Cell Death Induction Potential in Seed Extracts- Hidden and Bioactive Phytochemical Treasures

Seeds have been known to possess bioactive components with anti-cancer properties. This study aims to demonstrate the processes by which seed extracts from various sources induce cell death. Several assays have been employed to demonstrate the induction of cell death by the respective seed extracts. This review also underscores the importance of Grape Seed Proanthocyanidins (GSPs) in terms of inducing the aforesaid physiological form of seed extract-induced cell death. Furthermore, this review highlights the critical and pressing need to conduct comparative HTS-based strategies (with a battery of cell lines representing different cancers) to identify the major seed extracts that can reproducibly serve to augment the cell death induction capabilities of the existing battery of chemotherapeutic drugs/natural alternatives.

Theaflavins as a novel cross-linker quickly stabilize demineralized dentin collagen against degradation

To investigate the ability of theaflavins (TF) from black tea to protect dentin collagen against enzymatic degradation via cross-linking effect under clinically relevant conditions. 10-µm-thick dentin films were microtomed from dentin slabs of human molars. Following demineralization, films or slabs were treated with TF at two concentrations (0.4% and 2%) for 30 s. A well-known collagen cross-linker grape seed proanthocyanidins (PA) was used as control. Collagen cross-linking interactions and stabilization against enzymatic degradation were investigated by Fourier transform infrared spectroscopy, weight loss, hydroxyproline release, and scanning/transmission electron microscopy. Data were analyzed by ANOVA, Tukey’s and Student’s T test (α = 0.05%). The results showed collagen cross-linking and stabilization efficacy was dependent on TF/PA concentrations. At 2.0%, TF and PA offered nearly full protection to collagen; at 0.4%, TF exhibited a significantly better collagen stabilization effect than PA (P < 0.05), while untreated collagen was completely digested. It’s concluded that TF cross-links dentin collagen within a clinically relevant time (30 s) and offers excellent collagen protection against enzymatic degradation, with efficacy comparable to or better than PA. The study supports the potential use of TF as a novel, promising collagen cross-linker for degradation resistant, long-lasting dentin bonding in composite restorations.

Grape Seed Proanthocyanidins Inhibit Migration and Invasion of Bladder Cancer Cells by Reversing EMT through Suppression of TGF-β Signaling Pathway

Bladder cancer (BC) is the most common cancer of the urinary system. Despite advances in diagnosis and therapy, the prognosis is still poor because of recurrence and metastasis. Epithelial-mesenchymal transition (EMT) is considered to play an important role in the invasion and metastasis of BC. Grape seed proanthocyanidins (GSPs) exhibit chemopreventive and chemotherapeutic activities against several types of cancer. However, their effects and underlying mechanisms on the invasive potential of BC remain unclear. In this study, we found that GSPs inhibited migration, invasion, and MMP-2/-9 secretion of both T24 and 5637 bladder cancer cells at noncytotoxic concentrations. We also discovered that 5637 cells were more suitable than T24 cells for the EMT study. Further study showed that GSPs inhibited EMT by reversing the TGF-β-induced morphological change and upregulation of mesenchymal markers N-cadherin, vimentin, and Slug as well as downregulation of epithelial markers E-cadherin and ZO-1 in 5637 cells. GSPs also inhibited TGF-β-induced phosphorylation of Smad2/3, Akt, Erk, and p38 in 5637 cells without affecting the expression of total Smad2/3, Akt, Erk, and p38. Taken together, the results of the present study demonstrate that GSPs effectively inhibit the migration and invasion of BC cells by reversing EMT through suppression of the TGF-β signaling pathway, which indicates that GSPs could be developed as a potential chemopreventive and therapeutic agent against bladder cancer.

Neurotoxicity and Neuroinflammatory Effects of Bisphenol A in Male Rats. The Neuroprotective Role of Grape Seeds Proanthocyanidins

Exposure to bisphenol A (BPA) contributes to neurological disorders, but the underlying mechanisms are still not completely understood. We studied the neurotoxic effect of BPA and how it promotes inflammation and alteration in the neurotransmission synthesis, release and transmission. This study was also designed to investigate the neuroprotective effect of grape seed proanthocyanidins (GSPE) against BPA-induced neurotoxicity in rats. Rats were equally divided into 4 group with 7 rats in each as follows: control group, BPA group, GSPE + BPA group and GSPE group. Rats were orally treated with their respective doses (50 mg BPA/kg BW and/or 200 mg GSPE/kg BW) daily for 70 days. BPA elicits significant elevation in malondialdehyde (MDA) and nitric oxide (NO) associated with significant reduction in glutathione (GSH), total thiols, glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione-S-transferase (GST). BPA exposure result in increased dopamine and serotonin levels, elevation in acetylcholine esterase (AchE) activity and reduction in Na/K-ATPase and total ATPase activities in the brain. Also, BPA induces upregulation in the gene expression of the inflammatory markers; tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2), and in the tumor suppressor and pro-oxidant p53 protein. The pretreatment with GSPE attenuate or ameliorate all the oxidative and neurotoxic parameters induced by BPA. Our results suggest that GSPE has a promising role in modulating BPA-induced neuroinflammation and neurotoxicity and its antioxidant and free radical scavenging activities may in part be responsible for such effects.