Daturataturin A Ameliorates Psoriasis by Regulating PPAR Pathway.

Psoriasis is a kind of severe immune-mediated systemic skin disorder, becoming a worldwide public health concern. Daturataturin A (DTA), a withanolide compound, exerts excellent anti-inflammatory and anti-proliferative properties. The objective of this study is to elucidate the effect of DTA on psoriasis and its potential mechanism. We established psoriasis-like keratinocytes model by stimulating HaCaT cells with M5 cocktail cytokines including Interleukin (IL)-17A, IL-22, oncostatin M, IL-1α, and tumor necrosis factor-α (TNF-α), followed by intervention with DTA. The potential effects and mechanisms of DTA on psoriasis were evaluated in vitro. DTA was found to be able to inhibit hyperproliferation, promote apoptosis, decrease the release of pro-inflammatory cytokines, downregulate keratin expression, and improve lipid metabolism via regulating the peroxisome proliferator-activated receptor (PPAR) signaling pathway by M5 cocktail cytokines stimulation in HaCaT cells. DTA ameliorated lipid metabolism of psoriasis and exerted the potential anti-psoriasis effects by regulating PPAR pathway in vitro, suggesting that DTA may act as a new therapeutic agent for psoriasis.

Hedyotis diffusa-Sculellaria barbata (HD-SB) suppresses the progression of colorectal cancer cells via the hsa_circ_0039933/hsa-miR-204-5p/wnt11 axis.

Our previous study confirmed that the combination of Hedyotis diffusa (HD) and Scutellaria barbata (SB) significantly inhibited colorectal cancer cell proliferation and the WNT signaling pathway. However, the exact molecular modulation remains unclear. In this study, colorectal cancer cells (SW620) were treated with 1 mg/mL HD-SB for 24 h, and high-throughput sequencing of circRNAs was performed. The level of hsa_circ_0039933 in three colorectal cancer cell lines (HT-29, SW620, and HCT116) was verified by qPCR. After transfection of hsa_circ_0039933 overexpression plasmids or small interfering RNAs, CCK8, apoptosis, cell migration, and cell invasion were utilized to evaluate the function of hsa_circ_0039933 in the progression of colorectal cancer cells. We identified hsa_circ_0039933, which was downregulated in HD-SB-induced colorectal cancer cells and positively related to colorectal cancer progression. In SW620 cells with relatively high expression of hsa_circ_0039933, interfering with the expression of hsa_circ_0039933 inhibited the proliferation, invasion, and migration of SW620 cells. In HCT116 cells with relatively low expression of hsa_circ_0039933, overexpression of hsa_circ_0039933 promoted the proliferation and invasion and migration ability of HCT116. Mechanistically, hsa_circ_0039933 targeted hsa-miR-204-5p to increase the expression of wnt11, leading to the activation of the Wnt pathway, thereby promoting the proliferation of colorectal cancer cells. This work revealed the potential molecular mechanism of HD-SB for the treatment of colorectal cancer, which was to inhibit the Wnt signaling pathway through the hsa_circ_0039933/hsa-miR-204-5p/wnt11 axis, then suppressing proliferation, migration, and invasion in the colorectal cancer cell.

Xihuang pill induces pyroptosis and inhibits progression of breast cancer cells via activating the cAMP/PKA signalling pathway.

Xihuang pill (XHP), a traditional Chinese medicine, has been shown to be effective for breast cancer (BC) therapy in clinical trials. However, the molecular mechanism of XHP in BC remains unclear. The molecular mechanism of XHP in BC was investigated in vivo by generating murine mammary carcinoma 4T1 cell xenografts. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect pyroptosis-related indicators. Transcriptome sequencing was used to identify potential targets of XHP. Cell counting kit-8 (CCK-8), EdU, cell wound-healing, and transwell assays were performed to investigate the role of XHP in BC cells. Western blotting was performed to identify proteins related to the cAMP/PKA signalling pathway. XHP inhibited the growth of BC and induced pyroptosis. Western blotting confirmed the significant association between XHP and the cAMP/PKA signalling pathway revealed by Kyoto Encyclopedia of Genes and Genomes pathway analysis. XHP inhibited BC cell proliferation, migration, and invasion, and induced pyroptosis. Inhibiting the cAMP/PKA signalling pathway reversed the anti-cancer activity of XHP. XHP inhibits proliferation, migration, and invasion, and induces pyroptosis of BC cells via activating the cAMP/PKA signalling pathway.