Cargando…

Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis

BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Luo Tong formula (LTF), a classical traditional Chinese medicine (TCM) prescription, consists of four plants that have been widely and effectively used to treat DR. Previous work in our laboratory has confirmed...

Descripción completa

Detalles Bibliográficos
Autores principales: Di, Sha, Yao, Chensi, Qiao, Liping, Li, Xiuyang, Pang, Bing, Lin, Jiaran, Wang, Jia, Li, Min, Tong, Xiaolin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9717245/
https://www.ncbi.nlm.nih.gov/pubmed/36461068
http://dx.doi.org/10.1186/s13020-022-00688-3
_version_ 1784842861356777472
author Di, Sha
Yao, Chensi
Qiao, Liping
Li, Xiuyang
Pang, Bing
Lin, Jiaran
Wang, Jia
Li, Min
Tong, Xiaolin
author_facet Di, Sha
Yao, Chensi
Qiao, Liping
Li, Xiuyang
Pang, Bing
Lin, Jiaran
Wang, Jia
Li, Min
Tong, Xiaolin
author_sort Di, Sha
collection PubMed
description BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Luo Tong formula (LTF), a classical traditional Chinese medicine (TCM) prescription, consists of four plants that have been widely and effectively used to treat DR. Previous work in our laboratory has confirmed that LTF can effectively ameliorate DR. However, the potential mechanism underlying the therapeutic effect of LTF on DR has not been fully elucidated. To explore the potential mechanism of action through which LTF prevents and alleviates DR from an inflammation and gut microbiota perspective. MATERIALS AND METHODS: Metabolite profiling of LTF was performed using liquid chromatography–mass spectrometry (LC–MS) and gas chromatography–mass spectrometry (GC–MS). Type 1 diabetes was induced in male Sprague Dawley (SD) rats via tail vein injection of 45 mg/kg streptozotocin. Next, 100 SD rats were randomly divided into four groups, normal control; diabetic control; diabetic + insulin + calcium dobesilate; and diabetic + insulin + LTF. After 12 weeks of treatment, glucose metabolism, fundus oculi, blood-retinal barrier permeability, retinal thickness, microvascular damage, as well as cell junction expression in retinas were measured and the changes observed in different groups were compared. Finally, the alteration in gut microbiota and inflammatory cytokine expression in serum and tissues were monitored, and their correlation was analyzed. RESULTS: A total of 1024 valid peaks were obtained for LTF using GC–MS. The HbA1c and fasting blood glucose (FBG) levels in the LTF group were slightly decreased. LTF exerted protective effects on fundus oculi and the retina structure to different degrees. LTF attenuated systemic and local retinal inflammation by significantly decreasing the levels of seven pro-inflammatory cytokines, including ICAM-1, IL-6, IL-8, MCP-1, VCAM-1, VEGF, and IL-1β. LTF restored the intestinal microbiota of diabetic rats to levels that were similar to those of normal rats. Further analysis revealed that Enterobacteriales, Prevotellaceae, Enterobacteriaceae, Bacteroides, and Klebsiella were significantly and positively correlated with the inflammatory factors in DR after LTF treatment. CONCLUSIONS: Our results revealed the mechanisms underlying the preventive effects of LTF on DR development and progression. LTF inhibited pathological changes in retinal histopathology, cell composition, and cell junction proteins while effectively ameliorating systemic and local retinal inflammation via regulating pivotal gut microbiota.
format Online
Article
Text
id pubmed-9717245
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-97172452022-12-03 Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis Di, Sha Yao, Chensi Qiao, Liping Li, Xiuyang Pang, Bing Lin, Jiaran Wang, Jia Li, Min Tong, Xiaolin Chin Med Research BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Luo Tong formula (LTF), a classical traditional Chinese medicine (TCM) prescription, consists of four plants that have been widely and effectively used to treat DR. Previous work in our laboratory has confirmed that LTF can effectively ameliorate DR. However, the potential mechanism underlying the therapeutic effect of LTF on DR has not been fully elucidated. To explore the potential mechanism of action through which LTF prevents and alleviates DR from an inflammation and gut microbiota perspective. MATERIALS AND METHODS: Metabolite profiling of LTF was performed using liquid chromatography–mass spectrometry (LC–MS) and gas chromatography–mass spectrometry (GC–MS). Type 1 diabetes was induced in male Sprague Dawley (SD) rats via tail vein injection of 45 mg/kg streptozotocin. Next, 100 SD rats were randomly divided into four groups, normal control; diabetic control; diabetic + insulin + calcium dobesilate; and diabetic + insulin + LTF. After 12 weeks of treatment, glucose metabolism, fundus oculi, blood-retinal barrier permeability, retinal thickness, microvascular damage, as well as cell junction expression in retinas were measured and the changes observed in different groups were compared. Finally, the alteration in gut microbiota and inflammatory cytokine expression in serum and tissues were monitored, and their correlation was analyzed. RESULTS: A total of 1024 valid peaks were obtained for LTF using GC–MS. The HbA1c and fasting blood glucose (FBG) levels in the LTF group were slightly decreased. LTF exerted protective effects on fundus oculi and the retina structure to different degrees. LTF attenuated systemic and local retinal inflammation by significantly decreasing the levels of seven pro-inflammatory cytokines, including ICAM-1, IL-6, IL-8, MCP-1, VCAM-1, VEGF, and IL-1β. LTF restored the intestinal microbiota of diabetic rats to levels that were similar to those of normal rats. Further analysis revealed that Enterobacteriales, Prevotellaceae, Enterobacteriaceae, Bacteroides, and Klebsiella were significantly and positively correlated with the inflammatory factors in DR after LTF treatment. CONCLUSIONS: Our results revealed the mechanisms underlying the preventive effects of LTF on DR development and progression. LTF inhibited pathological changes in retinal histopathology, cell composition, and cell junction proteins while effectively ameliorating systemic and local retinal inflammation via regulating pivotal gut microbiota. BioMed Central 2022-12-02 /pmc/articles/PMC9717245/ /pubmed/36461068 http://dx.doi.org/10.1186/s13020-022-00688-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Di, Sha
Yao, Chensi
Qiao, Liping
Li, Xiuyang
Pang, Bing
Lin, Jiaran
Wang, Jia
Li, Min
Tong, Xiaolin
Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis
title Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis
title_full Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis
title_fullStr Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis
title_full_unstemmed Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis
title_short Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis
title_sort exploration of the mechanisms underlying the beneficial effect of luo tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9717245/
https://www.ncbi.nlm.nih.gov/pubmed/36461068
http://dx.doi.org/10.1186/s13020-022-00688-3
work_keys_str_mv AT disha explorationofthemechanismsunderlyingthebeneficialeffectofluotongformulaonretinalfunctionindiabeticratsviathegutmicrobiotainflammationretinaaxis
AT yaochensi explorationofthemechanismsunderlyingthebeneficialeffectofluotongformulaonretinalfunctionindiabeticratsviathegutmicrobiotainflammationretinaaxis
AT qiaoliping explorationofthemechanismsunderlyingthebeneficialeffectofluotongformulaonretinalfunctionindiabeticratsviathegutmicrobiotainflammationretinaaxis
AT lixiuyang explorationofthemechanismsunderlyingthebeneficialeffectofluotongformulaonretinalfunctionindiabeticratsviathegutmicrobiotainflammationretinaaxis
AT pangbing explorationofthemechanismsunderlyingthebeneficialeffectofluotongformulaonretinalfunctionindiabeticratsviathegutmicrobiotainflammationretinaaxis
AT linjiaran explorationofthemechanismsunderlyingthebeneficialeffectofluotongformulaonretinalfunctionindiabeticratsviathegutmicrobiotainflammationretinaaxis
AT wangjia explorationofthemechanismsunderlyingthebeneficialeffectofluotongformulaonretinalfunctionindiabeticratsviathegutmicrobiotainflammationretinaaxis
AT limin explorationofthemechanismsunderlyingthebeneficialeffectofluotongformulaonretinalfunctionindiabeticratsviathegutmicrobiotainflammationretinaaxis
AT tongxiaolin explorationofthemechanismsunderlyingthebeneficialeffectofluotongformulaonretinalfunctionindiabeticratsviathegutmicrobiotainflammationretinaaxis