Table 3.
Part of the important pharmacotherapy agents of iNOS inhibition.
| Author | Type of Study | Model | Agent | Dose | Method | Outcome | Conclusion |
|---|---|---|---|---|---|---|---|
| Yu et al., 2020 [100] | In vitro | New Zealand White rabbits | N-Monomethyl-L-arginine (L-NMMA) | Not mentioned |
L-NMMA on inhibiting NO to accelerate the influence of simvastatin |
L-NMMA inhibited NO and COX-2 production and NF-κB activation | L-NMMA enhanced the blocking effect of simvastatin on NF-κB activation by inhibiting NO production |
| Lee et al., 2012 [101] | In vitro | New Zealand White rabbits | L-NMMA | 0.5 mM/ 24 h |
L-NMMA on chondrocyte apoptosis | L-NMMA inhibited NO production and NF-kB binding activity | L-NMMA blocks PCB-initiated apoptosis effect |
| Eitner et al., 2021 [102] | In vitro | Human end-stage knee OA chondrocytes |
N-Iminoethyl-L-lysine (L-NIL) | 1, 10, or 20 µM/48 h | L-NIL on preventing release of NO, IL-6, PGE2, and iNOS | L-NIL prevented NO release and mitochondrial dysfunction |
L-NIL improves the impairment of mitochondrial respiration |
| Bentz et al., 2012 [103] | In vitro | Human OA chondrocytes |
L-NIL | 0-20 µM/ 24 h |
L-NIL on chondrocyte oxidative stress, apoptosis, inflammation, and catabolism | L-NIL stifled NO release, iNOS activity, nitrated proteins, and HNE generation and restored both HNE and GSTA4-4 levels |
L-NIL prevents LPO process and ROS production and attenuates cell death, inflammation, and catabolism |
| Castro et al., 2006 [104] | In vivo | OA rats induced by ligament transection surgery |
NG-nitro-L-arginine methyl ester (L-NAME) | 30 mg/kg/bid | L-NAME on joint pain, cell influx, nitrite levels and iNOS expression | L-NAME reduced the time of rats’ right hind paw fails to touch the surface while walking | Prophylactic L-NAME can reduce joint pain |
| Järvinen et al., 2008 [105] | In vitro | Cartilage tissue from OA patients | 1400W | 1 mM/120 h | 1400W on production of inflammatory mediators |
Treatment with 1400W enhanced the production of anti-catabolic IL-10 and reduced MMP-10 | The inhibiting effects of 1400W may point to its anti-inflammatory mechanisms for OA |
| Graverand et al., 2013 [106] | Clinical human study |
Kellgren and Lawrence Grade (KLG) 2 or 3 knee OA patients |
SD-6010 | 50 or 200 mg/day | A 2-year multicenter RCT of SD-6010 in patients with symptomatic knee OA |
In KLG2 patients, JSN after 48 weeks was lower with SD-6010 50 mg/day versus placebo. No improvement in KLG3 patients | SD-6010 may become effective only in “mild to moderate” OA patients, but it cannot slow the rate of JSN |
| Ma et al., 2020 [107] | In vitro | IL-1β induced Sprague-Dawley (SD) rat chondrocytes |
Aminoguanidine (AG) | 0.3, 1 or 3 mM/24,48 or 72 h | AG on COX-2, iNOS, phosphorylated (p)-p65 and NF-κB translocation |
AG downregulated iNOS and COX-2 expression by blocking the NF-κB signaling pathway |
AG may protect chondrocytes and serve as a potential therapeutic for OA |
| Lee et al., 2013 [108] | In vivo | MIA-induced Wistar rat OA model | Coenzyme Q10 (CoQ10) | 100 mg/kg/qd | CoQ10 on inflammatory mediators production and cartilage degradation |
CoQ10 had anti-nociceptive effect and attenuated cartilage degeneration in rat OA model |
CoQ10 exerts a therapeutic effect of OA by inhibiting inflammation |
| Park et al., 2018 [109] | In vitro | SW1353 cells and SD rats | Ethanol extract of sargassum serratifolium (EESS) |
Extract that hard to measure precise concentrations | EESS on inflammatory mediators production and signaling pathways activation |
EESS blocked ROS generation, attenuated NO production, and inhibited MAPK and PI3K/Akt pathways | EESS may have the potential chondroprotection in the prevention and treatment of OA |
| Khan et al., 2017 [110] | In vitro | IL-1β-stimulated human OA chondrocytes and cartilage explants |
Wogonin | 10–50 µM/24 h | Wogonin on inflammatory mediators production and MMPs, s-GAG and COL2A1 levels |
Wogonin mediated Nrf2/ARE pathways, inhibited matrix degradation and suppressed the expression and production of COX-2 and iNOS |
Wogonin exert chondro- and cartilage protection through the suppression of key molecular events |
| Yan et al., 2020 [111] | In vivo and in vitro | C57BL/6 wild-type (WT) rats | Myricitrin (Myr) | 0-100µM/24h in vitro, dose in vivo not mentioned | Myr on inflammatory mediators production and signaling pathway |
Myr suppressed the NF-κB and MAPK signaling pathways and decreased OARSI scores in OA rat models. |
Myr may have therapeutic potential in the treatment of OA |