Research on mechanism of action of astragaloside Ⅳ in preventing obesity-induced hypertension

  Objective  To investigate the mechanism of astragaloside Ⅳ (As Ⅳ) in preventing obesity-induced hypertension by improving inflammatory response and leptin resistance.

  Methods  A total of 35 male Wistar rats were divided into normal fat feed group (NC group, n=10) and high fat feed group (n=25). After 16 weeks, the obese rats were randomly divided into control group (n=6), As Ⅳ group (n=6), and As Ⅳ+α-bungaratoxin (As Ⅳ+α-BGT, n=6). Weight, blood pressure, plasma and renal norepinephrine (NE) levels were measured before and after intervention in each group. The levels of leptin receptor (LepRb), phosphorylation signal converter and transcription activator -3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), cytokine signal suppressor (SOCS3), tyrosine phosphatase (PTP1B), corticotropin (POMC) and neuropeptide Y (NPY) in the hypothalamus of each group were detected by Western blot or Quantitative real-time polymerase chain reaction (RT-qPCR). Levels of α7 nicotinic acetylcholine receptor (α7nAChR), inhibitor of nuclear factor κB kinase subunit β/nuclear factor κB (IKKβ/NF-KB) and pro-inflammatory cytokines[interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α)] were detected in hypothalamus and adipose tissue in each group.

  Results  Compared with the control group, glucose intolerance and homeostasis model assessment of insulin resistance (HOMA-IR) were improved, triglyceride (TG) and total cholesterol (TC) levels were decreased in the As Ⅳ group after intervention (P < 0.05). After 6 weeks of continuous intervention, the levels of systolic blood pressure (SBP), diastolic blood pressure (DBP) and NE in plasma and kidney tissue were increased in the control group, while the levels of SBP, DBP and NE were decreased in the As Ⅳ group (P < 0.05). Compared with the NC group, plasma leptin level in control group increased, LepRb mRAN expression decreased, leptin signaling molecule p-STAT3 expression decreased, p-PI3K, SOCS3 mRNA and PTP1B mRNA expression increased (P < 0.05). However, the mRNA expressions of p-STAT3, LepRb and POMC increased in the As Ⅳ group, while the mRNA levels of p-PI3K, SOCS3 and PTP1B decreased. Compared with the control group, the expression of α7nAChR protein and mRNA in the As Ⅳ group increased, while the expression of p-IKK β and NF-KB protein and their mRNA decreased (P < 0.05). Compared with the As Ⅳ group, α7nAChR blocker α-BGT in the As Ⅳ+α-BGT group decreased the expression levels of α7nAChR mRNA and protein expression, and the protein levels of IKKβ mRNA, NF-KB mRNA, p-IKK β, NF-KB, IL-1β and TNF-α were increased (P < 0.05). Compared with the control group and As Ⅳ+α-BGT group, α7nAChR mRNA expression was increased and p-IKK β, NF-KB, IL-1β and TNF-α expression were decreased in the As Ⅳ group (P < 0.05).

  Conclusion  As Ⅳ can effectively prevent obesity-related hypertension by inhibiting inflammatory response and improving leptin resistance, and the improvement of As Ⅳ is closely related to the increased expression of α7nAChR.