Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse Model
Intestinal mucositis is a common toxicity of many anti-neoplastic therapies that negatively influences health, the quality of life, economic outcomes, and even the success of cancer treatment. Unfortunately, there is presently no optimal medicine that is able to effectively manage this condition. l-...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-06-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00918/full |
| _version_ | 1818019919478915072 |
|---|---|
| author | Liping Qu Wanxian Tan Jing Yang Limin Lai Sili Liu Jianming Wu Wenjun Zou |
| author_facet | Liping Qu Wanxian Tan Jing Yang Limin Lai Sili Liu Jianming Wu Wenjun Zou |
| author_sort | Liping Qu |
| collection | DOAJ |
| description | Intestinal mucositis is a common toxicity of many anti-neoplastic therapies that negatively influences health, the quality of life, economic outcomes, and even the success of cancer treatment. Unfortunately, there is presently no optimal medicine that is able to effectively manage this condition. l-glutamine is one of the most frequently used agent in practice among the limited treatment choices due to its safety and inexpensiveness despite there being a lack of evidence. Previous studies indicated that l-glutamine may alleviate mucositis and mucosal atrophy but failed to improve patients' macroscopic conditions, such as the occurrence of diarrhea. A compound glutamine capsule (G-SJZ), composed of l-glutamine and the traditional Chinese herbal formula Si-Jun-Zi-Tang, has been used in China for 23 years to treat many types of gastrointestinal diseases, including gastrointestinal reactions induced by radiotherapy and chemotherapy. However, the exact effect of G-SJZ on intestinal mucositis is unclear, and moreover, whether l-glutamine combined with Si-Jun-Zi-Tang is more effective than l-glutamine alone have not been studied. In the current study, we explored the effects of G-SJZ and l-glutamine in a mouse model of intestinal mucositis induced by 5-fluorouracil (5-Fu). The results revealed that pretreatment with G-SJZ ameliorated the physical manifestations of weight loss and the severity of diarrhea following continuous 5-Fu injections in mice. Likewise, the histopathological damage and the destruction of villus and crypt structures in the intestinal mucosa as well as the increase in circulating intestinal injury markers caused by 5-Fu were reversed with G-SJZ pretreatment. Furthermore, the protective effect of G-SJZ was accompanied by modulations in the immunohistochemical expression of tight junction proteins. Interestingly, although treatment with a dose of l-glutamine alone that was equivalent to the dose in G-SJZ also showed a protective effect, it did not appear to be as strong as treatment with G-SJZ. Si-Jun-Zi-Tang in G-SJZ may compensate for the deficiencies of l-glutamine in this model which seems not to be related to the regulation of tight junction proteins. Our study is the first to suggest that the combined use of l-glutamine and Si-Jun-Zi-Tang might be more effective than l-glutamine alone despite exact mechanism still needs further study. Because of the limited number of therapeutic agents, G-SJZ is likely to be a preferable choice for intestinal mucositis. |
| first_indexed | 2024-04-14T07:58:10Z |
| format | Article |
| id | doaj.art-1ea29525548d4c4c8924b87215d5b31e |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-14T07:58:10Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-1ea29525548d4c4c8924b87215d5b31e2022-12-22T02:04:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-06-011110.3389/fphar.2020.00918513499Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse ModelLiping Qu0Wanxian Tan1Jing Yang2Limin Lai3Sili Liu4Jianming Wu5Wenjun Zou6School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaIntestinal mucositis is a common toxicity of many anti-neoplastic therapies that negatively influences health, the quality of life, economic outcomes, and even the success of cancer treatment. Unfortunately, there is presently no optimal medicine that is able to effectively manage this condition. l-glutamine is one of the most frequently used agent in practice among the limited treatment choices due to its safety and inexpensiveness despite there being a lack of evidence. Previous studies indicated that l-glutamine may alleviate mucositis and mucosal atrophy but failed to improve patients' macroscopic conditions, such as the occurrence of diarrhea. A compound glutamine capsule (G-SJZ), composed of l-glutamine and the traditional Chinese herbal formula Si-Jun-Zi-Tang, has been used in China for 23 years to treat many types of gastrointestinal diseases, including gastrointestinal reactions induced by radiotherapy and chemotherapy. However, the exact effect of G-SJZ on intestinal mucositis is unclear, and moreover, whether l-glutamine combined with Si-Jun-Zi-Tang is more effective than l-glutamine alone have not been studied. In the current study, we explored the effects of G-SJZ and l-glutamine in a mouse model of intestinal mucositis induced by 5-fluorouracil (5-Fu). The results revealed that pretreatment with G-SJZ ameliorated the physical manifestations of weight loss and the severity of diarrhea following continuous 5-Fu injections in mice. Likewise, the histopathological damage and the destruction of villus and crypt structures in the intestinal mucosa as well as the increase in circulating intestinal injury markers caused by 5-Fu were reversed with G-SJZ pretreatment. Furthermore, the protective effect of G-SJZ was accompanied by modulations in the immunohistochemical expression of tight junction proteins. Interestingly, although treatment with a dose of l-glutamine alone that was equivalent to the dose in G-SJZ also showed a protective effect, it did not appear to be as strong as treatment with G-SJZ. Si-Jun-Zi-Tang in G-SJZ may compensate for the deficiencies of l-glutamine in this model which seems not to be related to the regulation of tight junction proteins. Our study is the first to suggest that the combined use of l-glutamine and Si-Jun-Zi-Tang might be more effective than l-glutamine alone despite exact mechanism still needs further study. Because of the limited number of therapeutic agents, G-SJZ is likely to be a preferable choice for intestinal mucositis.https://www.frontiersin.org/article/10.3389/fphar.2020.00918/fullcombination compositionsl-glutamineSi-Jun-Zi-Tang5-fluorouracilintestinal mucositis |
| spellingShingle | Liping Qu Wanxian Tan Jing Yang Limin Lai Sili Liu Jianming Wu Wenjun Zou Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse Model Frontiers in Pharmacology combination compositions l-glutamine Si-Jun-Zi-Tang 5-fluorouracil intestinal mucositis |
| title | Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse Model |
| title_full | Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse Model |
| title_fullStr | Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse Model |
| title_full_unstemmed | Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse Model |
| title_short | Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse Model |
| title_sort | combination compositions composed of l glutamine and si jun zi tang might be a preferable choice for 5 fluorouracil induced intestinal mucositis an exploration in a mouse model |
| topic | combination compositions l-glutamine Si-Jun-Zi-Tang 5-fluorouracil intestinal mucositis |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00918/full |
| work_keys_str_mv | AT lipingqu combinationcompositionscomposedoflglutamineandsijunzitangmightbeapreferablechoicefor5fluorouracilinducedintestinalmucositisanexplorationinamousemodel AT wanxiantan combinationcompositionscomposedoflglutamineandsijunzitangmightbeapreferablechoicefor5fluorouracilinducedintestinalmucositisanexplorationinamousemodel AT jingyang combinationcompositionscomposedoflglutamineandsijunzitangmightbeapreferablechoicefor5fluorouracilinducedintestinalmucositisanexplorationinamousemodel AT liminlai combinationcompositionscomposedoflglutamineandsijunzitangmightbeapreferablechoicefor5fluorouracilinducedintestinalmucositisanexplorationinamousemodel AT sililiu combinationcompositionscomposedoflglutamineandsijunzitangmightbeapreferablechoicefor5fluorouracilinducedintestinalmucositisanexplorationinamousemodel AT jianmingwu combinationcompositionscomposedoflglutamineandsijunzitangmightbeapreferablechoicefor5fluorouracilinducedintestinalmucositisanexplorationinamousemodel AT wenjunzou combinationcompositionscomposedoflglutamineandsijunzitangmightbeapreferablechoicefor5fluorouracilinducedintestinalmucositisanexplorationinamousemodel |