Nymphaea candida was used to treat hepatitis in Ugyhur medicine, and nicotiflorin (kaempferol 3-O-β-rutinoside) is the main characteristic component in this plant. In this study, The the hepatoprotective activities of nicotiflorin from N. candida were investigated by Concanavalin A (Con A, 20 mg/kg bw)- and d-Galactosamine (d-GalN, 800 mg/kg bw)-induced acute liver injury in mice. Pretreatment with nicotiflorin (25, 50, 100 mg/kg bw/day, p.o.) for ten days significantly reduced the impact of Con A toxicity (20 mg/kg bw) on the serum markers of liver injury, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). The hepatic anti-oxidant parameters (malondialdehyde, MDA; superoxide dismutase, SOD; glutathione, GSH; and nitric oxide, NO) in mice with nicotiflorin treatment were significantly antagonized for the pro-oxidant effects of Con A. Moreover, pretreatment with nicotiflorin (100 mg/kg bw) significantly decreased Con A-induced elevation in the serum levels of pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) (p < 0.05). A protective effect was reconfirmed against d-GalN-induced chemical liver injury, elevated serum enzymatic and cytokines levels were significantly decreased by nicotiflorin, and liver homogenate antioxidant indicators were significantly restored toward normal levels. Both histopathological studies also supported the protective effects of nicotiflorin. Therefore, the presented results suggest that nicotiflorin is the potent hepatoprotective agent that could protect the liver against acute immunological and chemical injury; this ability might be attributed to its antioxidant and immunoregulation potential.

Cistanche tubulosa is a traditional Chinese herbal medicine that is widely used to regulate immunity, and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. However, the application of CPhGs is negatively affected by their poor absorption and low oral utilization. Targeted drug delivery is an important development direction for pharmaceutics. Previous studies have indicated that CPhGs could block the conduction of the signaling pathways in TGF-β1/smad and inhibit the activation of hepatic stellate cells (HSCs). The aim of this study was to evaluate the anti-hepatic fibrosis effect of CPhG liposomes by inhibiting HSC activation, promoting apoptosis, blocking the cell cycle, suppressing the conduction of signaling pathways in focal adhesion kinase(FAK)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), and determining their in vitro hepatoprotective activity. In vitro release studies demonstrated that CPhG liposomes have a sustained release effect compared to drug CPhGs. HSC proliferation was inhibited after treatment with the CPhG liposomes (29.45, 14.72, 7.36 µg/mL), with IC₅₀ values of 42.54 µg/mL in the MTT assay. Different concentrations of the CPhG liposomes could inhibit HSC proliferation, promote apoptosis, and block the cell cycle. The MTT method showed an obvious inhibition of HSC proliferation after CPhG liposome and Recombinant Rat Platelet-derived growth factor-BB(rrPDGF-BB) treatment. The levels of collagen-1, metallopeptidase inhibitor 1 (TIMP-1), α smooth muscle actin (α-SMA), and phosphorylated PI3K/Akt were downregulated, and matrix metalloproteinase-1 (MMP-1) was upregulated, by pretreatment with different concentrations of CPhG liposomes. Moreover, 29.45 μg/mL of CPhG liposomes could decrease the expression of the FAK protein and the phosphorylated PI3K and Akt protein downstream of FAK by overexpression of the FAK gene. This experiment suggests that CPhG liposomes may inhibit the activation of HSCs by inhibiting FAK and then reducing the expression of phosphorylated Akt/PI3K, thereby providing new insights into the application of CPhGs for liver fibrosis.

To study whether ACT exerts anti-fatigue activity against CRF by inducing skeletal muscle mitophagy via suppressing PHD2 to upregulate the HIF-1α/BNIP3 signaling pathway. In this study, the molecular docking virtual screening technique was used to screen active components in Cistanche tubulosa that act as potential PHD2 inhibitors; the preliminary verification was carried out by Surface plasmon resonance (SPR) technology. BALB/c mice were treated with Paclitaxel (PTX, 10 mg/kg) and ACT (50, 100 mg/kg) alone or in combination for 20 days. Fatigue-related behaviors, energy metabolism and skeletal muscle mitochondria were assessed. Murine C2C12 myoblast was cultured and differentiated; then, a C26 tumor cell-conditioned medium was added to induce cachexia. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential, mitochondrial microstructure and function, autophagy, PHD2/HIF-1 and PINK1/Parkin signal pathway proteins were analyzed. Then, interfering RNA technology was used to silence PHD2 and observe the efficacy of ACT. We demonstrated that ACT exerted good binding activity with PHD2; ACT administration ameliorated PTX-induced muscle fatigue-like behavior via improving muscle quality and mitochondria function, increasing mitophagy, upregulating COXIV, CytoC, PINK1, Parkin, HIF-1α and BNIP3 expression and inhibiting p62, LC3B, PHD2 and Beclin-1 expression. The protective effect of ACT disappeared after transfection with the PHD2 gene knockdown plasmid Egln-1-RNAi. These results suggest that ACT can improve CRF by promoting mitophagy via suppression of PHD2 to remove dysfunctional mitochondria, demonstrating that ACT has huge prospects for clinical application in CRF treatment.

Per- and polyfluoroalkyl substances (PFAS) have been associated with thyroid dysfunction, but their relationship with papillary thyroid carcinoma (PTC) and relevant molecular processes remains unclear. We integrated bioinformatics analyses, a hospital-based case–control study, and in vitro experiments to investigate associations between PFAS exposure and PTC and to explore potentially relevant post-transcriptional RNA regulatory processes. Transcriptomic data, PFAS-associated genes, and m⁷G-associated genes were integrated to identify candidate genes. Among 24 overlapping candidates, 21 remained differentially expressed between PTC and normal thyroid tissues after false discovery rate correction, and EIF4E, NCBP1, and AGO2 were identified as candidate hub genes. The case–control study included 60 patients with newly diagnosed PTC and 60 controls. Serum concentrations of 17 PFAS were measured, and individual and mixture associations with PTC status were evaluated using logistic regression, weighted quantile sum regression, quantile g-computation, and Bayesian kernel machine regression. Higher concentrations of several PFAS were associated with lower odds of PTC, although the findings were not fully consistent across analytical models. In vitro, high concentrations of PFOA and PFOS reduced relative thyroid-cell viability, whereas wound-healing responses were variable and did not show a consistent enhancement. PFOA and PFOS exposure was also accompanied by altered EIF4E and NCBP1 mRNA expression, respectively. Overall, these findings support an association between PFAS exposure and PTC and identify m⁷G-associated post-transcriptional regulatory candidates, particularly EIF4E and NCBP1, that may contribute to PFAS-related thyroid cellular responses and warrant further mechanistic investigation.