Fucoidan protects mesenchymal stem cells against oxidative stress and enhances vascular regeneration in a murine hindlimb ischemia model.

BACKGROUND: Mesenchymal stem cells (MSCs) have the potential to differentiate into multiple cell lineages. Given this potential for tissue regeneration, MSC-based therapeutic applications have been considered in recent years. However, ischemia-induced apoptosis has been reported to be one of the main causes of MSC death following transplantation. The primary objective of this study was to determine whether a natural antioxidant, fucoidan, could protect MSCs from ischemia-induced apoptosis in vitro and in vivo. Furthermore, we investigated the mechanism of action of fucoidan's anti-ischemic effect in MSCs. METHODS AND RESULT: Pre-treatment with fucoidan (10 µg/mL) suppressed the increase in H2O2-induced reactive oxygen species (ROS) levels and drastically reduced apoptotic cell death in MSCs. Fucoidan inhibited the activation of the pro-apoptotic proteins p38-mitogen-activated protein kinase (MAPK), Jun N-terminal kinase (JNK), and caspase-3, and augmented the expression of the anti-apoptosis protein cellular inhibitor of apoptosis (cIAP). Moreover, fucoidan significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the Akt pathway, resulting in enhanced cell survival. In a murine hindlimb ischemia model, transplanted fucoidan-treated MSCs showed significantly enhanced cell survival and proliferation in ischemic tissues. Functional recovery and limb salvage also remarkably improved in mice injected with fucoidan-stimulated MSCs compared with mice injected with non-stimulated MSCs. CONCLUSION: Taken together, these results show that fucoidan protects MSCs from ischemia-induced cell death by modulation of apoptosis-associated proteins and cellular ROS levels through regulation of the MnSOD and Akt pathways, suggesting that fucoidan could be powerful therapeutic adjuvant for MSC-based therapy in ischemic diseases.

Acute interstitial nephritis following kudzu root juice ingestion.

Recently, the use of herbal remedies and complementary and alternative medicine has increased globally. Kudzu root (Pueraria lobata) is a plant commonly used in traditional medicine to promote health. A middle-aged woman consumed kudzu root juice to promote health and well-being for 10 days. Subsequently, she developed anorexia, epigastric discomfort and azotemia. These symptoms improved rapidly within several days after discontinuation of the suspected offending agent and conservative treatment. Acute interstitial nephritis was diagnosed by renal biopsy. To our knowledge, this is the first case report describing acute interstitial nephritis following the ingestion of kudzu root juice.