Multiomics profiling of the therapeutic effect of Dan-deng-tong-nao capsule on cerebral ischemia-reperfusion injury.

BACKGROUND: Stroke is a complex physiological process associated with intestinal flora dysbiosis and metabolic disorders. Dan-deng-tong-nao capsule (DDTN) is a traditional Chinese medicine used clinically to treat cerebral ischemia-reperfusion injury (CIRI) for many years. However, little is known about the effects of DDTN in the treatment of CIRI from the perspective of gut microbiota and metabolites. PURPOSE: This study aimed to investigate the regulatory roles of DDTN in endogenous metabolism and gut microbiota in CIRI rats, thus providing a basis for clinical rational drug use and discovering natural products with potential physiological activities in DDTN for the treatment of CIRI. METHODS: The chemical composition of DDTN in vitro and in vivo was investigated using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLCHRMS), followed by target prediction using reverse molecular docking. Secondly, a biological evaluation of DDTN ameliorating neural damage in CIRI was performed at the whole animal level. Then, an integrated omics approach based on UHPLCHRMS and 16S rRNA sequencing was proposed to reveal the anti-CIRI effect and possible mechanism of DDTN. Finally, exploring the intrinsic link between changes in metabolite profiles, changes in the intestinal flora, and targets of components to reveal DDTN for the treatment of CIRI. RESULTS: A total of 112 chemical components of DDTN were identified in vitro and 10 absorbed constituents in vivo. The efficacy of DDTN in the treatment of CIRI was confirmed by alleviating cerebral infarction and neurological deficits. After the DDTN intervention, 21 and 26 metabolites were significantly altered in plasma and fecal, respectively. Based on the fecal microbiome, a total of 36 genera were enriched among the different groups. Finally, the results of the network integration analysis showed that the 10 potential active ingredients of DDTN could mediate the differential expression of 24 metabolites and 6 gut microbes by targeting 25 target proteins. CONCLUSION: This study was the first to outline the landscapes of metabolites as well as gut microbiota regulated by DDTN in CIRI rats using multi-omics data, and comprehensively revealed the systematic relationships among ingredients, targets, metabolites, and gut microbiota, thus providing new perspectives on the mechanism of DDTN in the treatment of CIRI.

Pseudo-allergic reactions induced by Chinese medicine injections: a review.

Traditional Chinese medicine injections (TCMIs) is a new dosage form of Chinese medicine, which plays a unique role in rescuing patients with critical illnesses that are difficult to replace. With the rapid development and widespread application of TCMIs in recent years, their adverse events have emerged and attracted much attention. Among them, pseudo-allergic reactions, i.e., the most significant adverse reactions occurring with the first dose without immunoglobulin E mediated conditions. Currently, studies on the types of TCMIs and antibiotic mechanisms that cause pseudo-allergic reactions are incomplete, and standard models and technical guidelines for assessing TCMIs have not been established. First, this review describes the causes of pseudo-allergic reactions, in which the components and structures responsible for pseudo-allergic reactions are summarized. Second, the mechanisms by which pseudo-allergic reactions are discussed, including direct stimulation of mast cells and complement activation. Then, research models of pseudo-allergic reaction diseases are reviewed, including animal models and cellular models. Finally, the outlook and future challenges for the development of pseudo-allergic reactions in traditional Chinese medicine (TCM) are outlined. This shed new light on the assessment and risk prevention of pseudo-allergic reactions in TCM and the prevention of clinical adverse reactions in TCM.

Alpiniae oxyphyllae Fructus and Alzheimer's disease: An update and current perspective on this traditional Chinese medicine.

Alzheimer's disease (AD) is a common progressive neuro-degenerative disease, and the morbidity and mortality are still on the rise. In spite of recent advances in AD treatment, their clinical efficacy has been limited, non-curative and easy to drug resistance. Alpiniae oxyphyllae Fructus (AOF), derived from the dried and mature fruits of the Zingiberaceae plant Alpinia oxyphylla Miq, is a choice in traditional Chinese medicine to treat AD, which has a good effect and has been used for a long time. Recent studies have demonstrated its potent activities in modulating multiple signaling pathways associated with ß-amyloid deposition, tau protein phosphorylation, chronic inflammation, oxidative stress. The neuropharmacological mechanism of AOF in AD have been fully illustrated in numerous studies. In this review, we first briefly described the active components of AOF and related mechanism for treating AD. And we also provide a systematic overview of recent progress on the pharmacokinetic characteristics of the active ingredients of AOF and analyzed their bioavailability differences in the development of AD. Thus, AOF hold a great therapeutic potential in the treatment of AD and is worthy of further research and promotion.

A Hollow NaGdF4 /AFn Nanosystem Based on "Relay Race" Release for Therapy.

To develop a multifunctional nanomaterial for dual-mode imaging and synergetic chemotherapy, curcumin (CUR) was physically entrapped into hollow upconversion NaGdF4 nanomaterial, then apoferritin (AFn) loaded with doxorubicin (DOX) was attached to the NaGdF4 surface. Subsequent modification with the targeting reagent folic acid (FA) led to generation of the CUR/NaGdF4 -DOX/AFn-FA conjugate for cancer treatment. X-ray diffraction, scanning (SEM) and transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy demonstrated the successful preparation of hexagonal-phase NaGdF4 and NaGdF4 -AFn-FA. Moreover, no toxicity was observed for NaGdF4 -AFn-FA. In vitro and in vivo experiments demonstrated that the two drugs are sequentially released from the nanocomposites. This two-drug system showed strong growth inhibitory effects on MCF-7 cells. Upconversion luminescence imaging and magnetic resonance (MR) imaging of NaGdF4 -AFn-FA were carried out. The results of this study show that NaGdF4 -AFn-FA can be used for targeted anticancer drug delivery as well as imaging, a novel multi-pronged theranostic system for tumor treatment.