Inflammation-oriented montmorillonite adjuvant enhanced oral delivery of anti-TNF-α nanobody against inflammatory bowel disease.

Oral delivery of proteins faces challenges due to the harsh conditions of the gastrointestinal (GI) tract, including gastric acid and intestinal enzyme degradation. Permeation enhancers are limited in their ability to deliver proteins with high molecular weight and can potentially cause toxicity by opening tight junctions. To overcome these challenges, we propose the use of montmorillonite (MMT) as an adjuvant that possesses both inflammation-oriented abilities and the ability to regulate gut microbiota. This adjuvant can be used as a universal protein oral delivery technology by fusing with advantageous binding amino acid sequences. We demonstrated that anti-TNF-α nanobody (VII) can be intercalated into the MMT interlayer space. The carboxylate groups (-COOH) of aspartic acid (D) and glutamic acid (E) interact with the MMT surface through electrostatic interactions with sodium ions (Na+). The amino groups (NH2) of asparagine (N) and glutamine (Q) are primarily attracted to the MMT layers through hydrogen bonding with oxygen atoms on the surface. This binding mechanism protects VII from degradation and ensures its release in the intestinal tract, as well as retaining biological activity, leading to significantly enhanced therapeutic effects on colitis. Furthermore, VII@MMT increases the abundance of short-chain fatty acids (SCFAs)-producing strains, including Clostridia, Prevotellaceae, Alloprevotella, Oscillospiraceae, Clostridia_vadinBB60_group, and Ruminococcaceae, therefore enhance the production of SCFAs and butyrate, inducing regulatory T cells (Tregs) production to modulate local and systemic immune homeostasis. Overall, the MMT adjuvant provides a promising universal strategy for protein oral delivery by rational designed protein.

A new ocotillol-type ginsenoside from stems and leaves of Panax quinquefolium L. and its anti-oxidative effect on hydrogen peroxide exposed A549 cells.

A new ocotillol-type ginsenoside, namely 12-one-pseudoginsenoside F11 (12-one-PF11), was isolated from stems and leaves of Panax quinquefolium, whose structure was elucidated 6-O-[α-L-rhamnopyranosyl-(1-2)-ß-D-glucopyranosyl]-dammar-12-one-20S,24R-epoxy-3ß,6α,25-triol. 12-one-PF11 significantly suppressed hydrogen peroxide induced oxidative stress in human lung carcinoma A549 cells. As compared with model group, 12-one-PF11 improved cell viability of A549 cells in a dose-dependent manner, and significantly decreased the generation of malondialdehyde (MDA) and increased production of superoxide dismutase (SOD) and glutathione (GSH) and protein expression levels of nuclear related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in A549 cells.

Berberine suppresses mast cell-mediated allergic responses via regulating FcɛRI-mediated and MAPK signaling.

The anti-allergic effect of berberine was evaluated in cellular and animal models of allergic responses. In this study, the results of the in vitro model of immunoglobulin (Ig) E-mediated mast cell degranulation showed that berberine significantly inhibited the release of ß-hexosaminidase (ß-HEX), histamine, IL-4 and TNF-α in rat basophilic leukemia cells (RBL-2H3 cells). Pretreatment with berberine prevented morphological changes in IgE-stimulated RBL-2H3 cells such as the recovery of an elongated shape. Pretreatment with berberine also suppressed the phosphorylation of antigen-induced Lyn, Syk, and Gab2, thus suppressing the downstream MAPK pathways. In the in vivo model of allergic responses, administration of berberine inhibited passive cutaneous anaphylaxis (PCA) in mice. The above results indicate berberine could suppress mast cell activation and allergic responses.

Coptisine Suppresses Mast Cell Degranulation and Ovalbumin-Induced Allergic Rhinitis.

Coptisine is one of the main components of isoquinoline alkaloids in the coptidis rhizome. The effect of coptisine on allergic rhinitis has not been investigated. In this study, we report the effects and mechanisms of coptisine using monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA)-stimulated rat basophilic leukemia cells (RBL-2H3 cells) in vitro and an ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. The results showed that coptisine markedly decreased the levels of ß-hexosaminidase, histamine, interleukin (IL)-4, and tumor necrosis factor (TNF)-α. Coptisine also prevented morphological changes, such as restoring an elongated shape, inhibiting granule release on toluidine blue staining, and reorganizing inhibited filamentous actins (F-actin). Additionally, coptisine blocked the phosphorylation of phosphoinositide3-kinase (PI3K)/Akt (as known as protein kinase B(PKB)) in RBL-2H3 cell. Furthermore, the results showed that coptisine suppressed OVA-induced allergic rhinitis symptoms, such as nasal rubbing and OVA-specific IgE, and histamine, IL-4 and TNF-α levels in the serum of AR mice. These data suggested that coptisine should have inhibitory effects on the inflammatory responses of mast cells, and may be beneficial for the development of coptisine as a potential anti-allergic drug.

Inhibitory effects of bisdemethoxycurcumin on mast cell-mediated allergic diseases.

Most allergic reactions are induced by mast cell activation. Mast cells play vital roles in the pathogenesis of allergic diseases. Bisdemethoxycurcumin (BDMC), a natural curcuminoid, has potential anti-allergic effects. Hence, we explored the effect of BDMC on mast cell-mediated allergic diseases. The study proved that BDMC suppresses ß-hexosaminidase release, granule release, and membrane ruffling in monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA)-stimulated rat basophilic leukaemia cells (RBL-2H3 cells), and BDMC suppressed ovalbumin (OVA)-induced allergic rhinitis (AR) symptoms and OVA-specific IgE levels in AR mice. Furthermore, BDMC increased the survival of compound 48/80 anaphylaxis shock mice and elevated the decreased rectal temperature in OVA-induced active systemic anaphylaxis mice. These findings indicate that BDMC regulates the degranulation of mast cells, demonstrating its potential in the treatment of mast cell-induced allergic reactions.