Protective Effects and Underlying Mechanisms of Compound Herba Houttuyniae in db/db Mice

Abstract

ObjectiveHouttuynia cordata Thunb and Fructus Arctii are two traditional Chinese medicine (TCM) compounds widely used for reducing heat and toxins in the body. In addition, Fructus Arctii has been used in clinical therapy for diabetic nephropathy. On the basis of the TCM theory of heat in diabetes mellitus and the clinical efficacy of Fructus Arctii, the two compounds were used to develop a formula named Compound Herba Houttuyniae. This study evaluated the renoprotective effects of different Compound Herba Houttuyniae extracts and assessed their mechanisms through the Janus kinase/signal transducer and activator of transcription (JAK/STAT)-suppressors of cytokine signaling (SOCS)-1 pathway. MethodsThe normal group comprised db/m mice (n = 8); db/db mice were randomly divided into six groups according to the applied treatment method: model group (no treatment), AG490 group, petroleum ether extract (PEE) group, ethyl acetate extract (EAE) group, N-butanol extract (NE) group, and water extract (WE) group (n = 6 in each group). The general status, biochemical indicators, and renal histological changes in the mice were evaluated, and the JAK/STAT-SOCS-1 pathway was assessed. ResultsThe NE and WE groups showed a decrease in 24-h urinary protein and albumin levels as well as serum uric acid and fibronectin levels but showed no changes in fasting plasma glucose and hemoglobin A1c levels. The protein expression of JAK2, STAT3, P-JAK2, and P-STAT3 and the gene expression of JAK2 and STAT3 in kidney tissues were significantly increased (P < 0.05) in the model group. Compared with the model group, the expression of P-JAK2 and P-STAT3 was downregulated in the extract treatment groups. The expression of SOCS-1 was increased in the NE and WE groups (P < 0.05). However, the expression of JAK2, STAT3, JAK2mRNA, and STAT3mRNA in the treatment groups did not show any significant differences. ConclusionCompound Herba Houttuyniae showed renoprotective effects in db/db mice, and the strongest effects were observed in the WE and NE groups. The underlying mechanism for these effects might involve the regulation of the JAK/STAT-SOCS-1 pathway.