Nestoron is a 19-norprogesterone derivative with high affinity and selectivity for progesterone receptors. Nestoron (400 μCi 3H Nestoron/kg BW; subcutaneous injection; female Sprague-Dawley rats) treatment results in the Cmax in the blood and plasma are 58.1 and 95.5 ng equiv. 3H Nestoron/g, with t1/2 of 15.6 hours. Approximately, 81.4% and 7.62% of the administered dose is excreted via feces and urine, respectively[3]. Nestorone® (NES) is a potent nonandrogenic progestin being developed for contraception. The neuroprotective and myelin regenerative effects of NES are mediated via PR (progesterone receptor) binding and not via its interaction with the GABAAR(γ-aminobutyric acid type A receptor)[4]. NES (Nestorone®) alone or with E2 (Estradiol) increased the levels of transcription factors, essential for myelin synthesis[5]. The increase in oligodendroglial cells by Nestorone resulted from enhanced NG2(+) and Olig2(+) oligodendrocyte progenitor cell (OPC) recruitment. Nestorone stimulated the migration of OPC towards demyelinated axons. In this coculture paradigm, Nestorone indeed markedly increased the number of EGFP(+) cells migrating into the demyelinated cerebellar slices[6].
Nestoron/醋酸烯诺孕酮 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A549 cells
0.01, 0.1, 1, 10, 100 µM
24 hours
To evaluate the inhibitory effect of NES on LPS-induced inflammatory cytokine secretion, results showed NES significantly reduced IL-6, KC, TNF-α, and MCP-1 secretion.
Inflammopharmacology. 2025 Mar;33(3):1473-1489
THP-1 cell-derived macrophages
0.01, 0.1, 1, 10, 100 µM
24 hours
To evaluate the inhibitory effect of NES on LPS-induced TLR-4 signaling pathways, results showed NES significantly inhibited NF-κB/AP-1 and IRF activation.
Inflammopharmacology. 2025 Mar;33(3):1473-1489
Nestoron/醋酸烯诺孕酮 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
LPS-induced acute lung injury model
Intratracheal instillation
0.1, 1, 10 mg/kg
Administered 2 h prior to LPS exposure, observed for 24 hours
To evaluate the protective effect of NES on LPS-induced acute lung injury, results showed NES significantly reduced inflammatory cell infiltration and cytokine secretion, and improved survival rates.
Inflammopharmacology. 2025 Mar;33(3):1473-1489
Female mice
Chronic demyelinating lesions induced by cuprizone
Subcutaneous mini-osmotic pumps
1, 4, 6, 8 or 16 µg/day
For 3 weeks
Increase the density of NG2+ oligodendrocyte progenitor cells and CA II+ mature oligodendrocytes and enhance the formation of MBP- and PLP-immunoreactive myelin
Glia. 2015 Jan;63(1):104-17
C57/Bl6 female mice
Cuprizone (CUP)-induced demyelination model
Subcutaneous injection
8 µg
3 weeks
To evaluate the effect of NES alone or combined with E2 on remyelination in a demyelination model. Results showed that NES alone or combined with E2 significantly enhanced the expression of transcription factors (Olig2, Myt1, and Sox17) involved in myelin synthesis and promoted remyelination.
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