Background: Baicalin (BAN) has attracted widespread attention due to its low-toxicity and efficient antitumor activity, but its poor water solubility and low bioavailability severely limit its clinical application. Development of a targeted drug delivery system is a good strategy to improve the antitumor activity of baicalin. Methods: We prepared a BAN nano-drug delivery system [email protected]@BAN with a zeolite imidazole framework-8 (ZIF-8) as a carrier, which can achieve the response of folate receptor (FR). We characterized this system in terms of morphology, particle size, zeta-potential, infrared (IR), ultraviolet (UV), x-ray diffraction (XRD), and Brunel-Emmett-Teller (BET), and examined the in vitro cytotoxicity and cellular uptake properties of [email protected]@BAN using MCF-7 cells. Lastly, we established a 4T1 tumor-bearing mouse model and evaluated its in vivo anti-mammary cancer activity. Results: The [email protected]@BAN nano-delivery system had good dispersion with a BAN loading efficiency of 41.45 ± 1.43%, hydrated particle size of 176 ± 8.1 nm, Zeta-potential of − 23.83 ± 1.1 mV, and slow and massive drug release in an acidic environment (pH 5.0), whereas release was 11.03% in a neutral environment (pH 7.4). In vitro studies showed that [email protected]@BAN could significantly enhance the killing effect of BAN on MCF-7 cells, and the folic acid-mediated targeting could lead to better uptake of nanoparticles by tumor cells and thus better killing of cancer cells. In vivo studies also showed that [email protected]@BAN significantly increased the inhibition of the proliferation of solid breast cancer tumors (p < 0.01 or p < 0.001). Conclusion: The [email protected]@BAN nano-drug delivery system significantly enhanced the anti-breast cancer effect of baicalin both in vivo and in vitro, providing a more promising drug delivery system for the clinical applications and tumor management.

Pterostilbene is a natural 3,5-dimethoxy analog of resveratrol. This stilbene compound has a strong bioactivity and exists widely in Dalbergia and Vaccinium spp. Besides natural extraction, pterostilbene can be obtained by biosynthesis. Pterostilbene has become popular because of its remarkable pharmacological activities, such as anti-tumor, anti-oxidation, anti-inflammation, and neuroprotection. Pterostilbene can be rapidly absorbed and is widely distributed in tissues, but it does not seriously accumulate in the body. Pterostilbene can easily pass through the blood-brain barrier because of its low molecular weight and good liposolubility. In this review, the studies performed in the last three years on resources, synthesis, bioactivity, and pharmacokinetics of pterostilbene are summarized. This review focuses on the effects of pterostilbene on certain diseases to explore its targets, explain the possible mechanism, and look for potential therapeutic applications.

Sophoricoside, an isoflavone glycoside isolated from Sophora japonica (Leguminosae), has been widely reported as an immunomodulator. In this study, the effects of sophoricoside on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were investigated. Treatment with sophoricoside at concentrations of 1–10 μM inhibited lipid accumulation in HepG2 cells in a dose-dependent manner. At the same concentration range, no effect on cell viability was observed in the MTT assay. Inhibition of lipogenesis was associated with the downregulation of SREBP-1a, SREBP-1c, SREBP-2 and their downstream target genes (FAS, ACC, HMGR) as revealed by realtime quantitative PCR. The lipid-lowering effect was mediated via the phosphorylation of AMPK. Further investigation of the activities of this isoflavone showed that sophoricoside has the capability to increase glucose uptake by C2C12 myotubes. It also effectively inhibited the activities of α-glucosidase and α-amylase in vitro and remarkably lowered postprandial hyperglycaemia in starch-loaded C57BL6/J mice. These results suggest that sophoricoside is an effective regulator of lipogenesis and glucose consumption and may find utility in the treatment of obesity and type 2 diabetes.

Cadmium (Cd) is a hazardous heavy metal environmental pollutant that has carcinogenic, teratogenic, and mutagenic properties. Excessive exposure to Cd can induce oxidative stress, which greatly harms the male reproductive system. Anthocyanins have remarkable antioxidative, anti-inflammatory, and anti-stress properties. In this study, we investigated the effects of anthocyanins and the underlying mechanisms through which anthocyanins mitigate Cd-induced reproductive damage. We isolated and purified Lycium ruthenicum Murray anthocyanin extract (LAE) and performed UHPLC-MS/MS to identify 30 different anthocyanins. We established an ICR mouse Cd injury model by administering 5 mg/kg/day CdCl₂ for 28 consecutive days. LAE at 500 mg/kg/day effectively ameliorated testicular damage and preserved spermatogenesis. The mice in the LAE-treated group had elevated testosterone and inhibin B levels. Additionally, the treatment restored the activity of antioxidant enzymes, including T-SOD, CAT, and GR, and substantially increased the levels of the non-enzymatic antioxidant GSH. Research findings indicate that LAE can activate the SIRT1/Nrf2/Keap1 antioxidant pathway. This activation is achieved through the upregulation of both the SIRT1 gene and protein levels, leading to the deacetylation of Nrf2. Moreover, LAE reduces the expression of Keap1, alleviating its inhibitory effect on Nrf2. This, in turn, facilitates the uncoupling process, promoting the translocation of Nrf2 to the nucleus, where it governs downstream expression, including that of HO-1 and GPX1. LAE effectively mitigated toxicity to the reproductive system associated with exposure to the heavy metal Cd by alleviating oxidative stress in the testes.

We introduce the use of Ingenuity Pathway Analysis to analyzing global metabonomics in order to characterize phenotypically biochemical perturbations and the potential mechanisms of the gentamicin-induced toxicity in multiple organs. A single dose of gentamicin was administered to Sprague Dawley rats (200 mg/kg, n = 6) and urine samples were collected at −24–0 h pre-dosage, 0–24, 24–48, 48–72 and 72–96 h post-dosage of gentamicin. The urine metabonomics analysis was performed by UPLC/MS, and the mass spectra signals of the detected metabolites were systematically deconvoluted and analyzed by pattern recognition analyses (Heatmap, PCA and PLS-DA), revealing a time-dependency of the biochemical perturbations induced by gentamicin toxicity. As result, the holistic metabolome change induced by gentamicin toxicity in the animal's organisms was characterized. Several metabolites involved in amino acid metabolism were identified in urine, and it was confirmed that gentamicin biochemical perturbations can be foreseen from these biomarkers. Notoriously, it was found that gentamicin induced toxicity in multiple organs system in the laboratory rats. The proof-of-knowledge based Ingenuity Pathway Analysis revealed gentamicin induced liver and heart toxicity, along with the previously known toxicity in kidney. The metabolites creatine, nicotinic acid, prostaglandin E2, and cholic acid were identified and validated as phenotypic biomarkers of gentamicin induced toxicity. Altogether, the significance of the use of metabonomics analyses in the assessment of drug toxicity is highlighted once more; furthermore, this work demonstrated the powerful predictive potential of the Ingenuity Pathway Analysis to study of drug toxicity and its valuable complementation for metabonomics based assessment of the drug toxicity.

Ginsenoside Rg1, a natural triterpenoid saponins compound isolated from the Panax species, has been found to possess neuroprotective properties in neurodegenerative diseases such as Alzheimer’s disease (AD). However, its pharmacological mechanism on AD has not been studied. In this study, an ultra-performance liquid chromatography combined with quadrupole time of-flight mass spectrometry (UPLC-Q/TOF-MS) based non-targeted metabolomics strategy was performed to explore the mechanism of Ginsenoside Rg1 protecting against AD mice by characterizing metabolic biomarkers and regulation pathways changes. A total of nineteen potential metabolites in serum were discovered and identified to manifest the difference between wild-type mice and triple transgenic mice in control and model group, respectively. Fourteen potential metabolites involved in ten metabolic pathways such as linoleic acid metabolism, arachidonic acid metabolism, tryptophan metabolism and sphingolipid metabolism were affected by Rg1. From the ingenuity pathway analysis (IPA) platform, the relationship between gene, protein, metabolites alteration and protective activity of ginsenoside Rg1 in AD mice are deeply resolved, which refers to increased level of albumin, amino acid metabolism and molecular transport. In addition, quantitative analysis of key enzymes in the disturbed pathways by proteomics parallel reaction was employed to verify changed metabolic pathway under Ginsenoside Rg1. The UPLC-Q/TOF-MS based serum metabolomics method brings about new insights into the pharmacodynamic studies of Ginsenoside Rg1 on AD mice.