{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:24:14Z","timestamp":1789269854569,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Over the last decade, extensive use of coccidiostats to treat and control\n                      <jats:italic>Eimeria<\/jats:italic>\n                      infection has developed drug resistance, prompting the search for new alternative therapies. Rhatany is proven to have various pharmacological properties.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The present study aimed to\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      evaluate the effect of Rhatany roots extract (RRE) as an anti-eimerial and anti-apoptotic agent against murine eimeriosis induced by\n                      <jats:italic>Eimeria papillata<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Phytochemical screening by gas chromatography-mass spectrometry analysis (GC-MS) was used to detect active compounds in RRE.\n                      <jats:italic>In vitro<\/jats:italic>\n                      anti-eimerial activity of RRE (200, 100, 50 mg\/ml), amprolium, phenol, Dettol\u2122, and formalin were studied after incubation with non-sporulated\n                      <jats:italic>Eimeria<\/jats:italic>\n                      oocysts. For the\n                      <jats:italic>in vivo<\/jats:italic>\n                      study, twenty-five male C57BL\/6 mice were randomly allocated into five groups. Animals in the first group were just given distilled H\n                      <jats:sub>2<\/jats:sub>\n                      O, while those in the second group were given 200 mg\/kg RRE for 5 days. The\n                      <jats:italic>Eimeria<\/jats:italic>\n                      parasite\u2019s oocysts were infected into the third, fourth, and fifth groups. For treatment, RRE (200 mg\/kg) and amprolium (120 mg\/kg) were orally given to the 4\n                      <jats:sup>th<\/jats:sup>\n                      and 5\n                      <jats:sup>th<\/jats:sup>\n                      groups for five days, respectively. All mice were euthanized, on day 5 post-infection, to collect the jejunal tissues under study. Investigations were undertaken into the oocyst output in feces and goblet cells in mice jejuna. Assays for glutathione peroxidase (GPx), hydrogen peroxide (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      ), and myeloperoxidase (MPO) were also performed. In jejunal tissue, cysteine aspartic acid protease-3 (Caspase-3) was counted using immunohistochemistry, while BCL2-associated X protein (Bax) and B-cell lymphoma-2 (BCL-2) were assayed using ELISA. In addition, mRNA expression of the goblet cell response gene (MUC2) was detected using real-time PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Phytochemical screening by GC-MS demonstrated the presence of 22 compounds in the RRE. The\n                      <jats:italic>in vitro<\/jats:italic>\n                      study revealed that RRE significantly inhabited the oocyst sporulation in a dose-dependent manner. By day 5 after infection with the\n                      <jats:italic>Eimeria<\/jats:italic>\n                      parasite, the number of oocysts in mice feces was significantly reduced after RRE treatment (1.308 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \u00b1 1.36 \u00d7 10\n                      <jats:sup>5<\/jats:sup>\n                      oocysts\/g feces) compared to the infected group (5.387 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \u00b1 4.29 \u00d7 10\n                      <jats:sup>5<\/jats:sup>\n                      oocysts\/g feces). Moreover, the\n                      <jats:italic>Eimeria<\/jats:italic>\n                      infection reduced the number of goblet cells of mice jejuna and its specific gene, MUC2. The treatment with RRE increased the number of goblet cells\/villus from 3.45 \u00b1 0.17 to 6.04 \u00b1 0.23, associated with upregulation for MUC2 from 0.26 to 2.39-fold. Also, the\n                      <jats:italic>Eimeria<\/jats:italic>\n                      experimental infection lowered the activity of the antioxidant enzyme represented by GPx (23.99 \u00b1 3.68 mg\/g tissue), while increasing the stress parameters of hydrogen peroxide (0.07 \u00b1 0.01 mM\/g) as well as the activity of MPO (66.30 \u00b1 3.74 U\/mg). The production of apoptotic markers including Caspase-3 (68.89 \u00b1 2.67 U\/g) and Bax (159.05 \u00b1 6.50 pg\/ml) was significantly elevated while decreasing the anti-apoptotic marker of BCL2 (0.42 \u00b1 0.07 pg\/ml). Our study proved that RRE significantly reduced oxidative stress, and apoptotic markers as well as the inflammatory activity of MPO. Also, antioxidant enzyme and anti-apoptotic activity in the jejunum of\n                      <jats:italic>E. papillata<\/jats:italic>\n                      -infected mice were enhanced after RRE treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study highlights the potential of RRE as a natural solution for coccidiosis management by modulating apoptosis in\n                      <jats:italic>E. papillata<\/jats:italic>\n                      host cells. However, further research is needed to fully understand the underlying mechanisms and enhance our understanding of its therapeutic efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1430960","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:39:35Z","timestamp":1720658375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Fighting eimeriosis by using the anti-eimerial and anti-apoptotic properties of rhatany root 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