Effect of Plant Extracts Combinations on TNF-α, IL-6 and IL-10 Levels in Serum of Rats Exposed to Acute and Chronic Stress

Abstract

Oxydative stress, anxiety and depression are associated with changes in cytokine levels. Natural products, including individual and combined plant extracts, have the potential to be used in the treatment of neuropsychiatric disorders. The goal of this study is to investigate the effects of two combined plant extracts, rich in flavonoids, on the levels of the cytokines TNF-α, IL-6, and IL-10 in rats subjected to models of acute cold stress and chronic unpredictable stress. The study utilized common medicinal plants such as Valeriana officinalis, Melissa officinalis, Crataegus monogyna, Hypericum perforatum, and Serratula coronata, which were combined in two unique combinations—Antistress I and Antistress II. The compositions of the used extracts were determined by HPLC methods. Pro- and anti-inflammatory cytokines in rats’ serum were measured with Enzyme-linked immunosorbent assay. The results from the acute stress model revealed that the individual extract of Crataegus monogyna decreased levels of TNF-α, while Serratula coronata, Hypericum perforatum, and Valeriana officinalis effectively reduced IL-6 levels. Both combinations, Antistress I and Antistress II, were effective in reducing TNF-α and IL-6 levels, with Antistress II also increasing IL-10 levels. In the chronic stress model, Hypericum perforatum extract decreased the levels of the pro-inflammatory cytokines TNF-α and IL-6, whereas extracts of Serratula coronata and Valeriana officinalis only reduced TNF-α levels. The two combined extracts, Antistress I and Antistress II, decreased TNF-α and IL-6 levels, while Antistress I also reduced the levels of the anti-inflammatory cytokine IL-10. The combinations of plant extracts used in our experiment have not been previously studied or documented in the available literature. However, based on our own experimental results, we can draw the conclusion that the combinations exhibit a more pronounced effect in reducing cytokine levels compared to the individual plant extracts.

Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease

“…Furthermore, chronic stress studies have reported significantly increased [137] or decreased [138] serum IL-10 in female rodents. Xia et al measured no difference in serum IL-10 in male rodents following chronic stress, whereas others measured a significant decrease [138,139] or increase [109]. The clarification of conflicting findings of increased, decreased, or no change in serum and HPC IL-10 levels following chronic stress could reveal possible sex differences in susceptibility to chronic-stress-induced depression.…”

“…Alternative medicine approaches have also decreased IL-6 levels in models of chronic stress. These include the following reagents: prebiotic, Eucommiae cortex polysaccharides (Epss) [73]; rice germ with gamma-aminobutyric acid (GABA) [45]; theanine [45]; isofraxidin [39]; hypericum perforatum [109]; serratula coronate [109]; pumpkin extract [110]; RSNP [111]; crocin-1 [111]; bilobalide [112]; TSPG [113]; and B-glucan pretreatment [94,95]. Therapeutic approaches like acupuncture [85] and enriched environment [37] and transcutaneous vagus nerve stimulation (taVNS) [114] decreased IL-6 in either the AMY, HPC, or serum.…”

“…Plant extracts have reduced TNF-α in animal models, including Serratula coronata, Hypericum perforatum, and Valeriana officinalis [109]; Isofraxidin [39]; SSd [47]; L-Menthone [130]; RL-118 [131]; bilobalide [112]; ginsenosides [113]; polydatin from Polygonum cuspidatum [50]; escitalopram, Dapa, and co-treatment with BQ-788 and Dapa [58]; and Lilium saponins and Fluoxetine [92]. The anti-inflammatory mechanisms of co-treatments were mediated through the inactivation of the COX-2/PGE2/IL-22 axis [92] or the promotion of NLRP3 ubiquitination via the MARCHF7 protein, ultimately inhibiting the activation of the NLRP3 inflammasome [47].…”

“…IL-10 is produced by Th2 cells, macrophages, and CD8+ cells and inhibits the synthesis of a wide range of proinflammatory cytokines, including IFN-γ, IL-6, and TNF-α [136]. IL-10 antagonists are effective in the treatment of autoimmune diseases such as systemic lupus erythematosus, and stress has been shown to aggravate the course of this disease [109]. A correlation between distress and IL-10 levels has been suggested and further investigated using rodent models of chronic stress.…”

“…These effects are mediated through NF-κB modulation, ultimately inhibiting proinflammatory activation and promoting anti-inflammatory genes, which modulates the microglial phenotype in the HPC. Unique combinations of plant extracts decreased serum IL-10 compared to the stress group; however, the effects on depression-like behaviors need to be analyzed [109].…”