Abstract
Background:
Modern lifestyle, which is characterized by a high-fat diet, increases the risk of hyperlipidemia, a primary trigger for cardiovascular diseases and metabolic disorders. Excessive fat consumption can trigger hepatic steatosis and oxidative stress, leading to inflammation and liver damage, which contributes to the development of non-alcoholic fatty liver disease. Conventional cholesterol-lowering therapies are often expensive and come with side effects, making herbal alternatives such as kecemcem leaves a promising option. Kecemcem leaves extract contains flavonoids such as quercetin and catechin, which exhibit antioxidant properties, regulate lipid metabolism, and reduce inflammation.

Aim:
This study aimed to evaluate the therapeutic effects of kecemcem leaves extract [Spondias pinnata (L.f.) Kurz] in reducing low-density lipoprotein (LDL) levels and its impact on pro-inflammatory cytokines [Interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and anti-inflammatory cytokines Interleukin-10 (IL-10)], as well as liver histology in hyperlipidemic Wistar rats.

Methods:
Hyperlipidemia was induced through a high-fat diet for 16 weeks, after which the rats were administered kecemcem leaves extract at doses of 250, 500, and 1,000 mg/kg body weight for 1 week. One week after the administration of kecemcem leaves extract, blood and liver samples were collected from all rats to measure LDL, IL-1β, TNF-α, and IL-10 levels, as well as to perform liver histological analysis.

Results:
Kecemcem leaves extract significantly reduced LDL, IL-1β, and TNF-α levels while increasing IL-10 levels in hyperlipidemic rats, particularly at the 250 mg/kg body weight dose. In addition, there was an improvement in liver histology, as evidenced by decreased steatosis and hepatocyte ballooning. These effects are attributed to the flavonoid content in kecemcem, such as quercetin and catechins, which inhibit cholesterol synthesis, reduce oxidative stress, and decrease liver fat accumulation.

Conclusion:
Kecemcem leaves extract potentially reduced LDL, IL-1β, and TNF-α levels, increased IL-10 levels, and improved liver histology. This effect is supported by the flavonoid content of quercetin and catechin. Thus, kecemcem leaves extract has shown promising therapeutic effects in managing conditions related to hyperlipidemia and inflammation.

Key words: Cytokines, Hyperlipidemia, Immunology, LDL, Spondias pinnata (L.f.) Kurz