Raddeanin A 是一种齐墩果烷型三萜皂苷，具备口服活性。Raddeanin A 可抑制 SRC、mTOR、JNK、VEGFR2、NLRP3 炎症小体、Wnt/β-catenin、Wee1、PI3K/AKT 信号通路、MAPK/ERK 信号通路、AR-FL、AR-Vs，并下调 p-PI3K 和 p-AKT 的表达。Raddeanin A 可抑制破骨细胞形成、骨吸收、溶骨作用、癌细胞侵袭、迁移、增殖、血管生成及上皮-间质转化，同时诱导细胞凋亡 (apoptosis)、细胞周期阻滞、ROS 产生、免疫原性细胞死亡及树突状细胞成熟。Raddeanin A 可改善血视网膜屏障功能、减轻炎症、调控肿瘤微环境，并提升抗 PD-1 抗体的活性。Raddeanin A 可用于乳腺癌相关溶骨症、人骨肉瘤、结直肠癌、胶质母细胞瘤、阿尔茨海默病、胆管癌、黑色素瘤、非小细胞肺癌、去势抵抗性前列腺癌及多发性骨髓瘤的研究。
Raddeanin A is an oleanane-type triterpenoid saponin with oral activity. Raddeanin A inhibits SRC, mTOR, JNK, VEGFR2, NLRP3 inflammasome, Wnt/β-catenin, Wee1, PI3K/AKT signaling pathway, MAPK/ERK signaling pathway, AR-FL, AR-Vs, and downregulates the expression of p-PI3K and p-AKT. Raddeanin A inhibits osteoclast formation, bone resorption, osteolysis, cancer cell invasion, migration, proliferation, angiogenesis and epithelial-mesenchymal transition, while induces apoptosis, cell cycle arrest, ROS production, immunogenic cell death and dendritic cell maturation. Raddeanin A improves blood-retinal barrier function, alleviates inflammation, regulates the tumor microenvironment, and enhances the activity of anti-PD-1 antibody. Raddeanin A is applicable to the research of breast cancer-associated osteolysis, human osteosarcoma, colorectal cancer, glioblastoma, Alzheimer's disease, cholangiocarcinoma, melanoma, non-small cell lung cancer, castration-resistant prostate cancer and multiple myeloma[1][2][3][4][5][6][7][8][9][10][11].
RANKL-induced mouse bone marrow-derived macrophages (BMMs)
Concentration:
0.4 μM
Incubation Time:
5 days; 7 days
Result:
Dramatically suppressed mRNA expression of cathepsin k (CTSK) and nuclear factor of activated T cells 1 (NFATc1). Reduced protein expression levels of CTSK and NFATc1.
Showed no significant difference in ALP activity between control and treated groups at day 7. Resulted in a larger total mineralized area compared to the control group at 0.2 μM at day 21. Significantly increased secreted protein acidic and rich in cysteine (SPARC) mRNA expression after 14 days of treatment. Showed no significant cytotoxic effect on MC3T3-E1 cells at doses below 0.781 μM.
Increased bone volume to total volume (BV/TV) ratio compared to vehicle group. Decreased percentage of total porosity compared to vehicle group. Reduced number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts compared to vehicle group. Reduced number of cathepsin K (CTSK)-positive multinucleated osteoclasts compared to vehicle group.
Animal Model:
BALB/c nu/nu (5-week-old female; breast cancer-induced osteolysis model)[1]
Dosage:
100 μg/kg
Administration:
i.p.; every other day; 28 days
Result:
Increased trabecular bone volume to total volume (BV/TV) ratio compared to vehicle group. Reduced trabecular separation (Tb. Sp) compared to vehicle group. Preserved intact bone cortex (versus extensive trabecular bone resorption and discrete cortical bone in vehicle controls). Increased apoptosis in the treated group, as shown by TUNEL assay.
Significantly decelerated tumor growth in a dose-dependent manner. Reduced tumor volumes in all treatment groups. Induced significant apoptosis in tumor tissues via TUNEL staining. Increased p-JNK protein expression and decreased p65 protein expression in tumor tissues via immunohistochemistry analysis. Caused no significant body weight loss during treatment.
Reduced mean tumor volume to 765.3 mm3. Reduced mean tumor weight to 1.2 g. Decreased intratumoral microvessel density to ~20 vessels/mm2. Increased the percentage of TUNEL-positive apoptotic cells to ~60%. Increased tumor necrosis area to ~70%. Caused no significant body weight loss.
Significantly reduced the number of degenerated retinal capillaries compared to untreated 3×Tg-AD mice. Increased retinal expression of tight junction proteins ZO-1, Occludin, and Claudin 5. Ameliorated retinal structural abnormalities: restored total retinal thickness, ganglion cell layer + inner plexiform layer thickness, inner nuclear layer thickness, and outer nuclear layer thickness; improved disorganization of retinal cell layers. Increased the Bcl-2/Bax protein expression ratio in retinal tissue. Reduced retinal expression of NLRP3 inflammasome components (NLRP3, pro-Caspase-1, Caspase-1, ASC) and pro-inflammatory cytokines (IL-1β, IL-18). Decreased retinal expression of β-catenin and phosphorylated LRP5/6, and increased retinal expression of GSK-3β, indicating inhibition of the Wnt/β-catenin pathway.
i.p., four times at indicated time points; i.t., four times at indicated time points
Result:
Caused considerable inhibition of tumor volume and tumor weight. Induced 60% tumor-free survival 30 days after rechallenge with live MC38 cells. Markedly elevated the population of tumor-infiltrating CD8+ T cells and CD103+CD11c+ DCs, and increased levels of CD8+ T cell effector molecules GZMB and IFN-γ within the tumor microenvironment. Upregulated CD40, CD80, CD86, and MHC-II expression on tumor-infiltrating CD103+CD11c+ DCs.
Had its MC38 tumor inhibition attenuated by anti-CD8 depletion antibody. Had its MC38 tumor growth inhibition abolished by DC depletion via cytochrome c. When combined with anti-PD-1 antibody, achieved greater tumor growth inhibition than either treatment alone, increased populations of tumor-infiltrating CD8+ T cells and CD103+CD11c+ DCs, increased cleaved caspase 3 levels, decreased populations of regulatory T cells and monocytic MDSCs, and upregulated CD40, CD80, CD86, and MHC-II expression on tumor-infiltrating CD103+CD11c+ DCs.
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (protect from light)。-80°C储存时，请在6个月内使用，-20°C储存时，请在1个月内使用。
可选溶剂
浓度溶剂体积质量
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
1.1147 mL
5.5735 mL
11.1470 mL
27.8676 mL
5 mM
0.2229 mL
1.1147 mL
2.2294 mL
5.5735 mL
10 mM
0.1115 mL
0.5574 mL
1.1147 mL
2.7868 mL
15 mM
0.0743 mL
0.3716 mL
0.7431 mL
1.8578 mL
20 mM
0.0557 mL
0.2787 mL
0.5574 mL
1.3934 mL
25 mM
0.0446 mL
0.2229 mL
0.4459 mL
1.1147 mL
30 mM
0.0372 mL
0.1858 mL
0.3716 mL
0.9289 mL
40 mM
0.0279 mL
0.1393 mL
0.2787 mL
0.6967 mL
50 mM
0.0223 mL
0.1115 mL
0.2229 mL
0.5574 mL
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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