Paeoniflorin improves pressure overload-induced cardiac remodeling by modulating the MAPK signaling pathway in spontaneously hypertensive rats.

Paeoniflorin (PF) is a main bioactive component of the root of Paeonia lactiflora Pal, and previous investigations suggest that it may impact cardiac remodeling in spontaneous hypertensive rats (SHR) via the MAPK signaling pathway. Thus, the purpose of this investigation was to examine the impacts of paeoniflorin cardiac function in SHR rats. Cardiac function and blood pressure were observed using echocardiography and non-invasive tail pressure gauge. Heart histopathology was assessed by histological staining and transmission electron microscopy. Genomic sequencing was performed and signaling pathway enrichment analyzed the function of differentially expressed genes(DEGs). Biochemical kits were used to analyze the serum level of proinflammatory cytokines including TNF-α, IL-6 and MCP-1. qRT-PCR proved the mRNA expression of Ngfr, Grin2b, and Ntf4. MAPK pathways were determined via western blot. Paeoniflorin decreased blood pressure and increased hemodynamic indexes. 131 DEGs were identified (SHR vs. PF), and mainly enriched on the MAPK signaling pathway. Paeoniflorin reduced IL-6, MCP-1, Ngfr, Grin2b, and Ntf4, and also decreased p-JNK, p-Erk1/2, and p-p38 proteins compared with the SHR group. Paeoniflorin attenuated cardiac hypertrophy, cardiac fibrosis, and inflammation, and subsequently improved LV function. In conclusion, the cardioprotective role of paeoniflorin was associated with the inhibition of MAPK signaling pathway.

[Role of serotoninergic/melatoninergic system in melanin metabolism in melanocytes exposed to serum of rabbits fed with Liuwei Dihuang decoction].

OBJECTIVE: To investigate the effects of Liuwei Dihuang (LWDH) decoction on serotonine (5-HTs), melatonin and the activity of the rate-limiting enzymes ANNAT and HIOMT in cultured human melanocytes and in melanocytes co-cultured with keratinocytes. METHODS: CCK-8 assay was used to assess the proliferation of melanocytes and melanocytes co-cultured with keratinocytes after treatment with the serum from rabbits fed with LWDH decoction. High-performance liquid chromatography was used to determine 5-HT and melatonin contents, and real-time fluorescent PCR was employed to evaluate the ANNAT and HIOMT activities in the cell cultures. RESULTS: The serum from rabbits fed with LWDH Decoction at low doses did not affect the proliferation of melanocytes co-cultured with keratinocytes, but at the concentrations of 20%-40%, the serum significantly inhibited the proliferation of melanocytes, and the effect was optimal with a concentration of 40% (P<0.05). 5-HT and melatonin contents in the cell culture decreased as the serum concentration increased (P<0.05), which was the most obvious with a serum concentration of 40% (P<0.01). Exposure of the cells to low and moderate doses of the serum caused a dose-dependent decrease in AANAT activity (P<0.05), but the serum produced no significant changes in the level of HIOMT mRNA expression in the cells. COUCLUSIONS: The serotoninergic/melatoninergic system mediate the regulation of melanin metabolism by LWDH Decoction, the mechanism of which may involve 5-HTs, melatonin and ANNAT.