Seagrass Enhalus acoroides extract mitigates obesity and diabetes via GLP-1, PPARγ, SREBP-1c modulation and gut microbiome restoration in diabetic zebrafish

Abstract Background The global rise in obesity and type 2 diabetes highlights the need for safe and effective therapeutic interventions. Enhalus acoroides is a tropical seagrass rich in carotenoids and other bioactives. Its potential for metabolic regulation has been suggested in vitro, but in vivo...

Full description

Saved in:
Bibliographic Details
Main Authors: Marcello Mikhael Kadharusman, Rony Abdi Syahputra, Rudy Kurniawan, Edwin Hadinata, Raymond Rubianto Tjandrawinata, Nurpudji Astuti Taslim, Raffaele Romano, Antonello Santini, Fahrul Nurkolis
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Diabetology & Metabolic Syndrome
Subjects:
Online Access:https://doi.org/10.1186/s13098-025-01823-4
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850111810045214720
author Marcello Mikhael Kadharusman
Rony Abdi Syahputra
Rudy Kurniawan
Edwin Hadinata
Raymond Rubianto Tjandrawinata
Nurpudji Astuti Taslim
Raffaele Romano
Antonello Santini
Fahrul Nurkolis
author_facet Marcello Mikhael Kadharusman
Rony Abdi Syahputra
Rudy Kurniawan
Edwin Hadinata
Raymond Rubianto Tjandrawinata
Nurpudji Astuti Taslim
Raffaele Romano
Antonello Santini
Fahrul Nurkolis
author_sort Marcello Mikhael Kadharusman
collection DOAJ
description Abstract Background The global rise in obesity and type 2 diabetes highlights the need for safe and effective therapeutic interventions. Enhalus acoroides is a tropical seagrass rich in carotenoids and other bioactives. Its potential for metabolic regulation has been suggested in vitro, but in vivo efficacy and molecular mechanisms remain unexplored. This study aimed to evaluate the anti-obesity and anti-diabetic effects of Enhalus acoroides extract (SEAE) in a zebrafish model of diet- and glucose-induced metabolic dysfunction. Methods Adult zebrafish were subjected to overfeeding and glucose immersion, after overfeeding and 14 days of glucose immersion to induce diabetes, adult zebrafish were randomized into three groups: untreated diabetic, SEAE-treated (5 mg/L), and metformin-treated (3.3 mg/L) for 20 days. Body weight, fasting blood glucose, lipid profile, gene expression (GLP-1, PPARγ, SREBP-1c), and gut microbiota profiles via 16 S rRNA sequencing were assessed. Results SEAE significantly reduced body weight and blood glucose in diabetic zebrafish (p < 0.05), with efficacy comparable to or exceeding Metformin. It upregulated GLP-1 and downregulated PPARγ and SREBP-1c. SEAE also reduced total cholesterol, triglycerides, and LDL levels, while increasing HDL levels. Moreover, SEAE restored the Firmicutes/Bacteroidetes ratio, increased alpha diversity, and shifted beta diversity toward healthy controls. SEAE-treated fish showed microbial profiles closer to normal than those treated with Metformin. Conclusions SEAE exhibits strong anti-obesity and anti-hyperglycemic effects by modulating key metabolic pathways and restoring gut microbial homeostasis. These findings highlight SEAE as a promising marine-derived therapeutic candidate for metabolic syndrome and warrant further investigation as a functional food or nutraceutical. Clinical trial Not applicable.
format Article
id doaj-art-b6b5d293d6ca488a8fc2f8b417d66f83
institution OA Journals
issn 1758-5996
language English
publishDate 2025-06-01
publisher BMC
record_format Article
series Diabetology & Metabolic Syndrome
spelling doaj-art-b6b5d293d6ca488a8fc2f8b417d66f832025-08-20T02:37:33ZengBMCDiabetology & Metabolic Syndrome1758-59962025-06-0117111210.1186/s13098-025-01823-4Seagrass Enhalus acoroides extract mitigates obesity and diabetes via GLP-1, PPARγ, SREBP-1c modulation and gut microbiome restoration in diabetic zebrafishMarcello Mikhael Kadharusman0Rony Abdi Syahputra1Rudy Kurniawan2Edwin Hadinata3Raymond Rubianto Tjandrawinata4Nurpudji Astuti Taslim5Raffaele Romano6Antonello Santini7Fahrul Nurkolis8Faculty of Medicine, Universitas IndonesiaDepartment of Pharmacology, Faculty of Pharmacy, Universitas Sumatera UtaraGraduate School of Medicine, Faculty of Medicine, Hasanuddin UniversityFaculty of Medicine, Ciputra University of SurabayaCenter for Pharmaceutical and Nutraceutical Research and Policy, Faculty of Biotechnology, Atma Jaya Catholic University of IndonesiaDivision of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin UniversityDepartment of Agricultural Sciences, University of Naples Federico IIDepartment of Pharmacy, University of Napoli Federico IIState Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga)Abstract Background The global rise in obesity and type 2 diabetes highlights the need for safe and effective therapeutic interventions. Enhalus acoroides is a tropical seagrass rich in carotenoids and other bioactives. Its potential for metabolic regulation has been suggested in vitro, but in vivo efficacy and molecular mechanisms remain unexplored. This study aimed to evaluate the anti-obesity and anti-diabetic effects of Enhalus acoroides extract (SEAE) in a zebrafish model of diet- and glucose-induced metabolic dysfunction. Methods Adult zebrafish were subjected to overfeeding and glucose immersion, after overfeeding and 14 days of glucose immersion to induce diabetes, adult zebrafish were randomized into three groups: untreated diabetic, SEAE-treated (5 mg/L), and metformin-treated (3.3 mg/L) for 20 days. Body weight, fasting blood glucose, lipid profile, gene expression (GLP-1, PPARγ, SREBP-1c), and gut microbiota profiles via 16 S rRNA sequencing were assessed. Results SEAE significantly reduced body weight and blood glucose in diabetic zebrafish (p < 0.05), with efficacy comparable to or exceeding Metformin. It upregulated GLP-1 and downregulated PPARγ and SREBP-1c. SEAE also reduced total cholesterol, triglycerides, and LDL levels, while increasing HDL levels. Moreover, SEAE restored the Firmicutes/Bacteroidetes ratio, increased alpha diversity, and shifted beta diversity toward healthy controls. SEAE-treated fish showed microbial profiles closer to normal than those treated with Metformin. Conclusions SEAE exhibits strong anti-obesity and anti-hyperglycemic effects by modulating key metabolic pathways and restoring gut microbial homeostasis. These findings highlight SEAE as a promising marine-derived therapeutic candidate for metabolic syndrome and warrant further investigation as a functional food or nutraceutical. Clinical trial Not applicable.https://doi.org/10.1186/s13098-025-01823-4Metabolic syndromeFunctional foodSeagrassGut microbiomeIn vivoMarine product
spellingShingle Marcello Mikhael Kadharusman
Rony Abdi Syahputra
Rudy Kurniawan
Edwin Hadinata
Raymond Rubianto Tjandrawinata
Nurpudji Astuti Taslim
Raffaele Romano
Antonello Santini
Fahrul Nurkolis
Seagrass Enhalus acoroides extract mitigates obesity and diabetes via GLP-1, PPARγ, SREBP-1c modulation and gut microbiome restoration in diabetic zebrafish
Diabetology & Metabolic Syndrome
Metabolic syndrome
Functional food
Seagrass
Gut microbiome
In vivo
Marine product
title Seagrass Enhalus acoroides extract mitigates obesity and diabetes via GLP-1, PPARγ, SREBP-1c modulation and gut microbiome restoration in diabetic zebrafish
title_full Seagrass Enhalus acoroides extract mitigates obesity and diabetes via GLP-1, PPARγ, SREBP-1c modulation and gut microbiome restoration in diabetic zebrafish
title_fullStr Seagrass Enhalus acoroides extract mitigates obesity and diabetes via GLP-1, PPARγ, SREBP-1c modulation and gut microbiome restoration in diabetic zebrafish
title_full_unstemmed Seagrass Enhalus acoroides extract mitigates obesity and diabetes via GLP-1, PPARγ, SREBP-1c modulation and gut microbiome restoration in diabetic zebrafish
title_short Seagrass Enhalus acoroides extract mitigates obesity and diabetes via GLP-1, PPARγ, SREBP-1c modulation and gut microbiome restoration in diabetic zebrafish
title_sort seagrass enhalus acoroides extract mitigates obesity and diabetes via glp 1 pparγ srebp 1c modulation and gut microbiome restoration in diabetic zebrafish
topic Metabolic syndrome
Functional food
Seagrass
Gut microbiome
In vivo
Marine product
url https://doi.org/10.1186/s13098-025-01823-4
work_keys_str_mv AT marcellomikhaelkadharusman seagrassenhalusacoroidesextractmitigatesobesityanddiabetesviaglp1ppargsrebp1cmodulationandgutmicrobiomerestorationindiabeticzebrafish
AT ronyabdisyahputra seagrassenhalusacoroidesextractmitigatesobesityanddiabetesviaglp1ppargsrebp1cmodulationandgutmicrobiomerestorationindiabeticzebrafish
AT rudykurniawan seagrassenhalusacoroidesextractmitigatesobesityanddiabetesviaglp1ppargsrebp1cmodulationandgutmicrobiomerestorationindiabeticzebrafish
AT edwinhadinata seagrassenhalusacoroidesextractmitigatesobesityanddiabetesviaglp1ppargsrebp1cmodulationandgutmicrobiomerestorationindiabeticzebrafish
AT raymondrubiantotjandrawinata seagrassenhalusacoroidesextractmitigatesobesityanddiabetesviaglp1ppargsrebp1cmodulationandgutmicrobiomerestorationindiabeticzebrafish
AT nurpudjiastutitaslim seagrassenhalusacoroidesextractmitigatesobesityanddiabetesviaglp1ppargsrebp1cmodulationandgutmicrobiomerestorationindiabeticzebrafish
AT raffaeleromano seagrassenhalusacoroidesextractmitigatesobesityanddiabetesviaglp1ppargsrebp1cmodulationandgutmicrobiomerestorationindiabeticzebrafish
AT antonellosantini seagrassenhalusacoroidesextractmitigatesobesityanddiabetesviaglp1ppargsrebp1cmodulationandgutmicrobiomerestorationindiabeticzebrafish
AT fahrulnurkolis seagrassenhalusacoroidesextractmitigatesobesityanddiabetesviaglp1ppargsrebp1cmodulationandgutmicrobiomerestorationindiabeticzebrafish