Protective Effects of Proanthocyanidin-Rich Fraction from Red Rice Germ and Bran on Lung Cell Inflammation via Inhibition of NF-κB/NLRP3 Inflammasome Pathway.

The activation of the NLRP3 inflammasome pathway during infectious pathogen-induced immunopathology can lead to chronic inflammation and various adverse health outcomes. Identification of functional foods with anti-inflammatory properties is crucial for preventing inflammation triggered by NLRP3 inflammasome activation. This study aimed to investigate the anti-inflammatory properties of a proanthocyanidin-rich fraction obtained from red rice germ and bran against lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced condition in A549 lung cells. The proanthocyanidin-rich fraction from Yamuechaebia 3 red rice extract (YM3-PRF) was obtained using column chromatography with Sephadex LH20, and its total proanthocyanidin content was determined to be 351.43 ± 1.18 mg/g extract using the vanillin assay. A549 lung cells were pretreated with YM3-PRF at concentrations of 5-20 µg/mL prior to exposure to LPS (1 µg/mL) and ATP (5 nM). The results showed that YM3-PRF significantly inhibited the expression of inflammatory mRNAs (NLRP3, IL-6, IL-1ß, and IL-18) and the secretion of cytokines (IL-6, IL-1ß, and IL-18) in a dose-dependent manner (p < 0.05). Mechanistically, YM3-PRF exerted its anti-inflammatory effects by inhibiting NF-κB translocation and downregulating proteins associated with the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). These findings suggest that the proanthocyanidin-rich fraction from red rice germ and bran has protective effects and may serve as a potential therapeutic option for chronic inflammatory diseases associated with NLRP3 inflammasome activation.

Hesperetin from Root Extract of Clerodendrum petasites S. Moore Inhibits SARS-CoV-2 Spike Protein S1 Subunit-Induced NLRP3 Inflammasome in A549 Lung Cells via Modulation of the Akt/MAPK/AP-1 Pathway.

Inhibition of inflammatory responses from the spike glycoprotein of SARS-CoV-2 (Spike) by targeting NLRP3 inflammasome has recently been developed as an alternative form of supportive therapy besides the traditional anti-viral approaches. Clerodendrum petasites S. Moore (C. petasites) is a Thai traditional medicinal plant possessing antipyretic and anti-inflammatory activities. In this study, C. petasites ethanolic root extract (CpEE) underwent solvent-partitioned extraction to obtain the ethyl acetate fraction of C. petasites (CpEA). Subsequently, C. petasites extracts were determined for the flavonoid contents and anti-inflammatory properties against spike induction in the A549 lung cells. According to the HPLC results, CpEA significantly contained higher amounts of hesperidin and hesperetin flavonoids than CpEE (p < 0.05). A549 cells were then pre-treated with either C. petasites extracts or its active flavonoids and were primed with 100 ng/mL of spike S1 subunit (Spike S1) and determined for the anti-inflammatory properties. The results indicate that CpEA (compared with CpEE) and hesperetin (compared with hesperidin) exhibited greater anti-inflammatory properties upon Spike S1 induction through a significant reduction in IL-6, IL-1ß, and IL-18 cytokine releases in A549 cells culture supernatant (p < 0.05). Additionally, CpEA and hesperetin significantly inhibited the Spike S1-induced inflammatory gene expressions (NLRP3, IL-1ß, and IL-18, p < 0.05). Mechanistically, CpEA and hesperetin attenuated inflammasome machinery protein expressions (NLRP3, ASC, and Caspase-1), as well as inactivated the Akt/MAPK/AP-1 pathway. Overall, our findings could provide scientific-based evidence to support the use of C. petasites and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation.

Skin Wound-Healing Potential of Polysaccharides from Medicinal Mushroom Auricularia auricula-judae (Bull.).

Auricularia auricula-judae, a nutrient-rich mushroom used in traditional medicine, is a macrofungi that exhibits various biological properties. In this study, we have reported on the mechanisms that promote the wound-healing effects of a water-soluble polysaccharide-rich extract obtained from A. auricula-judae (AAP). AAP contained high amounts of polysaccharides (349.83 ± 5.00 mg/g extract) with a molecular weight of 158 kDa. The main sugar composition of AAP includes mannose, galactose, and glucose. AAP displayed antioxidant activity in vitro and was able to abort UVB-induced intracellular ROS production in human fibroblasts in cellulo. AAP significantly promoted both fibroblast and keratinocyte proliferation, migration, and invasion, along with augmentation of the wound-healing process by increasing collagen synthesis and decreasing E-cadherin expression (All p < 0.05). Specifically, the AAP significantly accelerated the wound closure in a mice skin wound-healing model on day 9 (2.5%AAP, p = 0.031 vs. control) and day 12 (1% and 2.5%AAP with p = 0.009 and p < 0.001 vs. control, respectively). Overall, our results indicate that the wound-healing activities of AAP can be applied in an AAP-based product for wound management.