Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jep Exploring the effect and mechanism of Hibiscus sabdariffa on urinary tract infection and experimental renal inflammation Shun-Ting Chou a,1 , Hsin-Yi Lo a,1 , Chia-Cheng Li a , Lu-Chen Cheng a,b , Pei-Chi Chou c , Yu-Chen Lee d,e , Tin-Yun Ho a,f, ⁎ , Chien-Yun Hsiang g,⁎⁎ a Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan b Hung Tsung Lin Hospital and Nursing Home of Hong’s Hospital, Changhua 52658, Taiwan c School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan d Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan e Division of Chinese Acupuncture, China Medical University Hospital, 40447 Taichung, Taiwan f Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan g Department of Microbiology, China Medical University, Taichung, Taiwan ARTICLE INFO Keywords: Hibiscus sabdariffa Urinary tract infection Renal inflammation ABSTRACT Ethnopharmacological relevance: Hibiscus sabdariffa Linn., also known as roselle, is used in folk medicine as an anti-inflammatory agent. Urinary tract infection (UTI) is a common problem in long-term care facilities. However, effects of roselle on UTI and renal inflammation remained to be analyzed. Aim: Here we surveyed the effect of roselle drink on the prevention of UTI in long-term care facilities and analyzed the anti-inflammatory potential of roselle on lipopolysaccharide (LPS)-induced renal inflammation in mice. Materials and methods: Survey questionnaires and clinical observation were applied to evaluate the use of roselle and the incidence of UTI in long-term care facilities. Mice were administrated roselle orally for 7 consecutive days and then challenged with LPS. Anti-renal inflammatory effects of roselle were analyzed by microarray and immunohistochemical staining. Results: Clinical observation showed that taking roselle drink in residents with urinary catheters reduced the incidence of UTI in long-term care facilities. Renal inflammation is a key event of UTI. Roselle suppressed LPS- induced nuclear factor-κB (NF-κB) activation in cells and LPS-induced interleukin-1β production in mice a dose-dependent manner. Immunohistochemical staining showed that roselle inhibited LPS-induced NF-κB activation and inflammatory cell infiltration in kidney. Gene expression profiling further showed that roselle suppressed the expression of pro-inflammatory cytokine genes and enzyme genes involved in the production of prostaglandin and nitric oxide. In addition, NF-κB was the main transcription factor involved in the regulation of roselle-regulated gene expression in kidney. Conclusions: This is the first report applying clinical observation-guided transcriptomic study to explore the application and mechanism of roselle on UTI. Our findings suggested that roselle drink ameliorated LPS- induced renal inflammation via downregulation of cytokine network, pro-inflammatory product production, and NF-κB pathway. Moreover, this report suggested the potential benefit of roselle drink on UTI. http://dx.doi.org/10.1016/j.jep.2016.10.059 Received 24 May 2016; Received in revised form 17 October 2016; Accepted 19 October 2016 ⁎ Corresponding author at: Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan. ⁎⁎ Corresponding author. 1 These authors contributed equally to this work. E-mail addresses: tyh@mail.cmu.edu.tw (T.-Y. Ho), cyhsiang@mail.cmu.edu.tw (C.-Y. Hsiang). Abbreviations: Ccl12, chemokine (C-C motif) ligand 12; Cox2, cyclooxygenase 2; Cxcl2, chemokine (C-X-C motif) ligand 2; D3S, delphinidin-3-sambubioside; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HPLC, high-performance liquid chromatography; IHC, immunohistochemical staining; IL-1β, interleukin- 1β; iNOS, inducible nitric oxide; LPS, lipopolysaccharide; MTT, methylthiazolyldiphenyl-tetrazolium bromide; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein 1; NF-κB, nuclear factor-κB; qPCR, quantitative real-time polymerase chain reaction; TCM, traditional Chinese medicine; TNF, tumor necrosis factor; UTI, urinary tract infection Journal of Ethnopharmacology 194 (2016) 617–625 0378-8741/ © 2016 Published by Elsevier Ireland Ltd. Available online 20 October 2016 crossmark