# Salvadora persica Fruit Methanolic Extract, Nutritional Profiling, Therapeutic Potential in High‐Fat Diet‐Induced Hyperlipidemic Rats: In Vivo, In Vitro, and In Silico Approaches

**Authors:** Nudrat Khursheed, Mostafa A. Abdel‐Maksoud, Salman Alrokayan, Khurram Afzal, Muhammad Naeem Zubairi, Muhammad Tauseef Sultan, Asad Abbas, Hassan Raza, Ahmad Mujtaba Noman, Heba A. S. El‐Nashar, Mohammad S. Mubarak

PMC · DOI: 10.1002/fsn3.71595 · 2026-03-05

## TL;DR

Salvadora persica fruit extract shows strong antioxidant and health benefits in rats with high-fat diet-induced hyperlipidemia.

## Contribution

The study combines in vivo, in vitro, and in silico methods to demonstrate the therapeutic potential of S. persica extract.

## Key findings

- The extract significantly reduced oxidative stress and improved lipid profiles in hyperlipidemic rats.
- GC–MS identified oleic acid as the main bioactive compound in the extract.
- Molecular docking showed strong binding of extract compounds to HMG-CoA reductase.

## Abstract

This manuscript presents original research on Salvadora persica fruit, investigating its antioxidant and metabolic properties using in vivo, in vitro, and in silico approaches in high‐fat‐diet induced hyperlipidemic rat models. Nutritional profiling, phytochemical analysis (TPC, DPPH, FRAP, ABTS), and GC–MS analysis identified key bioactive compounds. The antioxidant tests revealed high activity of the methanolic extract, with TPC (62.1 mg GAE/g), DPPH (67.8%), FRAP (335.4 μmol Fe2+/g), and ABTS (540.2 μmol Trolox/g) assays. GC–MS analysis revealed oleic acid as the predominant compound (56.64%), followed by (9E,11E)‐octadecadienoic acid (18.10%) and n‐hexadecanoic acid (10.92%). Molecular docking studies confirmed strong binding affinities with HMG‐CoA reductase. Furthermore, in vivo studies in male Wistar albino rats (n = 5 per group) confirmed that 
S. persica
 significantly restored antioxidant enzyme activities (SOD, Catalase, and GSH) and reduced oxidative stress markers (MDA and NO) in a dose‐dependent manner (p < 0.05). Lipid parameters (TG, TC, LDL, and VLDL) in animals treated with 
S. persica
 were significantly reduced, and liver and kidney markers, including AST, ALT, creatinine, and urea, were significantly improved (p < 0.05). Additionally, glucose levels in hyperlipidemic rats treated with 
S. persica
 methanolic extract were lower than those in the negative control (p < 0.05). These results underscore the promising antioxidant, hypoglycemic, hypolipidemic, hepatoprotective, and renoprotective potential of the methanolic extract of 
S. persica
.

Salvadora persica methanolic extract exhibited strong antioxidant, hypolipidemic, and hypoglycemic effects in high‐fat diet‐induced hyperlipidemic rats. In vitro antioxidant assays, GC–MS profiling, and in vivo studies confirmed improvements in the lipid profile and in markers of oxidative stress, liver, and kidney function. In silico studies also confirm bioactive compounds have strong binding affinities with key lipid‐regulating targets, such as HMG‐CoA reductase.

## Linked entities

- **Proteins:** HMG1 (hydroxy methylglutaryl CoA reductase 1)
- **Chemicals:** oleic acid (PubChem CID 445639), (9E,11E)-octadecadienoic acid (PubChem CID 5282796), n-hexadecanoic acid (PubChem CID 985)
- **Diseases:** hyperlipidemia (MONDO:0021187)
- **Species:** Salvadora persica (taxon 4326)

## Full-text entities

- **Genes:** HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) [NCBI Gene 3156] {aka LDLCQ3, LGMDR28, MYPLG}, Alb (albumin) [NCBI Gene 24186] {aka Alb1, Albza}, Got2 (glutamic-oxaloacetic transaminase 2) [NCBI Gene 25721] {aka ASPATA, mAAT}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Pdlim3 (PDZ and LIM domain 3) [NCBI Gene 114108] {aka Actn2lp, Alp}, Hmgcr (3-hydroxy-3-methylglutaryl-CoA reductase) [NCBI Gene 25675] {aka 3H3M}
- **Diseases:** atherosclerosis (MESH:D050197), hepatomegaly (MESH:D006529), cardiovascular disease (MESH:D002318), toxicity (MESH:D064420), liver damage (MESH:D056486), lipid disorders (MESH:D011017), Hyperlipidemia (MESH:D006949), liver-related diseases (MESH:D008107), inflammation (MESH:D007249), diabetic dyslipidemia (MESH:D050171), cancer (MESH:D009369), diabetes (MESH:D003920), obesity (MESH:D009765), weight gain (MESH:D015430), noncommunicable diseases (MESH:D000073296), myocardial injury (MESH:D009202), metabolic disorders (MESH:D008659)
- **Chemicals:** helium (MESH:D006371), NO (MESH:D009614), isolinoleic acid (MESH:C073957), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulphonate (-), Superoxide anion (MESH:D013481), hydrogen peroxide (MESH:D006861), atorvastatin (MESH:D000069059), TG (MESH:D013866), Urea (MESH:D014508), coconut oil (MESH:D000074263), carbohydrate (MESH:D002241), acetone (MESH:D000096), MDA (MESH:D008315), potassium persulfate (MESH:C009007), riboflavin (MESH:D012256), Ketamine hydrochloride (MESH:D007649), GSH (MESH:D005978), polyphenols (MESH:D059808), sodium carbonate (MESH:C005686), Lipid (MESH:D008055), ABTS (MESH:C002502), hydrogen (MESH:D006859), TBARS (MESH:D017392), oleic acid (MESH:D019301), sodium acetate (MESH:D019346), reactive oxygen species (MESH:D017382), sulfanilic acid (MESH:D013425), flavonoids (MESH:D005419), Glucose (MESH:D005947), chlorogenic acid (MESH:D002726), Creatinine (MESH:D003404), NaCl (MESH:D012965), Trolox (MESH:C010643), Methanol (MESH:D000432), Fat (MESH:D005223), gallic acid (MESH:D005707), formazan (MESH:D005562), TC (MESH:D013667), phosphate (MESH:D010710), Folin-Ciocalteau reagent (MESH:C029556), MDA (MESH:D015104), nitrogen (MESH:D009584), EDTA (MESH:D004492), Bilirubin (MESH:D001663), Rutin (MESH:D012431), ferrous sulfate (MESH:C020748), cholic acid (MESH:D019826), FeCl3 (MESH:C024555), hydrazine (MESH:C029424), TG (MESH:D014280), essential fatty acids (MESH:D005228), 1,1-Diphenyl-2-Picrylhydrazyl (MESH:C004931), Water (MESH:D014867), cinnamic acid (MESH:C029010), terpenoids (MESH:D013729), catechin (MESH:D002392), hydroxy benzoic acid (MESH:C017616), Vitamin C (MESH:D001205), blood glucose (MESH:D001786), cholesterol (MESH:D002784)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Rodentia (rodent, order) [taxon 9989], Salvadora persica (species) [taxon 4326], Withania somnifera (ashwagandha, species) [taxon 126910], Syringa persica (species) [taxon 2563121]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961557/full.md

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Source: https://tomesphere.com/paper/PMC12961557