Skip to main content


Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Fig. 7 | BMC Complementary and Alternative Medicine

Fig. 7

From: Larrea divaricata Cav. aqueous extract and nordihydroguariaretic acid modulate oxidative stress in submandibular glands of diabetic rats: a buccal protective in diabetes

Fig. 7

Probable mechanism of the antioxidant action exerted by AE and NDGA on submandibular glands from diabetic rats. a- Hyperglycemia induces oxidative stress through MAPK, NADPH oxidase and 5-LOX activation. The ROS generated activate the IGF1R-PI3K-AKT pathway, which inhibites FoxO protein and decreases Px and SOD expression. Besides, Px activity is inhibited, leading to an increase in hydrogen peroxide levels. Hydrogen peroxide, in turn, activates SOD by oxidation and more hydrogen peroxide from superoxide anion is generated. Hydrogen peroxide activates the NFk-B pathway and the up-regulation of iNOS, leading to an increase of NO. b- The extract and NDGA inhibit NADPH oxidase and 5-LOX, thus decreasing superoxide anion levels and hydrogen peroxide formation. Low ROS levels activate FoxO protein, which induces the expression of Px and SOD. Moreover, Px is activated, so hydrogen peroxide is transformed into oxygen + water. Low levels of hydrogen peroxide do not activate SOD, therefore, less hydrogen peroxide is formed. NFk-B is not activated therefore, the iNOS expression decreases together with the production of NO.Inhibitory effects are marked in red, while stimulatory effects are marked in black.STZ: streptozotocin, ROS: reactive oxygen species, SOD: superoxide dismutase, Px: peroxidase, 5-LOX: 5 lipooxigenase, iNOS: inducible nitric oxide synthase, FoxO: Forkhead box O transcription factor; AKT: RAC-alpha serine/threonine-protein kinase; IGF1 R: insulin-like factor 1 receptor; PI3K: phosphoinositoside 3 kinase; MAPK: mitogen-activated protein kinase; JNK: c-Jun N terminal kinase; NFκB: nuclear factor kappa-light-chain-enhancer of activated B cells (transcription factor); P-38: P38 mitogen-activated protein kinases; ERK1/2: extracellular signal-regulated kinases

Back to article page