# Acute sleep deprivation-induced hepatotoxicity and dyslipidemia in middle-aged female rats and its amelioration by butanol extract of Tinospora cordifolia

## TL;DR

This study shows that sleep deprivation harms liver function and lipid metabolism in middle-aged female rats, but these effects can be reduced by a plant extract from Tinospora cordifolia.

## Contribution

The study introduces the use of butanol extract of Tinospora cordifolia to mitigate sleep deprivation-induced liver damage and dyslipidemia in middle-aged female rats.

## Key findings

- Sleep deprivation increased oxidative stress and disrupted liver function in middle-aged female rats.
- Butanol extract of Tinospora cordifolia reduced oxidative stress and improved liver and lipid metabolism.
- B-TCE may work by targeting AMPK and p-Akt/cyclinD1/p-bad pathways to protect the liver.

## Abstract

Sleep deprivation (SD) due to an unhealthy lifestyle poses an oxidative challenge and is closely associated with an increased risk and prevalence of different metabolic disorders. Although the negative consequences of SD are well reported on mental health little is known about its detrimental effects on liver function and lipid metabolism. Tinospora cordifolia is reported for its hepatoprotective activity in different pre-clinical model systems. The current study was designed to elucidate the cumulative effects of aging and acute SD on liver functions, oxidative stress, and lipid metabolism, and their management by butanol extract of T. cordifolia (B-TCE) using middle-aged female acyclic rats as the model system.

Rats were divided into 4 groups: (1) Vehicle-undisturbed (VUD) (2) Vehicle-sleep deprived (VSD) (3) B-TCE pre-treated sleep-deprived (TSD) (4) B-TCE pre-treated undisturbed sleep (TUD). TSD and TUD groups were given 35 mg/kg of B-TCE once daily for 15 days followed by 12 h of sleep deprivation (6 a.m.–6 p.m.) of VSD and TSD group animals using the gentle-handling method while VUD and TUD group animals were left undisturbed. SD of VSD group animals increased oxidative stress, liver function disruption, and dyslipidemia which were ameliorated by B-TCE pre-treatment. Further, B-TCE was observed to target AMPK and its downstream lipid metabolism pathways as well as the p-Akt/cyclinD1/p-bad pathway of cell survival as possible underlying mechanisms of its hepatoprotective activity.

These findings suggest that B-TCE being a multi-component extract may be a potential agent in curtailing sleep-related problems and preventing SD-associated hepatotoxicity and dyslipidemia in postmenopausal women.

Graphical abstract to depict mechanism of action of B-TCE on liver function and lipid metabolism.