In free-fatty-acid-induced insulin resistance muscle cells, berberine improves insulin resistance and improves glucose uptake by decreasing biological activity PPAR�� and FAT/CD36 protein expression [37]. Another study reported increased insulin receptor (InsR) mRNA and protein expression increases insulin sensitivity in liver cells after berberine treatment [38]. In Caco-2 cells, berberine inhibited alpha-glucosidase and disaccharidases activities, leading to reduced glucose levels [39]. In Hep G2 cells, berberine also improved insulin signal transduction through various mechanisms such as decreased phosphorylation of PERK and eLF2-��, increased phosphorylation of IRS-1 tyrosine and AKT serine [40]. In intestinal NCI-H716 cells, berberine enhanced glucagon-like peptide 1 (GLP-1) release and promotes proglucagon mRNA expression [41].
These results demonstrate that berberine has great potential for insulin resistance treatment and should be explored further in animal and human studies.3.2. PANTHER Analysis of Berberine TargetsDistribution of berberine therapeutic targets in vitro varied in each of these functional classifications. Tables Tables3,3, ,4,4, and and55 show various distributions of the most frequent occurring berberine targets in vitro based on molecular functions, biological processes, and pathways, respectively.Table 3Distribution of berberine’s targets in vitro according to molecular functions.Table 4Distribution of berberine’s targets in vitro according to biological functions.Table 5Distribution of berberine’s targets in vitro according to pathway categories.
As shown in Table 3, berberine acts on a diverse range of molecular targets in vitro. The most common classes of molecular functions include receptor binding, kinase activity, protein binding, transcription activity, DNA binding, and kinase regulator activity. Known berberine targets in vitro from the receptor binding class AV-951 include epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), interleukin-1�� (IL1B) and interleukin-6 (IL6), growth/differentiation factor 15 (NAG-1), and glucagon-like peptide (GLP1).Based on the biological process classification of in vitro berberine targets, those targets related to signal transduction, intracellular signalling cascade, cell surface receptor linked signal transduction, cell motion, cell cycle control, immunity system process, and protein metabolic process are most frequently involved (Table 4).