Oxysophoridine   中文名称: 氧化槐定碱

Biochemical reagent; natural alkaloid

氧槐定碱（OSR）是从苦豆子中提取的一种天然生物碱，具有多种药理活性。之前的一项研究表明，OSR具有多种药理作用，包括抗心律失常、保护心肌、抗病毒、抗肿瘤作用。此外，OSR具有抗病毒药理作用，与槐定碱相似。OSR具有抗炎作用并抑制白三烯B4的生物合成。本研究假设OSR的抗炎作用通过抗炎、抗氧化应激和抗凋亡作用拯救SCI[1]。

氧槐定碱（OSR）是从苦豆子中提取的生物碱，具有多种药理活性。本研究旨在在大鼠模型中研究OSR对脊髓损伤（SCI）的保护作用和潜在机制，SCI是一种临床常见的严重创伤。本研究的结果表明，OSR的抗炎作用提高了脊髓损伤大鼠模型中Basso、Beatie和Bresnahan运动评定量表的评分，并降低了脊髓组织的含水量。通过ELISA测定炎症激活，并使用蛋白质印迹法测定前列腺素E2（PGE2）、细胞间粘附分子-1（ICAM-1）、环氧化酶-2（COX-2）、核因子κB（NF-κB）和B细胞淋巴瘤2（Bcl-2）/Bcl-2相关X（Bax）蛋白表达水平。结果显示，OSR治疗降低了SCI大鼠模型血清中的肿瘤坏死因子α、白细胞介素（IL）-1β、IL-6、IL-8和丙二醛水平，并提高了超氧化物歧化酶和谷胱甘肽过氧化物酶水平。OSR显著降低了SCI大鼠模型脊髓组织中炎症相关蛋白PGE2、ICAM-1、COX-2、NF-κB和Bcl-2/Bax比值的蛋白表达。此外，本研究的结果表明，OSR通过抗炎、抗氧化应激和抗凋亡作用改善SCI。[1]

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氧槐定碱（OSR）是从苦豆子中提取的一种具有生物活性的生物碱。我们的目的是探索OSR在脑缺血损伤中的潜在抗炎机制。用OSR（62.5、125和250mg/kg）或尼莫地平（Nim）（6mg/kg）对小鼠进行腹膜内预处理7天，然后进行脑缺血。通过免疫组织化学染色、Western blot和酶联免疫吸附试验（ELISA）测定脑缺血半球组织中的炎症相关细胞因子。OSR治疗组显著抑制了核因子κB（NF-κB）、细胞间粘附分子-1（ICAM-1）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）。OSR治疗组（250mg/kg）显著降低了炎症相关蛋白前列腺素E2（PGE2）、肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）、白介素-6（IL-6）和白细胞介蛋白-8（IL-8）。同时，它显著增加了白细胞介素-10（IL-10）。我们的研究表明，OSR通过下调促炎细胞因子和阻断NF-κB通路保护小鼠神经元免受缺血诱导的损伤[2]。

ELISA检测炎症活化[1]
全血（500µl）在4°C下以2000×g离心10分钟，收集每只大鼠的血清，根据制造商的方案使用商业ELISA试剂盒测定肿瘤坏死因子-α（TNF-α；H052）、白细胞介素（IL）-1β（H002）、IL-6（H007）、IL-8（H008）、丙二醛（MDA；A003-1）、SOD（A001-1）和GSH-Px（A005）的水平。

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蛋白质印迹[1]
从每只大鼠中分离脊髓组织，并在RIPA试验中均质化。使用BCA蛋白测定试剂盒测量蛋白质浓度。蛋白质（50-80µg）通过12%SDS-PAGE分级，并转移到硝化纤维膜上。在室温下，在摇床上将膜在TBS-Tween-20（TBS-T；0.05%）中的5%脱脂乳中封闭1小时，并与以下一抗一起孵育.

Animals [1]
Female adult Sprague-Dawley rats (weight, 200–230 g, n=50) were maintained in standard cages (22–24°C and 55–60% humidity) with water and food ad libitum and a 12-h light/dark cycle. All rats were randomly assigned into five groups; sham-operation group, SCI model group, 60 mg/kg Oxysophoridine (OSR) group, 120 mg/kg Oxysophoridine (OSR) group and 180 mg/kg Oxysophoridine (OSR) group. Anesthetized Sprague-Dawley rats received a midline 150 kdyne contusion injury in spinal level T10 using an Infinite Horizon impactor device, which was considered to be the SCI model. The establishment of the SCI model was confirmed by analysis of the Basso, Beatie and Bresnahan (BBB) Locomotor Rating Scale and spinal cord tissue water content. In the 60, 120 and 180 mg/kg OSR groups, SCI rats were administered intragastrically with 60, 120 and 180 mg/kg OSR once per day for 10 days. OSR was purchased from Jinghua Pharmaceutical Group Co., Ltd. (Yanchi, China). In sham-operation group and SCI model group, rats were administered normal saline intragastrically.

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Behavioral assessments [1]
Functional recovery was assessed following treatment with Oxysophoridine (OSR) using the BBB Locomotor Rating Scale to ensure consistency of the lesion. Following 10 days treatment with OSR, the rats were narcotized with 35 mg/kg of pentobarbital and then sacrificed using decollation. Subsequently, abdomen of rats was cut open, spinal level T10 was peeled and spinal cord tissues were collected and washed with PBS. Spinal cord tissues were weighed as wet weight and heated at 80°C for 48 h, and subsequently weighed as dry weight. Spinal cord tissue water content was calculated by (wet weight/dry weight) ×100.

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Experimental Design [2]
Male Institute of Cancer Research (ICR) mice weighing 25–30 g were housed in cages for 6 days at room temperature under a controlled 12 h light/dark cycle and allowed access to pellet food and water ad libitum. Mice were randomly divided into six groups. The first was the sham-treated group. The second was the vehicle-treated group, that is, ischemia was induced for 2 h of middle cerebral artery occlusion (MCAO) followed by reperfusion for 24 h. The Oxysophoridine (OSR)-treated groups were separated into low dosage group (OSR 62.5 mg/kg), moderate dosage group (OSR 125 mg/kg), and high dosage group (OSR 250 mg/kg). The sixth was the Nim-treated group (6 mg/kg). Before ischemia/reperfusion (I/R), all groups were intraperitoneally pretreated with drug or reagent (0.1 ml/10 g) for 7 consecutive days.

Interactions
The combination of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait. was extensively used in traditional Chinese medicine to treat inflammatory diseases, such as acne, heart disease, and hepatitis. Sodium ferulate (SF) and oxymatrine (OMT) were effective component of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait., respectively. In this study, /the authors/ investigated the synergistic anti-inflammatory effect of the combination of SF and OMT, and its modulation on inflammation-associated mediators in RAW 264.7 cells. In vivo, the anti-inflammatory effects of the combination of SF and OMT were evaluated with the xylene-induced mouse ear edema model and the carrageenan-induced rat paw edema model. In vitro, chemokines and cytokines mRNA expressions in lipopolysaccharide (LPS)-activated RAW 264.7 cells were determined by real-time PCR (RT-PCR) microarray analysis. The levels of interleukin-11 (IL-11), C-reactive protein (CRP) and interferon-gamma (INF-gamma) in the supernatant of LPS-stimulated RAW 264.7 cells were measured by enzyme-linked immune-sorbent assay (ELISA). The combination of SF and OMT could significantly inhibit the edema in the xylene-induced mouse ear edema and carrageenan-induced rat paw edema, but no effect was found when each drug was used alone according to above doses. The combination exhibited a better effect in down-regulating mRNA expressions of inflammation-associated mediators in LPS-stimulated RAW 264.7 cells than SF or OMT alone. The ELISA results showed that the combination synergistically inhibited LPS-induced IL-11, CRP and INF-gamma production in a dose-dependent manner. The combination of SF and OMT showed synergistic anti-inflammatory effect, and the activity was probably related to its modulation on inflammation-associated mediators, especially IL-11, CRP and INF-gamma.
Sodium ferulate (SF) and Oxymatrine (OMT) were compounds extracted from Chinese herbs, and have been used in clinical treatment of heart and hepatic diseases, respectively, in China for many years. The objective of this study was to examine the analgesic effect and the mechanism of the combined treatment of SF and OMT. Using the animal pain models by applying Acetic Acid Writhing Test and Formalin Test, the combination of SF and OMT showed significant analgesic effect in dose-dependent manner. In vitro, the combined treatment inhibited the increase in intracellular calcium concentration evoked by capsaicin in the dorsal root ganglion neurons. Importantly, a synergistic inhibitory effect of SF and OMT on the capsaicin-induced currents was demonstrated by whole-cell patch-clamp. Our results suggest that SF and OMT cause significant analgesic effect which may be related to the synergistic inhibition of transient receptor potential vanilloid-1.
/The aim of this was/ to study the effect of oxymatrine-baicalin combination (OB) against HBV replication in 2.2.15 cells and alpha smooth muscle actin (alpha SMA) expression, type I, collagen synthesis in HSC-T6 cells. The 2.2.15 cells and HSC-T6 cells were cultured and treated respectively. HBsAg and HBeAg in the culture supernatants were detected by ELISA and HBV DNA levels were determined by fluorescence quantitative PCR. Total RNA was extracted from HSC-T6 cells and reverse transcribed into cDNA. The cDNAs were amplified by PCR and the quantities were expressed in proportion to beta actin. The total cellular proteins extracted from HSC-T6 cells were separated by electrophoresis. Resolved proteins were electrophoretically transferred to nitrocellulose membrane. Protein bands were revealed and the quantities were corrected by beta actin. In the 2.2.15 cell culture system, the inhibitory rate against secretion of HBsAg and HBeAg in the OB group was significantly stronger than that in the oxymatrine group (HBsAg, P = 0.043; HBeAg, P = 0.026; respectively); HBV DNA level in the OB group was significantly lower than that in the oxymatrine group (P = 0.041). In HSC-T6 cells the mRNA and protein expression levels of alpha SMA in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P = 0.013; protein, P = 0.042; respectively); The mRNA and protein expression levels of type I collagen in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P < 0.01; protein, P < 0.01; respectively). /The authors concluded that/ OB combination has a better effect against HBV replication in 2.2.15 cells and is more effective against alpha SMA expression and type I collagen synthesis in HSC-T6 cells than oxymatrine in vitro.
Oxymatrine is proven to protect ischemic and reperfusion injury in liver, intestine and heart, this effect is via anti-inflammation and anti-apoptosis. Whether this protective effect applies to ischemic injury in brain, /the authors/ therefore investigate the potential neuroprotective role of oxymatrine and the underlying mechanisms. Male, Sprague-Dawley rats were randomly assigned to four groups: permanent middle cerebral artery occlusion (pMCAO), high dose (pMCAO+oxymatrine 120 mg/kg), low dose (pMCAO+oxymatrine 60 mg/kg) and sham operated group. /The authors/ used a permanent middle cerebral artery occlusion model and administered oxymatrine intraperitoneally immediately after cerebral ischemia and once daily on the following days. At 24 hr after MCAO, neurological deficit was evaluated using a modified six point scale; brain water content was measured; NF-kappaB expression was measured by immunohistochemistry, Western blotting and RT-PCR. Infarct volume was analyzed with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 hr. Compared with pMCAO group, neurological deficit in high dose group was improved (P < 0.05), infarct volume was decreased (P < 0.001) and cerebral edema was alleviated (P < 0.05). Consistent with these indices, immunohistochemistry, Western blot and RT-PCR analysis indicated that NF-kappaB expression was significantly decreased in high dose group. Low dose of oxymatrine did not affect NF-kappaB expression in pMCAO rats. Oxymatrine reduced infarct volume induced by pMCAO, this effect may be through the decreasing of NF-kappaB expression.

[1]. Oxysophoridine rescues spinal cord injury via anti inflammatory, anti oxidative stress and anti apoptosis effects. Mol Med Rep. 2018 Feb;17(2):2523-2528.

[2]. Anti-inflammation Effects of Oxysophoridine on Cerebral Ischemia-Reperfusion Injury in Mice. Inflammation. 2015 Dec;38(6):2259-68.

Therapeutic Uses
Anti-Arrhythmia Agents; Antiviral Agents
The aim of this study was/ to evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B. A randomized double-blind and placebo-controlled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo. After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed. Among the 216 patients, six were dropped off, and 11 inconsistent with the standard were excluded. Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47% became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33% became normal in ALT level, 43.33% and 39.29% became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00% became normal in ALT level, 7.46% and 6.45% became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84% in the capsule treated patients, and 33.33% and 50.00% in the injection treated patients, and 2.99% and 41.79% in the placebo treated patients, respectively. There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule, injection and placebo were 7.77%, 6.67% and 8.82%, respectively. There was no statistically significant difference among them. /It was concluded that/ oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

C15H24N2O2

264.36

264.183

54809-74-4

114850

White to off-white solid powder

208 °C

-0.35

49.74

0

2

0

19

400

4

C1C[C@@H]2[C@H]3CCC[N+]4([C@H]3[C@@H](CCC4)CN2C(=O)C1)[O-]

XVPBINOPNYFXID-LHDUFFHYSA-N

InChI=1S/C15H24N2O2/c18-14-7-1-6-13-12-5-3-9-17(19)8-2-4-11(15(12)17)10-16(13)14/h11-13,15H,1-10H2/t11-,12+,13+,15-,17?/m0/s1

(1R,2R,9S,17S)-13-oxido-7-aza-13-azoniatetracyclo[7.7.1.02,7.013,17]heptadecan-6-one

Oxymatrine; oxysophoridine; Matrine 1beta-oxide; Oxysophoridine; 54809-74-4; Sophoridine N-oxide; N-Oxysophoridine; (41S,7aS,13aR,13bR)-10-Oxohexadecahydrodipyrido[2,1-f:3',2',1'-ij][1,6]naphthyridine 4-oxide; Matrine N-oxide; Matrine oxide; Ammothamnine

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)

DMSO : ~25 mg/mL (~94.57 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (9.46 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 25.0 mg/mL澄清DMSO储备液加入到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: ≥ 2.5 mg/mL (9.46 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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配方 3 中的溶解度: ≥ 2.5 mg/mL (9.46 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 25.0 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 4 中的溶解度: 100 mg/mL (378.27 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：
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。