"Dual sensitive supramolecular curcumin nanoparticles" in "advanced yeast particles" mediate macrophage reprogramming, ROS scavenging and inflammation resolution for ulcerative colitis treatment.

Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on ß-cyclodextrin (ß-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for "supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects" in "advanced yeast particles", but also provided strong theoretical support multi-effect therapy for UC.

Chemotaxis-guided Self-propelled Macrophage Motor for Targeted Treatment of Acute Pneumonia.

Immune cells exhibit great potential as carriers of nanomedicine, attributed to their high tolerance to internalized nanomaterials and targeted accumulation in inflammatory tissues. However, the premature efflux of internalized nanomedicine during systemic delivery and slow infiltration into inflammatory tissues have limited their translational applications. Herein, a motorized cell platform as a nanomedicine carrier for highly efficient accumulation and infiltration in the inflammatory lungs and effective treatment of acute pneumonia are reported. ß-Cyclodextrin and adamantane respectively modified manganese dioxide nanoparticles are intracellularly self-assembled into large aggregates mediated via host-guest interactions, to effectively inhibit the efflux of nanoparticles, catalytically consume/deplete H2 O2 to alleviate inflammation, and generate O2 to propel macrophage movement for rapid tissue infiltration. With curcumin loaded into MnO2 nanoparticles, macrophages carry the intracellular nano-assemblies rapidly into the inflammatory lungs via chemotaxis-guided, self-propelled movement, for effective treatment of acute pneumonia via immunoregulation induced by curcumin and the aggregates.

Folic acid-modified lactoferrin nanoparticles coated with a laminarin layer loaded curcumin with dual-targeting for ulcerative colitis treatment.

Curcumin (CUR) is a promising natural compound in ulcerative colitis (UC) treatment, but limited by its low oral bioavailability and poor targeting ability. Therefore, given the targeting action of lactoferrin (LF) by binding to the LF receptors of intestinal epithelial cells (IECs) and of folic acid (FA) by binding to the FA receptors of macrophages, we developed an oral dual-targeting nanosystem. Laminarin (LA)-coated, FA-modified LF nanoparticles (NPs) were used to encapsulate CUR (LA/FA/CUR-NPs) with a food-grade, enzyme-sensitive, and dual-targeting capacity. For the generated NPs, LF improved the loading efficiency of CUR (95.08 %). The LA layer could improve the upper gastrointestinal tract stability of the NPs while improve drug release around colon lesion through ß-glucanase digestion. Based on the cellular uptake evaluation, FA/CUR-NPs were capable of specifically targeting colonic epithelial cells and macrophages through LF and FA ligands, respectively, to enhance the uptake efficiency. Moreover, based on the advantage of the dual-targeting strategy, oral administration of FA/CUR-NPs obviously reduced colitis symptoms by alleviating inflammation, accelerating colonic mucosal barrier repair and restoring the balance of the intestinal microbiota. This dual-targeted nanodesign corresponded to the multi-bioresponsibilities of CUR, thus offering a promising approach in UC treatment.

Recent advances in natural polysaccharides-based controlled release nanosystems for anti-cancer phototherapy.

Phototherapy, which relies on light to trigger phototherapeutic agents (PAs) to generate cytotoxic reactive oxygen species or hyperthermia, has received much attention in cancer treatment. However, traditional PAs have shortcomings such as low water solubility, easy aggregation-induced fluorescence quenching and low target site accumulation efficiency, which severely limit clinical anticancer applications. Naturally derived polysaccharides have attracted great attention in the scientific community in nano-drug delivery systems (NDDS) due to their abundant resources, biocompatibility, targeting ability, bioactivity and so on, which is expected to assist PAs to play a synergistic effect. This article reviews the recent progress of polysaccharides in the field of cancer phototherapy, including the advantages of polysaccharides as nanocarrier materials to deliver PAs; the main mechanism for the preparation of PAs-loaded polysaccharides nanoformulation; construction of polysaccharides-based NDDS for delivery of PAs and its functional modification strategy, hoping to further improve the therapeutic effect of phototherapy against cancer.

Potential mechanisms of Lian-Zhi-Fan solution for TNBS-induced ulcerative colitis in rats via a metabolomics approach.

Lian-Zhi-Fan (LZF) decoction is a hospital-prescribed traditional Chinese medicine botanical drug prepared by the fermentation of decocted Coptidis Rhizome (Huanglian), Gardeniae Fructus (Zhizi), and alum (Baifan). It has been used clinically in China for the treatment of anal fistula, perianal abscess, ulcerative colitis (UC), and other anorectal diseases for hundreds of years. However, due to the complexity of traditional Chinese medicine, the potential mechanisms of LZF in the treatment of UC have remained unknown. This study primarily investigated the remarkable pharmacological effects of LZF on TNBS-induced UC rats. To explore the complex targets and regulatory mechanisms of metabolic networks under LZF intervention, a metabolomics approach mediated by HPLC/Q-TOF-MS analysis was used to screen the different metabolites and their metabolic pathways in the serum in order to characterize the possible anti-UC mechanisms of LZF. After rectal administration of LZF for seven consecutive days, significant amelioration effects on body weight loss, DAI score, and colon inflammation were found in UC rats. Based on this, further metabolomics identified 14 potential biomarkers in the treatment of UC with LZF, of which five possessed diagnostic significance: L-alanine, taurocholic acid, niacinamide, cholic acid, and L-valine. These metabolites are mainly involved in 12 metabolic pathways, including nicotate and nicotinamide metabolism, glycospholipid metabolism, arginine and proline metabolism, primary bile acid biosynthesis, and pantothenate and CoA biosynthesis. These metabolic pathways suggest that LZF ameliorates UC by regulating amino acid metabolism, fat metabolism, and energy production. This study provides a useful approach for exploring the potential mechanisms of herbal prescription in UC treatment mediated by metabolomics.

Anti-inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K/Akt/mTOR signaling pathway and regulating gut microbiota.

This study aimed to analyze the therapeutic effect of Rhein on ulcerative colitis (UC) in mice and its possible mechanism. LPS-induced UC cell model and DSS-induced UC mouse model were used to analyze the antiinflammatory effect of Rhein on UC in vitro and in vivo, respectively. Network pharmacology analysis was conducted to identify potential signaling pathways involved in Rhein treating UC, and the results were further confirmed through western blotting assay. 16sRNA sequencing was performed to study the regulatory effect of Rhein on gut microbiota in UC mice. As indicated by the results, Rhein could significantly inhibit the production of pro-inflammatory cytokines (e.g., TNF-α, IL-6 and IL-1ß) in vivo and in vitro, and alleviate DSS-induced UC-associated symptoms in mice (e.g., colon shortening, weight loss, diarrhea and hematochezia). The PI3K/Akt/mTOR signaling pathway was predicted as the potential interacting protein of Rhein in the treatment of UC through network pharmacology analysis. It was found through western blotting assay that the Rhein treatment could significantly inhibit the PI3K/Akt/mTOR signaling pathway by decreasing the phosphorylated protein levels of PI3K, Akt, mTOR and p70S6K1. By 16sRNA gene sequencing analysis, Rhein administration could partially reverse the gut dysbacteriosis of mice induced by DSS and decrease pathogenic bacteria (e.g., Enterobacteriaceae and Turicibacter). It was positively correlated with the production of pro-inflammatory cytokines above, whereas the increase in probiotics (e.g., Unspecified-S24-7 and Rikenellaceae) was negatively correlated with the production of pro-inflammatory cytokines. In conclusion, Rhine had anti-UC efficacy, which was demonstrated by mitigating the UC symptoms and reducing intestinal inflammation by inhibiting the PI3K/Akt/mTOR signaling pathway and modulating gut microbiota.

pH/ROS dual-sensitive and chondroitin sulfate wrapped poly (ß-amino ester)-SA-PAPE copolymer nanoparticles for macrophage-targeted oral therapy for ulcerative colitis.

An oral nanoparticle (NPs) encapsulated in chitosan/alginate hydrogel (CA-Gel) with dual-sensitive in pH and reactive oxygen species (ROS) was developed to load curcumin (CUR) based on the intracellular-specific characteristics of macrophages. Chondroitin sulfate (CS) wrapped PBAE-SA-PAPE with intracellular pH/ROS dual-sensitive characteristics and CUR via a simple nanoprecipitation method to form NPs (CS-CUR-NPs), and mixed CA-Gel to acquire the final preparation (CS-CUR-NPs-Gel). CS-CUR-NPs displayed an ideal average particle size (179.19±5.61nm) and high encapsulating efficiency (94.74±1.15%). CS showed a good targeting ability on macrophages and the CA-Gel contribution in protecting NPs from being destroyed in the upper gastrointestinal tract. As expected, CS-CUR-NPs-Gel could significantly alleviate inflammation in DSS-induced UC mice via TLR4-MAPK/NF-κB pathway. This study is the first to attempt to design a novel pH/ROS dual-stimulated release strategy in helping intracellular CUR delivery and anticipated for efficient anti-UC therapy.

Calcium pectinate and hyaluronic acid modified lactoferrin nanoparticles loaded rhein with dual-targeting for ulcerative colitis treatment.

Herein, dual-bioresponsive of Rhein (RH) in promoting colonic mucous damage repair and controlling inflammatory reactions were combined by the dual-targeting (intestinal epithelial cells and macrophages) oral nano delivery strategy for effective therapy of ulcerative colitis (UC). Briefly, two carbohydrates, calcium pectinate (CP) and hyaluronic acid (HA) were used to modify lactoferrin (LF) nanoparticles (NPs) to encapsulate RH (CP/HA/RH-NPs). CP layer make CP/HA/RH-NPs more stable and protect against the destructive effects of the gastrointestinal environment and then release HA/RH-NPs to colon lesion site. Cellular uptake evaluation confirmed that NPs could specifically target and enhance the uptake rate via LF and HA ligands. in vivo experiments revealed that CP/HA/RH-NPs significantly alleviated inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway and accelerated colonic healing. Importantly, with the help of CP, this study was the first to attempt for LF as a targeting nanomaterial in UC treatment and offers a promising food-based nanodrug in anti-UC.

[Research progress of effect of Rhei Radix et Rhizoma and its anthraquinone in treatment of autoimmune diseases].

Rhei Radix et Rhizoma was first recorded in Shennong Ben Cao Jing, with a wide range of pharmacological activities. Autoimmune disease is a kind of disease that damages the tissue structure and function of immune cells and their components due to the impairment of immune tolerance function, including atherosclerosis, multiple sclerosis, gout, rheumatoid arthritis, autoimmune thyroiditis, ulcerative colitis, type 1 diabetes and IgA nephropathy. In recent years, clinical and experimental studies show that Rhei Radix et Rhizoma has potential therapeutic effects on autoimmune diseases. Under the guidance of the theory of traditional Chinese medicine, this paper reviews therapeutic and intervening effects of Rhei Radix et Rhizoma and its main active ingredient anthraquinone on autoimmune diseases. It also puts forward new study directions in view of the existing problems in studies of rhubarb and its anthraquinone, with the aim to provide reference for clinical treatment and scientific studies of effect of Rhei Radix et Rhizomaon autoimmune diseases.

Therapeutic efficacy and safety of Kangfuxin in combination with rabeprazole in the treatment of peptic ulcer: A systematic review and meta-analysis.

BACKGROUND: Kangfuxin (KFX), a well-known Chinese patent medicine which extracted from Periplaneta americana, is widely used as an adjuvant in the treatment of peptic ulcers (PUs) with proton pump inhibitors (PPIs) such as rabeprazole, in China. However, no clear consensus has been reached on the efficacy for PU treatment. METHODS: We searched in 7 electronic databases to find randomized controlled trials (RCTs) completed before May 31, 2020 to explore the clinical efficiency of KFX plus rabeprazole in the treatment of PU. Risk ratio (RR) corresponding to 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by both Egger's and Begg's tests. Statistical analyses were performed using RevMan 5.4 and Stata version 10.0. RESULTS: Twenty-five RCTs, comprising 2555 PU patients, were included in this study. Meta-analysis showed that, when compared with rabeprazole-based treatment alone, KFX plus rabeprazole significantly improved the healing rate (RR = 1.34, 95% CI 1.25-1.44) and overall response rate of ulcers (RR = 1.16, 95% CI 1.13-1.20), alleviated the clinical symptoms of PU (RR = 1.14, 95% CI 1.08-1.21), and reduced the recurrence of PU (RR = 0.38, 95% CI 0.24-0.61) without an increase in the occurrence of adverse events (RR = 0.92, 95% CI 0.66-1.28). CONCLUSION: Our study suggests that KFX combined with rabeprazole showed positive therapeutic effects and is safe for treating PU, which may provide more reliable evidence for the clinical use of KFX in the treatment of PU.

Genipin-crosslinked human serum albumin coating using a tannic acid layer for enhanced oral administration of curcumin in the treatment of ulcerative colitis.

Curcumin (CUR) is a promising edible phytochemical compound with ideal ulcerative colitis (UC) treatment activity; however, it is characteristically instable in the digestive tract and has a short retention time in colon. Therefore, we designed and fabricated an oral food-grade nanocarrier composed of tannic acid (TA)-coated, Genipin (Gnp)-crosslinked human serum albumin (HSA) to encapsulate CUR (TA/CUR-NPs). The resulting CUR nanoparticles (NPs) were about 220 nm and -28.8 mV. With the assistance of TA layer and Gnp-crosslinking, the entire nano-scaled system effectively delayed CUR release in simulated gastric fluid, prolonged its colon adhesion and increased its uptake in Caco-2 cells. As expected, TA/CUR-NPs oral administration significantly alleviated colitis symptoms in DSS-treated mice when compared with controls by inhibiting the TLR4-linked NF-κB signaling pathway. Collectively, this study indicates that we have developed a convenient, eco-friendly, nano-scaled vehicle for oral delivery of CUR with anti-UC benefit.

[Research progress on anti-tumor effects and mechanisms of triptolide and its combined application].

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.

Assessment of antibacterial properties and the active ingredient of plant extracts and its effect on the performance of crucian carp (Carassius auratus gibelio var. E'erqisi, Bloch).

BACKGROUND: In this study, the antibacterial properties and active ingredient of plant extracts and its effect on the performance of crucian carp (Carassius auratus gibelio var. E'erqisi, Bloch) were assessed. RESULTS: The transmission electron microscopy and flow cytometric analysis showed that the antibacterial activity of plant extracts is due to the disruption of the cell membrane and the leakage of cytoplasmic contents. The UPLC-MS/MS analysis showed that the contents of gallic acid, (-)-epigallocatechin, (+)-catechin, (-)-epigallocatechin gallate, (-)-epicatechin gallate, aloe-emodin, rhein, emodin, chrysophanol, and physcion, were 5.27%, 3.30%, 1.08%, 19.32%, 5.46%, 0.23%, 0.56%, 1.28%, 0.75% and 0.39% in plant extracts, respectively. Results of feeding experiment showed that feeding crucian carp with 1.0% and 2.0% plant extracts significantly enhanced specific growth rate, serum total protein, lysozyme, catalase and superoxide dismutase activities, and decreased the feed conversion rate, malondialdehyde contents and the mortality rate (P < 0.05). CONCLUSION: It can be concluded that plant extracts added to fish feed can act as natural antimicrobial and immunostimulants to prevent pathogenic infection, enhance immune response, and promote growth of the fish.