# The Constituents of Phyllanthus emblica Fruit Ameliorate Hyperlipidemia Through the Modulation of SREBPs, HMG‐CoA Reductase, and LDL Receptor Pathway

## TL;DR

Phyllanthus emblica fruit powder reduces high-fat diet-induced hyperlipidemia in rats by affecting key lipid metabolism genes.

## Contribution

The study shows PEF modulates SREBPs, HMG-CoA reductase, and LDL receptor pathways to ameliorate hyperlipidemia.

## Key findings

- PEF reduced oxidative stress and harmful plasma lipids in hyperlipidemic rats.
- PEF suppressed the expression of SREBP-1c, SREBP-2, and HMGCR while increasing LDLR expression.
- Bioactive compounds in PEF interact with proteins involved in lipid metabolism.

## Abstract

The current study investigated the effects of dietary supplementation with antioxidant‐rich Phyllanthus emblica fruit powder (PEF) in high‐fat diet (HFD)–induced hyperlipidemic Wistar rats. In silico pharmacokinetic activity prediction and molecular docking studies were performed for several bioactive compounds of the P. emblica fruit. Wistar rats were arranged into four groups and fed one of the following four diets: standard diet (Control), 2% (w/w) PEF‐supplemented standard diet (Control + PEF), HFD, and 2% (w/w) PEF‐supplemented HFD (HFD + PEF). The treatment was continued for 8 weeks, after which the effects of PEF on oxidative stress, fat deposition, plasma lipids, and gene expression of relevant proteins were explored. Several proteins involved in lipid metabolism and homeostasis interact with bioactive phenolic compounds, such as ellagic acid, quercetin, catechin, kaempferol, and chrysin. The presence of these compounds in the P. emblica fruit was confirmed by HPLC analysis. In vivo experiments showed that HFD‐induced increased oxidative stress, mesenteric fat weight, and harmful plasma lipids were reduced significantly (p < 0.05) due to the feeding of PEF‐supplemented HFD. On the other hand, HFD‐mediated reductions in antioxidant enzyme activity and the level of HDL cholesterol were restored in rats fed with PEF. The HFD‐mediated increase in the transcript levels of SREBP‐1c, SREBP‐2, and HMGCR reductase was significantly (p < 0.05) suppressed by feeding PEF with a parallel increase in the expression of LDLR. However, the increased expression of LXRα, PPARγ, and FABP4 was not changed by PEF feeding, although these proteins strongly interacted with several compounds of PEF. This study demonstrated that a PEF‐supplemented diet can reduce HFD‐induced hyperlipidemia by modulating the expression of SREBP‐1c, SREBP‐2, HMG‐CoA reductase, and LDL receptor at the transcriptional level.