Notopterol (NOT) is a major bioactive ingredient extracted from the rhizomes of either Notopterygium incisum Ting ex H. T. Chang or N. forbesii Boiss (Qianghuo in Chinese), a botanical drug that was adopted as a traditional Chinese medicine. NOT inhibited the activity of CYP2D6 in a time-, concentration- and NADPH-dependent manner. The values of KI and kinact were 10.8 μM and 0.62 min-1, respectively[3]. Notopterol induces apoptosis and inhibits cell cycle-specific, it's a natural product isolated and purified from the roots of Notopterygium incisum. Notopterol could induce apoptosis, differentiation, and G0/G1 arrest in human AML HL-60 cells, suggesting that notopterol has potential therapeutic effects on AML. The combination application of notopterol (20 and 40 μM) and ATRA (2 μM) could augment differentiation of HL-60 cells[4]. Mechanistically, notopterol directly binds Janus kinase (JAK)2 and JAK3 kinase domains to inhibit JAK/signal transducers and activators of transcription (JAK-STAT) activation, leading to reduced production of inflammatory cytokines and chemokines[5]. NOT could arrest osteoclastogenesis and bone resorptive activity by attenuating RANKL-mediated MAPK, NF-κB, calcium and NFATc1 signaling transduction pathways and enhancing ROS scavenging enzymes in Nrf2/Keap1/ARE pathways in vitro, and prohibit bone loss induced by OVX in vivo[6].
Notopterol/羌活醇 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mahlavu cells
30 µM
0, 24, 48 hours
Treatment with 30 μM NOT significantly downregulated the expression levels of ATF4, p-JAK2, GPX1, CAT, and SOD1 proteins in Mahlavu cells.
Nutrients. 2023 May 24;15(11):2447
HepJ5 cells
30 µM
0, 24, 48 hours
Treatment with 30 μM NOT significantly downregulated the expression levels of ATF4, p-JAK2, GPX1, CAT, and SOD1 proteins in HepJ5 cells.
Nutrients. 2023 May 24;15(11):2447
HL-60 cells
0, 5, 10, 20, 40 µM
2 weeks
Notopterol significantly reduced the number of colonies formed by HL-60 cells.
Drug Des Devel Ther. 2019 Jun 6;13:1927-1940
RAW264.7 cells
20 µM
24 hours
Evaluate the ROS and NO scavenging ability of NBOP nanoparticles. Results showed that NBOP nanoparticles significantly reduced ROS and NO levels in LPS-stimulated macrophages.
Acta Pharm Sin B. 2023 Dec;13(12):5016-5029
H9c2 cells
25 µM
24 hours
To investigate the effect of Notopterol on uric acid-induced pyroptosis in H9c2 cells, results showed that notopterol inhibited uric acid-triggered proinflammatory cytokine production including IL-1β and IL-18.
Pharmaceuticals (Basel). 2023 Feb 27;16(3):361
H9c2 cells
200 mg/L
24 hours
To investigate the effects of uric acid on pyroptosis in H9c2 cells, results showed that uric acid stimulation increased NLRP3, caspase1, and cleaved caspase-1 p20 expression.
Pharmaceuticals (Basel). 2023 Feb 27;16(3):361
A549 lung adenocarcinoma cells
0–100 µM
24, 48, 72 hours
To evaluate the effect of Notopterol on the viability of A549 cells, results showed that Notopterol significantly reduced the viability of A549 cells in a dose- and time-dependent manner.
Int J Mol Sci. 2023 Oct 11;24(20):15057
Mahlavu cells
0-100 µM
24, 48, 72 hours
Notopterol significantly suppressed Mahlavu cell viability in a dose- and time-dependent manner. Treatment with 100 μM NOT for 24, 48, and 72 h resulted in a 39%, 60%, and 79% reduction in viability, respectively.
Nutrients. 2023 May 24;15(11):2447
HepJ5 cells
0-100 µM
24, 48, 72 hours
Notopterol significantly suppressed HepJ5 cell viability in a dose- and time-dependent manner. Treatment with 100 μM NOT for 24, 48, and 72 h resulted in a 33%, 49%, and 64% reduction in viability, respectively.
Nutrients. 2023 May 24;15(11):2447
HL-60 cells
0, 10, 20, 40, 60, 80 µM
24-120 hours
Notopterol inhibited the proliferation of HL-60 cells in a concentration-dependent manner.
Drug Des Devel Ther. 2019 Jun 6;13:1927-1940
Human pulmonary arterial smooth muscle cells (HPASMCs)
5, 10, 20 µM
36 hours
To evaluate the effect of Notopterol on the proliferation and migration of HPASMCs. Results showed that Notopterol significantly inhibited the proliferation and migration of HPASMCs under hypoxic conditions.
Front Cardiovasc Med. 2022 Jun 3;9:859422
C28I2
5, 10, 20 µM
48 hours
Notopterol significantly reduced IL-18 and TNF-α levels in inflamed cells, reduced ROS production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thereby protecting chondrocytes from inflammation.
Heliyon. 2024 Mar 13;10(6):e28094
C20A4
5, 10, 20 µM
48 hours
Notopterol significantly reduced IL-18 and TNF-α levels in inflamed cells, reduced ROS production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thereby protecting chondrocytes from inflammation.
Heliyon. 2024 Mar 13;10(6):e28094
Normal human skin fibroblast cells
100 µM
48 hours
To evaluate the effect of Notopterol on the viability of normal human skin fibroblast cells, results showed that Notopterol at 100 µM did not significantly affect cell viability.
Int J Mol Sci. 2023 Oct 11;24(20):15057
HepJ5 cells
30 µM
48 hours
After 48 h treatment with 30 μM NOT, HepJ5 cells transformed from elongated spindle-like to cuboid morphology.
Nutrients. 2023 May 24;15(11):2447
HL-60 cells
0, 5, 10, 20, 40, 60 µM
48 hours
Notopterol promoted apoptosis of HL-60 cells in a dose-dependent manner.
Drug Des Devel Ther. 2019 Jun 6;13:1927-1940
Bone marrow monocytes (BMMs)
1, 2.5, 5, 10 µM
5 days
Notopterol inhibits RANKL-activated osteoclast formation and bone resorption function by calculating tartrate resistant acid phosphatase (TRAcP) staining and hydroxyapatite resorption assays.
Front Pharmacol. 2021 Jun 3;12:664836
HL-60 cells
1, 2.5, 5, 10, 25, 50, 100 µM
72 hours
Notopterol significantly inhibited the growth of HL-60 cells with an IC50 value of 40.32 μM.
Drug Des Devel Ther. 2019 Jun 6;13:1927-1940
Notopterol/羌活醇 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Ovariectomized (OVX) mouse model
Intraperitoneal injection
10 mg/kg
Every two days for 6 weeks
Notopterol diminished the loss of bone mass in OVX mice by blocking osteoclastogenesis determined by bone histomorphometry, TRAcP staining and H&E staining.
Front Pharmacol. 2021 Jun 3;12:664836
C57BL/6J mice
Hyperuricemic mouse model
Gavage
20 mg/kg
Once daily for four weeks
To investigate the effect of Notopterol on cardiac function in hyperuricemic mice, results showed that Notopterol improved exercise capacity and alleviated cardiac dysfunction in hyperuricemic mice.
Pharmaceuticals (Basel). 2023 Feb 27;16(3):361
Male Sprague-Dawley rats
Monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) model
Intragastric administration
20 mg/kg/day
Once daily for 3 weeks
To evaluate the therapeutic effect of Notopterol on MCT-induced PAH rats. Results showed that Notopterol significantly reduced mortality, improved right ventricular function, decreased right ventricular systolic pressure (RVSP), alleviated right ventricular hypertrophy and fibrosis, and reduced pulmonary vascular remodeling and the expression of inflammatory factors (IL-1β and IL-6).
Front Cardiovasc Med. 2022 Jun 3;9:859422
Wistar rats
Collagen-induced arthritis (CIA) model
Intravenous injection
5 mg/kg (Notopterol) and 15 mg/kg (BR-PEG/oPDA-PEG)
Every three days for 30 days
Evaluate the therapeutic efficacy of NBOP nanoparticles in the CIA model. Results showed that NBOP nanoparticles significantly alleviated arthritis symptoms, reduced joint swelling, and decreased inflammatory cytokine levels.
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