Anti-cervical cancer effects of Compound Yangshe granule through the PI3K/AKT pathway based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Yangshe granule is a characteristic Chinese preparation against cervical cancer used at Fudan University Shanghai Cancer Center, and it consists of Hedyotis Diffusae Herba, Solani Lyrati Herba, Rubiae Radix et Rhizoma, Echinopsis Radix, Angelicae Sinensis Radix, Codonopsis Radix and Atractylodis Macrocephalae Rhizoma. AIM OF THE STUDY: The objective of the current study was to investigate the preclinical efficacy of compound Yangshe granule against cervical cancer and elucidate the underlying mechanisms. MATERIALS AND METHODS: Antitumor effect of the preparation was investigated in U14 cells in vitro and subcutaneous xenograft mice in vivo. The underlying mechanisms were investigated by through network pharmacological analysis and identified by in vitro study. The components of compound Yangshe granule were collected from the Traditional Chinese Medicine Systems Pharmacology database, and the corresponding targets were predicted by the SwissTargetPrediction database. The targets involved in cervical cancer were collected from the GeneCards, Online Mendelian Inheritance in Man and DrugBank databases. A protein‒protein interaction network was constructed by using the String platform. The drug-disease-target network was plotted by Cytoscape software. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed to investigate hub targets. RESULTS: After treatment with 0.5-10 mg/mL compound Yangshe granule, the survival rates of U14 cells gradually declined to 53.32% for 24 h, 23.62% for 48 h, and 12.81% for 72 h. The apoptosis rates of U14 cells gradually increased to 15.52% for 24 h, 23.87% for 48 h, and 65.01% for 72 h after treatment with 2-10 mg/mL compound Yangshe granule. After oral administration of compound Yangshe granule by xenograft mice, the tumor inhibition rates reached 52.27%, 74.62%, and 82.70% in the low, middle, and high dose groups, respectively. According to the network pharmacological analysis, quercetin, luteolin and naringenin were the most bioactive ingredients of the preparation. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that compound Yangshe granule may combat cervical cancer through the PI3K/AKT pathway. CONCLUSION: In summary, network pharmacology combined with biological experiments demonstrated that the main bioactive components including quercetin, luteolin and naringenin could inhibit the tumor growth by regulating the PI3K/AKT pathway and Bcl-2 family. Thus, compound Yangshe granule may be a promising adjuvant therapy for cervical cancer.

Orally Deliverable Dual-Targeted Pellets for the Synergistic Treatment of Ulcerative Colitis.

PURPOSE: The effective treatment of ulcerative colitis (UC) poses substantial challenges, and the aetiopathogenesis of UC is closely related to infectious, immunological and environmental factors. Currently, there is a considerable need for the development of orally bioavailable dosage forms that enable the effective delivery of therapeutic drugs to local diseased lesions in the gastrointestinal tract. METHODS: Berberine (BBR) and Atractylodes macrocephala Koidz (AM) volatile oil, derived from the Chinese herbs Coptis chinensis Franch and Atractylodes macrocephala Koidz, have anti-inflammatory and immunomodulatory activities. In this study, we prepared colon-targeted pellets loaded with BBR and stomach-targeted pellets loaded with AM volatile oil for the synergistic treatment of UC. The Box-Behnken design and ß-cyclodextrin inclusion technique were used to optimize the enteric coating formula and prepare volatile oil inclusion compounds. RESULTS: The two types of pellets were spherical and had satisfactory physical properties. The pharmacokinetic results showed that the AUC and MRT values of the dual-targeted (DPs) pellets were higher than those of the control pellets. In addition, in vivo animal imaging confirmed that the DPs could effectively deliver BBR to the colon. Moreover, compared with sulfasalazine and monotherapy, DPs exerted a more significant anti-inflammatory effect by inhibiting the expression of inflammatory factors including IL-1ß, IL-4, IL-6, TNF-α and MPO both in serum and tissues and enhancing immunity by decreasing the production of IgA and IgG. CONCLUSION: The DPs play a synergistic anti-UC effect by exerting systemic and local anti-inflammatory and provide an effective oral targeted preparation for the treatment of UC.

Hybrid Membrane-Coated Biomimetic Nanoparticles (HM@BNPs): A Multifunctional Nanomaterial for Biomedical Applications.

The application of nanoparticles in the diagnosis and treatment of diseases has undergone different developmental stages, but phagocytosis and nonspecific distribution have been the main factors restricting the transformation of nanobased drugs into clinical practice. In the past decade, the design of membrane-coated nanoparticles has gained increasing attention. It is hoped that the combination of the cell membrane's natural biological properties and the functional integration of synthetic nanoparticle systems can compensate for the shortage of traditional nanoparticles. The membrane coating gives the nanoparticles unique biological functions such as immune evasion and targeting capability. However, when the encapsulation of monotypic membranes does not meet the diverse demands of biomedicine, the combination of different cell membranes may offer more possibilities. In this review, the composition, preparation, and advantages of biomimetic nanoparticles coated with hybrid cell membranes are summarized, and the applications of hybrid membrane-coated biomimetic nanoparticles (HM@BNPs) in drug delivery, phototherapy, liquid biopsy, tumor vaccines, immune therapy, and detoxification are reviewed. Finally, the current challenges and opportunities with regard to HM@BNPs are discussed.

Wenxin Keli attenuates ischemia-induced ventricular arrhythmias in rats: Involvement of L­type calcium and transient outward potassium currents.

Wenxin Keli is the first state­sanctioned traditional Chinese medicine (TCM)-based antiarrhythmic drug. The present study aimed to examine whether long­term treatment with Wenxin Keli reduces ischemia­induced ventricular arrhythmias in rats in vivo, and if so, which mechanisms are involved. Male rats were treated with either saline (control group) or Wenxin Keli for 3 weeks and were subjected to myocardial ischemia for 30 min with assessment of the resulting ventricular arrhythmias. The L­type calcium current (ICa,L) and transient outward potassium current (Ito) were measured by the patch clamp technique in normal rat cardiac ventricular myocytes. During the 30­min ischemia, Wenxin Keli significantly reduced the incidence of ventricular fibrillation (VF) (P<0.05). The number of ventricular tachycardia (VT)+VF episodes and the severity of arrhythmias were significantly reduced by Wenxin Keli administration compared to the control group (P<0.05). In addition, Wenxin Keli inhibited ICa,L and Ito in a concentration­dependent manner. These results suggest that long­term treatment with Wenxin Keli may attenuate ischemia­induced ventricular arrhythmias in rats and that ICa,L and Ito may be involved in this attenuation.

Assessment of ventricular electrophysiological characteristics at periinfarct zone of postmyocardial infarction in rabbits following stellate ganglion block.

UNLABELLED: Assessment of Ventricular Electrophysiological Characteristics. INTRODUCTION: The aim of this study was to investigate the characteristics of ventricular electrophysiology following stellate ganglion block (SGB) at periinfarct zone in rabbits with myocardial infarction (MI). METHODS AND RESULTS: Sixty-four rabbits were randomly assigned to 2 groups: MI (n = 32), ligation of the anterior descending coronary and sham operation (SO) (n = 32), without coronary ligation. Both MI and SO groups were divided into 4 subgroups according to right or left SGB and corresponding control (n = 8, each). After 8 weeks, 90% of monophasic action potential duration (MAPD90) of epicardium, midmyocardium and endocardium, transmural dispersion of repolarization (TDR), effective refractory period (ERP), and ventricular fibrillation threshold (VFT) were measured at the infarct border zone (MI group) and corresponding zone (SO group) following SGB. For SGB, 0.5 mL of 0.25% bupivacaine was used. Compared with the corresponding control group, in both the MI and SO groups, left SGB (LSGB) prolonged the MAPD90 of the 3 layers, reduced TDR, and increased ERP and VFT (P < 0.05). However, right SGB (RSGB) shortened MAPD90, increased TDR, and reduced ERP and VFT (P < 0.05). CONCLUSION: The results of this study demonstrate that LSGB can increase the electrophysiological stability of ventricular myocardium.