RESUMEN
Non-small-cell lung cancer (NSCLC) is renowned for its aggressive and highly metastatic nature. In recent years, there has been a surge in interest regarding the therapeutic potential of traditional medicinal plants. Dracaena loureirin (D. loureirin), Ficus racemosa Linn. (F. racemosa), and Harrisonia perforata (Blanco) Merr. (H. perforata) are prominent traditional medicinal herbs in Thailand, recognized for their diverse biological activities, including antipyretic and anti-inflammatory effects. However, their prospective anti-cancer properties against NSCLC remain largely unexplored. This study aimed to evaluate the anti-cancer attributes of ethanolic extracts obtained from D. loureiri (DLEE), F. racemosa (FREE), and H. perforata (HPEE) against the A549 lung adenocarcinoma cell lines. Sulforhodamine B (SRB) assay results revealed that only DLEE exhibited cytotoxic effects on A549 cells, whereas FREE and HPEE showed no such cytotoxicity. To elucidate the anti-cancer mechanisms of DLEE, cell cycle and apoptosis assays were performed. The findings demonstrated that DLEE inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase in A549 cells through the downregulation of key cell cycle regulator proteins, including cyclin D1, CDK-2, and CDK-4. Furthermore, DLEE treatment facilitated apoptosis in A549 cells by suppressing anti-apoptotic proteins (Bcl-2, Bcl-xl, and survivin) and enhancing apoptotic proteins (cleaved-caspase-3 and cleaved-PARP-1). In summary, our study provides novel insights into the significant anti-cancer properties of DLEE against A549 cells. This work represents the first report suggesting that DLEE has the capability to impede the growth of A549 lung adenocarcinoma cells through the induction of apoptosis.
RESUMEN
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.
Asunto(s)
Oryza , Neumonía , Proantocianidinas , FN-kappa B , Inflamasomas , Interleucina-18 , Proteína con Dominio Pirina 3 de la Familia NLR , Interleucina-6 , Lipopolisacáridos , Proantocianidinas/farmacología , Inflamación , Alimentos Funcionales , Adenosina Trifosfato , Pulmón , Extractos Vegetales/farmacologíaRESUMEN
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.
Asunto(s)
Antipiréticos , Tratamiento Farmacológico de COVID-19 , Clerodendrum , Hesperidina , Petasites , Células A549 , Antiinflamatorios/farmacología , Caspasa 1/metabolismo , Clerodendrum/metabolismo , Citocinas/metabolismo , Flavonoides/farmacología , Hesperidina/farmacología , Humanos , Inflamasomas/metabolismo , Interleucina-18 , Interleucina-6 , Pulmón/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt , SARS-CoV-2 , Solventes , Glicoproteína de la Espiga del Coronavirus , Factor de Transcripción AP-1RESUMEN
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.