title: Medicinal plants and natural molecules with in vitro and in vivo activity against rotavirus: A systematic review.
abstract: BACKGROUND
  Rotaviruses can cause life-threatening health disorders, such as severe dehydrating gastroenteritis and diarrhea in children. Vaccination is the main preventive strategy to reduce rotavirus diarrhea and the severity of episodes, but vaccines are not fully effective and new episodes may occur, even in vaccinated children. The WHO recommends oral rehydration therapy and zinc supplementation for rotavirus-induced diarrhea management. There is little preclinical evidence to support the use of phytotherapeutics in the management of rotaviral infections.
  
  
  OBJECTIVE
  We aim to review the use of medicinal plants and natural molecules in the management of rotavirus infections in experimental studies.
  
  
  METHODS
  Articles, published in the English language between 1991 and 2016, were retrieved from PubMed, Scopus and Web of Science using relevant keywords. The scientific literature mainly focusing on plant natural products with therapeutic efficacies against experimental models of rotavirus, were identified and tabulated. In addition, an assessment of the reliability of animal experiments was determined under ``Risk of Bias'' criteria.
  After an initial search and a revision of the inclusion criteria, 41 reports satisfied the objectives of the study. 36 articles were found concerning the anti-rotaviral potential in rotavirus infected cell lines. Among the active secondary metabolites screened for rotavirus inhibition, the polyphenols of flavonoid structure had acquired the highest number of studies in our survey, compared to phenolic acids, stilbenoids, tannins, pectins, terpenoids and flavonoid glycosides. Also, many phytochemicals reduced the efficacy of viral capsid proteins foremost to their elimination and improved the tendency of host-cell inhibiting virus absorption or by prevention of viral replication. Furthermore, five in vivo studies reported that herbs, as well its components, reduced the duration and severity of diarrhea in mice and piglets. The anti-rotavirus efficacy were highlighted based on improvements in reduction on liquid stool, fecal virus shedding, small intestinal histology, levels of inflammation related cytokines and signaling receptors. However, the quality of the experiments in animal studies contained certain types of bias in terms of how they were conducted and reported.
  
  
  CONCLUSIONS
  We identified and summarized studies on medicinal plants and natural molecules having anti-rotavirus activity in order to further future developments of cures for rotavirus gastroenteritis.
authors.affiliation: Division of Paediatrics, Department of Medicine, Federal University of Sergipe, Rua Cláudio Batista, s/n, Cidade Nova, Aracaju, Sergipe 49.100-000, Brazil; Laboratory of Neuroscience and Pharmacological Assays (LANEF), Department of Physiology, Federal University of Sergipe, São Cristóvão, Aracaju, Sergipe 49.100-000, Brazil; Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Aracaju, Sergipe 49.100-000, Brazil.
authors.forename: Gopalsamy Rajiv
authors.initials: GR
authors.lastname: Gandhi
authors.affiliation: Department of Medicine, Tiradentes University, Avenida Murilo Dantas, 300-Bairro Farolandia, Aracaju, Sergipe 49.032-490, Brazil.
authors.forename: Paula Gurgel
authors.initials: PG
authors.lastname: Barreto
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Aracaju, Sergipe 49.100-000, Brazil.
authors.forename: Bruno Dos Santos
authors.initials: BD
authors.lastname: Lima
authors.affiliation: Laboratory of Neuroscience and Pharmacological Assays (LANEF), Department of Physiology, Federal University of Sergipe, São Cristóvão, Aracaju, Sergipe 49.100-000, Brazil.
authors.forename: Jullyana de Souza Siqueira
authors.initials: JS
authors.lastname: Quintans
authors.affiliation: Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Aracaju, Sergipe 49.100-000, Brazil.
authors.forename: Adriano Antunes de Souza
authors.initials: AA
authors.lastname: Araújo
authors.affiliation: Laboratory of Flavor and Chromatographic Analysis, Federal University of Sergipe, São Cristóvão, Aracaju, Sergipe 49.100-000, Brazil.
authors.forename: Narendra
authors.initials: N
authors.lastname: Narain
authors.affiliation: Laboratory of Neuroscience and Pharmacological Assays (LANEF), Department of Physiology, Federal University of Sergipe, São Cristóvão, Aracaju, Sergipe 49.100-000, Brazil. Electronic address: lucindojr@gmail.com.
authors.forename: Lucindo Jose
authors.initials: LJ
authors.lastname: Quintans-Júnior
authors.affiliation: Division of Paediatrics, Department of Medicine, Federal University of Sergipe, Rua Cláudio Batista, s/n, Cidade Nova, Aracaju, Sergipe 49.100-000, Brazil.
authors.forename: Ricardo Queiroz
authors.initials: RQ
authors.lastname: Gurgel
mesh_terms: D000818:Animals; D003967:Diarrhea / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal; D012401:Rotavirus / Q000187:drug effects* / Q000502:physiology; D012400:Rotavirus Infections / Q000188:drug therapy* / Q000821:virology; D014764:Viral Proteins; D014779:Virus Replication
chemical_list: D010936:Plant Extracts; D014764:Viral Proteins
keywords: Diarrhea; Gastroenteritis; Inflammation; Medicinal plants; Natural molecules; Rotavirus