# Therapeutic Potential of Holothuria leucospilota Extract in STZ‐Induced Diabetic Rats: Targeting Inflammation and Apoptosis at the Gene Expression Level

## TL;DR

A sea cucumber extract reduced diabetes-related inflammation and improved blood sugar in rats, suggesting potential as a natural treatment.

## Contribution

The study identifies bioactive compounds in Holothuria leucospilota extract that modulate inflammation and apoptosis in diabetic rats.

## Key findings

- H. leucospilota extract reduced glucose, amyloid beta, and inflammatory markers in diabetic rats.
- The extract upregulated anti-inflammatory genes like IL-10 and miR-146a while downregulating pro-inflammatory genes.
- GC–MS analysis identified key compounds like olean-12-ene-3,28-diol and oleic acid in the extract.

## Abstract

Chronic inflammation is a key contributor to diabetes pathogenesis. Marine‐derived bioactive compounds offer a promising source of therapeutic agents. This study investigated the effects of
Holothuria leucospilota
n‐hexane extract on biochemical and inflammatory markers in diabetic male rats.

Male Wistar rats were divided into four groups: control, diabetic, and diabetic treated with
H. leucospilota
extract (100 or 200 mg/kg). Diabetes was induced by streptozotocin. Animals received daily intraperitoneal injections of saline or extract. One‐third of the animals in each group (n = 8) were euthanised and sampled on days 1, 15, and 30. The extract composition was analysed by GC–MS. Serum glucose, insulin, amyloid beta, and expression of TGF‐β, TNF‐α, FasL, IL‐10, and miR‐146a were measured in blood, while leptin gene expression was assessed in liver samples.

GC–MS revealed major compounds including olean‐12‐ene‐3,28‐diol (14.1%), cyclohexane derivatives (8.2%), oleic acid (4.8%), and cis‐13‐eicosenoic acid (4.2%). Diabetic rats showed elevated glucose, amyloid beta, leptin, TGF‐β, TNF‐α, and FasL levels, with reduced insulin, IL‐10, and miR‐146a levels compared to the control group. Treatment with
H. leucospilota
extract (100 and 200 mg/kg) significantly reversed these changes at both 15 and 30 days compared to the diabetic group.

H. leucospilota
n‐hexane extract improved biochemical and inflammatory markers in diabetic rats, suggesting its potential as a natural therapeutic agent to mitigate diabetes‐associated inflammation and metabolic dysfunction. The identified bioactive compounds may underlie these beneficial effects, highlighting the therapeutic relevance of marine‐derived extracts in diabetes management.

Holothuria leucospilota
n‐hexane extract shows antidiabetic, anti‐inflammatory, and anti‐apoptotic effects in STZ‐induced diabetic rats. The extract modulates key pathways in glucose metabolism, insulin secretion, inflammation, and apoptosis. Treatment significantly decreased glucose and amyloid beta levels, increased insulin, and improved glycemic control and protection against amyloid toxicity. Expression of leptin, TGF‐β, TNF‐α, and FasL was downregulated, while IL‐10 and miR‐146a were upregulated, indicating reduced inflammation and enhanced anti‐inflammatory responses. These results support the potential of sea cucumber compounds as adjunct diabetes therapies; further clinical and toxicity studies are needed.