Valeriana jatamansi Jones Inhibits Rotavirus-Induced Diarrhea via Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Rotavirus (RV), as the main cause of diarrhea in children under 5 years, contributes to various childhood diseases. Valeriana jatamansi Jones is a traditional Chinese herb and possesses antiviral effects. In this study we investigated the potential mechanisms of V. jatamansi Jones in RV-induced diarrhea. MTT assay was performed to evaluate cell proliferation and the diarrhea mice model was constructed using SA11 infection. Mice were administered V. jatamansi Jones and ribavirin. Diarrhea score was used to evaluate the treatment effect. The enzyme-linked immunosorbent assay was performed to detect the level of cytokines. Western blot and quantitative reverse transcription-PCR were used to determine protein and mRNA levels, respectively. Hematoxylin-eosin staining was applied to detect the pathological change of the small intestine. TdT-mediated dUTP nick-end labeling was conducted to determine the apoptosis rate. The results showed V. jatamansi Jones promoted MA104 proliferation. V. jatamansi Jones downregulated phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in protein level, which was consistent with the immunohistochemistry results. Moreover, V. jatamansi Jones combined with ribavirin regulated interleukin-1β (IL-1β), interferon γ, IL-6, tumor necrosis factor α, and IL-10, and suppressed secretory immunoglobulin A secretion to remove viruses and inhibit dehydration. V. jatamansi Jones + ribavirin facilitated the apoptosis of small intestine cells. In conclusion, V. jatamansi Jones may inhibit RV-induced diarrhea through PI3K/AKT signaling pathway, and could therefore be a potential therapy for diarrhea.
Abstract
Rotavirus (RV), as the main cause of diarrhea in children under 5 years, contributes to various childhood diseases. Valeriana jatamansi Jones is a traditional Chinese herb and possesses antiviral effects. In this study we investigated the potential mechanisms of V. jatamansi Jones in RV-induced diarrhea. MTT assay was performed to evaluate cell proliferation and the diarrhea mice model was constructed using SA11 infection. Mice were administered V. jatamansi Jones and ribavirin. Diarrhea score was used to evaluate the treatment effect. The enzyme-linked immunosorbent assay was performed to detect the level of cytokines. Western blot and quantitative reverse transcription-PCR were used to determine protein and mRNA levels, respectively. Hematoxylin-eosin staining was applied to detect the pathological change of the small intestine. TdT-mediated dUTP nick-end labeling was conducted to determine the apoptosis rate. The results showed V. jatamansi Jones promoted MA104 proliferation. V. jatamansi Jones downregulated phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in protein level, which was consistent with the immunohistochemistry results. Moreover, V. jatamansi Jones combined with ribavirin regulated interleukin-1β (IL-1β), interferon γ, IL-6, tumor necrosis factor α, and IL-10, and suppressed secretory immunoglobulin A secretion to remove viruses and inhibit dehydration. V. jatamansi Jones + ribavirin facilitated the apoptosis of small intestine cells. In conclusion, V. jatamansi Jones may inhibit RV-induced diarrhea through PI3K/AKT signaling pathway, and could therefore be a potential therapy for diarrhea.
참고문헌 (25)
- Chiappini E, "Viraemia is a common finding in immunocompetent children with rotavirus infection", J. Med. Virol, 76, pp.265~267 (2005)
- Dennehy PH, "Transmission of rotavirus and other enteric pathogens in the home", Pediatr. Infect. Dis. J, 19, pp.S103~ (2000)
- Clarke P, "Reovirus-induced apoptosis : a minireview", Apoptosis, 8, pp.141~150 (2003)
- Lepage P, "Prevention of childhood rotavirus disease through the use of Rotarix(TM)and Rota Teq vaccines", Expert Opin. Biol. Ther, 7, pp.1881~1892 (2007)
- Kochhar S, "Introducing new vaccines in developing countries", Expert Rev. Vaccines, 12, pp.1465~1478 (2013)
- Mathela CS, "Compositional diversity of terpenoids in the Himalayan Valeriana genera", Chem. Biodivers, 2, pp.1174~1182 (2005)
- Wang C, "Isolation and screened neuroprotective active constituents from the roots and rhizomes of Valeriana amurensis", Fitoterapia, 96, pp.48~55 (2014)
- Li YD, "Iridoids from the roots of Valeriana jatamansi", Helvetica Chimica Acta, 96, pp.424~430 (2013)
- Xu J, "Iridoids from the roots of Valeriana jatamansi and their biological activities", Nat. Prod. Res, 26, pp.1996~2001 (2013)
- Wang RJ, "Iridoids from the roots of Valeriana jatamansi Jones", Phytochemistry, 141, pp.156~161 (2017)
- Bhatt, ID, "Characterization of essential oil composition, phenolic content, and antioxidant properties in wild and planted individuals of Valeriana jatamansi Jones", Sci. Hortic, 136, pp.61~68 (2012)
- Dong FW, "Iridoids and sesquiterpenoids from the roots of Valeriana jatamansi Jones", Fitoterapia, 102, pp.27~34 (2015)
- Simpson E, "Use of formative research in developing a knowledge translation approach to rotavirus vaccine introduction in developing countries", BMC Public Health, 7, pp.281~ (2007)
- Lopez S, "Simian rotavirus SA11 strains", J. Virol, 66, pp.1832~1832 (1992)
- Liu YH, "Cytotoxic and antibacterial activities of iridoids and sesquiterpenoids from Valeriana jatamansi", Fitoterapia, 123, pp.73~78 (2017)
- Sun Y, "Pirfenidone suppresses TGF-β1-induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K", AKT signaling pathway, 2018, pp.18, 3907~3913
- Khedr RM, "Sitagliptin attenuates intestinal ischemia", reperfusion injury via cAMP, Akt pathway in a glucagon-like peptide 1 receptor-dependent manner, pp.Life Sci, 2018[DOI]
- Shao Y, "Zinc enhances intestinal epithelial barrier function through the PI3K", AKT, J. Nutr. Biochem, pp.2017, 43[DOI]
- Liu X, "The role of PI3K", Akt in human herpesvirus infection: from the bench to the bedside, 2015, pp.479-480, 568~577
- Zhang X, "PI3K", Akt, Infect. Genet. Evol, pp.2015, 34[DOI]
- Kong N, "Suppression of virulent porcine epidemic diarrhea virus proliferation by the PI3K", Akt, β pathway, pp.PLoS One, 2016[DOI]
- Ding S, "Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells", Elife, 7, pp.e39494~ (2018)
- Yin Y, "PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target", Virulence, 9, pp.83~98 (2018)
- Murray JL, "Inhibition of influenza A virus replication by antagonism of a PI3K-AKT-mTOR pathway member identified by gene-trap insertional mutagenesis", Antivir. Chem. Chemother, 22, pp.205~215 (2012)
- Liu J, "Development of a rapid immunochromatographic strip test for the detection of porcine epidemic diarrhea virus specific SIgA in colostrum", J. Virol. Methods, 279, pp.113855~ (2020)
