Ultraviolet B (UVB) exposure is the primary risk factor for the deadliest type of skin cancer—melanoma. Incorporating natural antioxidants in skin protection products is currently a favored research theme. For this study, we selected Phyllanthus emblica L. fruit extract (PE) to assess its potential use in dermal protection against UVB-induced keratinocyte inflammation and apoptosis. High-performance liquid chromatography (HPLC) was used to investigate PE’s phytochemical constituents (ascorbic acid, ellagic acid, gallic acid, chlorogenic acid, and quercetin), while ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), total ROS, OH^•, O₂^•−, and H₂O₂-scavenging activities were used to determine the antioxidant properties. PE significantly increased the cell viability (MTT assay) and reduced apoptosis (Hoechst staining) in HaCaT cells exposed to UVB (40 mJ/cm²). PE abolished oxidative stress by reducing the production of intracellular ROS, O₂^•− and H₂O₂ production. Catalase activity (but not superoxide dismutase or glutathione peroxidase activity) was enhanced in keratinocytes incubated with PE prior to UVB exposure. Western blot analysis suggested that PE inhibited cytochrome c release and inhibited the dysregulation of PI3K/Akt without any impact on p38 activation. PE attenuated the inflammatory response to UVB irradiation by inhibiting AP-1, NF-κB, and the mediator PGE₂. Thus, PE is a candidate with great potential for use as an active ingredient in skin care products.

Methylglyoxal (MGO), a highly reactive dicarbonyl compound, causes endothelial oxidative stress and vascular complications in diabetes. Excessive MGO-induced ROS production triggers eNOS uncoupling, inflammatory responses, and cell death signaling cascades. Our previous study reported that unripe Carica papaya (UCP) had antioxidant activities that prevented H₂O₂-induced endothelial cell death. Therefore, this study investigated the preventive effect of UCP on MGO-induced endothelial cell damage, inflammation, and apoptosis. The human endothelial cell line (EA.hy926) was pretreated with UCP for 24 h, followed by MGO-induced dicarbonyl stress. Treated cells were evaluated for intracellular ROS/O₂^•− formation, cell viability, apoptosis, NO releases, and cell signaling through eNOS, iNOS, COX-2, NF-κB, Akt, MAPK (JNK and p38), and AMPK/SIRT1 autophagy pathways. UCP reduced oxidative stress and diminished phosphorylation of Akt, stress-activated MAPK, leading to the decreases in NF-kB-activated iNOS and COX-2 expression. However, UCP had no impact on the autophagy pathway (AMPK and SIRT1). Although UCP pretreatment decreased eNOS phosphorylation, the amount of NO production was not altered. The signaling of eNOS and NO production were decreased after MGO incubation, but these effects were unaffected by UCP pretreatment. In summary, UCP protected endothelial cells against carbonyl stress by the mechanisms related to ROS/O₂^•− scavenging activities, suppression of inflammatory signaling, and inhibition of JNK/p38/apoptosis pathway. Thus, UCP shows considerable promise for developing novel functional food and nutraceutical products to reduce risks of endothelial inflammation and vascular complications in diabetes.

It has been proven that high consumption of fruit and vegetable lowers the risks of cardiovascular and other oxidative stress-related diseases. Here we evaluated the effects of a tropical fruit, unripeCarica papaya(UCP), on endothelial protection against oxidative damage induced by H₂O₂. The antioxidant properties of UCP were investigated using the assays of FRAP and ORAC and specific ROS scavenging activities (H₂O₂,O2•-, OH^•, HOCl). Cytoprotective property was tested in human endothelial cell line EA.hy926 with respect to cell survival, intracellular ROS levels, antioxidant enzyme activities (CAT, SOD, GPX), survival/stress signaling (AKT, JNK, p38), and nuclear signaling (Nrf2, NF-kB). UCP processed high antioxidant activity and scavenging activity against H₂O₂> OH^•>O2•-> HOCl, respectively. UCP improved cell survival in the milieu of ROS reduction. While SOD was increased by UCP, CAT activity was enhanced when cells were challenged with H₂O₂. UCP had no impact on H₂O₂-activated AKT, JNK, and p38 signaling but significantly decreased nuclear NF-κB levels. The overactivation of Nrf2 in response to oxidative stress was constrained by UCP. In conclusion, UCP protected endothelial cells against oxidative damage through intracellular ROS reduction, enhanced CAT activity, suppression of NF-kB, and prohibition of Nrf2 dysregulation. Thus, UCP might be a candidate for development of nutraceuticals against CVD and oxidative-related diseases and conditions.

Suvara K. Wattanapitayakul, Wattanased Jarisarapurin, Khwandow Kunchana, Vasun Setthawong, and Linda Chularojmontri. Prev Nutr Food Sci 2023;28:235-45. https://doi.org/10.3746/pnf.2023.28.3.235

Breast cancer is one of the most prevalent malignancies among women worldwide; its incidence and mortality are expected to increase annually. Cancer is composed not only malignant cells but also a complex and dynamic network of interacting stromal cells, specifically immune cells, which contribute to tumor development and progression. Increasing evidence highlights the critical role of tumor-associated macrophages (TAMs) and their inflammasome-driven signaling pathways in tumor progression and therapeutic resistance. Curcumin, a natural compound with anti-carcinogenic potential, has a role in the regulation of cancer development and progression. However, its specific effects on inflammasome activation in TAMs within the tumor microenvironment (TME) remain insufficiently characterized. THP-1 monocytes differentiated into macrophages acquire the TAM-like phenotype when treated with conditioned media from breast cancer cells. Our present study aimed to investigate the effects of curcumin on inflammasome activation in macrophages induced by breast cancer-derived conditioned media. Breast cancer-derived conditioned medium stimulation induced manifestation of a pro-inflammatory TAM-like phenotype, characterized by increased interleukin (IL)-1β secretion and upregulation of NOD-like receptor protein 3 (NLRP3), caspase-1, and IL-1β. Curcumin pretreatment significantly reduced IL-1β secretion as well as NLRP3 protein levels. Moreover, it also suppressed IL1B and CASP1 mRNA expression. In conclusion, curcumin attenuates tumor-induced inflammasome activation, highlighting its potential to modulate TME-driven breast cancer progression via the NLRP3/caspase-1/IL-1β axis.

Inflammation is a crucial defence mechanism against infections and harmful stimuli. However, uncontrolled inflammation can lead to low-grade inflammatory conditions that disrupt tissues and systemic function. Anti-inflammatories relieve symptoms. However, it can cause side effects and lack targeted control. These limitations are addressed by “peptide-based therapeutics.” The secretory leukocyte protease inhibitor (SLPI) has anti-inflammatory effects. However, SLPI has a short half-life and low cellular uptake. Using short peptides is a promising therapeutic strategy due to their small size, high effectiveness, and low immunogenicity. This research investigates the anti-inflammatory effect of SLPI-derived short peptides (SDSPs). SLPI was enzymatically digested in silico to produce SDSPs. The physiological properties of SDSPs and their anti-inflammatory activities in an LPS-induced RAW 264.7 cell inflammatory model were examined. Digested fragments, including 11 from pepsin (P1-11) and 9 from trypsin (T1-T9) digestion, plus the N-terminal fragment, were obtained. SDSPs are diverse physiological properties, and some are anti-inflammatory peptides (AIPs). Determination in the LPS-induced macrophage inflammation model found four potential SDSPs, specifically T6, T7, T8, and P7, exhibit anti-inflammatory properties by reducing excessive ROS generation and the activation of the MAPK/NF-κB pathway, similar to SLPI. This study identifies possible candidates for anti-inflammatory medicines warranting further investigation in in vivo and clinical trials for inflammation-related disorders.