In this study, dextran sulfate sodium (DSS)-induced in vivo model and LPS-stimulated in vitro model were used to confirm whether ethanol extract of Cnidii Rhizoma (EtCR) could ameliorate UC. EtCR improved symptoms of UC, including body weight loss, colon length shortening, disease activity index (DAI), and colon mucosal damage. In addition, EtCR decreased inflammatory mediators, including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), in colon tissue. To further confirm the UC improving mechanism, RAW 264.7 cells and HT29 human epithelial cells were used. EtCR reduced expression of inflammatory cytokines (IL-1β, TNF-α, and IL-6) and inflammatory mediators (nitric oxide and prostaglandin E₂) via JNK and NF-κB signaling pathway in RAW 264.7 cells. In addition, EtCR increased expression of trefoil factor 3 (TFF3), which is an epithelial cell protective factor, in HT29 cells. Taken together, our study suggests that EtCR has treatment effect on UC and can be a therapeutic agent.

Andrographis paniculata leaves have been widely used in traditional medicine due to their rich content of phenolic compounds. In this study, we evaluated the total phenolic and flavonoid content of Andrographis paniculata leaf extracts (ALE), as well as its antioxidant activities against DPPH, ABTS, and hydrogen peroxide radicals. Additionally, we conducted cell viability assays, RT-PCR, and western blot analysis to investigate the biochemical effects of ALE on UVB-induced HaCaT cells. Our results revealed that ALE exhibited a high concentration of polyphenols and flavonoids, which were associated with potent abiotic antioxidant properties. Furthermore, ALE treatment effectively abrogated the damage caused by UVB radiation on key molecules such as hyaluronan synthase 1, Aquaporin 3, and loricrin in HaCaT cells. ALE also demonstrated the ability to reduce the overactivation of mitogen-activated protein kinases (MAPKs) and the expression of pro-inflammatory cytokines, including interleukin-6 and interleukin-1β in UVB-induced HaCaT cells. Additionally, ALE positively influenced the peroxisome proliferator-activated receptor alpha in these cells. Overall, our findings highlight the antioxidant and anti-inflammatory effects of ALE, as well as its significant role in modulating skin barrier functions. These results contribute to the growing body of evidence supporting the therapeutic potential of ALE in skincare and dermatological applications.

Mayaro virus (MAYV) hijacks the host´s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPKs inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126 or Losmapimod were quantified using plaque assay. Also, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

The human innate immune response to the pore-forming toxin of Vibrio cholerae VCC, is currently under study. Here, in vitro studies on a human macrophage cell line (THP-1), helped explore the activated pathways involved on the onset the innate immune response towards the cytotoxin. The secreted monomeric 65 KDa form interacts with mature macrophages in pg/ml concentrations, determined by dose response experiments after treatments under 1 h. Non vacuolating concentrations (pg/ml) were applied to the cells; immunoblots revealed activation of MAPKs: early overexpression of p38 and ERK. Cell lysis by release of lactate dehydrogenase (LDH) was not apparent in the first hour, nonetheless it was positive after 24 h. Finally, to discern whether the VCC stimulates transcriptional activators via MAPKs pathway, NF-κB and AP-1 were studied by real time quantitation. Increased expression of p50 (NF-κB), cJun and cFos (AP-1) was observed. Given that NF-κB is the transcription factor initiating inflammation of innate immune response and in turn, AP-1 is responsible for cell surviving response, results from this study lead us to conclude that VCC in vitro treatments, induce a pro-inflammatory and a surviving response, in less than one hour on activated macrophages.