Study on Network Pharmacological Analysis and Preliminary Validation to Understand the Mechanisms of Plantaginis Semen in Treatment of Gouty Nephropathy

Abstract

Plantaginis Semen (PS) has been used to promote diuresis and clear away dampness. Recent reports have shown that PS can be used to treat gouty nephropathy (GN). However, the action and mechanism of PS have not been well defined in treating GN. The present study aimed to define the molecular mechanisms of PS as a potential therapeutic approach to treat GN. A combination of network pharmacology and validation experiments in GN is used to understand the potential mechanism. Information on pharmaceutically active compounds in PS and gene information related to GN was obtained from public databases. The compound target network and protein-protein interaction network were constructed to study the mechanism of action of PS in the treatment of GN. The mechanism of action of PS in the treatment of GN was analyzed via Gene Ontology (GO) biological process annotation and Kyoto Gene and Genomics Encyclopedia (KEGG) pathway enrichment. Validation experiments were performed to verify the core targets. The GN rat model was prepared by the method of combining yeast and adenine. Hematoxylin-eosin (HE) staining was used to observe the morphology of renal tissue in rats. ELISA was applied to detect TGF-β1, TNF-α, and IL-1β levels in renal tissue. The expressions of TGF-β1, TNF-α, and IL-1β were determined using immunohistochemistry. Through the results of network pharmacology, we obtained 9 active components, 118 predicted targets, and 149 GN targets from the public database. Based on the protein-protein interaction (PPI), 26 hub genes for interaction with PS treating for GN were screened, including MMP9, TNF, IL1β, and IL6. The enrichment analysis results showed that the treatment of GN with PS was mainly involved in the TGF-β1 signaling pathway, MAPK signaling pathway, TNF signaling pathway, NF-κB signaling pathway, and PI3K Akt signaling pathway. Validation experiment results showed that PS could reduce the content of urinary protein and UA and deregulate the expression of TGF-β1, TNF-α, and IL-1β in the treatment of GN. The molecular mechanism of PS in the treatment of GN indicated the synergistic features of multicomponent, multitarget, and multipathway of traditional Chinese medicine, which provided an essential scientific basis for further elucidating the mechanism of PS in the treatment of GN.

Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat

“…URAT1 plays a central role in renal urate reabsorption and Plantaginis Semen can affect the expression of URAT1 in the kidney [ 14 – 17 ]. The PI3K/Akt pathway is able to trigger inflammatory and kidney injuries, impairing renal excretion of uric acid and HUA [ 18 – 24 ], the treatment of gouty nephropathy with Plantaginis Semen is mainly involved with the PI3K/Akt signaling pathway [ 25 ]. HUA also is related to disorders of lipid metabolism, about 60% of patients with HUA have abnormal lipid metabolism [ 26 ].…”

Research progress of treating hyperuricemia in rats and mice with traditional Chinese medicine

“…a herb commonly employed for uric acid reduction ( Zeng et al, 2018 ; Sun et al, 2019 ). The phosphoinositide 3-kinase/Protein kinase B (PI3K/Akt) signaling pathway, an inflammatory pathway implicated in severe kidney injury and indirect modulation of uric acid excretion, can be inhibited by Plantago to ameliorate nephropathy and enhance uric acid excretion ( Dragos et al, 2020 ; Santos et al, 2020 ; Zhao et al, 2020 ). Furthermore, hyperuricemia has been associated with lipid metabolism ( Guo et al, 2020 ), but it remains unknown whether lipid metabolism plays a role in the therapeutic effects of Plantago on hyperuricemia treatment.…”

Effect of Bining decoction on gouty nephropathy: a network pharmacology analysis and preliminary validation of gut microbiota in a mouse model

“…In the study, n refers to number of animals and the individual mouse was considered the experimental unit within the studies. The sample size calculation was based on a similar experiment reported in the literature and a preliminary experiment conducted under identical conditions to the planned experiment (19). A total of 30 male Institute of Cancer Research (ICR) mice (18±2 g), were provided by the Heilongjiang University of Chinese Medicine (Harbin, China).…”