Erxian Decoction modulates Th17/Treg cells differentiation through LFA-1/ICAM-1/STAT3 pathway in menopausal dry eye disease.

With the development of modern societies and the ageing of the population, the treatment of menopausal dry eye disease (MDED) has become a thorny issue for the medical profession. Erxian Decoction (EXD) is a traditional Chinese medicine prescription, which has performed good clinical effect on dry eye disease. In this research, we purposed to investigate the molecular mechanisms of EXD for the treatment of MDED. A MDED rat model was established, the results indicated that high concentration of EXD could significantly improve the tear secretion and tear film stability of the animal model. Next, we found that EXD worked through the LFA-1/ICAM-1/STAT3 pathway in the body, and EXD could regulate IL-17, IL-10, CTLA-4 and TGF-ß1 to get Th17/Treg balance. In vitro experiments, the results indicated that EXD affected the differentiation of CD4+ T cells into Th17/Treg cells by inhibiting the expression and activation of LFA-1 on CD4+ T cells, thus exerting immunotherapy effect. Our research provided the experimental basis and associated mechanisms for the clinical application of EXD in dry eye disease.

Uncovering the protective mechanism of Taohong Siwu decoction against diabetic retinopathy via HIF-1 signaling pathway based on network analysis and experimental validation.

BACKGROUND: Diabetic retinopathy (DR) is a common and serious microvascular complication of diabetes. Taohong Siwu decoction (THSWD), a famous traditional Chinese medicine (TCM) prescription, has been proved to have a good clinical effect on DR, whereas its molecular mechanism remains unclear. Our study aimed to uncover the core targets and signaling pathways of THSWD against DR. METHODS: First, the active ingredients of THSWD were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database. Second, the targets of active ingredients were identified from ChemMapper and PharmMapper databases. Third, DR associated targets were searched from DisGeNET, DrugBank and Therapeutic Target Database (TTD). Subsequently, the common targets of active ingredients and DR were found and analyzed in STRING database. DAVID database and ClueGo plug-in software were used to carry out the gene ontology (GO) and KEGG enrichment analysis. The core signaling pathway network of "herb-ingredient-target" was constructed by the Cytoscape software. Finally, the key genes of THSWD against DR were validated by quantitative real-time PCR (qRT-PCR). RESULTS: A total of 2340 targets of 61 active ingredients in THSWD were obtained. Simultaneously, a total of 263 DR-associated targets were also obtained. Then, 67 common targets were found by overlapping them, and 23 core targets were identified from protein-protein interaction (PPI) network. Response to hypoxia was found as the top GO term of biological process, and HIF-1 signaling pathway was found as the top KEGG pathway. Among the key genes in HIF-1 pathway, the mRNA expression levels of VEGFA, SERPINE1 and NOS2 were significantly down-regulated by THSWD (P < 0.05), and NOS3 and HMOX1 were significantly up-regulated (P < 0.05). CONCLUSION: THSWD had a protective effect on DR via regulating HIF-1 signaling pathway and other important pathways. This study might provide a theoretical basis for the application of THSWD and the development of new drugs for the treatment of DR.

[Effects of acupuncture on lactoferrin content in tears and tear secretion in patients suffering from dry eyes: a randomized controlled trial].

BACKGROUND: With the understanding of the immune inflammatory response in the pathogenesis of dry eyes, and the limitations of widely used artificial tears and numerous pharmaceuticals and methods to promote tear secretion, clinicians pay more attention to the therapies that can promote tear secretion actively. Acupuncture treatment for dry eye may meet this requirement. OBJECTIVE: To observe the clinical efficacy of acupuncture treatment on dry eye and the effects on duration, and to examine the mechanisms of acupuncture in treating patients with dye eyes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The study was performed at Department of Ophthalmology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine from August 2010 to May 2011. Patients with the primary diagnosis of dry eye were enrolled. Sixty-five patients were randomly divided into treatment group and control group, and were given 3 weeks of acupuncture treatment or artificial tear therapy respectively. MAIN OUTCOME MEASURES: The enzyme-linked immunosorbent assay was used to detect the lactoferrin content of the tears before and after treatment. In order to evaluate the efficacy of the treatment methods, the Schirmer I test and break-up time were also measured. RESULTS: Compared with before treatment, the lactoferrin content in the tears of patients in the treatment group increased, break-up time was prolonged and the result of the Schirmer I test showed improvement after 3 weeks of treatment. The indexes mentioned above did not change in the control group after treatment. There were no significant differences in tear lactoferrin and Schirmer I test between one week after treatment and after 3-week treatment in the treatment group, but break-up time was significantly shortened. The result of Schirmer I test in the treatment group was significantly higher than that in the control group one week after treatment. CONCLUSION: Acupuncture can increase tear lactoferrin level, extend tear film break-up time and promote tear secretion in patients with dry eye in a time-limited trial. With the end of treatment, the effect decreased.