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Isorhynchophylline Inhibits NLRP3 Inflammasome and Improves Gestational Diabetes

Li Pu

Li Pu

Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow UniversitySuzhou, China
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Pu, Li
, 
Li Chen

Li Chen

Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow UniversitySuzhou, China
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Chen, Li
, 
Kun Yu

Kun Yu

Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow UniversitySuzhou, China
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Yu, Kun
, 
Yueming Zhang

Yueming Zhang

Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow UniversitySuzhou, China
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Zhang, Yueming
, 
Caifeng Wang

Caifeng Wang

Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow UniversitySuzhou, China
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Wang, Caifeng
, 
Feizhou Jiang

Feizhou Jiang

Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow UniversitySuzhou, China
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Jiang, Feizhou
, 
Jia Shi

Jia Shi

Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow UniversitySuzhou, China
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Shi, Jia
 e 
Jingjing Meng

Jingjing Meng

Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow UniversitySuzhou, China
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Meng, Jingjing
  
14 mar 2025
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Categoria dell'articolo: Original
Pubblicato online: 14 mar 2025
Ricevuto: 09 ott 2024
Accettato: 17 gen 2025
DOI: https://doi.org/10.2478/aite-2025-0006
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© 2025 Li Pu et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig 1.

Effect of IRN on blood glucose levels and insulin sensitivity in GDM mice. (A) Structural formula of IRN. (B) The IPGTT was performed on gestational day 10, with blood samples collected at 0, 30, 60, and 120 min post glucose injection. (C) The IPITT was conducted on the same day, with blood samples collected at 0, 15, 30, 60, and 120 min post insulin injection. (D) Bar graphs showing fasting blood glucose levels, serum insulin levels, and liver glycogen content in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. GDM, gestational diabetes mellitus; IPGTT, intraperitoneal glucose tolerance test; IPITT, intraperitoneal insulin tolerance test; IRN, isorhynchophylline; ns, no significant.
Effect of IRN on blood glucose levels and insulin sensitivity in GDM mice. (A) Structural formula of IRN. (B) The IPGTT was performed on gestational day 10, with blood samples collected at 0, 30, 60, and 120 min post glucose injection. (C) The IPITT was conducted on the same day, with blood samples collected at 0, 15, 30, 60, and 120 min post insulin injection. (D) Bar graphs showing fasting blood glucose levels, serum insulin levels, and liver glycogen content in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. GDM, gestational diabetes mellitus; IPGTT, intraperitoneal glucose tolerance test; IPITT, intraperitoneal insulin tolerance test; IRN, isorhynchophylline; ns, no significant.

Fig 2.

Effect of IRN on the inflammation of serum and placenta tissues of GDM mice. (A) Bar graphs of ELISA assays showing serum levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). (B) Bar graphs of ELISA assays showing placenta tissue levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. ELISA, enzyme-linked immunosorbent assay; GDM, gestational diabetes mellitus; IL, interleukin; IRN, isorhynchophylline; ns, no significant; TNF, tumor necrosis factor.
Effect of IRN on the inflammation of serum and placenta tissues of GDM mice. (A) Bar graphs of ELISA assays showing serum levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). (B) Bar graphs of ELISA assays showing placenta tissue levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. ELISA, enzyme-linked immunosorbent assay; GDM, gestational diabetes mellitus; IL, interleukin; IRN, isorhynchophylline; ns, no significant; TNF, tumor necrosis factor.

Fig 3.

Effect of IRN on the oxidative stress of tissues of GDM mice. The corresponding kits showed the levels of MDA, SOD, GPx, and GSH in placenta tissues from control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. GDM, gestational diabetes mellitus; GPx, glutathione peroxidase; GSH, glutathione; IRN, isorhynchophylline; MDA, malondialdehyde; ns, no significant; SOD, superoxide dismutase.
Effect of IRN on the oxidative stress of tissues of GDM mice. The corresponding kits showed the levels of MDA, SOD, GPx, and GSH in placenta tissues from control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. GDM, gestational diabetes mellitus; GPx, glutathione peroxidase; GSH, glutathione; IRN, isorhynchophylline; MDA, malondialdehyde; ns, no significant; SOD, superoxide dismutase.

Fig 4.

Effect of IRN on the litter size and offspring weight. (A) Litter size in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). (B) Offspring weight in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. GDM, gestational diabetes mellitus; IRN, isorhynchophylline; ns, no significant.
Effect of IRN on the litter size and offspring weight. (A) Litter size in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). (B) Offspring weight in control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. GDM, gestational diabetes mellitus; IRN, isorhynchophylline; ns, no significant.

Fig 5

Effect of IRN on the NF-κB/NLRP3 pathway in GDM mice. (A) Immunoblot showed the expression of NLRP3 in placenta tissues from control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). (B) Immunoblot showed the expression of cleaved caspase-1, IL-1β, and IL-18 in placenta tissues from control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. GDM, gestational diabetes mellitus; IL, interleukin; IRN, isorhynchophylline; NF-κB/NLRP3, nuclear factor-κB/NOD-like receptor protein 3; ns, no significant.
Effect of IRN on the NF-κB/NLRP3 pathway in GDM mice. (A) Immunoblot showed the expression of NLRP3 in placenta tissues from control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). (B) Immunoblot showed the expression of cleaved caspase-1, IL-1β, and IL-18 in placenta tissues from control, GDM, and IRN-treated GDM mice (20 mg/kg and 40 mg/kg). Data are presented as mean ± SD. *p < 0.001, GDM vs. control, **p < 0.001, GDM + IRN vs. GDM. GDM, gestational diabetes mellitus; IL, interleukin; IRN, isorhynchophylline; NF-κB/NLRP3, nuclear factor-κB/NOD-like receptor protein 3; ns, no significant.
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Inglese
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Medicina, Scienze medicali di base, Biochimica, Immunologia, Medicina clinica, Medicina clinica, altro, Chimica clinica
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