Cannabidiol attenuates inflammatory impairment of intestinal cells expanding biomaterial-based therapeutic approaches

Boehm, Elisa; Droessler, Linda; Amasheh, Salah

doi:10.1016/j.mtbio.2023.100808

Cited by 4 publications

(4 citation statements)

References 72 publications

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“…Our results suggest that CBD may have a strengthening modulatory effect on the TJ assembly of claudins after 24 h. In addition, our group showed that CBD in IPEC J2 cells in the concentration of 40 μM has a decreasing effect on the paracellular permeability of [ 3 H]-D-Mannitol after 48 h, also indicating a barrier-strengthening effect. Furthermore, the claudin-4 expression was markedly increased [ 25 ]. However, a general difference and prerequisite of the current study is a lack of endogenous CB receptors in the oocytes, allowing the study of immediate effects on tight junction integrity [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cannabidiol (CBD), as the major non-psychoactive phytocannabinoid component of the herbal Cannabis sativa L., has been shown to have beneficial, anti-inflammation effects including positive effects on epithelial barrier integrity. This mechanism was analyzed in the non-transformed porcine intestinal epithelial cell line IPEC-J2 by our group recently, including the observation of an enhancement of barrier protein claudin-4 expression [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Cannabidiol Strengthening of Gastric Tight Junction Complexes Analyzed in an Improved Xenopus Oocyte Assay

Stein,

Vollstaedt,

Amasheh

2024

Membranes

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Cannabidiol (CBD), the non-psychoactive compound derived from the cannabis plant, has gained attention in recent years as a remedy against gastrointestinal disorders ranging from nausea and inflammation to abdominal pain. Recent advances demonstrated an effect on inflammatory pathways and barrier proteins. However, information on possible direct effects is scarce and needs to be addressed, as applications are currently increasing in popularity. To accomplish this, we have employed Xenopus laevis oocytes as a heterologous expression system for analysis of the direct effects on stomach-specific claudins and further developed tight junction (TJ) protein interaction assays. Human claudin-4, claudin-5, and claudin-18.2 were expressed in Xenopus oocytes, clustered in pairs to form contact areas, and analyzed in a two-cell model approach, including measurement of the contact area and contact strength. CLDN4/5/18 + CLDN4/5/18 oocyte pairs were incubated with 20 µM CBD or with 40 µM CBD and were compared to cells without CBD treatment (ctrl). For interaction analysis, the contact area was measured after 24 h and 48 h. Whereas CBD did not affect the size of the protein interaction area, Double Orbital Challenge experiments revealed an increased contact strength after 24 h incubation with CBD. In addition, the Xenopus oocyte experiments were accompanied by an analysis of claudin-4, -5, and -18 expression in gastric epithelium by immunoblotting and immunohistochemistry. Claudin-4, -5, and -18 were strongly expressed, indicating a major role for gastric epithelial barrier function. In summary, our study shows direct effects of 40 µM CBD on Xenopus oocytes heterologously expressing a stomach-specific claudin combination, indicating a supportive and beneficial effect of CBD on gastric TJ proteins.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cannabidiol Strengthening of Gastric Tight Junction Complexes Analyzed in an Improved Xenopus Oocyte Assay

Stein,

Vollstaedt,

Amasheh

2024

Membranes

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“…After the detection of the total protein amount with the ChemiDoc MP Luminescence imager, Clarity Western ECL Blotting Substrate (Bio-Rad Laboratories GmbH, Munich, Germany) was used to visualize the protein bands. Signals were normalized to the total protein amount and were expressed relative to the control values, which were set to 100%, as described previously [38,65]. Whole Western blot membranes and the corresponding total protein amount are shown in Figure S1.…”

Section: Immunoblotting and Densitometrymentioning

confidence: 99%

“…Furthermore, nutritional factors can influence TJ composition [26], for example, the trace-element zinc [33], the amino acids glutamine and glycine [34,35], or medium-chain fatty acids [36]. Secondary plant compounds are another group of substances with barrier-affecting properties, e.g., cannabidiol, curcumin, kampferol, berberine, or quercetin [26,37,38].…”

Section: Introductionmentioning

confidence: 99%

Quercetin Improves Barrier Properties in Porcine Small Intestine but Not in Peyer’s Patches

Cornelius,

Droessler,

Amasheh

2024

IJMS

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Peyer’s patches (PPs) are part of the gut-associated lymphatic tissue (GALT) and represent the first line of the intestinal immunological defense. They consist of follicles with lymphocytes and an overlying subepithelial dome with dendritic cells and macrophages, and they are covered by the follicle-associated epithelium (FAE). A sealed paracellular pathway in the FAE is crucial for the controlled uptake of luminal antigens. Quercetin is the most abundant plant flavonoid and has a barrier-strengthening effect on tight junctions (TJs), a protein complex that regulates the paracellular pathway. In this study, we aimed to analyze the effect of quercetin on porcine PPs and the surrounding villus epithelium (VE). We incubated both tissue types for 4 h in Ussing chambers, recorded the transepithelial electrical resistance (TEER), and measured the unidirectional tracer flux of [3H]-mannitol. Subsequently, we analyzed the expression, protein amount, and localization of three TJ proteins, claudin 1, claudin 2, and claudin 4. In the PPs, we could not detect an effect of quercetin after 4 h, neither on TEER nor on the [3H]-mannitol flux. In the VE, quercetin led to a higher TEER value, while the [3H]-mannitol flux was unchanged. The pore-forming claudin 2 was decreased while the barrier-forming claudin 4 was increased and the expression was upregulated. Claudin 1 was unchanged and all claudins could be located in the paracellular membrane by immunofluorescence microscopy. Our study shows the barrier-strengthening effect of quercetin in porcine VE by claudin 4 upregulation and a claudin 2 decrease. Moreover, it underlines the different barrier properties of PPs compared to the VE.

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Pharmacotherapeutic advances in fibromyalgia: what’s new on the horizon?

Sarzi-Puttini,

Giorgi,

Sirotti

et al. 2024

Expert Opinion on Pharmacotherapy

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Cannabidiol attenuates inflammatory impairment of intestinal cells expanding biomaterial-based therapeutic approaches

Cited by 4 publications

References 72 publications

Cannabidiol Strengthening of Gastric Tight Junction Complexes Analyzed in an Improved Xenopus Oocyte Assay

Cannabidiol Strengthening of Gastric Tight Junction Complexes Analyzed in an Improved Xenopus Oocyte Assay

Quercetin Improves Barrier Properties in Porcine Small Intestine but Not in Peyer’s Patches

Pharmacotherapeutic advances in fibromyalgia: what’s new on the horizon?

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