Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be its main bioactive component. Recently, the antidepressant-like mechanism of icariin has been increasingly evaluated and demonstrated. However, there are few studies that have focused on the involvement of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT) signaling in mediating the perimenopausal depression effects of icariin. Perimenopausal depression is a chronic recurrent disease that leads to an increased risk of suicide, and poses a significant risk to public health. The aim of the present study was to explore the effect of icariin on the expression of the PI3K–AKT pathway related to proteins in a rat model of perimenopausal depression. Eighty percent of the left ovary and the entire right ovary were removed from the model rats. A perimenopausal depression model was created through 18 days of chronic unpredictable stimulation, followed by the gavage administration of target drugs for 30 consecutive days. We found that icariin administered at various doses significantly improved the apparent symptoms in the model rats, increased the organ indices of the uterus, spleen, and thymus, and improved the pathological changes in the ovaries. Moreover, icariin administration elevated the serum levels of female hormone estradiol (E₂), testosterone (T), and interleukin (IL)-2, decreased those of follicle stimulating hormone (FSH) and luteotropic hormone (LH), promoted the expression levels of estrogen receptor (ER) and ERα in the hypothalamus, and increased those of serotonin (5-HT), dopamine (DA), and noradrenaline (NA) in the brain homogenate. Furthermore, icariin elevated the expression levels of AKT, phosphorylation-akt (p-AKT), PI3K (110 kDa), PI3K (85 kDa), and B-cell lymphoma 2 (Bcl-2) in the ovaries, and inhibited those of Bax. These results show that icariin administration rebalanced the disordered sex hormones in perimenopausal depression rats, regulated the secretion of neurotransmitters in the brain, boosted immune function, and improved the perimenopausal syndrome. The mechanism of action may be related to the regulation of the expression of PI3K–AKT pathway-related proteins.

The present study was envisaged to investigate the chemical constituents and the intervention effects of Portulaca oleracea extract (POE) on acute alcoholic liver injury of rats. The chemical composition of POE was detected by high performance liquid chromatography (HPLC). Sixty male Wistar rats were divided into 6 groups: Normal control (NC) group, acute alcoholic liver injury model group (ALI), low, medium and high dose of POE (25, 50, 100 mg/kg) groups and bifendate (BF, 3.75 mg/kg) group. Each group was given by intragastrical administration for 7 days. Alcoholic liver injury was induced in the experimental model by administering 50% ethanol at 8 mL/kg and repeated administration after 6 h, for a period of 7 days. The results showed that pretreatment with POE significantly reduced the ethanol-elevated serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglyceride (TG). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were enhanced followed by administration of POE, while the content of nitric oxide (NO) and malondialdehyde (MDA) was found to decrease. Hepatic content of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was also reduced by POE treatment. These results indicated that POE could increase the antioxidant capacity and relieve the inflammatory injury of the liver cells induced by ethanol. Meanwhile, in our study, POE reduced the expression of miR-122, acetyl coenzyme A carboxylase (ACC) 1 mRNA and protein and increased the expression of lipoprotein lipase (LPL) mRNA and protein in liver, which indicated that POE could improve the lipid metabolism disorder induced by ethanol. Our findings suggested that POE had protective effects on acute alcoholic liver injury of rats.

The first reported case of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei, China. Thereafter, it spread through China and worldwide in only a few months, reaching a pandemic level. It can cause severe respiratory illnesses such as pneumonia and lung failure. Since the onset of the disease, the rapid response and intervention of traditional Chinese medicine (TCM) have played a significant role in the effective control of the epidemic. Yinqiaosan (YQS) was used to treat COVID-19 pneumonia, with good curative effects. However, a systematic overview of its active compounds and the therapeutic mechanisms underlying its action has yet to be performed. The purpose of the current study is to explore the compounds and mechanism of YQS in treating COVID-19 pneumonia using system pharmacology. A system pharmacology method involving drug-likeness assessment, oral bioavailability forecasting, virtual docking, and network analysis was applied to estimate the active compounds, hub targets, and key pathways of YQS in the treatment of COVID-19 pneumonia. With this method, 117 active compounds were successfully identified in YQS, and 77 potential targets were obtained from the targets of 95 compounds and COVID-19 pneumonia. The results show that YQS may act in treating COVID-19 pneumonia and its complications (atherosclerosis and nephropathy) through Kaposi sarcoma-related herpesvirus infection and the AGE-RAGE signaling pathway in diabetic complications and pathways in cancer. We distinguished the hub molecular targets within pathways such as TNF, GAPDH, MAPK3, MAPK1, EGFR, CASP3, MAPK8, mTOR, IL-2, and MAPK14. Five of the more highly active compounds (acacetin, kaempferol, luteolin, naringenin, and quercetin) have anti-inflammatory and antioxidative properties. In summary, by introducing a systematic network pharmacology method, our research perfectly forecasts the active compounds, potential targets, and key pathways of YQS applied to COVID-19 and helps to comprehensively clarify its mechanism of action.

Objective: To develop a lactoferrin-modified sodium alginate nanogel loaded with saikosaponin A (SA-Lf-NG@SAA) and evaluate its potential antidepressant-like effects following intranasal administration. Methods: SA-Lf-NG@SAA nanogels were prepared and optimized using single-factor experiments combined with response surface methodology. The optimized formulation was characterized in terms of particle size, zeta potential, stability, morphology, drug-loading performance, and in vitro release behavior. Male C57BL/6J mice were used to establish a chronic unpredictable mild stress (CUMS) model to evaluate the antidepressant-like effects of SA-Lf-NG@SAA after intranasal administration. Histopathological changes in the hippocampus and striatum were observed by hematoxylin and eosin staining. Western blotting was used to detect the expression of OLFM-1, OLFM-3, and OLFM-4 in olfactory bulb tissues, and immunofluorescence staining was performed to further examine their expression in the hippocampus and striatum. Results: The optimized SA-Lf-NG@SAA nanogels had an average particle size of approximately 85 nm and a zeta potential ranging from 0 mV to −10 mV, and they maintained their basic particle characteristics during a 14-day short-term physical stability study after dispersion in PBS. In vitro release analysis showed that SA-Lf-NG@SAA exhibited a distinct initial lag phase, followed by sustained drug release, with a cumulative release rate of approximately 75% at 72 h. Kinetic fitting using zero-order, first-order, Higuchi, and Korsmeyer–Peppas models showed that the post-lag release profile was best described by the Higuchi model, suggesting a prolonged release pattern under the present in vitro conditions. In CUMS mice, intranasal administration of SA-Lf-NG@SAA effectively improved depression-like behaviors, alleviated pathological damage in the hippocampus and striatum, and enhanced neuronal morphology. Western blotting showed that SA-Lf-NG@SAA increased the expression of OLFM-1, OLFM-3, and OLFM-4 in olfactory bulb tissues. Immunofluorescence staining further confirmed that the expression of these proteins was significantly enhanced in the hippocampus and striatum, especially in the high-dose SA-Lf-NG@SAA group. Conclusions: SA-Lf-NG@SAA nanogels were successfully developed as a potential nanogel-based formulation intranasal administration of saikosaponin A, showing favorable physicochemical properties, short-term stability, and prolonged release behavior. Intranasal administration of SA-Lf-NG@SAA alleviated depression-like behaviors in CUMS mice and improved histopathological alterations in the hippocampus and striatum. The antidepressant-like effects of SA-Lf-NG@SAA may be associated with the regulation of OLFM-family protein expression in depression-related brain regions. These findings suggest that SA-Lf-NG@SAA has potential as a nanogel-based intranasal formulation for the delivery of active components from traditional Chinese medicine in depression therapy. However, the specific contribution of lactoferrin modification requires further validation using unmodified SA-NG@SAA as a control.