Overlooked Spherical Nanoparticles Exist in Plant Extracts: From Mechanism to Therapeutic Applications.

To date, plant medicine research has focused mainly on the chemical compositions of plant extracts and their medicinal effects. However, the therapeutic or toxic effects of nanoparticles in plant extracts remain unclear. In this study, large numbers of spherical nanoparticles were discovered in some plant extracts. Nanoparticles in Turkish galls extracts were used as an example to examine their pH responsiveness, free radical scavenging, and antibacterial capabilities. By utilizing the underlying formation mechanism of these nanoparticles, a general platform to produce spherical nanoparticles via direct self-assembly of Turkish gall extracts and various functional proteins was developed. The results showed that the nanoparticles retained both the antibacterial ability and intracellular carrier ability of the original protein or catechol. This work introduces a new member of the plant-derived edible nanoparticle (PDEN) family, establishes a simple and versatile platform for mass production nanoparticles, and provides new insight into the formation mechanism of nanoparticles during plant extraction.

Natural polyphenol self-assembled pH-responsive nanoparticles loaded into reversible hydrogel to inhibit oral bacterial activity.

Periodontitis is one of the most prevalent chronic inflammatory diseases and Polyphenols isolated from Turkish gall play a major role in the treatment of inflammatory diseases for their antibacterial, anti-inflammatory and antioxidant activities. In this work, Turkish Galls effective constituent (TGEC, T) was prepared into nanoparticles (T-NPs) by principle of oxidative self-polymerization. The pH-sensitive T-NPs was encapsulated into thermosensitive type in-situ hydrogel, and 42.29 ± 1.12% of effective constituent from T-NPs were continuously released within 96 h under the periodontitis environment. In addition, the weakly alkaline oral micro-environment of patients with periodontitis is more conducive to the sustained release of effective constituent, which is 10.83% more than that of healthy periodontal environment. The bacteriostatic test showed that T-NPs had stronger antibacterial activity on oral pathogens than that of TGEC. Compared with TGEC, the minimum inhibitory concentration (MIC) of T-NPs against P. gingivalis and A. viscosus was reduced by 50% and 25%, respectively. Interestingly, T-NPs induced bacteria lysis by promoting the excessive production of ROS without periodontal tissue damage caused by excessive oxidation reaction. In conclusion, a simple method of preparing microspheres with natural polyphenols was developed, which provides beneficial reference for one-step prepared drug carriers from effective components of natural product, likewise the method offers a green and effective solution to synthesis a new adjuvant therapy drugs for treatment of gingivitis associated with periodontal pockets.

Stepwise tracking strategy to screen ingredient from Galla Chinensis based on the "mass spectrometry guided preparative chromatography coupled with systems pharmacology".

ETHNOPHARMACOLOGICAL RELEVANCE: Galla chinensis, a traditional Chinese herbal medicine, was widely used to treat ulcerative colitis (UC) in folk prescriptions, however, its active ingredients and mechanism of action in the treatment of UC remain unclear. AIM OF THE STUDY: The aim of our study was to discover the lead compounds and anti-inflammatory active ingredients of Galla chinensis and clarify their molecular mechanism for UC treatment. MATERIALS AND METHODS: The ingredients of Galla chinensis were prepared by column and mass spectrometry guided preparative chromatography. Besides, the relationship among the ingredients of Galla chinensis and targets was predicted by systems pharmacology. Additionally, Lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as in vitro model. The cell viability, the level of the pro-inflammatory factors, the generation of reactive oxygen species (ROS), and trans epithelial electric resistance (TEER) values were detected to screen out the active ingredients of Galla chinensis. Moreover, 4% dextran sodium sulfate (DSS)-induced ulcerative colitis mice were used as the UC animal model. The disease activity index (DAI), pathological degree of colon tissue, activities of antioxidant-related enzymes and expression level of pro-inflammatory cytokines were performed to assess the anti-UC effects of the active ingredients. Meanwhile, the mRNA expression level of inflammatory factors and antioxidant related genes were analyzed by real-time quantitative polymerase chain reaction (Q-PCR). And the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) pathway related proteins, intestinal mucosal proteins and nuclear factor kappa-B (NF-κB) pathway related proteins in colon tissues were analyzed by Western Blotting. RESULTS: Herein, a stepwise tracking strategy was adopted to screen out the anti-inflammatory active ingredients of Galla Chinensis based on "preparative chromatography pharmacology combined with mass spectrometry guidance and system". 11 categories of ingredients of Galla chinensis were prepared and ethyl gallate (EG) was screened out the lead compound and anti-inflammatory active ingredient of Galla Chinensis through in silico, in vitro and in vivo studies. In addition, EG had a significant therapeutic effect on ameliorating DSS-induced UC mice and protected intestinal mucosal integrity through Nrf2 and NF-κB signaling pathway. CONCLUSION: Ethyl gallate was the lead compound and anti-inflammatory active ingredient in Galla chinensis. And it was discovered for the first time that EG could treat mice with ulcerative colitis. This research not only found the lead compound of Galla Chinensis for UC treatment and determined the possible mechanism, but also provided valuable references for finding lead compounds from natural products by systems pharmacology coupled with equivalent components group technology.

Study Effect of Vitamin D on the Immunopathology Responses of the Bronchi in Murine Model of Asthma.

Allergic asthma is a complicated respiratory problem characterized by airway inflammation, airway hyperresponsiveness (AHR), breathlessness, mucus hyper-secretion, and goblet cell hyperplasia. Asthma is controlled by genetic and environmental factors. Allergy is the main trigger of asthma and is mediated by Th2 cytokines along with IgE production. Vitamin D (Vit D) is the main supplementary factor for the immune system. In the present study, we investigated the effect of Vit D on the exacerbation of allergic asthma. A murine model of allergic asthma was induced by ovalbumin (OVA) in four of five groups of studied female BALB/c mice (each group, n=20). One group was considered as control. Of OVA-induced mice, two groups received Vit D via oral (10,000 IU/kg diet) or intranasal (inhalation) forms (30 min on days 25, 27, and 29), and the third group received budesonide. At least, AHR, the levels of IL-4, IL-5, IL-13, and INF-g in bronchoalveolar lavage fluid (BALF), serum IgE and histamine, IL-25 and IL-33 gene expression, as well as histopathology study of the lung were done. The Penh values, type2 Cytokines in BALF (in both protein and molecular levels), total IgE and histamine, perivascular and peribronchial inflammation, goblet cell hyperplasia, and mucus hypersecretion decreased significantly in both oral and intranasal Vit D-treated asthmatic mice groups, especially on day 38 of orally treated mice. Here, we found Vit D as a promising agent in control of allergic asthma with a remarkable ability to decrease the severity of inflammation. Therefore, Vit D sufficiency is highly recommended in asthmatic patients.

[Effect of different isoforms of tocopherols on expression of intercellular adhesion molecule-1 in human umbilical vein endothelial cells].

OBJECTIVE: To observe the influence of different tocopherol isoforms on oxidized low density lipoprotein (oxLDL) or recombinant human C-reactive protein (rhCRP)-induced expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) and to investigate the potential mechanisms and effects of different tocopherols on atherosclerosis. METHODS: Cultured HUVECs were incubated with oxLDL, oxLDL + alpha-tocopherol, oxLDL + gamma-tocopherol, oxLDL + mixed-tocopherols, rhCRP, rhCRP + alpha-tocopherol, rhCRP + gamma-tocopherol rhCRP + mixed-tocopherols for 24 hours, respectively. The ICAM-1 expressions of protein and mRNA were detected by cell enzyme linked immunosorbent assay (ELISA), flow cytometric technique and RT-PCR. RESULTS: Incubation of HUVECs with oxLDL or rhCRP for 24 hours significantly increased ICAM-1 expressions of proteins and mRNA. The different tocopherols inhibited oxLDL-induced ICAM-1 expression in HUVECs in a concentration-dependent manner (50-200 micromol/L) and mixed-tocopherols were more potent than alpha-tocopherol or gamma-tocopherol alone. However, rhCRP-induced ICAM-1 expression in HUVECs was not inhibited by tocopherols. CONCLUSION: The different tocopherols inhibited oxLDL-induced ICAM-1 expression in HUVECs and mixed-tocopherols were more potent than alpha-tocopherol or gamma-tocopherol alone, which may be important for the beneficial effects of tocopherols on atherosclerosis and cardiovascular disease.