K Siwi, A Tejosukmono, N Anggorowati, N Arfian, J Yunus
{"title":"Chlorogenic acid ameliorates muscle wasting by upregulating mRNA expressions of calcineurin and PGC-1α in diabetic rat model.","authors":"K Siwi, A Tejosukmono, N Anggorowati, N Arfian, J Yunus","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Muscle health in diabetes mellitus (DM) is often neglected, which leads to muscle wasting. Increased reactive oxygen species in DM could decrease antioxidant enzymes such as superoxide dismutase-1 (SOD-1) and -2 (SOD-2) and inhibit calcineurin (CN) and PGC-1α signalling pathways. Chlorogenic acid (CGA) is known as a potent antioxidant and activators of CN and PGC-1α. This study aimed to determine the effect of CGA on mRNA expressions of SOD-1, SOD-2, CN and PGC-1α in inhibiting the progression of DM to muscle wasting.</p><p><strong>Materials and methods: </strong>This study was conducted at Department of Anatomy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada starting on July 20th, 2020. A total of 24 male Wistar rats were randomly divided into six groups (four rats per group), i.e., control, DM 1.5 months (DM1.5), and DM 2 months (DM2); and DM groups treated with CGA in three different doses, namely CGA1 (12.5 mg/kg BW), CGA2 (25 mg/kg BW), and CGA3 (50 mg/kg BW). Control group was only injected with normal saline, while diabetic model was induced by intraperitoneal injection of streptozotocin. Blood glucose levels were measured twice (one week after diabetic induction and before termination). The soleus muscle tissue was harvested to analyse the mRNA expressions of SOD-1, SOD- 2, CN and PGC-1α using RT-PCR. In addition, the tissue samples were stained with immunohistochemistry for CN and haematoxylin-eosin (HE) for morphologic analysis under light microscopy.</p><p><strong>Results: </strong>The mRNA expressions of SOD-1 and SOD-2 in the CGA1 group were relatively higher compared to the DM2 groups. The mRNA expression of CN in the CGA1 group was significantly higher compared to the DM2 group (p = 0.008). The mRNA expression of PGC-1α in the CGA1 group was significantly higher compared to the DM2 group (p = 0.025). Immunohistochemical staining showed that CNimmunopositive expression in the CGA1 group was more evident compared to the other groups. Haematoxylin-eosin staining showed that muscle tissue morphology in the CGA1 group was similar to that in the control group.</p><p><strong>Conclusion: </strong>Chlorogenic acid at a dose of 12.5 mg/kg BW shows lower blood glucose level, good skeletal muscle tissue morphology and higher mRNA expressions of SOD-1, SOD-2, CN and PGC-1α compared to the DM groups.</p>","PeriodicalId":39388,"journal":{"name":"Medical Journal of Malaysia","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Journal of Malaysia","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Muscle health in diabetes mellitus (DM) is often neglected, which leads to muscle wasting. Increased reactive oxygen species in DM could decrease antioxidant enzymes such as superoxide dismutase-1 (SOD-1) and -2 (SOD-2) and inhibit calcineurin (CN) and PGC-1α signalling pathways. Chlorogenic acid (CGA) is known as a potent antioxidant and activators of CN and PGC-1α. This study aimed to determine the effect of CGA on mRNA expressions of SOD-1, SOD-2, CN and PGC-1α in inhibiting the progression of DM to muscle wasting.
Materials and methods: This study was conducted at Department of Anatomy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada starting on July 20th, 2020. A total of 24 male Wistar rats were randomly divided into six groups (four rats per group), i.e., control, DM 1.5 months (DM1.5), and DM 2 months (DM2); and DM groups treated with CGA in three different doses, namely CGA1 (12.5 mg/kg BW), CGA2 (25 mg/kg BW), and CGA3 (50 mg/kg BW). Control group was only injected with normal saline, while diabetic model was induced by intraperitoneal injection of streptozotocin. Blood glucose levels were measured twice (one week after diabetic induction and before termination). The soleus muscle tissue was harvested to analyse the mRNA expressions of SOD-1, SOD- 2, CN and PGC-1α using RT-PCR. In addition, the tissue samples were stained with immunohistochemistry for CN and haematoxylin-eosin (HE) for morphologic analysis under light microscopy.
Results: The mRNA expressions of SOD-1 and SOD-2 in the CGA1 group were relatively higher compared to the DM2 groups. The mRNA expression of CN in the CGA1 group was significantly higher compared to the DM2 group (p = 0.008). The mRNA expression of PGC-1α in the CGA1 group was significantly higher compared to the DM2 group (p = 0.025). Immunohistochemical staining showed that CNimmunopositive expression in the CGA1 group was more evident compared to the other groups. Haematoxylin-eosin staining showed that muscle tissue morphology in the CGA1 group was similar to that in the control group.
Conclusion: Chlorogenic acid at a dose of 12.5 mg/kg BW shows lower blood glucose level, good skeletal muscle tissue morphology and higher mRNA expressions of SOD-1, SOD-2, CN and PGC-1α compared to the DM groups.
期刊介绍：
Published since 1890 this journal originated as the Journal of the Straits Medical Association. With the formation of the Malaysian Medical Association (MMA), the Journal became the official organ, supervised by an editorial board. Some of the early Hon. Editors were Mr. H.M. McGladdery (1960 - 1964), Dr. A.A. Sandosham (1965 - 1977), Prof. Paul C.Y. Chen (1977 - 1987). It is a scientific journal, published quarterly and can be found in medical libraries in many parts of the world. The Journal also enjoys the status of being listed in the Index Medicus, the internationally accepted reference index of medical journals. The editorial columns often reflect the Association''s views and attitudes towards medical problems in the country. The MJM aims to be a peer reviewed scientific journal of the highest quality. We want to ensure that whatever data is published is true and any opinion expressed important to medical science. We believe being Malaysian is our unique niche; our priority will be for scientific knowledge about diseases found in Malaysia and for the practice of medicine in Malaysia. The MJM will archive knowledge about the changing pattern of human diseases and our endeavours to overcome them. It will also document how medicine develops as a profession in the nation. We will communicate and co-operate with other scientific journals in Malaysia. We seek articles that are of educational value to doctors. We will consider all unsolicited articles submitted to the journal and will commission distinguished Malaysians to write relevant review articles. We want to help doctors make better decisions and be good at judging the value of scientific data. We want to help doctors write better, to be articulate and precise.
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