Oxidative Stress Modulation by Cameroonian Spice Extracts in HepG2 Cells: Involvement of Nrf2 and Improvement of Glucose Uptake

Abstract

Oxidative stress plays a relevant role in the progression of chronic conditions, including cardiometabolic diseases. Several Cameroonian plants, including spices, are traditionally used as herbal medicines for the treatment of diseases where oxidative stress contributes to insulin resistance, like type 2 diabetes mellitus. This study evaluated the antioxidant capacity and the effects on oxidative-stress-induced impairment of glucose uptake of 11 Cameroonian spice extracts. H2O2-induced reactive oxygen species (ROS) production by human HepG2 cells was significantly reduced by 8/11 extracts. The most effective extracts, Xylopia parviflora, Echinops giganteus, and Dichrostachys glomerata, showed a concentration-dependent ROS-scavenging activity, which involved Nrf2 translocation into the nucleus. Xylopia parviflora, Tetrapleura tetraptera, Dichrostachys glomerata, Aframomum melegueta, and Aframomum citratum extracts showed the highest antioxidant capacity, according to oxygen radical absorbance capacity (ORAC) (2.52–88 μM Trolox Eq/g of extract), ferric-reducing antioxidant power (FRAP) (40.23–233.84 mg gallic acid Eq/g of extract), and total phenol (8.96–32.96% mg gallic acid Eq/g of extract) assays. In HepG2 cells, glucose uptake was stimulated by 4/11 extracts, similarly to insulin and metformin. H2O2-induced oxidative stress reduced glucose uptake, which was rescued by pretreatment with Xylopia aethiopica, Xylopia parviflora, Scorodophloeus zenkeri, Monodora myristica, and Dichrostachys glomerata extracts. The ROS-scavenging ability of the spice extracts may reside in some secondary metabolites observed by phytochemical profiling (reverse-phase high-performance liquid chromatography coupled to a diode array detector (HPLC-UV-DAD)). Further studies are needed to better clarify their biological activities and potential use to control oxidative stress and promote insulin sensitivity.

Cameroonian Spice Extracts Modulate Molecular Mechanisms Relevant to Cardiometabolic Diseases in SW 872 Human Liposarcoma Cells

“…In this study, T. tetraptera, A. melegueta and Z. leprieurii increased glucose uptake in a dose-dependent manner. Interestingly, in another in-vitro model, the HepG2 cells, T. tetraptera and A. melegueta, but not Z. leprieurii increased glucose uptake [7], underlining the relationship between the complex molecular composition of the spice extracts, the observed effect and the specificity linked to the tested cell model. In differentiated SW 872 cells, the tested spice extracts do not appear to modulate the Akt upstream pathway whether or not in the presence of insulin, suggesting that they may increase glucose uptake by promoting other molecular events, like glucose transporter translocation to the membrane.…”

“…Moreover, insulin resistance, glucose uptake impairment and metabolic disfunction appear to be sustained by the secretion from dysfunctional adipocytes of several pro-inflammatory cytokines [31] as well as by the resultant ROS production [1,32]. Based on these considerations, we evaluated the secretory profile of IL-6 and IL-8, two NF-kB-dependent molecular mediators released in the context of chronic inflammation [7]. Among the 11 tested extracts, four (A. melegueta, D. glomerata, T. tetraptera and E. giganteus) were effective in significantly reducing (−29/−43%) IL-6 release.…”

“…They were then lyophilized and stored at −20 • C. Spice extract stock solutions (100 mg/mL) dissolved in DMSO were prepared, aliquoted, and kept at −80 • C. The stock solution of spice extracts in DMSO was diluted in culture medium to the appropriate concentrations for cell treatments. For more details, please check Table 1 in [7]. The same concentration of DMSO (in any case never exceeding 0.1%) was also added to all control cultures.…”

“…Preliminary experiments were conducted to assess the effect of 11 Cameroonian spice extracts on the viability of differentiated SW 872 cells by MTS assay and morphological analysis. The extraction protocol, molecular composition, and potential cytotoxic effects in other cell lines of the spice extracts used in this study have been previously reported [5][6][7]. The MTS assay was conducted after treatment with different concentrations (1-100 µg/mL) of extracts for 24 h and 48 h. Viability threshold was set at 80% [15].…”

“…Our research group, along with other researchers, has previously investigated the composition and the molecular effects of several spice extracts from Cameroonian plants commonly used in traditional medicine. In particular, we explored the ability of these extracts to modulate the activity of some enzymes relevant to the control of cardiometabolic functions [5], the antioxidant and anti-inflammatory activities by gastric epithelial cells [6] and glucose uptake and antioxidant activity in human HepG2 cells [7].…”