Treatment with Pluchea indica (L.) Less. leaf ethanol extract alleviates liver injury in multiple low‑dose streptozotocin‑induced diabetic BALB/c mice

Nopparat,Jongdee; Nualla‑Ong,Aekkaraj; Phongdara,Amornrat

doi:10.3892/etm.2020.8877

Treatment with Pluchea indica (L.) Less. leaf ethanol extract alleviates liver injury in multiple low‑dose streptozotocin‑induced diabetic BALB/c mice

Authors:
- Jongdee Nopparat
- Aekkaraj Nualla‑Ong
- Amornrat Phongdara
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Affiliations: Department of Anatomy, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand, Center for Genomics and Bioinformatics Research, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
Published online on: June 11, 2020 https://doi.org/10.3892/etm.2020.8877
Pages: 1385-1396
Copyright: © Nopparat et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hyperglycemia-induced oxidative stress and inflammation are hallmarks of liver damage in diabetes mellitus. Accumulating evidence has demonstrated that Pluchea indica leaf ethanol extract (PILE) possesses strong antioxidant and anti‑inflammatory properties. However, studies of its effects on liver damage in streptozotocin (STZ)‑induced diabetic animals remain insufficient. To the best of our knowledge, the present study was the first to illustrate that PILE mitigated liver injury in STZ animals. Mice were first pretreated with PILE at either 50 mg/kg (PILE 50) or 100 mg/kg (PILE 100) 2 weeks prior to the induction of hyperglycemia by multiple low doses of STZ. The mice were then fed with PILE 50 or PILE 100 for 4 or 8 weeks, following which liver weight, pathological changes, oxidative stress parameters, inflammation‑related markers and caspase‑mediated apoptosis were measured at each time point. Untreated STZ mice exhibited abnormal increases in liver weight and severe pathological changes. However, PILE 100 reduced the severity of the STZ‑induced diabetic phenotype at both time points. A significant decrease in the levels of superoxide dismutase and catalase, in addition to an increase in malondialdehyde, were observed in the livers of untreated STZ mice, all of which were significantly reversed by treatment with PILE 100 for 8 weeks. Western blot analysis revealed reduced levels of liver inflammatory markers, including interleukin‑6, tumor necrosis factor‑α, NF‑κB p65, transforming growth factor‑β1 and protein kinase C following PILE 100 treatment. Additionally, changes in the levels of apoptotic markers indicated that PILE 100 significantly attenuated caspase‑9 and ‑3 expression, whilst preserving that of the Bcl‑2 protein. In conclusion, the present study revealed that PILE alleviates hyperglycemia‑induced liver injury by normalizing the various mediators of oxidative stress, inflammation and apoptosis.

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