The effect of antioxidant dietary supplements and diet-derived circulating antioxidants on vitiligo outcome: evidence from genetic association and comprehensive Mendelian randomization.

Background: Previous studies have indicated that antioxidant diets may have a positive impact on vitiligo by interfering with oxidative stress mechanisms. However, there has been a lack of research utilizing the Mendelian randomization (MR) method to analyze the relationship between antioxidant diet intake and vitiligo. Methods: In this study, we employed both univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) approaches. The specific antioxidant dietary supplements (such as coffee intake, green tea intake, herbal tea intake, standard tea intake, and average weekly red wine intake) as well as diet-derived circulating antioxidants, including Vit. C (ascorbate), Vit. E (α-tocopherol), Vit. E (γ-tocopherol), Carotene, Vit. A (retinol), Zinc, and Selenium (N = 2,603-428,860) were significantly associated with independent single-nucleotide polymorphisms (SNPs). We obtained pooled statistics on vitiligo from a meta-analysis of three genome-wide association studies (GWASs) of European ancestry, including 4,680 cases and 39,586 controls. Inverse variance weighted (IVW) was employed as the primary analytical method, and sensitivity analysis was conducted to assess the robustness of the main findings. Results: Genetically, coffee intake [odds ratio (OR) = 0.17, 95% confidence interval (CI) 0.07-0.37, p = 1.57 × 10-5], average weekly red wine intake (OR = 0.28, 95% CI 0.08-1.00, p = 0.049), and standard tea intake (OR = 0.99, 95% CI 0.98-0.99, p = 5.66 × 10-7) were identified as protective factors against vitiligo. However, no causal effect between the intake of other antioxidant diets and vitiligo was found. Moreover, no instances of pleiotropy or heterogeneity were observed in this study. Conclusion: Our study indicates that coffee, standard tea, and red wine consumption can potentially reduce the risk of vitiligo. However, there is insufficient evidence to support that other antioxidant diets have a significant effect on vitiligo.

Theory of the exterior-interior relationship between the lungs and the large intestine to explore the mechanism of Eriobotrya japonica leaf water extract in the treatment of cough variant asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Eriobotrya japonica (Thunb.) Lindl leaf (EJL) is used as a traditional Chinese medicine. E. japonica is a member of the Rosaceae family. EJL suppresses cough and relieves asthma and is widely used to treat lung diseases. In the present study, guided by the traditional Chinese medicine theory of the exterior-interior relationship between the lungs and the large intestine, the pathogenesis of cough variant asthma (CVA) and the treatment mechanism of EJL on CVA were explored. AIM OF THE STUDY: This study aimed to explore the airway remodeling effects of EJL in CVA from the perspective of the intestinal flora and the matrix metallopeptidase 9/tissue inhibitor of metalloproteinases-1 (MMP-9/TIMP-1) pathway. MATERIALS AND METHODS: The oleanolic acid and ursolic acid contents in EJL were measured by high-performance liquid chromatography (HPLC) to ensure the quality of EJL. BALB/c mice were used to establish a CVA model through ovalbumin (OVA) sensitization and atomization. EJL (at 5, 10, or 20 g/kg/day) was intragastrically administered. The body weight, ratio of total bronchial wall area (WAt) to bronchial basement membrane perimeter (Pbm) (WAt/Pbm), the number of coughs, and cough latency were measured. The pathological changes of the lung tissue were analyzed by hematoxylin and eosin (HE) staining. The expression of α-smooth muscle actin (α-SMA) was measured by immunohistochemistry (IHC). The expressions of MMP-9 and TIMP-1 were detected in the lung tissue by reverse transcription quantitative polymerase chain reaction (RT-PCR) and Western blot analysis. Additionally, an Illumina Hiseq platform was used for 16S ribosomal DNA (16S rDNA) high-throughput sequencing to detect the intestinal flora in feces samples. RESULTS: The results confirmed the positive effects of EJL on CVA. After administration of EJL, the number of coughs and the WAt/Pbm ratio decreased, the cough latency was prolonged, body weight was increased, and the general status was better than that of the CVA model mice. HE staining revealed that EJL decreased inflammatory cell infiltration and improved the histopathological structure of the lung tissue. EJL also showed significant inhibitory effects on the expression of α-SMA, MMP-9, and TIMP-1 and normalized the intestinal flora to a certain extent. CONCLUSIONS: The results demonstrated that EJL alleviated airway remodeling of CVA mice, which might be related to the inhibition of the MMP-P/TIMP-1 pathway and the regulation of intestinal flora.

Research on mechanism of charred hawthorn on digestive through modulating "brain-gut" axis and gut flora.

ETHNOPHARMACOLOGICAL RELEVANCE: Hawthorn is a traditional Chinese medicine for high-calorie-diet-induced dyspepsia (HC-DID) for thousands of years old. Based on traditional Chinese medicine (TCM) theory and clinical and non-clinical trials, its stir-frying processed product, charred hawthorn, possesses better effect. At present, most research mainly focuses on chemical constituents of hawthorn before and after stir-frying process, but there is no relevant action-mechanism study about fragrant odor promoting HC-DID during the stir-frying process of the hawthorn. AIM OF THE STUDY: The purpose of the present study is to research on mechanism of hawthorn decoction coupled with odor of charred hawthorn on digestive in rats with HC-DID. MATERIALS AND METHODS: The SPF Kunming (KM) mice and Sprague Dawley (SD) rats were randomly divided into 7 groups: control group, model group, cisapride group, hawthorn group (HT), charred hawthorn group (CHT), odor of charred hawthorn (OCHT), CHT + OCHT group. The rats were modeled as HC-DID, whose treatment by intragastric administration and odor administration. Obvious symptoms of HC-DID were observed. Gastrointestinal motility were detected. Histopathology was performed in hypothalamus and gastrointestinal tract. Related brain-gut peptides were assayed in serum, hypothalamus and gastrointestinal tract. Illumina Miseq platform was used for 16S rDNA high-throughput sequencing to detect the intestinal flora structure of the caecum of rats. RESULTS: Traditional Chinese medicine decoction of hawthorn (HT and CHT) regulated the body weight, food intake, gastrointestinal motility and abnormal secretion of brain-gut peptides in rats with HC-DID, and the odor of charred hawthorn also had good curative effect for it. Moreover, the intestinal dysbiosis was induced by high-calorie diet in rats with dyspepsia, and hawthorn decoction could ease this trend. CONCLUSION: The above study showed that hawthorn decoction coupled with the odor of charred hawthorn effectively alleviate HC-DID in rats by regulating the "Brain-Gut" axis and gut flora. Odor treatment of hawthorn could be a potential therapeutic approach for HC-DID.

ADAM17 participates in the protective effect of paeoniflorin on mouse brain microvascular endothelial cells.

Paeoniflorin (PF), the most abundant active ingredient of traditional Chinese herbal medicine Paeoniae Radix, has been recognized as a potential neuroprotectant due to its remarkable efficacy on mitigating cerebral infarction and preventing the neurodegenerative diseases. However, the precise mechanisms of PF remain incompletely understood. In this study, we first provided evidence for the protective effect of PF on hydrogen peroxide-induced injury on mouse brain microvascular endothelial bEnd.3 cells, and for transactivation of the epidermal growth factor receptor (EGFR) signal induced by PF, suggesting that EGFR transactivation might be involved in the beneficial role of PF. Next, by detecting the phosphorylation of a disintegrin and metalloprotease 17 (ADAM17) at Thr 735 and performing loss-of-function experiments with the ADAM17 inhibitor and ADAM 17-siRNA, we showed that PF-induced transactivation of EGFR and downstream ERKs and AKT signaling pathways were dependent on ADAM17. Furthermore, PF-induced phosphorylation of ADAM17 and the EGFR transactivation were inhibited by the inhibitors of adenosine A1 receptor (A1R) or Src kinase that were applied to cells prior to PF treatment, implying the involvement of A1R, and Src in the activation of ADAM17. Finally, PF reduced the cell surface level of TNF-receptor 1 (TNFR1) and increased the content of soluble TNFR1 (sTNFR1) in the culture media, indicating that PF might enhance the shedding of sTNFR1. Taken together, we conclude that A1R and Src-dependent activation of ADAM17 participates in PF-induced EGFR transactivation and TNFR1 shedding on mouse brain microvascular endothelial cells, which may contributes to the neuroprotective effects of PF.