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Planta Med 2023; 89(09): 916-934
DOI: 10.1055/a-2053-0950
Pharmacokinetic Investigations
Original Papers

Metabolic Alterations in Streptozotocin–nicotinamide-induced Diabetic Rats Treated with Muntingia calabura Extract via 1H-NMR-based Metabolomics

Nur Khaleeda Zulaikha Zolkeflee
1   Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Pei Lou Wong
2   Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
M. Maulidiani
3   Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus, Terengganu, Malaysia
,
Nurul Shazini Ramli
2   Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Azrina Azlan
4   Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Faridah Abas 
1   Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
2   Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
› Author AffiliationsSupported by: Universiti Putra Malaysia UPM/700/2/1/GPB/2017/9597400
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Abstract

Diabetes mellitus (DM) is a metabolic endocrine disorder caused by decreased insulin concentration or poor insulin response. Muntingia calabura (MC) has been used traditionally to reduce blood glucose levels. This study aims to support the traditional claim of MC as a functional food and blood-glucose-lowering regimen. The antidiabetic potential of MC is tested on a streptozotocin–nicotinamide (STZ-NA)-induced diabetic rat model by using the 1H-NMR-based metabolomic approach. Serum biochemical analyses reveal that treatment with 250 mg/kg body weight (bw) standardized freeze-dried (FD) 50% ethanolic MC extract (MCE 250) shows favorable serum creatinine (37.77 ± 3.53 µM), urea (5.98 ± 0.84 mM) and glucose (7.36 ± 0.57 mM) lowering capacity, which was comparable to the standard drug, metformin. The clear separation between diabetic control (DC) and normal group in principal component analysis indicates the successful induction of diabetes in the STZ-NA-induced type 2 diabetic rat model. A total of nine biomarkers, including allantoin, glucose, methylnicotinamide, lactate, hippurate, creatine, dimethylamine, citrate and pyruvate are identified in ratsʼ urinary profile, discriminating DC and normal groups through orthogonal partial least squares-discriminant analysis. Induction of diabetes by STZ-NA is due to alteration in the tricarboxylic acid (TCA) cycle, gluconeogenesis pathway, pyruvate metabolism and nicotinate and nicotinamide metabolism. Oral treatment with MCE 250 in STZ-NA-induced diabetic rats shows improvement in the altered carbohydrate metabolism, cofactor and vitamin metabolic pathway, as well as purine and homocysteine metabolism.

Key words

Muntingia calabura - Muntingiaceae - STZ-NA-induced diabetic rats - 1H-NMR-based metabolomics - carbohydrate metabolism - cofactors and vitamins metabolism - urine metabolites

Supporting Information

    Chromatographic separation details; tables of variable importance of projection (VIP) value and coefficient value of the significant metabolites in the OPLS-DA of week 0 and 4; representative of 500 MHz 1H-NMR urinary spectra; external validation method with 100-permutations test and CV scores plot generated from OPLS-DA model of week 0 and week 4 and summary of impacted metabolic pathway by MetaboAnalyst are available as Supporting Information.

  • Supporting Information


Publication History

Received: 03 July 2022

Accepted after revision: 12 March 2023

Accepted Manuscript online:
13 March 2023

Article published online:
15 May 2023

© 2023. Thieme. All rights reserved.

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