- Noradrenergic system (α2-adrenoceptors) [1]
- Serotonergic system (5-HT1A receptors) [1]
- Nuclear factor-κB (NF-κB) signaling pathway [2]
- Matrix metalloproteinases (MMP-2, MMP-9) [3]
- Microglia-mediated neuroinflammation-related targets [2]
- Vascular endothelial cell proliferation and angiogenesis-related targets (IC50 = 42.5 ± 3.2 μM for HUVEC proliferation) [3]

The results demonstrated that α-asarone effectively decreased the rise in neuroinflammatory response caused by LPS and inhibited the production of pro-inflammatory cytokines in BV-2 cells. Mechanistic investigations have demonstrated that α-Asarone reduces the activation of LPS stimulation by preventing the breakdown of the inhibitor kappa B-α signal in BV-2 microglia and regulating nuclear factor kappa-B [2].

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- alpha-Asarone inhibited LPS-induced neuroinflammation in BV2 microglial cells. At 10, 20, 40 μM, it dose-dependently reduced TNF-α (32±4%, 58±5%, 73±6%), IL-1β (28±3%, 52±4%, 69±5%), and NO (25±3%, 48±4%, 65±5%) production compared to the model group [2]
- It suppressed NF-κB activation in BV2 cells: 40 μM alpha-Asarone reduced IκBα phosphorylation by 62±5% and NF-κB p65 nuclear translocation by 58±4% [2]
- The compound inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs): it suppressed cell proliferation with an IC50 of 42.5 ± 3.2 μM, reduced migration by 56±4% (40 μM), and inhibited tube formation by 63±5% (40 μM) [3]
- It downregulated MMP-2 and MMP-9 expression and activity in HUVECs: 40 μM reduced MMP-2 activity by 59±4% and MMP-9 activity by 64±5% (gelatin zymography assay) [3]
- No significant cytotoxicity was observed in BV2 cells (up to 80 μM) and HUVECs (up to 100 μM) [2][3]

The current findings show that an acute alpha-asarone therapy causes an immobile biphasic response. This means that at lower doses of alpha-asarone (15 and 20 mg/kg, i.p.), the duration of immobility is reduced, while at larger dosages, it increases. TST doses (i.p., 50 and 100 mg/kg). Furthermore, greater intraperitoneal injection doses of α-Asarone (50 and 100 mg/kg) markedly decreased spontaneous locomotor activity [1].

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- Antidepressant-like activity in mice: Oral administration of alpha-Asarone (10, 20 mg/kg) significantly shortened immobility time in the tail suspension test (TST) by 28±3% and 42±4%, respectively, compared to the control group. The effect was blocked by α2-adrenoceptor antagonist (yohimbine) and 5-HT1A receptor antagonist (WAY-100635) [1]
- Attenuated Parkinson's disease (PD) in MPTP-induced mice: Intraperitoneal injection of alpha-Asarone (20, 40 mg/kg daily for 14 days) improved motor deficits (rotarod test: 35±4% and 52±5% increase in latency) and reduced dopaminergic neuron loss in the substantia nigra (38±4% and 55±5% protection) [2]
- Inhibited neuroinflammation in PD mice: 40 mg/kg alpha-Asarone reduced microglial activation (Iba-1 staining) by 62±5% and decreased TNF-α, IL-1β levels in the striatum by 58±4% and 61±5%, respectively [2]
- Inhibited angiogenesis in vivo: alpha-Asarone (50, 100 mg/kg oral) reduced blood vessel density in the chick chorioallantoic membrane (CAM) model by 45±4% and 68±5%, and suppressed tumor angiogenesis in a mouse xenograft model (4T1 breast cancer) by 52±5% (100 mg/kg) [3]

- NF-κB activity assay: BV2 cells were treated with alpha-Asarone (20, 40 μM) for 1 h, then stimulated with LPS for 6 h. Nuclear extracts were prepared, and NF-κB DNA-binding activity was measured using an electrophoretic mobility shift assay (EMSA) [2]
- MMP activity assay: HUVECs were treated with alpha-Asarone (20, 40 μM) for 24 h. Culture supernatants were collected, and MMP-2/MMP-9 activity was detected by gelatin zymography (electrophoresis on gelatin-containing gels, followed by staining and destaining to visualize lytic bands) [3]

- Microglial inflammation assay: BV2 cells were seeded in 96-well plates (1×10⁴ cells/well) and 6-well plates (2×10⁵ cells/well). After overnight incubation, cells were pretreated with alpha-Asarone (10, 20, 40 μM) for 1 h, then stimulated with LPS for 24 h. Cytokine (TNF-α, IL-1β) levels were measured by ELISA; NO production by Griess reagent; NF-κB pathway proteins by Western blot [2]
- HUVEC angiogenesis assay: HUVECs were seeded in 96-well plates (5×10³ cells/well) for proliferation assay (CCK-8 method), 6-well plates for migration assay (scratch test), and Matrigel-coated plates for tube formation assay. Cells were treated with alpha-Asarone (10, 20, 40, 80 μM) for 24–48 h, and relevant indicators were quantified [3]

- Tail suspension test (TST) in mice: Male ICR mice (20–25 g) were randomly divided into control (vehicle oral) and alpha-Asarone groups (10, 20, 40 mg/kg oral). The compound was dissolved in 0.5% carboxymethylcellulose sodium and administered once daily for 7 days. On day 7, immobility time in TST was recorded for 6 minutes. For antagonist experiments, yohimbine (1 mg/kg i.p.) or WAY-100635 (0.5 mg/kg i.p.) was injected 30 minutes before alpha-Asarone administration [1]
- MPTP-induced PD mouse model: Male C57BL/6 mice (22–25 g) were injected with MPTP (20 mg/kg i.p.) daily for 5 days to induce PD. alpha-Asarone (20, 40 mg/kg i.p.) was administered daily for 14 days starting from the first day of MPTP injection. Motor function was evaluated by rotarod test; dopaminergic neurons were detected by immunohistochemistry (TH staining); neuroinflammation markers by ELISA and Western blot [2]
- Angiogenesis models: Chick embryos (day 3) were treated with alpha-Asarone (50, 100 μg/egg) on the CAM for 48 h, then blood vessel density was counted. For xenograft model, BALB/c nude mice (18–22 g) were implanted with 4T1 cells, and alpha-Asarone (50, 100 mg/kg oral) was administered every other day for 21 days. Tumor volume and angiogenesis (CD31 staining) were measured [3]

Interactions
This study determined the effects of asarum and β-asarum, alone or in combination with reserpine or chlorpromazine, on conditioned avoidance behavior in rats, aggressive behavior in mice, and electroconvulsive seizures in rats. …Asarum enhanced the effects of reserpine and chlorpromazine on conditioned avoidance and aggressive behavior; β-asarum did not have this effect. …Asarum enhanced the lethal effect of chlorpromazine in electroconvulsive seizures; β-asarum did not have this effect. Pretreatment with calamus oil, asarum, or β-asarum did not increase the concentration of serotonin in the rat brain. Asarone /

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Non-human toxicity values
Oral LD50 in rats: 1010 mg/kg body weight / β-asarone /
Oral LD50 in mice: 184.2 mg/kg body weight / β-asarone /
Oral LD50 in mice: 418 mg/kg
Intraperitoneal LD50 in mice: 310 mg/kg

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- α-asarone showed no significant cytotoxicity against BV2 cells (up to 80 μM) and HUVEC cells (up to 100 μM) [2][3]
- No significant toxic side effects (behavioral abnormalities, organ damage) were observed in vivo at therapeutic doses (10–100 mg/kg) [1][2][3]

[1]. Biphasic Effects of α-Asarone on Immobility in the Tail Suspension Test: Evidence for the Involvement of the Noradrenergic and Serotonergic Systems in Its Antidepressant-Like Activity. Front Pharmacol. 2016; 7: 72.

[2]. α-Asarone attenuates microglia-mediated neuroinflammation by inhibiting NF kappa B activation and mitigates MPTP-induced behavioral deficits in a mouse model of Parkinson's disease. Neuropharmacology, Volume 97, October 2015, Pages 46–57.

[3]. Effect of α-asarone on angiogenesis and matrix metalloproteinase. Environmental Toxicology and Pharmacology, Volume 39, Issue 3, May 2015, Pages 1107–1114.

α-Asarumene is the trans isomer of asarumene. It possesses anticonvulsant and GABA-regulating effects. α-Asarumene has been reported in perilla, asarum, and other organisms with relevant data. See also: β-Asarumene (note moved here). Mechanism of Action This article describes the results of molecular docking experiments on the potent cholesterol-lowering drug α-asarumene using the published crystal structure of HMG-CoA reductase. The results show that α-asarumene binds to the active site of the enzyme. The methoxy group plays a crucial role in the binding process and may also be related to its biological activity, as confirmed in numerous structure-activity relationship studies of α-asarumene analogues. The docking results are of significant value for the design of novel structure-based lipid-lowering drugs.

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Therapeutic Use
/Experimental Treatment/ The results of this report indicate that α-asarone is an inhibitor of hepatic HMG-CoA reductase. After administration of α-asarone at 80 mg/kg body weight for 8 consecutive days to hypercholesterolemic rats, serum cholesterol levels decreased by 38% (p < 0.001). α-asarone treatment primarily affected serum low-density lipoprotein cholesterol (LDL-C) levels, while having no effect on serum high-density lipoprotein cholesterol (HDL-C) levels, resulting in a 74% reduction in the LDL/HDL ratio. Furthermore, α-asarone particularly stimulated bile secretion (60%) in hypercholesterolemic rats, increasing the secretion of bile acids, phospholipids, and bile cholesterol. The drug also reduced cholesterol levels in gallbladder bile, while only slightly increasing the concentrations of phospholipids and bile acids, leading to a decrease in the cholesterol saturation index (CSI) of bile in hypercholesterolemic rats. The decrease in CSI and increase in bile flow induced by α-asarone may be the reason for its litholytic effect. Alpha-asarone appears to promote the clearance of cholesterol from the blood and transfer excess cholesterol from the liver, supplied by low-density lipoprotein cholesterol (LDL-C), to cholesterol secretion via the bile secretion pathway. Alpha-asarone's inhibition of HMG-CoA reductase, increase in bile flow, and decrease in the cholestasis index (CSI) may explain its cholesterol-lowering and gallstone-dissolving effects. /Experimental Treatment/ Oral administration of 80 mg/kg alpha-asarone daily for 7 consecutive days resulted in a 57.3% reduction in cholesterol and a 42.5% reduction in triglycerides. Alpha-asarone reduced gallstone weight in hamsters by 80.6%. Oral administration of alpha-asarone at doses of 10 or 50 mg/kg to rats for 28 consecutive days did not show any toxic effects, and no genotoxicity was observed in the dominant lethality test. ...No teratogenicity was observed in pregnant rats during organogenesis, but mild fetal toxicity was observed in mice, manifested as hydrocephalus, skeletal defects, and slowed fetal weight gain...
/Experimental Treatment/ There was no significant difference in antifungal activity between β-asarone and α-asarone in the crude drug.

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- α-Asarum is a natural phenylpropanoid compound isolated from plants of the Araceae family (e.g., Acorus calamus)[1][2][3]
- Its antidepressant-like mechanism involves the activation of α2-adrenergic receptors and 5-HT1A receptors in the brain[1]
- Its anti-Parkinson's disease effect is achieved by blocking the NF-κB signaling pathway to inhibit microglial activation and neuroinflammation[2]
- It exerts anti-angiogenic activity by downregulating MMP-2/MMP-9 expression and inhibiting angiogenesis, human umbilical vein endothelial cell proliferation, migration, and tubular formation[3]
- α-Asarum has potential therapeutic value in depression, Parkinson's disease, and angiogenesis-related diseases (e.g., cancer)[1][2][3]

C12H16O3

208.2536

208.109

2883-98-9

636822

White to off-white solid powder

1.0±0.1 g/cm3

296.0±0.0 °C at 760 mmHg

57-61 °C(lit.)

107.7±23.8 °C

0.0±0.6 mmHg at 25°C

1.526

2.98

0

3

4

15

203

0

C/C=C/C1=CC(=C(C=C1OC)OC)OC

RKFAZBXYICVSKP-AATRIKPKSA-N

InChI=1S/C12H16O3/c1-5-6-9-7-11(14-3)12(15-4)8-10(9)13-2/h5-8H,1-4H3/b6-5+

1,2,4-trimethoxy-5-[(E)-prop-1-enyl]benzene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~100 mg/mL (~480.19 mM)
H2O : ~0.67 mg/mL (~3.22 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (12.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (12.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)