Protective Effects of Gomisin N against Hepatic Cannabinoid Type 1 Receptor-Induced Insulin Resistance and Gluconeogenesis

: Berberine is an alkaloid found in plants. It has e.g. neuroprotective, anti-inflammatory and hypolipidemic activity. The research proves that it also strongly impacts the carbohydrate metabolism. The compound also protects pancreatic βcells and increases sensitivity to insulin in peripheral tissues via the induction of GLUT-1, GLUT-4 and insulin type 1 (Ins1) receptors activity. It also stimulates glycolysis and leads to a decrease in insulin resistance by macrophages polarization, lipolytic processes induction and energy expenditure enhancement (by reducing body mass and limiting insulin resistance caused by obesity). In liver berberine inhibits FOX01, SREBP1 and ChREBP pathways, and HNF-4α (hepatocyte nuclear factor 4 alpha) mRNA that hinder gluconeogenesis processes. In intestines it blocks α-glucosidase contributing to glucose absorption decrease. Its interference in intestinal flora reduces levels of monosaccharides and suppresses diabetes mellitus complications development.

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Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

International Journal of Molecular Sciences ◽

10.3390/ijms22073595 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3595

Author(s):

Md Afjalus Afjalus Siraj ◽

Md. Sajjadur Rahman ◽

Ghee T. Tan ◽

Veronique Seidel

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Binding Affinity ◽

Docking Studies ◽

Dynamics Simulation ◽

Simulation Studies ◽

Cannabinoid Type 1 Receptor ◽

Docking Approach

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

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Type 1 Immunity Provides Optimal Protection against Both Mucosal and Systemic Trypanosoma cruzi Challenges

Infection and Immunity ◽

10.1128/iai.70.12.6715-6725.2002 ◽

2002 ◽

Vol 70 (12) ◽

pp. 6715-6725 ◽

Cited By ~ 38

Author(s):

D. F. Hoft ◽

C. S. Eickhoff

Keyword(s):

Trypanosoma Cruzi ◽

Neutralizing Antibody ◽

Secretory Iga ◽

Immune Memory ◽

Interleukin 12 ◽

Intracellular Pathogens ◽

Protective Effects ◽

Culture Techniques

ABSTRACT Chagas' disease results from infection with Trypanosoma cruzi, a protozoan parasite that establishes systemic intracellular infection after mucosal invasion. We hypothesized that ideal vaccines for mucosally invasive, intracellular pathogens like T. cruzi should induce mucosal type 2 immunity for optimal induction of protective secretory immunoglobulin A (IgA) and systemic type 1 immunity protective against intracellular replication. However, differential mucosal and systemic immune memory could be difficult to induce because of reciprocal inhibitory actions between type 1 and type 2 responses. To test our hypotheses, we investigated the protective effects of type 1 and type 2 biased vaccines against mucosal and systemic T. cruzi challenges. Intranasal vaccinations were given with recombinant interleukin-12 (IL-12)- and IL-4-neutralizing antibody (Ab) for type 1 immune bias, or recombinant IL-4 and gamma interferon-neutralizing Ab for type 2 immune bias. Cytokine RNA and protein studies confirmed that highly polarized memory immune responses were induced by our vaccination protocols. Survival after virulent subcutaneous T. cruzi challenge was used to assess systemic protection. Mucosal protection was assessed by measuring the relative inhibition of parasite replication in mucosal tissues early after oral T. cruzi challenge, using both PCR and quantitative culture techniques. As expected, only type 1 responses protected against systemic challenges (P < 0.01). However, contrary to our original hypothesis, type 1 responses optimally protected against mucosal challenges as well (P < 0.05). Type 1 and type 2 biased vaccines induced similar secretory IgA responses. We conclude that future vaccines for T. cruzi and possibly other mucosally invasive, intracellular pathogens should induce both mucosal and systemic type 1 immunity.

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