Apigenin is a member of the flavone subclass of flavonoids present in fruits and vegetables. Apigenin has long been considered to have various biological activities, such as antioxidant, anti-inflammatory, and antitumorigenic properties, in various cell types. Cisplatin was known to exhibit cytotoxic effect to renal cells by inducing apoptosis through activation of p53. The present study investigated the antiapoptotic effects of apigenin on the cisplatin-treated human renal proximal tubular epithelial (HK-2) cells. HK-2 cells were pretreated with apigenin (5, 10, 20 μM) for 1 h and then treated with 40 μM cisplatin for various times. Apigenin inhibited the cisplatin-induced apoptosis of HK-2 cells. Interestingly, apigenin itself exerted cytostatic activity because of its ability to induce cell cycle arrest. Apigenin inhibited caspase-3 activity and PARP cleavage in cisplatin-treated cells. Apigenin reduced cisplatin-induced phosphorylation and expression of p53, with no significant influence on production of ROS that is known to induce p53 activation. Furthermore, apigenin promoted cisplatin-induced Akt phosphorylation, suggesting that enhanced Akt activation may be involved in cytoprotection. Taken together, these results suggest that apigenin ameliorates cisplatin-induced apoptosis through reduction of p53 activation and promotion of PI3K/Akt pathway in HK-2 cells.

Aged or fermented garlic extract (FGE) is a natural remedy that improves vascular function through increasing vascular nitric oxide (NO) bioavailability. This is because nitrite (NO2−), a NO metabolite, can be produced through bioconversion with macrobacteria during the fermentation of foods like garlic. We aimed to evaluate the effects of NO2− in FGE on blood flow (BF), blood pressure (BP), velocity of the common carotid artery (CCA) and internal carotid artery (ICA), regional cerebral BF (rCBF), and peripheral BF (PBF). The study was divided into two parts: (1) Thirty healthy adults were divided into FGE and placebo groups to compare BP and velocity of the CCA and ICA; and (2) Twenty-eight healthy adults were divided into FGE and placebo groups to compare rCBF and PBF and determine changes before/after ingestion. Significant changes were noted in BP and the velocity of both CCA 30–60 min after FGE ingestion. FGE ingestion resulted in significant increases in rCBF and increases in body surface temperature through alterations in PBF. No detectable clinical side effects were noted. Overall, oral administration of NO2− containing FGE demonstrated acute positive effects in upregulating BF, including the CCA, BP, rCBF, and PBF. Follow-up studies with larger sample sizes and long-term ingestion may be needed.