Abstract
Zhibaidihuang decoction (ZBDHD) is a Chinese herbal formula, which is used in Chinese traditional medicine to treat symptoms of Yinxuhuowang (Yin deficiency and high fire) syndrome. This study elucidates the mechanism of ZBDHD on oral ulcers, one Yinxuhuowang syndrome. Simultaneously, some ingredients in ZBDHD were found and identified by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A Ganjiangfuzirougui decoction- (GJD-) induced Yinxuhuowang syndrome SD rat model was used to demonstrate the efficiency of ZBDHD treatment. The oral mucosa of rat in the GJD group, stained with hematoxylin and eosin (H&E), showed epidermal shedding and inflammatory cell infiltration. And an alleviation efficiency of ZBDHD in GJD-induced pathological changes in the oral mucosa could be obtained. ZBDHD treatment restored the GJD-induced imbalance of metabolites, which were choline, glycocholic acid, and palmitoyl-L-carnitine (PALC). GJD stimulated the expression of NF-κB. And the overexpressed of NF-κB in mucosa of rat in the GJD group could be inhibited by ZBDHD treatment. Simultaneously, the optimal efficiency of ZBDHD treatment on the cellular ATP content, oxygen consumption rate (OCR), and superoxide dismutase (SOD) concentration was evaluated, in vitro assay. Compared to the control cells, the ATP content, OCR, and SOD activity in the ZBDHD-treated cells were significantly higher. For the mechanisms study, seven cytokines were screened with a Dual-Luciferase Reporter gene assay. In the ARE assay, the luciferase signal was stimulated significantly by ZBDHD. In cells, the transcription of nrf2, maf, and keap1, which were related to the ARE pathway, was elevated by ZBDHD treatment. Our study demonstrated that high-dose GJD could lead to Yinxuhuowang syndrome, such as oral ulcers, and the imbalance in serum metabolites. And ZBDHD can improve oral cell inflammation and the imbalance of metabolism by inhibiting NF-κB and enhancing the activity of the ARE signalling pathway to ameliorate oxidative stress in the cell. This study provides a theoretical basis for the clinical application of ZBDHD.
Highlights
For all living aerobic creatures, molecular oxygen is the ultimate electron acceptor for cellular respiration
Reactive oxygen species (ROS) are generated during oxidative phosphorylation in mitochondria [1]. e first intermediate in the oxygen reduction process consists of superoxide radicals (O2.-), which are rapidly converted to hydrogen peroxide (H2O2) [2]
Since it has been recognized that antioxidants can alleviate inflammatory reactions, some antioxidants have been studied and proposed for therapeutic use based on their therapeutic effects [14], e.g., Evidence-Based Complementary and Alternative Medicine vitamin C, coenzyme Q10, and some polyphenols that are isolated from herbs [15]
Summary
For all living aerobic creatures, molecular oxygen is the ultimate electron acceptor for cellular respiration. Reactive oxygen species (ROS) are generated during oxidative phosphorylation in mitochondria [1]. H2O2 can be generated deliberately during phagocytosis in macrophages and neutrophils [3]. ROS can be exogenously stimulated, e.g., through cosmic radiation or UV light [4]. E term “oxidative stress” implies a physiological imbalance in the ROS creation and scavenging. Inflammation, which is triggered by oxidative stress, is associated with many diseases, such as oral ulcers [5], neurodegenerative diseases [6], tumour [7, 8], cardiovascular disease [9, 10], type 2 diabetes [11], nonalcoholic fatty liver disease [12], and Parkinson’s disease [13]. Since it has been recognized that antioxidants can alleviate inflammatory reactions, some antioxidants have been studied and proposed for therapeutic use based on their therapeutic effects [14], e.g., Evidence-Based Complementary and Alternative Medicine vitamin C, coenzyme Q10, and some polyphenols that are isolated from herbs [15]
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