姜黄素作为化学预防剂的部分作用是通过激活其抗氧化剂和 II 相解毒酶，以及核因子（红细胞 2 相关）因子 2 (Nrf2)[1]。 24、48 和 72 小时 MTT 实验中，姜黄素抑制 T47D 细胞的增殖，IC50 分别为 25、19 和 17.5 μM。暴露 24、48 和 72 小时，姜黄素和水飞蓟宾混合物对 T47D 细胞的 IC50 分别为 17.5、15 和 12 μM[2]。 AGS 和 HT-29 细胞系在姜黄素 (2.5-80 μM) 的作用下表现出细胞凋亡；这些细胞系的 IC50 值分别为 21.9±0.1 和 40.7±0.5 μM。在 AGS 和 HT-29 细胞中，半胱天冬酶活性对于姜黄素诱导的细胞凋亡是必需的。姜黄素会导致线粒体 Ca2+ 超载和 ER Ca2+ 下降[3]。姜黄素剂量依赖性地促进LNCaP和PC-3细胞进入G2/M细胞周期停滞。姜黄素降低 c-Jun 和 AR 的蛋白水平，同时增加 NF-kappaB 抑制剂 IkappaBalpha 的蛋白水平[5]。

与暴露于 CMS 的大鼠相比，姜黄素（10 mg/kg，口服）显着避免了蔗糖消耗百分比的下降。当应激大鼠接受姜黄素治疗时，其 TNF-α 和 IL-6 水平的上升得到显着抑制[4]。在慢性缩窄性损伤 (CCI) 大鼠中，姜黄素 20 mg/kg（腹腔注射）可降低 p300/CREB 结合蛋白 (CBP) 在脑源性神经营养因子 (BDNF) 启动子上的结合，以及 P300 的结合40 mg/kg 的 /CBP 以及 60 mg/kg 的 p300/CBP 和 H3K9ac/H4K5ac 的所有四种蛋白的结合[6]。

T47D 乳腺癌细胞系在补充有 10% FBS、2 mg/mL 碳酸氢钠、0.05 mg/mL 青霉素 G、0.08 mg/mL 链霉素的 RPMI 1640 中生长。培养物保存在塑料瓶中，并在 37°C、5% CO2 下孵育。生长足够量的细胞后，通过 24、48 和 72 小时 MTT 测定研究水飞蓟宾和姜黄素的细胞毒性作用，其中在 96 孔板中培养 1000 个细胞/孔。在 37°C、含有 5% CO2 的湿润气氛中孵育 24 小时后，用系列浓度的姜黄素 (5, 10, 20, 30, 40, 50, 60, 80, 100 µM)、水飞蓟宾 (20, 40、60、80、100、120、140、180、200 µM），以及姜黄素-水飞蓟宾混合物（分别为 5、10、20、30、40、50、60、80、100 µM）24、48 72 h，一式四份，另加 200 μL 含 10% DMSO 的培养基作为对照。孵育后，将板所有孔的培养基更换为新鲜培养基，并将细胞置于培养箱中24小时。然后，小心除去所有孔的培养基，并向每个孔中加入 50 μL 溶解于 PBS 的 2 mg/mL MTT，并用铝箔覆盖板，并再次孵育 4.5 h。除去孔中的内容物后，将 200 μL 纯 DMSO 添加到孔中。然后加入25 μL Sorensen甘氨酸缓冲液，立即使用EL×800微孔板吸光度读数器在570 nm处读取每个孔的吸光度，参考波长为630 nm。

Absorption, Distribution and Excretion
Curcumin displays poor absorption into the gastrointestinal tract. In a rat study, oral administration of a single dose of 2 g of curcumin resulted in a plasma concentration of less than 5 μg/mL, indicating poor absorption from the gut.
Following oral administration of curcumin to rats at a dose of 1 g/kg bw, about 75% of dose was excreted in the faeces and only traces of the compound was detected in the urine. When a single 400 mg dose of curcumin was administered orally to rats, about 60% was absorbed and 40% was excreted unchanged in the faeces over an period of 5 days. Intraperitoneal administration resulted in fecal excretion of 73% and biliary excretion of 11%.
Following oral administration of radio-labelled curcumin to rats, radioactivity was detected in the liver and kidneys.
No pharmacokinetic data available.
Oral & ip doses of (3)H-curcumin led to fecal excretion of most of radioactivity. Iv & ip doses were well excreted in bile of cannulated rats.
When admin orally in dose of 1 g/kg, curcumin was excreted in feces to about 75%, while negligible amt appeared in urine. Measurement of blood plasma levels & biliary excretion showed that curcumin was poorly absorbed from the gut.
The aim of this study was to develop a curcumin intranasal thermosensitive hydrogel and to improve its brain targeting efficiency. The hydrogel gelation temperature, gelation time, drug release and mucociliary toxicity characteristics as well as the nose-to-brain transport in the rat model were evaluated. The developed nasal hydrogel, composed of Pluronic F127 and Poloxamer 188, had shorter gelation time, longer mucociliary transport time and produced prolonged curcumin retention in the rat nasal cavity at body temperature. The hydrogel release mechanism was diffusion-controlled drug release, evaluated by the dialysis membrane method, but dissolution-controlled release when evaluated by the membraneless method. A mucociliary toxicity study revealed that the hydrogel maintained nasal mucosal integrity until 14 days after application. The drug-targeting efficiencies for the drug in the cerebrum, cerebellum, hippocampus and olfactory bulb after intranasal administration of the curcumin hydrogel were 1.82, 2.05, 2.07 and 1.51 times that after intravenous administration of the curcumin solution injection, respectively, indicating that the hydrogel significantly increased the distribution of curcumin into the rat brain tissue, especially into the cerebellum and hippocampus. A thermosensitive curcumin nasal gel was developed with favourable gelation, release properties, biological safety and enhanced brain-uptake efficiency. /Curcumin intranasal thermosensitive hydrogel/
...However, curcumin has a low systemic bioavailability, so it is imperative to improve the bioavailability of curcumin in its clinical application. Many methods, such as adjuvant drug delivery system and structural modification have been demonstrated to have a potential effect.
For more Absorption, Distribution and Excretion (Complete) data for CURCUMIN (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Initially, curcumin undergoes rapid intestinal metabolism to form curcumin glucuronide and curcumin sulfate via O-conjugation. Other metabolites formed include tetrahydrocurcumin, hexahydrocurcumin, and hexahydrocurcuminol via reduction. Curcumin may also undergo intensive second metabolism in the liver where the major metabolites were glucuronides of tetrahydrocurcumin and hexahydrocurcumin, with dihydroferulic acid and traces of ferulic acid as further metabolites. Hepatic metabolites are expected to be excreted in the bile. Certain curcumin metabolites, such as tetrahydrocurcumin, retain anti-inflammatory and antioxidant properties.
Iv & ip doses of (3)H-curcumin excreted in bile of cannulated rats. Major metab were glucuronides of tetrahydrocurcumin & hexahydrocurcumin. Minor metab was dihydroferulic acid together with traces of ferulic acid.
Curcumin has known human metabolites that include Curcumin 4-O-glucuronide and O-demethyl curcumin.

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Biological Half-Life
No pharmacokinetic data available.

Interactions
Groundwater arsenic contamination has been a health hazard for West Bengal, India. Oxidative stress to DNA is recognized as an underlying mechanism of arsenic carcinogenicity. A phytochemical, curcumin, from turmeric appears to be potent antioxidant and antimutagenic agent. DNA damage prevention with curcumin could be an effective strategy to combat arsenic toxicity. This field trial in Chakdah block of West Bengal evaluated the role of curcumin against the genotoxic effects of arsenic. DNA damage in human lymphocytes was assessed by comet assay and fluorescence-activated DNA unwinding assay. Curcumin was analyzed in blood by high performance liquid chromatography (HPLC). Arsenic induced oxidative stress and elucidation of the antagonistic role of curcumin was done by observation on reactive oxygen species (ROS) generation, lipid peroxidation and protein carbonyl. Antioxidant enzymes like catalase, superoxide dismutase, glutathione reductase, glutathioneS-transferase, glutathione peroxidase and non-enzymatic glutathione were also analyzed. The blood samples of the endemic regions showed severe DNA damage with increased levels of ROS and lipid peroxidation. The antioxidants were found with depleted activity. Three months curcumin intervention reduced the DNA damage, retarded ROS generation and lipid peroxidation and raised the level of antioxidant activity. Thus curcumin may have some protective role against the DNA damage caused by arsenic.
To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-alpha, and lymphotoxin-beta) or fibrogenic cytokines (transforming growth factor [TGF]-beta) during the same acute and chronic phases. Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-alpha, and lymphotoxin-beta) and the fibrogenic cytokine, TGF-beta, in cutaneous tissues at 21 days postradiation. Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.
The aim of this study is to evaluate the effect of curcumin in protecting against selenium-induced toxicity in liver and kidney of Wistar rats. Light microscopy evaluation of selenium alone administered rats showed liver to be infiltrated with mononuclear cells, vacuolation, necrosis, and pronounced degeneration. Control liver sections showed a regular morphology of parenchymal cells with intact hepatocytes and sinusoids. Kidney from selenium alone administered rats showed vacuolar degeneration changes in the epithelial cells, cellular proliferation with fibrosis, thickening of capillary walls, and glomerular tuft atrophy. Such changes were also observed in rats administered with selenium and curcumin simultaneously and rats administered first with selenium and then curcumin 24 hr later. Interestingly, such degenerative changes observed in liver and kidney induced by selenium were not seen in rats that were administered with curcumin first and selenium 24 hr later. This clearly suggests the protective nature of curcumin against selenium toxicity. To understand the probable mechanism of action of curcumin, /investigators/ analyzed inducible nitric oxide synthase (iNOS) expression by immunohistochemistry, and the results showed an increased iNOS expression in selenium-alone induced liver and kidney. Such high iNOS levels were inhibited in liver and kidney of rats pretreated with curcumin and then with selenium 24 hr later. Based on the histological results, it can be concluded that curcumin functions as a protective agent against selenium-induced toxicity in liver as well as kidney, and this action is probably by the regulatory role of curcumin on iNOS expression.
Zn(II)-curcumin, a mononuclear (1:1) zinc complex of curcumin was synthesized and examined for its antiulcer activities against pylorus-ligature-induced gastric ulcer in rats. The structure of Zn(II)-curcumin was identified by elemental analysis, NMR and TG-DTA analysis. It was found that a zinc atom was coordinated through the keto-enol group of curcumin along with one acetate group and one water molecule. Zn(II)-curcumin (12, 24 and 48 mg/kg) dose-dependently blocked gastric lesions, significantly reduced gastric volume, free acidity, total acidity and pepsin, compared with control group (P<0.001) and curcumin alone (24 mg/kg, P<0.05). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that Zn(II)-curcumin markedly inhibited the induction of nuclear factor-kappa B (NF-kappaB), transforming growth factor beta(1) (TGF-beta(1)) and interleukin-8 (IL-8), compared with control group (P<0.05). These findings suggested that Zn(II)-curcumin prevented pylorus-ligation-induced lesions in rat by inhibiting NF-kappaB activation and the subsequent production of proinflammatory cytokines, indicating a synergistic effect between curcumin and zinc.../Zinc(II)-curcumin complex/
For more Interactions (Complete) data for CURCUMIN (12 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mice oral more than 2000 mg/kg bw /Solid lipid curcumin particle/
LD50 Rats oral more than 2000 mg/kg bw /Solid lipid curcumin particle/
LD50 Zebrafish embryo 7.5 uM (24 hr); LD50 Zebrafish larvae 5 uM (24 hr)
LD50 Mice oral more than 2000 mg/kg
LD50 Rats oral more than 5000 mg/kg /Curcumin oil/

[1]. Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion. Food Chem Toxicol. 2013 Jul 18. pii: S0278-6915(13)004.

[2]. Curcumin and Silibinin Inhibit Telomerase Expression in T47D Human Breast Cancer Cells. Asian Pac J Cancer Prev. 2013;14(6):3449-53.

[3]. Cao A, et all. Curcumin induces apoptosis in human gastric carcinoma AGS cells and colon carcinoma HT-29 cells through mitochondrial dysfunction and endoplasmic reticulum stress. Apoptosis. 2013 Jul 24. [Epub ahead of print].

[4]. Antidepressant-like effects of curcumin in chronic mild stress of rats: Involvement of its anti-inflammatory action. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jul 20. pii: S0278-5846(13)00150-4.

[5]. Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of IkappaBalpha, c-Jun and androgen receptor. Pharmazie. 2013 Jun;68(6):431-4.

[6]. Curcumin alleviates neuropathic pain by inhibiting p300/CBP histone acetyltransferase activity-regulated expression of BDNF and cox-2 in a rat model. PLoS One. 2014 Mar 6;9(3):e91303.

[7]. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem. 2004 Dec 3;279(49):51163-71.

[8]. Curcumin induces stabilization of Nrf2 protein through Keap1 cysteine modification. Biochem Pharmacol. 2020 Mar;173:113820.

Therapeutic Uses
EXPL THER Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. /The authors/ have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application./ Curcumin-loaded nanoparticles/
EXPL THER Accumulation of amyloid peptide (Abeta) in senile plaques is a hallmark lesion of Alzheimer disease (AD). The design of molecules able to target the amyloid pathology in tissue is receiving increasing attention, both for diagnostic and for therapeutic purposes. Curcumin is a fluorescent molecule with high affinity for the Abeta peptide but its low solubility limits its clinical use. Curcumin-conjugated nanoliposomes, with curcumin exposed at the surface, were designed. They appeared to be monodisperse and stable. They were non-toxic in vitro, down-regulated the secretion of amyloid peptide and partially prevented Abeta -induced toxicity. They strongly labeled Abeta deposits in post-mortem brain tissue of AD patients and APPxPS1 mice. Injection in the hippocampus and in the neocortex of these mice showed that curcumin-conjugated nanoliposomes were able to specifically stain the Abeta deposits in vivo. Curcumin-conjugated nanoliposomes could find application in the diagnosis and targeted drug delivery in AD. In this preclinical study, curcumin-conjugated nanoliposomes were investigated as possible diagnostics and targeted drug delivery system in Alzheimer's disease, demonstrating strong labeling of Abeta deposits both in human tissue and in mice, and in vitro downregulation of amyloid peptide secretion and prevention of Abeta -induced toxicity./ Curcumin-conjugated nanoliposomes/
EXPL THER The anti-inflammatory agent curcumin can selectively eliminate malignant rather than normal cells. The present study examined the effects of curcumin on the Lewis lung carcinoma (LLC) cell line and characterized a subpopulation surviving curcumin treatments. Cell density was measured after curcumin was applied at concentrations between 10 and 60 uM for 30 hours. Because of the high cell loss at 60 uM, this dose was chosen to select for surviving cells that were then used to establish a new cell line. The resulting line had approximately 20% slower growth than the original LLC cell line and based on ELISA contained less of two markers, NF-kB and ALDH1A, used to identify more aggressive cancer cells. /The authors/ also injected cells from the original and surviving lines subcutaneously into syngeneic C57BL/6 mice and monitored tumor development over three weeks and found that the curcumin surviving-line remained tumorigenic. Because curcumin has been reported to kill cancer cells more effectively when administered with light, /the authors/ examined this as a possible way of enhancing the efficacy of curcumin against LLC cells. When LLC cells were exposed to curcumin and light from a fluorescent lamp source, cell loss caused by 20 uM curcumin was enhanced by about 50%, supporting a therapeutic use of curcumin in combination with white light. This study is the first to characterize a curcumin-surviving subpopulation among lung cancer cells. It shows that curcumin at a high concentration either selects for an intrinsically less aggressive cell subpopulation or generates these cells. The findings further support a role for curcumin as an adjunct to traditional chemical or radiation therapy of lung and other cancers.
EXPL THER 5-Fluorouracil (5-FU) is the first rationally designed antimetabolite, which achieves its therapeutic efficacy through inhibition of the enzyme thymidylate synthase (TS), which is essential for the synthesis and repair of DNA. However, prolonged exposure to 5-FU induces TS overexpression, which leads to 5-FU resistance in cancer cells. Several studies have identified curcumin as a potent chemosensitizer against chemoresistance induced by various chemotherapeutic drugs. In this study, /investigators/ report for the first time, with mechanism-based evidences, that curcumin can effectively chemosensitize breast cancer cells to 5-FU, thereby reducing the toxicity and drug resistance. /The authors/ found that 10 uM 5-FU and 10 uM curcumin induces a synergistic cytotoxic effect in different breast cancer cells, independent of their receptor status, through the enhancement of apoptosis. Curcumin was found to sensitize the breast cancer cells to 5-FU through TS-dependent downregulation of nuclear factor-kB (NF-kB), and this observation was confirmed by silencing TS and inactivating NF-kB, both of which reduced the chemosensitizing efficacy of curcumin. Silencing of TS suppressed 5-FU-induced NF-kB activation, whereas inactivation of NF-kB did not affect 5-FU-induced TS upregulation, confirming that TS is upstream of NF-kB and regulates the activation of NF-kB in 5-FU-induced signaling pathway. Although Akt/PI3kinase and mitogen-activated protein kinase pathways are activated by 5-FU and downregulated by curcumin, they do not have any role in regulating the synergism. As curcumin is a pharmacologically safe and cost-effective compound, its use in combination with 5-FU may improve the therapeutic index of 5-FU, if corroborated by in vivo studies and clinical trials.
For more Therapeutic Uses (Complete) data for CURCUMIN (23 total), please visit the HSDB record page.

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Pharmacodynamics
Intravenous application of 25 mg/kg bw curcumin to rats resulted in an increase in bile flow by 80 and 120%. In the rat model of inflammation, curcumin was shown to inhibit edema formation. In nude mouse that had been injected subcutaneously with prostate cancer cells, administration of curcumin caused a marked decrease in the extent of cell proliferation, a significant increase of apoptosis and micro-vessel density. Curcumin may exert choleretic effects by increasing biliary excretion of bile salts, cholesterol, and bilirubin, as well as increasing bile solubility. Curcumin inhibited arachidonic acid-induced platelet aggregation _in vitro_.

C21H20O6

368.38

368.125

458-37-7

Curcumin-d6;1246833-26-0

969516

Yellow to orange solid powder

1.3±0.1 g/cm3

593.2±50.0 °C at 760 mmHg

183 °C

209.7±23.6 °C

0.0±1.8 mmHg at 25°C

1.672

2.85

96.22

2

6

8

27

507

0

COC1=C(C=CC(=C1)/C=C/C(=O)CC(=O)/C=C/C2=CC(=C(C=C2)O)OC)O

VFLDPWHFBUODDF-FCXRPNKRSA-N

InChI=1S/C21H20O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h3-12,24-25H,13H2,1-2H3/b7-3+,8-4+

(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione

Turmeric Yellow NSC32982Diferuloylmethane NSC-32982Curcumincurcumin I C.I. 75300 Natural Yellow 3

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 (~271.46 mM)

配方 1 中的溶解度: ≥ 3 mg/mL (8.14 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 30.0 mg/mL 澄清的 DMSO 储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入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: 3 mg/mL (8.14 mM) 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), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 30.0 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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配方 3 中的溶解度: 25 mg/mL (67.86 mM) in 1% (w/v) carboxymethylcellulose (CMC) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。

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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。