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Gene & Protein in Disease                                                       NLRP3 in SCI and CHM




            Table 1. Herbal medicine targeting NLRP3 inflammasome   reducing  inflammation  associated  with  the  injury.   A
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            for the treatment of spinal cord injury            separate study has demonstrated that a scaffold enriched
                                                               with quercetin possesses anti-inflammatory effects and
            Herbal    Author     Model         Results
            medicine                                           facilitates functional recovery in rats with SCI, in addition
            Curcumin  Yarahmadi  Male Wistar rats  Nlrp3 downregulation;  to inhibiting NLRP3 activity. These findings suggest that
                       et al. 90             caspase-1 gene    quercetin plays a significant role in inhibiting NLRP3 and
                                             downregulation    alleviating inflammation during and after SCI. 28,83,95
                      Ghaffari    Male Wistar rats  Nlrp3 downregulation;  4.3. Resveratrol
                       et al. 87             caspase-1 gene
                                             downregulation    Resveratrol  (3,5,4’-trihydroxystilbene)  is  a  small
            Quercetin  Wang      Female     Inhibited NLRP3;   polyphenolic compound first extracted from the roots
                       et al. 94  Sprague-Dawley   reduced IL-1β levels;  of white hellebore. Initially, its properties were not well
                                  rats                         understood; however, over time, it has garnered significant
                      Ebrahimi   Male Wistar rats  Nlrp3 downregulation;  interest from researchers.  At present, numerous studies
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                       et al. 95             caspase-1 gene    have demonstrated that resveratrol may offer therapeutic
                                             downregulation    benefits in the treatment of cancer, cardiovascular diseases,
            Resveratrol  Jiang    Male Japanese   Nlrp3 downregulation;  ischemic injuries, and inflammation. 97,98  In the context of
                       et al. 104  big-ear rabbits  caspase-1 gene
                                             downregulation;   SCI, resveratrol has been shown to be particularly effective
                                           IL-1β downregulation  in mitigating the adverse effects associated with spinal
            Rutin     Wu et al. 107  Female Sprague–  Nlrp3 downregulation;  cord damage. Evidence suggests that the administration
                                Dawley rats  caspase-1 gene    of resveratrol can enhance neuronal protection and
                                             downregulation;   promote functional recovery in rat models of SCI. 99,100
                                           IL-1β downregulation  Furthermore, investigations have revealed that resveratrol
            Abbreviations: IL-1β: Interleukin-1 beta; NLRP3: NOD-like receptor   can inhibit various biological compounds associated with
            protein 3.                                         inflammation during SCI. 100,101
            4.2. Quercetin                                       The NLRP3 inflammasome has emerged as a
                                                               particularly intriguing target in the study of inflammation,
            Quercetin is a flavonoid found in various vegetables, fruits,    drawing significant attention from researchers. Evidence
            and nuts.  Its IUPAC name is 3,3’,4’,5,7-pentahydroxyf   has shown that resveratrol is capable of inhibiting
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            lvanone  (or its synonym 3,3’,4’,5,7-pentahydroxy-2-  the NLRP3 inflammasome in various inflammatory
            phenylchromen-4-one), and its molecular formula is   conditions,  including  lung  injury,   liver  disease,
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                                                                                             102
            C H O .  Extensive research has shown that quercetin   and SCI.  Notably, the biological characteristics of
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                10
             15
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            possesses  the  ability  to  inhibit  both  inflammation  and   resveratrol suggest a mechanism of action similar to that
            oxidative stress. Furthermore, it has been documented that   of  other polyphenolic  compounds,  such as  curcumin
            quercetin  exhibits  other  beneficial  properties,  including   and quercetin, in inhibiting the NLRP3 inflammasome.
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            anti-carcinogenic, anti-microbial, and anti-viral effects. 91,92    Research utilizing a rabbit model has demonstrated that
            Numerous studies have explored the relationship between   resveratrol promotes recovery in animals with SCI. The
            quercetin and the NLRP3 inflammasome, particularly   findings indicate that resveratrol is associated with the
            regarding its role in inflammation. This association has   downregulation of NLRP3 and caspase-1 compared to
            been observed across various disease models, including   the  control  group.  The authors  of  the  study  suggested
            osteoarthritis, diabetic retinopathy, and SCI, as evidenced   that, due to its anti-inflammatory properties, resveratrol
            by multiple investigations. 28,92,93               may effectively inhibit the NLRP3 inflammasome, thus
              It is important to note that, similar to other phenolic   playing a significant role in the treatment and prevention
            and flavonoid compounds, quercetin inhibits NLRP3   of complications related to SCI. 104
            and caspase-1,  which prevents the conversion of pro-
            IL-1β into its active, secreted form, ultimately leading to   4.4. Rutin
            a reduction in inflammation.  Research indicates that   Rutin, also known as 3,3’,4’,5,7-pentahydroxyflavone-3-
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            the administration of 100 mg of quercetin per kilogram   rhamnoglucoside, is a flavonol commonly found in various
            can inhibit the activation of the NLRP3 inflammasome   plant species such as passion flowers, buckwheat, tea, and
            and mitigate histopathological changes in a rat model   apples.  This  compound  is  characterized  by  its  lipophilic
            of SCI.  In  addition, quercetin  has  been  shown to   nature, which allows it to dissolve in organic solvents,
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            decrease the expression of NLRP3 following SCI, thereby   including pyridine, methanol, and ethanol. 105,106  Research

            Volume 4 Issue 3 (2025)                         5                               doi: 10.36922/gpd.4827
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