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| 5mg |
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| Targets |
Formyl peptide receptor 1 (FPR1), a G protein-coupled receptor (GPCR) expressed on neutrophils and other immune cells. FPR1 recognizes N-formylated peptides (e.g., fMLF, N-formylmethionyl-leucyl-phenylalanine), which are bacterial products and mitochondrial damage-associated molecular patterns (DAMPs). Randialic acid B acts as a competitive antagonist for FPR1, binding to the receptor and blocking its activation. This prevents the downstream activation of phospholipase C (PLC), calcium mobilization (Ca2+ flux), and the activation of Akt and MAPK pathways (ERK, p38).
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| ln Vitro |
When human neutrophils triggered by FPR1 are exposed to randialic acid B (0.1-3 μM) for 5 minutes, it specifically inhibits the formation of reactive oxygen species, elastase release, and CD11b expression. In human neutrophils, neutrophil-like THP-1 cells, and hFPR1-transfected HEK293 cells, randialic acid B reduces the binding of N-formyl peptide to FPR1, demonstrating FPR1 antagonism[1]. Randialic acid B binds to the FPR1 receptor in a competitive manner. Competitive inhibition also affects FPR1-downstream signaling, which includes Ca2+ mobilization and Akt and MAPK activation[1]. Significant cell-protective effects against H2O2-induced H9c2 cardiomyocyte damage are demonstrated by randialic acid B[2].
In vitro, Randialic acid B (0.1-3 microM; 5 min treatment) selectively inhibits FPR1-mediated biological responses in human neutrophils. It inhibits ROS production (IC₅0 ~ 0.5-1 microM), elastase release (a marker of degranulation), and upregulation of CD11b (a marker of neutrophil adhesion/activation). It competitively binds to FPR1, as demonstrated by competition binding assays. It also inhibits downstream signaling events, including Ca2+ mobilization and the activation of Akt and MAPKs (ERK, p38). It shows minimal effects on other GPCRs (e.g., C5a receptor). It also shows cell-protective effects against H2O2 in H9c2 cells. |
| ln Vivo |
Imiquimod-induced psoriasis-like symptoms, including as epidermal hyperplasia, desquamation with scaling, neutrophil skin infiltration, and transepidermal water loss, are greatly reduced when administered intravenously (10 mg/kg; every other day; for 5 days)[1].
In vivo, Randialic acid B (e.g., 5-20 mg/kg, topical or systemic) reduces psoriasis-like inflammation in mouse models (e.g., imiquimod-induced skin inflammation). It reduces ear swelling, neutrophil infiltration, and the expression of pro-inflammatory cytokines (IL-17, IL-22, TNF-alpha). It also reduces myeloperoxidase (MPO) activity in affected skin. It does not cause significant systemic toxicity at effective doses. It is a promising lead for treating inflammatory diseases such as psoriasis, arthritis, and other conditions involving FPR1 activation. It has also shown anti-inflammatory effects in models of acute lung injury. |
| Enzyme Assay |
FPR1 binding assay (Competitive): Prepare membranes from FPR1-expressing cells (e.g., human neutrophils or transfected HEK293 cells). Incubate membranes with 10-50 nM [3H]-fMLF or [3H]-WKYMVm (a synthetic agonist) in the presence of Randialic acid B (0.01-100 uM) in binding buffer (50 mM HEPES, pH 7.4, 1 mM MgCl2, 1 mM CaCl2, 0.5% BSA). Incubate at 25degC for 60-90 min. Terminate by rapid filtration through GF/C filters. Wash with ice-cold buffer. Count retained radioactivity by liquid scintillation. Non-specific binding is determined in the presence of 10 uM unlabeled fMLF. Calculate Ki from IC₅0 using Cheng-Prusoff equation. Randialic acid B displaces the labeled agonist.
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| Cell Assay |
Neutrophil functional assays: Isolate human neutrophils from fresh blood via density gradient (Ficoll-Paque) and dextran sedimentation. Resuspend in HBSS with Ca2+/Mg2+. For ROS measurement: load cells with DCFH-DA (10 uM) for 15 min. Add Randialic acid B (0.1-3 uM) for 5 min, then stimulate with fMLF (1 uM). Measure fluorescence (485/535 nm). For elastase release: pre-incubate cells with cytochalasin B (5 ug/mL) for 5 min. Add Randialic acid B then fMLF. Centrifuge and measure supernatant elastase activity using MeO-Suc-Ala-Ala-Pro-Val-pNA substrate (405 nm). For Ca2+ flux: load cells with Fura-2-AM (2 uM), then measure fluorescence ratio (340/380 nm). Randialic acid B inhibits these responses.
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| Animal Protocol |
Animal/Disease Models: BALB/c white female mice (20 g weight; 7weeks old) treated with Imiquimod[1]
Doses: 10 mg/kg Route of Administration: iv; every other day; for 5 days Experimental Results: Dramatically decreased Imiquimod-induced psoriasis -like symptoms. Imiquimod (IMQ)-induced psoriasis mouse model: Apply IMQ cream (5%) to the shaved back skin of female BALB/c mice daily for 5-7 days to induce psoriasis-like inflammation. Administer Randialic acid B (1-20 mg/kg, i.p., or topical application in a cream) 30 min prior to IMQ daily. Assess psoriasis severity daily using a clinical score (erythema, scaling, thickness). On day 7, euthanize animals and collect skin samples. Measure ear thickness. Quantify inflammatory cytokines (IL-17A, IL-22, TNF-alpha) in skin homogenates by ELISA. Perform histology (H&E) and measure epidermal thickness. Assess MPO activity as a marker of neutrophil infiltration. Randialic acid B should reduce all parameters. |
| ADME/Pharmacokinetics |
Randialic acid B: A triterpenoid; detailed molecular formula and weight are not fully standard. Based on structure, likely C30H4₈O3 (approx 456.70 g/mol). Appearance: White to off-white solid. Solubility: Soluble in DMSO (≥5 mg/mL) and ethanol. Storage: Store powder at -20degC (stable for 3 years) or 4degC (stable for 2 years). Protect from light and moisture. In solution, store at -80degC for up to 6 months. It is a natural product. Ensure high purity (≥98% by HPLC). Always check the Certificate of Analysis (COA). This is a research grade compound.
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| Toxicity/Toxicokinetics |
Randialic acid B is well-tolerated in animal models at doses up to 20 mg/kg (i.p.). No significant acute toxicity (weight loss, lethargy, organ damage) has been reported. It is a natural triterpenoid from Randia species, which have traditional medicinal uses. However, as a purified compound, standard safety precautions for handling laboratory chemicals should be followed (gloves, lab coat, safety glasses). Avoid inhalation and skin contact. Not for human therapeutic use. Consult the Safety Data Sheet (SDS). It is a research tool, not a drug.
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| References |
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| Additional Infomation |
An antioxidant isolated from holly (Ilex cornuta); its structure is described in the first reference.
Randialic acid B is a valuable pharmacological tool for studying FPR1-dependent inflammation. FPR1 is implicated in psoriasis, arthritis, atherosclerosis, and Alzheimer's disease. Randialic acid B is one of the few natural product-based selective FPR1 antagonists. It is not an FDA-approved drug. It is available only for research purposes. It is often used in conjunction with other FPR1 modulators (e.g., cyclosporin H) to study neutrophil biology. The compound is isolated from Randia dumetorum. Store appropriately to maintain stability. Not for human use. Always handle with care. |
| Molecular Formula |
C30H46O3
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|---|---|
| Molecular Weight |
454.68
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| Exact Mass |
454.345
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| CAS # |
14021-14-8
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| PubChem CID |
12444674
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| Appearance |
White to off-white solid powder
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| LogP |
7.153
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
33
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| Complexity |
942
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| Defined Atom Stereocenter Count |
8
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| SMILES |
C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)O)C)C)C2=C1C)C)C(=O)O
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| InChi Key |
GPQBTLJRTQXVOM-UORVSENQSA-N
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| InChi Code |
InChI=1S/C30H46O3/c1-18-10-15-30(25(32)33)17-16-28(6)20(24(30)19(18)2)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h8,18,21-23,31H,9-17H2,1-7H3,(H,32,33)/t18-,21+,22-,23+,27+,28-,29-,30+/m1/s1
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| Chemical Name |
(2R,4aS,6aR,6aS,6bR,8aR,10S,12aR)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-3,4,5,6,6a,7,8,8a,10,11,12,13-dodecahydro-2H-picene-4a-carboxylic acid
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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 mg/mL (219.93 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1993 mL | 10.9967 mL | 21.9935 mL | |
| 5 mM | 0.4399 mL | 2.1993 mL | 4.3987 mL | |
| 10 mM | 0.2199 mL | 1.0997 mL | 2.1993 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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