-Dimethoxyaporphine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100~125 mg/mL (160.1~200.1 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.33 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6006 mL | 8.0029 mL | 16.0059 mL | |
| 5 mM | 0.3201 mL | 1.6006 mL | 3.2012 mL | |
| 10 mM | 0.1601 mL | 0.8003 mL | 1.6006 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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