Table 4.
Effects of grape seed extract on fibromyalgia-like symptoms.
| First Author, Year [ref] | Experimental Design and Treatments | Results |
|---|---|---|
| In vitro studies | ||
| Fujishita, 2009 [47] | Oxidative stress-induced hippocampal neuronal cell death model | Compared to vehicle group, the GSE groups: |
| Neurons treated with GSE (0–100 µg/mL) for 2, 6 and 12 h. Neurons pre-incubated for 24 h with GSE-treated ACM in presence or absence of anti-IL-6 antibodies (50 ng/mL). Then, neurons were stimulated with H2O2 in presence or absence of IL-6 with and without anti-IL-6 antibody for 2 h |
↑ mRNA expression of IL-6, COX-2, IL-1α, | |
| in astrocytes with oxidative stress status | ||
| Protected against neuronal death induced by | ||
| oxidative stress | ||
| Narita, 2011 [48] | Hippocampal neurons at 8 DIV treated with 50 µM glutamate for 30 min, in presence or absence of 0.01, 0.1, 1.0, or 10 ng/mL of GSE | Compared to vehicle group, the GSE groups: |
| Protected Erk1/2 phosphorylation | ||
| Protected dendritic arborization and augmented cell survival | ||
| ↓ caspase-3 activity | ||
| Animal studies | ||
| Mun, 2010 [42] | i.p. injection in gastrocnemius muscle of acidic saline-induced FM-like model |
Compared to control group, proanthrocyanidin group: |
| (n = 15) | ||
| Female male SD rats (n = 15, 250–320 g) | ↑ anti-hyperalgesic effect in injected paw and contralateral paw | |
| Treatments: control, acidic saline i.p. injection, oligomeric proanthrocyanidin complexes at 300 mg/kg injection i.p. on day 7 | ↓ expression of acid sensing ion channel 3 in brain M1 and motor cortex area | |
| Xianchu, 2018 [49] | Exhaustive exercise-induced FM model | Compared to control group, GSPE-M and GSPE-H groups, |
| ↓ fatigue by prolonging the time to exhaustion in forced swimming test | ||
| ↓ lactic acid, LDH, and CK in serum | ||
| Male ICR mice (n = 32, 8-week-old, 25 g) | ↓ MDA, TNF-α, and IL-1β in serum and skeletal | |
| muscle of mice | ||
| ↑ SOD, CAT, and T-AOC in serum and skeletal | ||
| Treatments: control, low-dose GSPE-L group (1 mg/kg/day), medium-dose GSPE-M group (50 mg/kg/day), and high-dose GSPE-H group (100 mg/kg/day) for 28 days | muscle of mice | |
| ↑ SDH and Na+-K+-ATPase activities in | ||
| mitochondrial function of skeletal muscle | ||
| Human study | ||
| Edwards, 2000 [50] | Double-blind, randomized, crossover trial with moderate to severe primary FM (n = 12) | Compared to the placebo group, anthocyanidins at 80 mg daily group: |
| Treatments: placebo, 40 mg, 80 mg, and 120 mg anthocyanidins daily. Each dose for 3 months | ↓ fatigue and sleep disturbance in 80 mg dose group |
Abbreviations: CAT, catalase; CK, creatinine phosphokinase; COX2-, cyclooxygenase-2; FM, fibromyalgia; GSE, grape seed extract; GSPE, grape seed proanthrocyanidin extract; IL-1β, interleukin-1β; i.p., intraperitoneal; LDH, lactate dehydrogenase; MDA, malondialdehyde; SD, Sprague-Dawley; SDH, succinate dehydrogenase; SOD, superoxide dismutase; T-AOC, total antioxidative capability; TNF-α, tumor necrosis factor-α; ↑ increase; ↓ decrease; ↔ no difference.