Wenting Liao

Foods claiming specific efficacy are often marketed as safe and natural products; however, the illegal adulteration with synthetic chemical drugs to boost their purported efficacy is widespread (Bi...

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder with limited therapeutic agents. Rhynchophylline (RIN), a tetracyclic oxindole alkaloid isolated from Uncaria rhynchophylla, has multiple neuropharmacological activities, including anti-inflammatory, anti-depression, anti-neurodegenerative disease, and anti-drug addiction. Though it is reported that RIN exerts a neuroprotective effect against PD, the underlying protective mechanism remains obscure. In this study, a mass spectrometry-based metabolomic strategy combined with neurobehavioral tests, serum biochemical assays, and immunohistochemistry were employed to decipher the protective mechanism of RIN against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced subacute PD in mice. Our results indicated that RIN significantly improved the MPTP-induced behavioral abnormalities, reduced the loss of dopaminergic neurons, and reversed the secretion of inflammatory cytokines and oxidative stress indicators. Further studies showed that RIN significantly suppressed the expression of toll-like receptor 4, NOD-like receptor protein 3, and cyclooxygenase 2 in the mouse striatum. The results of serum metabolomics showed that RIN could ameliorate metabolic disorders in PD mainly through the regulation of retinol metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, and purine metabolism. These pieces of evidence revealed that RIN is a promising drug candidate for PD by alleviating neuroinflammation and maintaining metabolic homeostasis.

Rationale: Sini decoction (SND) is an efficient formula against DOX-induced cardiomyopathy (DCM), but the active ingredient combination (AIC) and mechanisms of SND remain unclear. Therefore, the present study aimed to identify the AIC and elucidate the underlying mechanism of AIC on DCM.

Breast cancer (BC) is a serious threat to women’s health and metastasis is the major cause of BC-associated mortality. Various techniques are currently used to preoperatively describe the metastatic status of tumors, based on which a comprehensive treatment protocol was determined. However, accurately staging a tumor before surgery remains a challenge, which may lead to the miss of optimal treatment options. More severely, the failure to detect and remove occult micrometastases often causes tumor recurrences. There is an urgent need to develop a more precise and non-invasive strategy for the detection of the tumor metastasis in lymph nodes and distant organs. Based on the facts that tumor metastasis is closely related to the primary tumor microenvironment (TME) evolutions and that metabolomics profiling of the circulatory system can precisely reflect subtle changes within TME, we suppose whether metabolomic technology can be used to achieve non-invasive and real-time monitoring of BC metastatic status. In this study, the metastasis status of BC mouse models with different tumor-bearing times was firstly depicted to mimic clinical anatomic TNM staging system. Metabolomic profiling together with metastasis-related changes in TME among tumor-bearing mice with different metastatic status was conducted. A range of differential metabolites reflecting tumor metastatic states were screened and in vivo experiments proved that two main metastasis-driving factors in TME, TGF-β and hypoxia, were closely related to the regular changes of these metabolites. The differential metabolites level changes were also preliminarily confirmed in a limited number of clinical BC samples. Metabolite lysoPC (16:0) was found to be useful for clinical N stage diagnosis and the possible cause of its changes was analyzed by bioinformatics techniques.

A “system to system” strategy of correlating drug-related and drug-induced UHPLC-Q-TOFMS serum metabolomic profiles was developed to screen effective constituents.

Hypoxic preconditioning (HPC) is well‑known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra‑performance liquid chromatography‑quadrupole time‑of‑flight mass spectrometry (UPLC‑QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC.