# Evaluating the toxicity and efficacy of the endophytic bacterium Kosakonia sp. ZO-Rh4 on antidiabetes and associated complications in a mouse model

## TL;DR

This study shows that a non-toxic extract from a ginger-derived bacterium can lower blood sugar and reduce diabetes-related complications in mice.

## Contribution

The first in vivo evaluation of Kosakonia sp. ZO-Rh4 extract's safety and antidiabetic potential in a mouse model.

## Key findings

- KE extract was non-toxic in both acute and sub-chronic toxicity tests in mice.
- KE reduced blood glucose, improved lipid profiles, and mitigated oxidative stress in diabetic mice.
- KE inhibited α-amylase and α-glucosidase enzymes, which are linked to glucose regulation.

## Abstract

The endophytic bacterium Kosakonia sp. ZO-Rh4, isolated from ginger, exhibited antioxidant properties in vitro. However, its safety and efficacy have never been assessed in vivo. This study examined the toxicity of the ethyl acetate extract from Kosakonia sp. ZO-Rh4 (KE) in mice and its potential to treat diabetes and its complications. Acute toxicity was investigated with a single KE dosage of 5000 mg/kg body weight (b.w.). Sub-chronic toxicity was studied with a daily dosage of 400 mg/kg b.w. for 45 and 90 days. After 14 days of acute toxicity and 45 or 90 days of daily dosing at 400 mg/kg body weight, all parameters were found to be within normal limits. In vitro antidiabetic tests indicated that KE has a strong inhibitory effect on the α-amylase and α-glucosidase enzymes. An in vivo study was conducted on diabetic mice induced with alloxan monohydrate, measuring the mice's body weight and blood glucose levels weekly. Following the experiment, mouse blood was collected to measure lipid parameters and liver function markers. The liver, kidneys, and pancreatic tissues were evaluated for oxidative stress by measuring malondialdehyde and glutathione levels. KE lowered blood glucose and enhanced body weight depending on the dosage. Furthermore, KE possesses anti-dyslipidemic properties, can restore liver function, and mitigates oxidative stress in all examined organs by decreasing malondialdehyde and increasing glutathione. The study confirmed the relative safety of KE and its effectiveness in treating diabetes and its complications, potentially representing a new option for functional foods and pharmaceuticals.

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•Kosakonia sp. ZO-Rh4 extract (KE) was obtained from the endophytic Kosakonia sp. ZO-Rh4.•KE was found to be non-toxic in both acute and sub-chronic studies in mice.•KE inhibited α-amylase and α-glucosidase, converting carbohydrates into glucose.•KE had hypoglycemic, antidyslipidemic, and cardiovascular risk-lowering properties.•KE reduced liver damage and oxidative stress in the liver, kidneys, and pancreas.

Kosakonia sp. ZO-Rh4 extract (KE) was obtained from the endophytic Kosakonia sp. ZO-Rh4.

KE was found to be non-toxic in both acute and sub-chronic studies in mice.

KE inhibited α-amylase and α-glucosidase, converting carbohydrates into glucose.

KE had hypoglycemic, antidyslipidemic, and cardiovascular risk-lowering properties.

KE reduced liver damage and oxidative stress in the liver, kidneys, and pancreas.