Rutaecarpine inhibited COX-2 and COX-1 dependent phases of PGD2 generation in BMMC in a concentration-dependent manner with an IC50 of 0.28 microM and 8.7 microM, respectively. It inhibited COX-2-dependent conversion of exogenous arachidonic acid to PGE2 in a dose-dependent manner by the COX-2-transfected HEK293 cells. However, rutaecarpine inhibited neither PLA2 and COX-1 activity nor COX-2 protein and mRNA expression up to the concentration of 30 microM in BMMC, indicating that rutaecarpine directly inhibited COX-2 activity. Furthermore, rutaecarpine showed in vivo anti-inflammatory activity on rat lambda-carrageenan induced paw edema by intraperitoneal administration[3]. Rutaecarpine is an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa and related herbs, which has shown a variety of intriguing biological properties such as anti-thrombotic, anticancer, anti-inflammatory and analgesic, anti-obesity and thermoregulatory, vasorelaxing activity, as well as effects on the cardiovascular and endocrine systems[4]. Rutaecarpine significantly decreased the number of antibody-forming cells and caused weight decrease in spleen in a dose-dependent manner, when mice were administered with rutaecarpine at 10 mg/kg, 20 mg/kg, 40 mg/kg or 80 mg/kg once intravenously. A single bolus intravenous injection of rutaecarpine from 20 mg/kg might cause immunosuppressive effects, and that rutaecarpine-induced immunosuppression might be mediated, at least in part, through the inhibition of cytokine production and cell cycle arrest in G(0)+G(1) phase, and caused possibly by mechanisms associated with metabolic activation[5].
Rutaecarpine/吴茱萸次碱 细胞实验
Cell Line
Concentration
Treated Time
Description
References
C4-2 cells
5 µM
24 hours
Rutaecarpine inhibits cell proliferation
Theranostics. 2020 Feb 10;10(8):3366-3381
LNCaP cells
5 µM
24 hours
Rutaecarpine inhibits cell proliferation
Theranostics. 2020 Feb 10;10(8):3366-3381
HepG2 cells
0.035, 0.35, 3.48, 34.80 µM
18 hours
RUT triggered promoters of ABCA1 and CLA-1 genes, increasing ABCA1 and SR-BI/CLA-1 expression
J Lipid Res. 2014 Aug;55(8):1634-47
HCT116 cells
5 µM
18 hours
To test the protective effect of RUT on H2O2-induced cytotoxicity, results showed that RUT pretreatment significantly increased the LD50 for H2O2-induced cell damage
Free Radic Biol Med. 2020 Feb 20;148:33-41
RAW 264.7 cells
10–40 µM
20 min pretreatment followed by 24 hours LTA stimulation
To evaluate the effect of Rutaecarpine on LTA-induced inflammatory responses in RAW 264.7 cells, results showed that Rutaecarpine inhibited NO production and the expression of iNOS, COX-2, and IL-1β without cytotoxicity.
Int J Mol Sci. 2022 May 24;23(11):5889
Human platelets
2.5–100 µM
20 minutes
Rutaecarpine showed no significant cytotoxicity to platelets at concentrations ranging from 2.5 to 100 μM.
Int J Mol Sci. 2021 Oct 15;22(20):11109
RAW264.7 cells
0.035, 0.35, 3.48, 34.80 µM
24 hours
RUT induced cholesterol efflux in RAW264.7 cells, reducing lipid accumulation
J Lipid Res. 2014 Aug;55(8):1634-47
Mouse chondrocytes
1, 2.5, 5, 10 µM
24 hours
To evaluate the anti-inflammatory, anti-catabolic, and pro-anabolic effects of Rutaecarpine on IL-1β-stimulated chondrocytes. Results showed that Rutaecarpine significantly inhibited the expression of inflammatory cytokines (COX2, IL-6, TNF-α), reduced the production of catabolic enzymes (MMP3, MMP13), and promoted the expression of anabolic enzymes (COL II, aggrecan, SOX9).
Int J Mol Med. 2023 Oct;52(4):97
RAW264.7 cells
1, 10, 25 µM
24 hours
To evaluate the inhibitory effect of Rutaecarpine on SARS-CoV-2-induced inflammatory responses, results showed that Rutaecarpine significantly reduced the mRNA levels of inflammatory cytokines.
Int J Mol Sci. 2023 Jan 1;24(1):762
HEK293T cells
1, 10, 25, 50, 100 µM
24 hours
To evaluate the inhibitory effect of Rutaecarpine on SARS-CoV-2 pseudovirus entry into cells, results showed that Rutaecarpine inhibited viral entry in a dose-dependent manner with a maximum inhibition rate of ~80%.
Int J Mol Sci. 2023 Jan 1;24(1):762
Primary mouse intestinal epithelial cells
10 µM and 20 µM
24 hours
To detect the expression of NRF2 target genes, results showed that RUT significantly induced the expression of NRF2 target gene mRNAs
Free Radic Biol Med. 2020 Feb 20;148:33-41
HepG2 cells
1.25 µM and 2.5 µM
24 hours
To detect NRF2 activation by luciferase reporter assay, results showed that RUT dose-dependently activated NRF2/ARE luciferase activity
Free Radic Biol Med. 2020 Feb 20;148:33-41
22Rv1 cells
5 µM
24 hours
Rutaecarpine selectively induces AR-V7 protein degradation
Theranostics. 2020 Feb 10;10(8):3366-3381
CL1-3 lung epithelial cells
5 µM
24 hours
Evaluate the inhibitory effect of F-RUT on TNF-α-induced COX-2 expression, results showed F-RUT was more effective than RUT in inhibiting COX-2 expression
Front Pharmacol. 2019 Feb 7;10:91
H460 lung epithelial cells
5 µM
24 hours
Evaluate the inhibitory effect of F-RUT on TNF-α-induced COX-2 expression, results showed F-RUT was more effective than RUT in inhibiting COX-2 expression
Front Pharmacol. 2019 Feb 7;10:91
Rat skeletal muscle cells
20–180 µM
24 hours
Promoted the phosphorylation of AMPK and ACC2, and increased glucose uptake
Acta Pharmacol Sin. 2016 Apr;37(4):483-96
Human endothelial EA.hy926 cells
1-10 µM
24 hours
To evaluate the effect of Rutaecarpine on endothelial cell viability and cytotoxicity. Results showed that Rutaecarpine at concentrations of 1 to 10 μM had no significant effect on cell viability or cytotoxicity.
Int J Mol Sci. 2021 Aug 30;22(17):9407
Human esophageal squamous cell carcinoma cell line CE81T/VGH
5–40 µM
24, 48, and 72 hours
To evaluate the effects of RTP on tumor cell growth. Results showed that RTP significantly inhibits CE81T/VGH cell growth in a dose- and time-dependent manner.
Int J Mol Sci. 2022 Mar 5;23(5):2843
Human platelets
1–5 µM
3 minutes
Rutaecarpine significantly inhibited collagen-induced platelet aggregation but had only a slight or no effect on platelets stimulated with other agonists (e.g., thrombin).
Int J Mol Sci. 2021 Oct 15;22(20):11109
Human endothelial EA.hy926 cells
10 µM
30 minutes
To investigate the effect of Rutaecarpine on eNOS phosphorylation. Results showed that Rutaecarpine significantly increased eNOS phosphorylation.
Int J Mol Sci. 2021 Aug 30;22(17):9407
PC12 cells
0.2, 0.4, 0.8 µM
48 hours
To investigate the protective effect of Rutaecarpine on H2O2-induced oxidative stress damage, results showed that Rutaecarpine significantly increased the survival rate of PC12 cells under oxidative stress, reduced ROS levels, and increased the activity of antioxidant enzymes CAT and SOD.
Front Pharmacol. 2022 Apr 12;13:807125
HCT116 cells
10 µM
6 hours
To detect NRF2 nuclear translocation by immunofluorescence, results showed that RUT significantly increased NRF2 nuclear translocation
Free Radic Biol Med. 2020 Feb 20;148:33-41
Rutaecarpine/吴茱萸次碱 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
ICR mice
Microvascular thrombosis model
Intraperitoneal injection
0.7 and 1.5 mg/kg
Single dose
Rutaecarpine significantly prolonged the occlusion time of microvascular thrombosis in mice without affecting bleeding time.
Int J Mol Sci. 2021 Oct 15;22(20):11109
BALB/c mice
4T1 xenograft model
Intratumoral injection
10 μM, 50 μL/d
Once daily, tumor growth was monitored
Rutaecarpine significantly inhibited tumor growth and induced the differentiation of tumor cells into luminal-like structures.
J Transl Med. 2023 Aug 18;21(1):553
ApoE-deficient mice
High-fat diet-induced atherosclerosis model
Intragastric administration
10, 20, 40 mg/kg
Once daily for 8 weeks
RUT significantly reduced atherosclerotic lesion area, decreased plasma TC and LDL-C levels, and increased fecal cholesterol excretion
To confirm in vitro findings. Results showed that high-dose RTP significantly reduces tumor size, tumor weight, and PCNA protein expression.
Int J Mol Sci. 2022 Mar 5;23(5):2843
C57BL/6J mice
Destabilization of the medial meniscus (DMM) model
Intra-articular injection
25 mg/kg
Once per week for 8 weeks
To evaluate the therapeutic effects of Rutaecarpine on a mouse model of osteoarthritis. Results showed that Rutaecarpine significantly alleviated articular cartilage abrasion and proteoglycan depletion, reduced OARSI scores, and improved subchondral bone remodeling.
Int J Mol Med. 2023 Oct;52(4):97
Sprague-Dawley rats
Fat-fed, streptozotocin-treated rat model of hyperlipidemia and hyperglycemia
Oral
25 mg/kg/day
Once daily for 7 weeks
Ameliorated hyperlipidemia and hyperglycemia, reduced obesity and visceral fat accumulation, enhanced insulin sensitivity, decreased inflammatory cytokine levels, and improved pathological changes in livers and pancreases
Acta Pharmacol Sin. 2016 Apr;37(4):483-96
KM mice
Ethanol-induced acute gastric mucosal injury model
Intragastrically
450 and 900 μg/kg
Once daily for 3 consecutive days
Rutaecarpine significantly alleviated ethanol-induced gastric mucosal injury by modulating genes related to inflammation, oxidative stress and apoptosis
Front Pharmacol. 2020 Nov 26;11:600295
ICR mice
Acetaminophen-induced acute liver injury model
Oral
5 or 20 mg/kg
Once daily for 7 consecutive days
Rutaecarpine pretreatment significantly decreased acetaminophen-induced serum ALT/AST activities, hepatic malondialdehyde content, and prevented acetaminophen-induced hepatic glutathione depletion. Furthermore, CYP2E1 expression was decreased by rutaecarpine pretreatment in a dose-dependent manner.
Antioxidants (Basel). 2021 Jan 10;10(1):86
Zebrafish
LPS-induced inflammation model
Embryo media
5 μg/mL
24 hours
Evaluate the inhibitory effect of F-RUT on LPS-induced ROS generation, results showed F-RUT significantly suppressed ROS generation
Front Pharmacol. 2019 Feb 7;10:91
C57BL/6 mice
Controlled cortical impact (CCI)-induced TBI mouse model
Intraperitoneal injection
5, 10, 20 mg/kg
24 h and 30 min before surgery, and 2, 24, 48, and 72 h after surgery
To evaluate the neuroprotective effects of Rutaecarpine in TBI mice, results showed that Rutaecarpine significantly improved neurological dysfunction, reduced brain tissue edema and apoptosis, and enhanced antioxidant capacity.
Front Pharmacol. 2022 Apr 12;13:807125
C57BL/6J mice
DSS-induced colitis model
Oral gavage
80 mg/kg
Once daily until the end of the experiment
To test the protective effect of RUT on DSS-induced colitis, results showed that RUT significantly ameliorated DSS-induced colitis, dependent on the presence of NRF2
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