Abstract
BackgroundJowiseungki decoction (JSD) is a prescription commonly used for the treatment of diabetic complications or diabetic nephropathy (DN) in traditional medicine clinics. However, the underlying therapeutic mechanisms of JSD are still unclear.MethodsStreptozotocin (STZ)-induced DN mice were administered 100 and 500 mg/kg JSD for 4 weeks, and the therapeutic mechanisms and targets of JSD were analyzed by network pharmacology and gut microbiota analyses.ResultsJSD significantly decreased the increase in food and water intake, urine volume, fasting blood glucose, serum glucose and triglyceride levels, and urinary albumin excretion. JSD administration significantly increased the decrease in insulin secretion and creatinine clearance and reduced the structural damage to the kidney tissues. Moreover, JSD administration significantly inhibited the expression of protein kinase C-alpha (PKC-α), transforming growth factor beta-1 (TGF-β1), α-smooth muscle actin (α-SMA), nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in the kidney tissues of DN mice, while it significantly increased the phosphorylation of insulin receptor substrate 1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (Akt). In the network pharmacological analysis, JSD obviously influenced phosphatase binding, protein serine/threonine kinase, and mitogen-activated protein kinase (MAPK)-related signaling pathways. Our data suggest that JSD can improve symptoms in STZ-induced DN mice through the inhibition of kidney dysfunction, in particular, by regulating the PKCα/PI3K/Akt and NF-κB/α-SMA signaling pathways. Gut microbiota analysis can help to discover the pharmaco-mechanisms of the influence of JSD on bacterial diversity and flora structures in DN.ConclusionJSD can improve the symptoms of DN, and the underlying mechanism of this effect is renal protection through the inhibition of fibrosis and inflammation. JSD can also change bacterial diversity and community structures in DN.
Highlights
Jowiseungki decoction (JSD) is a prescription commonly used for the treatment of diabetic complica‐ tions or diabetic nephropathy (DN) in traditional medicine clinics
With respect to the changes in the ratio of kidney weight to body weight (BW), a significant increase in kidney weight (p < 0.0001) was observed in the DN control group compared with the normal group, but the decrease in kidney weight was significantly decreased in the JSD-administered group (p < 0.01 for the low dose and p < 0.05 for the high dose) compared with the control group
The expression levels of Protein kinase C (PKC)-α (p < 0.0001 for protein and p < 0.001 for mRNA), Transforming growth factor β-1 (TGF-β1) (p < 0.0001 for protein, p < 0.01 for mRNA), and α-smooth muscle actin (α-SMA) (p < 0.01 for protein and p < 0.001 for mRNA) in kidney tissues were significantly increased in the DN control group compared with the normal group
Summary
Jowiseungki decoction (JSD) is a prescription commonly used for the treatment of diabetic complica‐ tions or diabetic nephropathy (DN) in traditional medicine clinics. DN is the end stage of this syndrome with very serious renal dysfunction and excessive urination [5] Therapeutic strategies, such as nourishing qi and yin, activating blood circulation and removing blood stasis, invigorating the spleen and kidney, clearing heat and relieving turbidity, are applied for DN treatment in traditional clinics. Rhubarb and Mirabilitum are cold-natured herbs in herbology and are applied to control inflammation [7, 8]. Their anti-inflammatory effects have been experimentally proven in both in vitro and in vivo studies [7,8,9]. JSD is a well-known prescription for DM in traditional medicines, the mechanisms responsible for its effects in experimental studies, including preclinical studies, are poorly understood
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