- Human dermal fibroblasts: enhances elastic fiber and collagen deposition via sodium-dependent vitamin C transporters (SVCTs), reduction of intracellular ROS, activation of c-Src kinase, and enhancement of IGF-1 receptor phosphorylation. [1]
- Neuronal T-type calcium channels: selectively inhibits Cav3.2 (α1H) subtype via metal-catalyzed oxidation of histidine 191 in domain I, with no effect on Cav3.1 or Cav3.3. [3]

- 抗坏血酸（L-抗坏血酸钠）（50–200 μM）显著促进正常人真皮成纤维细胞和脂肪来源成纤维细胞培养72小时后免疫检测到的弹性纤维和胶原纤维沉积。更高浓度（400 μM）无进一步促进，800 μM则抑制弹性纤维生成。NaCl或NaCl与抗坏血酸混合物无效果。 [1]
- 100 μM SA与脯氨酰羟化酶抑制剂DMOG联用可抑制胶原沉积但不减弱弹性增强效果；连续7天每日给予SA的培养物含有更多弹性蛋白，SA+DMOG进一步增加弹性纤维和不溶性弹性蛋白。 [1]
- SA（100 μM）上调原弹性蛋白mRNA（18小时）、细胞内原弹性蛋白（24小时）和不溶性弹性蛋白（72小时）。SVCT抑制剂丙磺舒（400 μM）消除了这些促弹性生成效应。 [1]
- SA（100 μM，2小时）显著降低成纤维细胞内活性氧水平（通过CM-H₂DCFDA荧光探针和流式细胞术检测），该效应可被丙磺舒阻断。 [1]
- SA仅在含5% FBS（含IGF-1）的培养基中促进弹性生成。在无血清培养基中，SA单独不诱导弹性生成，但能增强IGF-1诱导的原弹性蛋白合成。SA增强IGF-1受体磷酸化，该效应可被c-Src抑制剂PP2或IGF-1R激酶抑制剂PPP阻断。SA不增强胰岛素受体磷酸化。 [1]
- 来自皮肤膨胀纹的成纤维细胞中，SA（200 μM）上调胶原和弹性纤维沉积，而抗坏血酸则选择性抑制弹性生成。 [1]
- 抗坏血酸抑制急性分离的大鼠背根神经节神经元中的天然T型钙电流，IC₅₀为6.5 ± 3.9 μM，最大抑制率70.2 ± 2.1%（Hill系数0.56 ± 0.12）。抗坏血酸使激活电压依赖性向去极化方向偏移（V₅₀从-49.0 mV至-44.1 mV），稳态失活向超极化方向偏移（V₅₀从-75.0 mV至-80.4 mV），并减慢激活和失活动力学。 [3]
- 抗坏血酸（100–300 μM）可逆地抑制HEK293细胞中表达的重组人Cav3.2 T型通道，但对Cav3.1或Cav3.3无作用。抑制呈浓度依赖性。 [3]
- 定点突变确定结构域I的S3-S4胞外环中第191位组氨酸（H191）对抗坏血酸敏感性至关重要。H191Q或H191C突变消除抗坏血酸抑制。H191Q突变还使Cu²⁺敏感性降低>40倍。 [3]
- 金属螯合剂DTPA、分解H₂O₂的过氧化氢酶以及ROS清除剂c-PTIO均可阻止抗坏血酸的抑制作用。添加300 nM Cu²⁺可增强抗坏血酸的抑制。 [3]

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B16F10细胞条件培养基的活性成分相对分子质量小于5,000，可强烈减少L-抗坏血酸钠（10 mM）诱导的细胞凋亡[4]。

与未用L-抗坏血酸钠（Sodium L-ascorbate）治疗的Tg大鼠相比，用L-抗坏血酸钠（15.4％）治疗的Tg大鼠的癌症发病率更高（29.6％）。即使没有 L-抗坏血酸钠盐治疗，转基因大鼠也会出现多种器官癌症 [5]。 PEITC 治疗 12 周后，所有动物均出现单纯性增生和乳头状或结节性 (PN) 增生；然而，无论是否进行钠盐（L-抗坏血酸）治疗，大多数病变都会在 48 周后消退。到第 48 周，即经过 24 周的 PEITC 治疗后，少数病例中相同的病变已进展为不典型增生和癌症；然而，大鼠单纯性增生和PN增生是L-抗坏血酸钠盐治疗显示出增强作用的唯一情况。 [6]。

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L-抗坏血酸钠（Na-AsA）被公认为大鼠膀胱癌发生过程中的一种促进剂，但在标准的两年生物检测中结果为阴性。为进一步研究其致瘤潜力，本研究采用了高度易患膀胱癌的 Hras128 转基因大鼠。总共 40 只 7 周龄雄性转基因（Tg）大鼠和 42 只同窝非转基因（Non-tg）大鼠被分为四组，分别喂饲添加或不添加 5% Na-AsA 的粉末状 MF 饲料，持续 57 周。无论是否接受 Na-AsA 处理，Tg 大鼠的生存期均显著短于 Non-tg 大鼠。在 Tg 大鼠中，Na-AsA 处理组的癌发生率（29.6%）略高于未处理组（15.4%），但这一差异无统计学意义。此外，包括乳头状瘤在内的膀胱总肿瘤发生率在两个 Tg 组之间也无显著差异（Na-AsA 处理组为 37.0%，未处理组为 30.8%）。在所有 Non-tg 大鼠中均未检测到膀胱肿瘤。在 Tg 大鼠中，无论是否接受 Na-AsA 处理，均观察到多个器官出现多种其他病变，但组间未见明显差异。总之，Na-AsA 在高度易患膀胱癌的 Hras128 转基因大鼠模型中未表现出致瘤性。这些结果表明，Na-AsA 在大鼠中是一种纯粹的促进剂，而非完全致癌物。[5]

- 弹性生成研究：通过免疫染色、Western blot、RT-PCR以及使用[³H]缬氨酸标记的不溶性弹性蛋白定量测定。ROS水平通过CM-H₂DCFDA荧光探针和流式细胞术测量。 [1]
- T型钙通道研究：对急性分离的大鼠DRG神经元、丘脑脑片以及表达重组通道的HEK293细胞进行全细胞膜片钳记录。外液含10 mM Ba²⁺作为电荷载体。浓度-反应曲线拟合Hill-Langmuir方程。激活和失活的电压依赖性拟合Boltzmann分布。 [3]

- 人真皮成纤维细胞和脂肪来源成纤维细胞（2-4代）在含5% FBS的DMEM中培养。用SA（50–800 μM）处理18–72小时。进行弹性蛋白和胶原I免疫染色、原弹性蛋白Western blot、原弹性蛋白mRNA的RT-PCR以及[³H]缬氨酸掺入不溶性弹性蛋白测定。 [1]
- ROS测量：细胞负载10 μM CM-H₂DCFDA 30分钟，然后用SA（100 μM）处理2或24小时，通过显微镜或流式细胞术观察荧光。 [1]
- IGF-1R磷酸化研究：裂解细胞，用抗IGF-1R β亚基抗体免疫沉淀，然后用抗磷酸酪氨酸抗体进行Western blot。 [1]
- T型通道研究：使用急性分离的大鼠DRG神经元、丘脑脑片以及瞬时表达Cav3.1、Cav3.2或Cav3.3通道的HEK293细胞。室温下进行全细胞电压钳记录。抗坏血酸通过灌流系统施加。 [3]

At 6 weeks of age, animals were divided into six groups (Fig. 1). To examine the development of proliferative lesions in the urinary bladder at the end of different periods of PEITC exposure, animals in groups 1 and 2 were fed basal diet (control) or 0.1% PEITC for up to 48 weeks, and sacrificed at 12, 24, and 48 weeks (7–8 animals per time point). To examine the enhancing effect of Na‑AsA on the development of proliferative lesions induced by PEITC, animals of groups 4 and 6 were fed 0.1% PEITC for the initial 12 and 24 weeks, respectively, and then fed 5% Na‑AsA until week 48 (16 animals/group). Animals of groups 3 and 5 served as Na‑AsA negative controls for groups 4 and 6, respectively, and were fed basal diet instead of Na‑AsA after PEITC treatment (16 animals/group). Food and tap water were available ad libitum. Body weight and food consumption were recorded at least once every 2 weeks after the first 8 weeks. At the sacrifice points, all animals were euthanized under ether anesthesia. At autopsy, the liver, kidneys and urinary bladder were removed, and the liver and kidneys were weighed. The urinary bladder was inflated with 10% neutral buffered formalin (pH 7.4) before immersion in the fixative. Urinary bladders at terminal sacrifice were weighed after fixation and six slices were prepared from each. They were paraffin‑embedded together with slices of liver and kidneys, sectioned at 3 μm, and stained with hematoxylin and eosin. The lesions observed in the urinary bladder were histopathologically classified into simple hyperplasia, PN hyperplasia, dysplasia, and transitional cell carcinoma according to criteria described previously.[6]

Absorption, Distribution and Excretion
Ascorbic acid, the reduced form of vitamin C, functions as a potent antioxidant as well as in cell differentiation. Ascorbate is taken up by mammalian cells through the specific sodium/ascorbate co-transporters SVCT1 and SVCT2. Although skeletal muscle contains about 50% of the whole-body vitamin C, the expression of SVCT transporters has not been clearly addressed in this tissue. ... This work ... analyzed the expression pattern of SVCT2 during embryonic myogenesis using the chick as model system. ... Immunohistochemical analyses showed that SVCT2 is preferentially expressed by type I slow-twitch muscle fibers throughout chick myogenesis as well as in post-natal skeletal muscles of several species, including human...
Humans use two sodium-ascorbate cotransporters (hSVCT1 and hSVCT2) for transporting the dietary essential micronutrient ascorbic acid, the reduced and active form of vitamin C. Although the human liver plays a pivotal role in regulating and maintaining vitamin C homeostasis, vitamin C transport physiology and regulation of the hSVCT systems in this organ have not been well defined. Thus, this research used a human hepatic cell line (HepG2), confirming certain results with primary human hepatocytes and determined the initial rate of ascorbic acid uptake to be Na(+) gradient, pH dependent, and saturable as a function of concentration over low and high micromolar ranges. Additionally, hSVCT2 protein and mRNA are expressed at higher levels in HepG2 cells and native human liver, and the cloned hSVCT2 promoter has more activity in HepG2 cells. Results using short interfering RNA suggest that in HepG2 cells, decreasing hSVCT2 message levels reduces the overall ascorbic acid uptake process more than decreasing hSVCT1 message levels. Activation of PKC intracellular regulatory pathways caused a downregulation in ascorbic acid uptake not mediated by a single predicted PKC-specific amino acid phosphorylation site in hSVCT1 or hSVCT2. However, PKC activation causes internalization of hSVCT1 but not hSVCT2. Examination of other intracellular regulatory pathways on ascorbic acid uptake determined that regulation also potentially occurs by PKA, PTK, and Ca(2+)/calmodulin, but not by nitric oxide-dependent pathways...

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Metabolism / Metabolites
... Adrenal cortex is closely associated with ascorbate metabolism ... Hydrocortisone was reported ... to stimulate synthesis of ascorbate from gluconolactone, but deoxycorticosterone or aldosterone caused ... increase in ascorbate excretion in normal or adrenalectomized rats...

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Vitamin C is a normal component of human milk and is a key milk antioxidant. The recommended vitamin C intake in lactating women is 120 mg daily, and for infants aged 6 months or less is 40 mg daily. High daily doses up to 1000 mg increase milk levels, but not enough to cause a health concern for the breastfed infant and is not a reason to discontinue breastfeeding. Nursing mothers may need to supplement their diet to achieve the recommended intake or to correct a known deficiency. Maternal doses of vitamin C in prenatal vitamins at or near the recommended intake do not alter milk levels.
Freezing (-20 degrees C) freshly expressed mature milk from hospitalized mothers of term and preterm infants does not change milk vitamin C levels for at least 3 months of freezer storage. After 6 to 12 months of freezing (-20 degrees C), vitamin C levels can decrease by 15 to 30%. Storage at -80 degrees C preserves vitamin C levels for up to 8 months, with 15% loss by 12 months.
◉ Effects in Breastfed Infants
Sixty healthy lactating women between 1 and 6 months postpartum exclusively breastfeeding their infants were given vitamin C 500 mg plus vitamin E 100 IU once daily for 30 days, or no supplementation. Infants of supplemented mothers had increased biochemical markers of antioxidant activity in their urine. Clinical outcomes were not reported.
Eighteen preterm infants, seven of whom were less than 32 weeks gestational age, who were fed pooled, Holder-pasteurized donor milk beginning during the first three days of life had their average blood plasma ascorbic acid concentrations decrease from 15.5 mg/L at birth to 5.4 mg/L by 1 week of age, and to 4.1 mg/L by 3 weeks of age. The authors described the 1- and 3-week levels as subtherapeutic (<6 mg/L) and indicative of inadequate intake, potentially jeopardizing postnatal growth potential. Although this study was conducted before advances in the provision of parenteral nutrition and enteral milk fortification for preterm infants, contemporary studies suggest that inadequate vitamin C intake from pooled, pasteurized donor milk may be a potential health problem for preterm infants receiving donor milk.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Interactions
Tissues exposed to Na ascorbate responded more vigorously than untreated muscles when graded concentrations of calcium chloride added to bathing solution minus Ca2+ ions but with acetylcholine.
The effects of sodium ascorbate with or without Vitamin K3 was studied in vitro using cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermal carcinoma), and AN3-CA (endometrial adenocarcinoma) at concentrations of 0.198 ug/mL to 1.98 mg/mL. Culture media without sodium ascorbate and the vitamin were used as a control. At 50%confluence, different combinations of sodium ascorbate and Vitamin K3 were added to the cultures for a 1 hr incubation. DNA determinations were made. Sodium Ascorbate supplemented media had a growth inhibiting action only at high concentrations (5 x 10+3 mol/L). Combined administration demonstrated a synergisitic inhibition of cell growth at 10 to 50 times lower concentrations. These results are for all three cell types ...
Sodium ascorbate and/or sodium nitrite /was administered/ for 6 months to male and female Wistar rats (5 rats/group). The control group was fed a basal diet and water only. Treated groups were administered the following: 0.075%, 0.15%, or 0.3% sodium nitrite dissolved in water; 1%, 2%, or 4% sodium ascorbate; or a combination with both chemicals at low + low, middle + middle, and high + high doses. Body weight gain was significantly decreased in the combined-high dose group. Significant decreases of serum total protein, increase of BUN (blood urea nitrogen) and relative kidney weight were also found in the combined-high dose group. Histopathological examination showed moderate or severe squamous cell hyperplasia of the forestomach in the combined-high dose group and slight hyperplasia in the combined-middle dose group. No differences were seen between the sexes. The minimum toxic dose was 0.15% sodium nitrite+2% sodium ascorbate ...

[1]. Sodium L-ascorbate enhances elastic fibers deposition by fibroblasts from normal and pathologic human skin. J Dermatol Sci. 2014 Sep;75(3):173-82.

[2]. Sodium L-ascorbate enhances elastic fibers deposition by fibroblasts from normal and pathologic human skin. J Dermatol Sci. 2014 Sep;75(3):173-82.

[3]. Molecular mechanisms of subtype-specific inhibition of neuronal T-type calcium channels by ascorbate. J Neurosci. 2007 Nov 14;27(46):12577-83.

[4]. Mouse melanoma cell line B16F10-derived conditioned medium inhibits sodium L-ascorbate-induced B16F10 cell apoptosis. Nan Fang Yi Ke Da Xue Xue Bao. 2012 Feb;32(2):146-50.

[5]. Lack of urinary bladder carcinogenicity of sodium L-ascorbate in human c-Ha-ras proto-oncogene transgenic rats. Toxicol Pathol. 2005;33(7):764-7.

[6]. Limited tumor-initiating activity of phenylethyl isothiocyanate by promotion with sodium L-ascorbate in a rat two-stage urinary bladder carcinogenesis model. Cancer Lett. 2005 Mar 10;219(2):147-53.

- Sodium L-ascorbate (SA) is a stable salt form of vitamin C that can be transported into cells via sodium-dependent vitamin C transporters (SVCTs). Unlike L-ascorbic acid (AA), SA does not cause extracellular oxidation and effectively enhances both collagen and elastic fiber deposition at low micromolar concentrations (50–200 μM). Its elastogenic mechanism involves intracellular ascorbate anion influx, reduction of ROS, activation of c-Src, and enhanced IGF-1 receptor phosphorylation, ultimately up-regulating elastin gene expression. SA may have therapeutic potential for treating wrinkled skin, stretch marks, and keloids, especially when combined with prolyl hydroxylase inhibitors to reduce collagen deposition. [1]
- Ascorbate selectively inhibits Cav3.2 T-type calcium channels via metal-catalyzed oxidation of a specific histidine residue (H191) in domain I. This is the first demonstration of ion channel modulation by ascorbate via covalent modification. Ascorbate reduces Cav3.2 availability over a wide range of membrane potentials and inhibits low-threshold Ca²⁺ spikes and burst firing in reticular thalamic neurons at physiologically relevant concentrations (IC₅₀ ~6.5 μM). This suggests ascorbate may act as an endogenous neuromodulator. [3]

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Minute crystals or white powder. pH of aqueous solutions 5.6 to 7.0 or even higher (a 10% solution, made from a commercial grade, may have a pH of 7.4 to 7.7). (NTP, 1992)
Sodium ascorbate is an organic sodium salt resulting from the replacement of the proton from the 3-hydroxy group of ascorbic acid by a sodium ion. It has a role as a food antioxidant, a flour treatment agent, a coenzyme, a plant metabolite, a human metabolite, a Daphnia magna metabolite and a reducing agent. It is an organic sodium salt and a vitamin C. It contains a L-ascorbate.
A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.
See also: Ascorbic Acid (has active moiety) ... View More ...

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Mechanism of Action
Mechanism of action of ascorbate is a superoxide radical scavenger.
... Sodium ascorbate decreases cellular iron uptake by melanoma cells in a dose- and time-dependent fashion, indicating that intracellular iron levels may be a critical factor in sodium ascorbate-induced apoptosis. Indeed, sodium ascorbate-induced apoptosis is enhanced by the iron chelator, desferrioxamine (DFO) while it is inhibited by the iron donor, ferric ammonium citrate (FAC). Moreover, the inhibitory effects of sodium ascorbate on intracellular iron levels are blocked by addition of transferrin, suggesting that transferrin receptor (TfR) dependent pathway of iron uptake may be regulated by sodium ascorbate. Cells exposed to sodium ascorbate demonstrated down-regulation of TfR expression and this precedes sodium ascorbate-induced apoptosis. Taken together, sodium ascorbate-mediated apoptosis appears to be initiated by a reduction of TfR expression, resulting in a down-regulation of iron uptake followed by an induction of apoptosis...
Humans use two sodium-ascorbate cotransporters (hSVCT1 and hSVCT2) for transporting the dietary essential micronutrient ascorbic acid, the reduced and active form of vitamin C. Although the human liver plays a pivotal role in regulating and maintaining vitamin C homeostasis, vitamin C transport physiology and regulation of the hSVCT systems in this organ have not been well defined. Thus, this research used a human hepatic cell line (HepG2), confirming certain results with primary human hepatocytes and determined the initial rate of ascorbic acid uptake to be Na(+) gradient, pH dependent, and saturable as a function of concentration over low and high micromolar ranges. Additionally, hSVCT2 protein and mRNA are expressed at higher levels in HepG2 cells and native human liver, and the cloned hSVCT2 promoter has more activity in HepG2 cells. Results using short interfering RNA suggest that in HepG2 cells, decreasing hSVCT2 message levels reduces the overall ascorbic acid uptake process more than decreasing hSVCT1 message levels. Activation of PKC intracellular regulatory pathways caused a downregulation in ascorbic acid uptake not mediated by a single predicted PKC-specific amino acid phosphorylation site in hSVCT1 or hSVCT2. However, PKC activation causes internalization of hSVCT1 but not hSVCT2. Examination of other intracellular regulatory pathways on ascorbic acid uptake determined that regulation also potentially occurs by PKA, PTK, and Ca(2+)/calmodulin, but not by nitric oxide-dependent pathways...

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Therapeutic Uses
Antioxidants; Free Radical Scavengers
Ascorbic acid and calcium and sodium ascorbates are used as antoxidants in pharmaceutical manufacturing and in the food industry.
In 20 patients in acute asthmatic crisis, 16 recovered promptly after receiving 6 g sodium ascorbate iv. Chronic oral treatment (0.6-1 g/day/60 days) with Na ascorbate prevented asthmatic symptoms in 18/25 asthmatic patients.
8 patients with hyphema were treated with iv glycerin in combination with sodium ascorbate. The results showed that glycerol in combination with sodium ascorbate diminished the hemorrhage in eye within 12-24 hr.
For more Therapeutic Uses (Complete) data for Sodium ascorbate (6 total), please visit the HSDB record page.

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Drug Warnings
Each gram of sodium ascorbate contains approximately 5 mEq of sodium; this should be considered when the drug is used in patients on salt-restricted diets.

C6H7NAO6

198.11

198.014

C, 36.38; H, 3.56; Na, 11.60; O, 48.46

134-03-2

L-Ascorbic acid;50-81-7;L-Ascorbic acid (GMP Like);50-81-7

23667548

Off-white to light yellow solid powder

1.799 g/cm3

552.7ºC at 760 mmHg

220 °C (dec.)(lit.)

238.2ºC

1.62E-14mmHg at 25°C

105.5 ° (C=10, H2O)

110.05

3

6

2

13

237

2

[Na+].O1C(C(=C([C@@]1([H])[C@]([H])(C([H])([H])O[H])O[H])[O-])O[H])=O

PPASLZSBLFJQEF-RXSVEWSESA-M

InChI=1S/C6H8O6.Na/c7-1-2(8)5-3(9)4(10)6(11)12-5;/h2,5,7-10H,1H2;/q;+1/p-1/t2-,5+;/m0./s1

sodium;(2R)-2-[(1S)-1,2-dihydroxyethyl]-4-hydroxy-5-oxo-2H-furan-3-olate

Ascorbate; Vitamin C sodium; SODIUM ASCORBATE; 134-03-2; L-Ascorbic acid sodium salt; Sodium L-ascorbate; Vitamin C sodium; Sodium Ascorbate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

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

H2O : ~100 mg/mL (~504.77 mM)
DMSO : ~1 mg/mL (~5.05 mM)

配方 1 中的溶解度: 50 mg/mL (252.39 mM) in PBS (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。

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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：
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10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
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