Fig 2: Effects of Dahuang-Huangqi decoction (DHHQD) on PI3K-AKT pathway signaling pathway. Unilateral ureteral obstruction (UUO) rats were administered water or Dahuang-Huangqi decoction (DHHQD) at 20 mL·kg-1·d-1 by oral gavage for 14 d Sham group rats were administered equal volumes of water. (a) mRNA expression of inflammation-related genes in DHHQD-administered rats compared to that in UUO rats was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as the internal reference. (b, c) Protein expression levels were determined using western blotting. Data are presented as mean ± SEM. *p < 0.05, **p < 0.01.

Fig 3: A schematic representation of the proposed pathway responsible for CDM combined with ASA in AML-MDS cells. (A) The predictive pathways of CDM and ASA in AML-MDS through network pharmacology. (B) CDM combined with ASA could inhibited the activation of PI3K/AKT signaling pathways, and then affected the expression of cell cycle and apoptosis-related proteins to induce cell cycle arrest and apoptosis in AML-MDS cells through experimental validation.

Fig 4: Expressions of CB1, PI3K, AKT and STAT3 were detected using western-blot assay. (A) Western-blot stripes. (B) CB1/ACTIN: model (##p < 0.01) vs. control; Tan IIA-L + AM251 groups (#p < 0.05) vs. control; Tan IIA-L (*p < 0.05) vs model; Tan IIA-H (**p < 0.01) vs model. (C) P-PI3K/PI3K:model (#p < 0.05) vs. control; Tan IIA-L + AM251 groups (#p < 0.05) vs. control; Tan IIA-L (**p < 0.01) vs. model; Tan IIA-H (**p < 0.01) vs model. (D) P-AKT/AKT: model (##p < 0.01) vs. control; Tan IIA-L + AM251 groups (#p < 0.05) vs. control; Tan IIA-L (*p < 0.05) vs model; Tan IIA-H (**p < 0.01) vs. model. (E) P-STAT3/STAT3:model (##p < 0.01) vs. control; Tan IIA-L + AM251 groups (#p < 0.05) vs. control; Tan IIA-L (*p < 0.05) vs. model.

Fig 5: Signaling pathway prediction and experimental flow. (A) Sleep deprivation inhibited PI3K/AKT/STAT3 signaling pathway, caused hippocampal damage and reduced neuronal dendritic spine density in rats; Tanshinone IIA may activate PI3K/AKT/STAT3 signaling pathway through cannabinoid receptor 1, protect rat hippocampal neurons and inhibit the damage caused by sleep deprivation. (B) Experimental procedure and drug administration method.