**Elderberry (***Sambucus nigra* **L.) Fruit Extract Alleviates Oxidative Stress, Insulin Resistance, and Inflammation in Hypertrophied 3T3-L1 Adipocytes and Activated RAW 264.7 Macrophages**

#### **Joanna Zieli ´nska-Wasielica 1, Anna Olejnik 1,\*, Katarzyna Kowalska 1, Mariola Olkowicz 2 and Radosław Dembczy ´nski 1**


Received: 11 July 2019; Accepted: 4 August 2019; Published: 8 August 2019

**Abstract:** Oxidative stress and inflammation in hypertrophied adipose tissue with excessive fat accumulation play a crucial role in the development of obesity and accompanying metabolic dysfunctions. This study demonstrated the capacity of elderberry fruit (EDB) extract to decrease the elevated production of reactive oxygen species in hypertrophied 3T3-L1 adipocytes. Treatment with the EDB extract resulted in modulation of mRNA expression and protein secretion of key adipokines in hypertrophied adipocytes. Expression of leptin and adiponectin was, respectively, down- and up-regulated. Moreover, glucose uptake stimulation was noticed in mature adipocytes, both sensitive to insulin and insulin resistant. This may sugges<sup>t</sup> a positive effect of EDB extract on insulin resistance status. The extract was also found to alleviate the inflammatory response in activated RAW 264.7 macrophages by down-regulating the expression of proinflammatory genes (*TNF-*<sup>α</sup>, *IL-6*, *COX-2*, *iNOS*) and suppressing the enhanced production of inflammatory mediators (TNF-<sup>α</sup>, IL-6, PGE2, NO). *In vitro* experiments showed that the EDB extract could inhibit digestive enzymes, including α-amylase, α-glucosidase, and pancreatic lipase, leading to reduced intestinal absorption of dietary lipids and carbohydrates. Further *in vivo* studies could be postulated to support EDB as a functional food component for the prevention and treatment of obesity and metabolic-immune comorbidities.

**Keywords:** elderberry polyphenols; functional food; obesity; digestive enzymes; fat cells; intracellular reactive oxygen species; adipokines; glucose uptake; immune-metabolic effects
