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Maackiain (DL-Maackiain) is an orally active multi-target inhibitor with anti-tumor activity and neuroprotective effects. Maackiain activates the AMPK, NLRP3 and Nrf2/HO-1 pathways, and inhibits key targets such as NF-κB, mTOR, MAO-B, NFATc1 and PKCδ, thereby precisely regulating processes including apoptosis, autophagy and pyroptosis. Maackiain also effectively inhibits microglial activation, osteoclast formation, and proliferation and invasion of tumor cells, and protects dopaminergic neurons from damage. Maackiain is applicable to the research of various diseases such as Alzheimer's disease, osteoporosis, sepsis and dengue fever。
For research use only. We do not sell to patients.
Maackiain (DL-Maackiain) is an orally active multi-target inhibitor with anti-tumor activity and neuroprotective effects. Maackiain activates the AMPK, NLRP3 and Nrf2/HO-1 pathways, and inhibits key targets such as NF-κB, mTOR, MAO-B, NFATc1 and PKCδ, thereby precisely regulating processes including apoptosis, autophagy and pyroptosis. Maackiain also effectively inhibits microglial activation, osteoclast formation, and proliferation and invasion of tumor cells, and protects dopaminergic neurons from damage. Maackiain is applicable to the research of various diseases such as Alzheimer's disease, osteoporosis, sepsis and dengue fever[1][2][3][4][5][6][7][8][9]。
IC50 & Target
p38 MAP kinase
PKCδ
MAO-B
NLRP3
In Vitro
Maackiain exhibits no direct bactericidal or bacteriostatic activity against Escherichia coli, Enterobacter cloacae, or Staphylococcus aureus[1]. Maackiain (10-100 ng/mL; pre-incubated for 30 min; co-incubated with LPS for 24 h) inhibits LPS-induced production of proinflammatory cytokines IL-1β, IL-6 and TNF-α in RAW264.7 cells in a dose-dependent manner, suppresses LPS-induced nuclear translocation of NF-κB p65 in RAW264.7 cells, and attenuates oxidative stress by reducing ROS generation, restoring mitochondrial membrane potential, and reversing the levels of GSH, MDA and TEAC[1]. Maackiain (100 ng/mL; pre-incubated for 3 h following pretreatment with AMPK/Nrf2 inhibitors, then co-incubated with LPS for 24 h) exerts antioxidant and anti-inflammatory activities in RAW264.7 cells by activating the AMPK/Nrf2/HO-1 pathway[1]. Maackiain (10-50 μM; 6 h) dose-dependently inhibits Aβ42 (10 μM; 24 h)-induced apoptosis, oxidative stress, inflammatory response, cellular damage and loss of viability in PC12 cells; it also promotes nuclear translocation of Nrf2 in PC12 cells without altering the total expression of Nrf2[2]. Maackiain (5-40 μM; 5 days) dose-dependently inhibits RANKL-induced osteoclast formation in mouse bone marrow macrophages, and at the dose of 40 μM, disrupts the formation of functional F-actin belts in mature mouse osteoclasts[3]. Maackiain (20-40 μM; 5 days) downregulates the expression of key genes associated with osteoclast differentiation and function in RANKL-stimulated mouse bone marrow macrophages[3]. Maackiain (40 μM; 1-5 days) suppresses the expression of osteoclast-specific proteins c-Fos, Integrin β3, MMP9, CTSK and NFATc1 in RANKL-stimulated mouse bone marrow macrophages; meanwhile, it downregulates the protein level of NFATc1 and inhibits its nuclear translocation[3]. Maackiain (40 μM; 1 h) blocks IκB-α degradation and p65 phosphorylation, inhibits RANKL-induced activation of the NF-κB pathway in mouse bone marrow-derived macrophages, and thereby attenuates RANKL-induced calcium oscillations in mouse bone marrow-derived macrophages[3]. Maackiain (50-100 ng/mL; sequential treatment for 1 h after 3 h of LPS pre-treatment and 1 h of incubation with 5 μM nigericin (HY-127019)) enhances 5 μM nigericin-induced caspase-1 activation and mature IL-1β production in LPS-pretreated human monocytic cell line dTHP-1, and exhibits a dose-dependent effect at concentrations of 50 ng/mL and 100 ng/mL[4]. Maackiain (2.5-40 μM; 24 h after LPS incubation) potently inhibits NO production in LPS-stimulated BV2 microglia, with the strongest effect observed at 20 μM, and exhibits a concentration-dependent response at concentrations below 20 μM[5]. Maackiain (10-40 μM; 24 h after LPS incubation) potently inhibits LPS-induced lipid peroxidation in BV2 microglial cells, and the antioxidant activity at the dose of 40 μM is stronger than that of Ferrostatin-1[5]. Maackiain (100 ng/mL; 24 h) inhibits the proliferation of human cervical cancer HeLa and SiHa cells in a concentration-dependent manner, induces autophagy (elevated expression levels of LC3-II and Beclin-1, autophagosome formation) in human cervical cancer HeLa and SiHa cells, and induces cell apoptosis[6]. Maackiain (75 μM; 3 days) induces DNA fragmentation and apoptotic body formation in human promyelocytic leukemia HL-60 cells, and this effect is inhibited by pretreatment with the antioxidant N-acetyl-L-cysteine (5 mM; 2 h pre-incubation)[7]. (-)-maackiain (50-150 μM; 24 h) inhibits the upregulation of IL-4 mRNA in IgE/antigen-induced RBL-2H3 cells, whereas the synthetic (+)-maackiain exerts no significant inhibitory activity[8]. (-)-Maackiain (20, 40 μM; 24 h) inhibits PMA-induced phosphorylation of Tyr311 on PKCδ in HeLa cells[8]. (-)-Maackiain (30 μM; 24 h) inhibits phorbol 12-myristate 13-acetate (PMA)-induced translocation of protein kinase Cδ (PKCδ) to the Golgi apparatus in HeLa cells[8].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
3-24 h (time-dependent assay; 100 ng/ml); 24 h (dose-dependent assay; 10-100 ng/ml)
Result:
Increased nuclear Nrf2 levels (elevated at 3 h, peaked at 12 h), decreased cytoplasmic Nrf2 levels, increased HO-1 levels, and increased p-AMPKα levels in a time-dependent manner at 100 ng/ml. Increased nuclear Nrf2 levels, decreased cytoplasmic Nrf2 levels, increased HO-1 levels, and increased p-AMPKα levels in a dose-dependent manner at 10, 50, 100 ng/ml for 24 h.
LPS-primed differentiated THP-1 (dTHP-1) human monocyte cells
Concentration:
50-100 ng/mL
Incubation Time:
1 h (sequential treatment after 3 h LPS priming and 1 h 5 μM nigericin incubation)
Result:
Amplified nigericin-induced cleavage of pro-caspase-1 to its active p20 subunit and pro-IL-1β to mature IL-1β, with a dose-dependent effect at 50 and 100 ng/mL. Did not alter LPS-induced pro-IL-1β production when used alone with LPS. Significantly increased mature IL-1β release when combined with nigericin.
1 h (sequential treatment after 3 h MPL priming and 1 h nigericin incubation at 1 or 2 μM)
Result:
Amplified nigericin-induced cleavage of pro-caspase-1 to p20 and mature IL-1β production in MPL-primed cells, even at reduced nigericin concentrations (1 or 2 μM). Did not increase IL-1β release relative to MPL priming alone when used alone.
human cervical cancer HeLa cells, human cervical cancer SiHa cells
Concentration:
0-100 μM (alone); 50 μM (combined with cisplatin)
Incubation Time:
24 h
Result:
Induced apoptosis in HeLa and SiHa cells in a concentration-dependent manner at 50, 100 μM, increasing the percentage of apoptotic cells and upregulating expression of cleaved PARP1, cleaved Caspase 3, cleaved Caspase 7, and cleaved Caspase 9. Enhanced cisplatin-induced apoptosis and apoptotic protein expression when used in combination at 50 μM.
human cervical cancer HeLa cells, human cervical cancer SiHa cells
Concentration:
0-100 μM
Incubation Time:
24 h
Result:
Increased phosphorylated AMPK (p-AMPK) levels in a concentration-dependent manner. Decreased phosphorylated mTOR (p-mTOR), phosphorylated p70 S6K (p-p70 S6K), and phosphorylated 4E-BP1 (p-4E-BP1) levels in a concentration-dependent manner. Had no effect on total AMPK, mTOR, p70 S6K, 4E-BP1, ACC, or phosphorylated ACC (p-ACC) levels.
Significantly suppressed PMA-induced H1R mRNA elevation at all tested concentrations (purified (-)-maackiain). Significantly suppressed PMA-induced H1R mRNA elevation at 30 μM (synthesized (-)-maackiain). Significantly suppressed PMA-induced H1R mRNA elevation at 10 and 30 μM (synthesized (+)-maackiain).
In Vivo
Maackiain (2.5-5 mg/kg; i.p.; single dose 12 hours pre-CLP) protects against CLP-induced sepsis in mice via dose-dependent reductions in mortality, organ injury, systemic inflammation, and oxidative stress, with the 5 mg/kg dose reducing 7-day mortality to 40%[1]. Maackiain (25-50 mg/kg; i.g.; daily; 14 days) improves LPS-induced cognitive impairment, increases normal neuron counts, inhibits microglial activation, and reduces cortical pro-inflammatory mediator levels in male C57BL/6 mice, with the 50 mg/kg dose demonstrating superior efficacy in most metrics[5]. Maackiain (5 mg/kg; i.p.; once every 2 days; 6 total injections) reduces cervical tumor weight to ~40% of control levels and inhibits tumor growth by 50% relative to controls without causing significant systemic toxicity in nude mice[6]. Racemic maackiain (5-20 mg/kg; p.o.; daily; 21 days) alleviates TDI-induced allergic rhinitis symptoms and suppresses TDI-induced upregulation of H1R and IL-4 gene expression in Brown Norway rats, with significant effects observed at doses of 5, 10, and 20 mg/kg administered orally daily for 21 days[8]. Maackiain (10-50 μg/mL; immersion; single exposure) demonstrates potent larvicidal activity against Aedes aegypti 4th instar larvae, with an LC50 of 21.95 ± 1.34 μg/mL at 48 hours[9].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Reduced 7-day mortality rate from ~90% to 60% (2.5 mg/kg) and to 40% (5 mg/kg).\nImproved clinical scores of CLP-induced septic mice in a dose-dependent manner.\n Significantly alleviated CLP-induced pathological lesions in the lung, liver, spleen, and kidney.\nReduced serum levels of inflammatory cytokines IL-1β, IL-6, and TNF-α in a dose-dependent manner at 12 and 24 hours post-CLP.\n Reversed CLP-induced reductions in serum GSH levels and Trolox Equivalent Antioxidant Capacity (TEAC), and reversed CLP-induced increases in serum malondialdehyde (MDA) levels in a dose-dependent manner.\n Abrogated Maackiain-induced reductions in serum IL-1β, IL-6, and TNF-α levels at 12 and 24 hours post-CLP when pre-treated with Compound C or ML385.\n Reversed Maackiain-induced improvements in serum GSH levels, TEAC, and MDA levels when pre-treated with Compound C or ML385.\n Reduced the survival rate of Maackiain-treated septic mice, worsened their clinical scores, and diminished Maackiain's protective effects against CLP-induced organ injury when pre-treated with Compound C or ML385.
Significantly reduced escape latency in the Morris Water Maze training phase compared to the LPS group. Increased the time mice spent in the target quadrant during the probe trial and increased platform crossings at 50 mg/kg dose; showed no significant difference in these probe trial metrics vs the LPS group at 25 mg/kg dose.\n Increased the number of normal neurons in the hippocampus at 50 mg/kg dose, and increased the number of normal neurons in the cortex at 25 mg/kg dose, both compared to the LPS group.\n Reduced IBA-1 fluorescence intensity (a marker of microglial activation) in brain tissue compared to the LPS group at both doses, with the 50 mg/kg dose showing a greater inhibitory effect than the 25 mg/kg dose.\n Reduced COX-2 expression in the cortex compared to the LPS group at both doses, with the 50 mg/kg dose showing the strongest inhibitory effect.\n Reduced IL-6 expression in the cortex compared to the LPS group at both doses, with the 50 mg/kg dose showing a greater inhibitory effect; no significant differences in hippocampal IL-6 levels were observed between either maackiain dose group and the LPS group.
Reduced mean tumor volume to ~700 mm3 (control ~1400 mm3) 21 days after first treatment.\n Reduced mean tumor weight to ~40% of control levels.\n Caused no significant changes in mouse body weight.\n Showed no toxicity to the heart, kidney, or liver via hematoxylin and eosin staining.
Animal Model:
Brown Norway rats (6-week-old male, 200-250 g, allergic rhinitis model via TDI sensitization and challenge)[8]
Dosage:
5 mg/kg; 10 mg/kg; 20 mg/kg
Administration:
p.o.; daily; 21 days
Result:
Significantly reduced the number of sneezes and suppressed TDI-induced upregulation of IL-4 mRNA in nasal mucosa (5 mg/kg).\n Significantly reduced the number of sneezes, suppressed TDI-induced upregulation of IL-4 mRNA in nasal mucosa, and showed a trend toward reducing nasal scores (10 mg/kg).\n Significantly reduced the number of sneezes, reduced nasal scores, and suppressed TDI-induced upregulation of both H1R and IL-4 mRNA in nasal mucosa (20 mg/kg).
DMSO : 250 mg/mL (879.45 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
3.5178 mL
17.5889 mL
35.1778 mL
5 mM
0.7036 mL
3.5178 mL
7.0356 mL
10 mM
0.3518 mL
1.7589 mL
3.5178 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution.
If precipitation or phase separation occurs during preparation,
heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 0.5% CMC-Na/saline water
Solubility: 50 mg/mL (175.89 mM); Suspended solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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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