Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics
Ethnopharmacological relevance: Ardisia elliptica Thunb. (AE) (Primulaceae) is a medicinal plant found in the Malay Peninsula and has been traditionally used to treat diabetes. However, limited studies to date in providing scientific evidence to support the antidiabetic efficacy of this plant by in-...
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| Format: | Article |
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Elsevier
2024
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| _version_ | 1811137683196477440 |
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| author | Wong, Pei Lou Zolkeflee, Nur Khaleeda Zulaikha Ramli, Nurul Shazini Tan, Chin Ping Azlan, Azrina Tham, Chau Ling Shaari, Khozirah Abas, Faridah |
| author_facet | Wong, Pei Lou Zolkeflee, Nur Khaleeda Zulaikha Ramli, Nurul Shazini Tan, Chin Ping Azlan, Azrina Tham, Chau Ling Shaari, Khozirah Abas, Faridah |
| author_sort | Wong, Pei Lou |
| collection | UPM |
| description | Ethnopharmacological relevance: Ardisia elliptica Thunb. (AE) (Primulaceae) is a medicinal plant found in the Malay Peninsula and has been traditionally used to treat diabetes. However, limited studies to date in providing scientific evidence to support the antidiabetic efficacy of this plant by in-vitro and in-vivo models. Aim of the study: To investigate the anti-hyperglycemic potential of AE through in-vitro enzymatic activities and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat models using proton-nuclear magnetic resonance (1H-NMR)-based metabolomics approach. Materials and methods: Anti-α-amylase and anti-α-glucosidase activities of the hydroethanolic extracts of AE were evaluated. The absolute quantification of bioactive constituents, using ultra-high performance liquid chromatography (UHPLC) was performed for the most active extract. Three different dosage levels of the AE extract were orally administered for 4 weeks consecutively in STZ-NA induced diabetic rats. Physical assessments, biochemical analysis, and an untargeted 1H-NMR-based metabolomics analysis of the urine and serum were carried out on the animal model. Results: Type 2 diabetes mellitus (T2DM) rat model was successfully developed based on the clear separation observed between the STZ-NA induced diabetic and normal non-diabetic groups. Discriminating biomarkers included glucose, citrate, succinate, allantoin, hippurate, 2-oxoglutarate, and 3-hydroxybutyrate, as determined through an orthogonal partial least squares-discriminant analysis (OPLS-DA) model. A treatment dosage of 250 mg/kg body weight (BW) of standardized 70 ethanolic AE extract mitigated increase in serum glucose, creatinine, and urea levels, providing treatment levels comparable to that obtained using metformin, with flavonoids primarily contribute to the anti-hyperglycemic activities. Urinary metabolomics disclosed that the following disturbed metabolism pathways: the citrate cycle (TCA cycle), butanoate metabolism, glycolysis and gluconeogenesis, pyruvate metabolism, and synthesis and degradation of ketone bodies, were ameliorated after treatment with the standardized AE extract. Conclusions: This study demonstrated the first attempt at revealing the therapeutic effect of oral treatment with 250 mg/kg BW of standardized AE extract on chemically induced T2DM rats. The present study provides scientific evidence supporting the ethnomedicinal use of Ardisia elliptica and further advances the understanding of the fundamental molecular mechanisms affected by this herbal antidote. |
| first_indexed | 2024-09-25T03:38:11Z |
| format | Article |
| id | upm.eprints-105733 |
| institution | Universiti Putra Malaysia |
| last_indexed | 2024-09-25T03:38:11Z |
| publishDate | 2024 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | upm.eprints-1057332024-05-30T07:23:36Z http://psasir.upm.edu.my/id/eprint/105733/ Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics Wong, Pei Lou Zolkeflee, Nur Khaleeda Zulaikha Ramli, Nurul Shazini Tan, Chin Ping Azlan, Azrina Tham, Chau Ling Shaari, Khozirah Abas, Faridah Ethnopharmacological relevance: Ardisia elliptica Thunb. (AE) (Primulaceae) is a medicinal plant found in the Malay Peninsula and has been traditionally used to treat diabetes. However, limited studies to date in providing scientific evidence to support the antidiabetic efficacy of this plant by in-vitro and in-vivo models. Aim of the study: To investigate the anti-hyperglycemic potential of AE through in-vitro enzymatic activities and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat models using proton-nuclear magnetic resonance (1H-NMR)-based metabolomics approach. Materials and methods: Anti-α-amylase and anti-α-glucosidase activities of the hydroethanolic extracts of AE were evaluated. The absolute quantification of bioactive constituents, using ultra-high performance liquid chromatography (UHPLC) was performed for the most active extract. Three different dosage levels of the AE extract were orally administered for 4 weeks consecutively in STZ-NA induced diabetic rats. Physical assessments, biochemical analysis, and an untargeted 1H-NMR-based metabolomics analysis of the urine and serum were carried out on the animal model. Results: Type 2 diabetes mellitus (T2DM) rat model was successfully developed based on the clear separation observed between the STZ-NA induced diabetic and normal non-diabetic groups. Discriminating biomarkers included glucose, citrate, succinate, allantoin, hippurate, 2-oxoglutarate, and 3-hydroxybutyrate, as determined through an orthogonal partial least squares-discriminant analysis (OPLS-DA) model. A treatment dosage of 250 mg/kg body weight (BW) of standardized 70 ethanolic AE extract mitigated increase in serum glucose, creatinine, and urea levels, providing treatment levels comparable to that obtained using metformin, with flavonoids primarily contribute to the anti-hyperglycemic activities. Urinary metabolomics disclosed that the following disturbed metabolism pathways: the citrate cycle (TCA cycle), butanoate metabolism, glycolysis and gluconeogenesis, pyruvate metabolism, and synthesis and degradation of ketone bodies, were ameliorated after treatment with the standardized AE extract. Conclusions: This study demonstrated the first attempt at revealing the therapeutic effect of oral treatment with 250 mg/kg BW of standardized AE extract on chemically induced T2DM rats. The present study provides scientific evidence supporting the ethnomedicinal use of Ardisia elliptica and further advances the understanding of the fundamental molecular mechanisms affected by this herbal antidote. Elsevier 2024 Article PeerReviewed Wong, Pei Lou and Zolkeflee, Nur Khaleeda Zulaikha and Ramli, Nurul Shazini and Tan, Chin Ping and Azlan, Azrina and Tham, Chau Ling and Shaari, Khozirah and Abas, Faridah (2024) Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics. Journal of Ethnopharmacology, 318 (pt.B). art. no. 117015. pp. 1-13. ISSN 0378-8741; ESSN: 1872-7573 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85167566293&doi=10.1016%2fj.jep.2023.117015&partnerID=40&md5=47b01fd4acf64c14be3a2fc8600209eb 10.1016/j.jep.2023.117015 |
| spellingShingle | Wong, Pei Lou Zolkeflee, Nur Khaleeda Zulaikha Ramli, Nurul Shazini Tan, Chin Ping Azlan, Azrina Tham, Chau Ling Shaari, Khozirah Abas, Faridah Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics |
| title | Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics |
| title_full | Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics |
| title_fullStr | Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics |
| title_full_unstemmed | Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics |
| title_short | Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics |
| title_sort | antidiabetic effect of ardisia elliptica extract and its mechanisms of action in stz na induced diabetic rat model via 1h nmr based metabolomics |
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