Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System

Nutrients. 2021 Oct 12;13(10):3575. doi: 10.3390/nu13103575.


Numerous studies highlight that astaxanthin (ASTX) ameliorates hyperglycemic condition and hyperglycemia-associated chronic complications. While periodontitis and periodontic tissue degradation are also triggered under chronic hyperglycemia, the roles of ASTX on diabetes-associated periodontal destruction and the related mechanisms therein are not yet fully understood. Here, we explored the impacts of supplemental ASTX on periodontal destruction and systemic complications in type I diabetic mice. To induce diabetes, C57BL/6 mice received a single intraperitoneal injection of streptozotocin (STZ; 150 mg/kg), and the hyperglycemic mice were orally administered with ASTX (12.5 mg/kg) (STZ+ASTX group) or vehicle only (STZ group) daily for 60 days. Supplemental ASTX did not improve hyperglycemic condition, but ameliorated excessive water and feed consumptions and lethality in STZ-induced diabetic mice. Compared with the non-diabetic and STZ+ASTX groups, the STZ group exhibited severe periodontal destruction. Oral gavage with ASTX inhibited osteoclastic formation and the expression of receptor activator of nuclear factor (NF)-κB ligand, 8-OHdG, γ-H2AX, cyclooxygenase 2, and interleukin-1β in the periodontium of STZ-injected mice. Supplemental ASTX not only increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and osteogenic transcription factors in the periodontium, but also recovered circulating lymphocytes and endogenous antioxidant enzyme activity in the blood of STZ-injected mice. Furthermore, the addition of ASTX blocked advanced glycation end products-induced oxidative stress and growth inhibition in human-derived periodontal ligament cells by upregulating the Nrf2 pathway. Together, our results suggest that ASTX does not directly improve hyperglycemia, but ameliorates hyperglycemia-triggered periodontal destruction and oxidative systemic complications in type I diabetes.

Keywords: Nrf2 pathway; astaxanthin; diabetes; hyperglycemic complication; oxidative damage; periodontal destruction.

MeSH terms

  • Adolescent
  • Alveolar Process / pathology
  • Animals
  • Antioxidants / metabolism*
  • Blood Glucose / metabolism
  • Catalase / blood
  • Cell Proliferation
  • Cytokines / metabolism
  • DNA Damage
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / complications*
  • Dietary Supplements
  • Feeding Behavior
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Hyperglycemia / complications
  • Inflammation Mediators / metabolism
  • Injections
  • Lymphocytes / immunology
  • Male
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism*
  • Osteoclasts / drug effects
  • Osteoclasts / pathology
  • Oxidative Stress*
  • Periodontal Ligament / pathology
  • Periodontitis / blood
  • Periodontitis / drug therapy*
  • Periodontitis / etiology*
  • Reactive Oxygen Species / metabolism
  • Streptozocin / administration & dosage*
  • Superoxide Dismutase / blood
  • Up-Regulation
  • Xanthophylls / pharmacology
  • Xanthophylls / therapeutic use
  • Young Adult


  • Antioxidants
  • Blood Glucose
  • Cytokines
  • Glycation End Products, Advanced
  • Inflammation Mediators
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Xanthophylls
  • Streptozocin
  • astaxanthine
  • Catalase
  • Superoxide Dismutase