β-Cyclodextrin-Functionalized Sodium Alginate Nanocarrier Co-Loaded with Naringenin Attenuates Pregnancy-Induced Hypertension Via JAK/STAT3 Pathway Inhibition.

Pregnancy-induced hypertension (PIH) is a condition marked by elevated blood pressure during pregnancy, posing serious risks to both maternal and perinatal health, including increased mortality. Due to the safety concerns and side effects of current treatments for PIH, the search for new therapeutic agents is urgently needed. This study aimed to develop a β-cyclodextrin-functionalized sodium alginate (β-CD/SA) nanocarrier co-encapsulated with Naringenin (NR) to enhance its therapeutic potential. The β-CD/SA@NR nanocarriers were synthesized using ionic gelation and characterized by FTIR, XRD, and SEM, revealing a mean particle size of 142.6 ± 8.3 nm and an encapsulation efficiency of 68.4 ± 3.1%. A total of sixty pregnant mice were randomly assigned to five groups, with seven mice in each group (n = 7): control, PIH model, NR, β-CD/SA, and β-CD/SA@NR nanocarrier. Treatment with β-CD/SA@NR significantly reduced systolic blood pressure from 163.7 ± 5.2 mmHg to 123.5 ± 4.1 mmHg (p < 0.001), decreased urinary protein from 2.91 ± 0.27 mg/mL to 1.12 ± 0.13 mg/mL (p < 0.01), and increased fetal weights by 28.4% compared to the PIH group. Moreover, β-CD/SA@NR treatment downregulated JAK2 and STAT3 expression by 64.7% and 58.3%, respectively (p < 0.001), along with a significant reduction in IL-6 and TNF-α levels. These results indicate that β-CD/SA@NR nanocarriers effectively manage PIH by delivering NR to suppress JAK/STAT3 signaling, highlighting their translational potential as a safe maternal-fetal therapeutic strategy.