Angiotensinergic effect of β-Caryophyllene on Lipopolysaccharide- induced systemic inflammation.

Renin-Angiotensin System (RAS) is a peptidergic system, canonically known for its role in blood pressure regulation. Furthermore, a non-canonical RAS regulates pathophysiological phenomena, such as inflammation since it consists of two main axes: the pro-inflammatory renin/(pro)renin receptor ((P)RR) axis, and the anti-inflammatory angiotensin-converting enzyme 2 (ACE2)/Angiotensin-(1-7) (Ang-(1-7))/Mas Receptor (MasR) axis. Few phytochemicals have shown to exert angiotensinergic and anti-inflammatory effects through some of these axes; nevertheless, anti-inflammatory drugs, such as phytocannabinoids have not been studied regarding this subject.

Molecular Docking Integrated with Network Pharmacology Explores the Therapeutic Mechanism of against Type 2 Diabetes.

The incidence of type 2 diabetes (T2D) is rising, and finding new treatments is important. is a plant suggested as a potential treatment for T2D, but how it works needs to be clarified. This study explored the pharmacological mechanism of in treating T2D.

Functionalized Metal Nanoparticles in Cancer Therapy.

Currently, there are many studies on the application of nanotechnology in therapy. Metallic nanoparticles are promising nanomaterials in cancer therapy; however, functionalization of these nanoparticles with biomolecules has become relevant as their effect on cancer cells is considerably increased by photothermal and photodynamic therapies, drug nanocarriers, and specificity by antibodies, resulting in new therapies that are more specific against different types of cancer. This review describes studies on the effect of functionalized palladium, gold, silver and platinum nanoparticles in the treatment of cancer, these nanoparticles themselves show an anticancer effect.

β-Caryophyllene: A Therapeutic Alternative for Intestinal Barrier Dysfunction Caused by Obesity.

Obesity is an excessive accumulation of fat that exacerbates the metabolic and inflammatory processes. Studies associate these processes with conditions and dysregulation in the intestinal tract, increased concentrations of lipopolysaccharides (LPSs) in the blood, differences in the abundance of intestinal microbiota, and the production of secondary metabolites such as short-chain fatty acids. β-Caryophyllene (BCP) is a natural sesquiterpene with anti-inflammatory properties and with the potential purpose of fighting metabolic diseases.

Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults.

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)).

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study.

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers.

Alliin, an Nutraceutical, ReducesMetaflammation Markers in DIO Mice.

Obesity generates a chronic low-grade inflammatory state which promotes oxidativestress and triggers comorbidities. Alliin is the main organosulfur compound in garlic and has beenshown to induce a decrease in the expression of proinflammatory cytokines; its systemic effect onmetabolic parameters and adipose tissue is not yet known, however. After nine weeks of HFD andwith obesity established in C57BL/6 mice, we observed that a daily treatment with alliin for 3.

-Caryophyllene, a Natural Sesquiterpene, Attenuates Neuropathic Pain and Depressive-Like Behavior in Experimental Diabetic Mice.

Neuropathic pain (NP) is associated with chronic hyperglycemia and emotional disorders such as depression in diabetic patients, complicating the course of treatment. Drugs currently used to treat NP have undesirable side effects, so research on other natural sources has been required. -caryophyllene (BCP), a natural sesquiterpene found in some food condiments and considered an agonist to cannabinoid receptor type 2, could have potential therapeutic effects to treat conditions such as NP and emotional disorders.

An Endocannabinoid Uptake Inhibitor from Black Pepper Exerts Pronounced Anti-Inflammatory Effects in Mice.

Guineensine is a dietary N-isobutylamide widely present in black and long pepper (Piper nigrum and Piper longum) previously shown to inhibit cellular endocannabinoid uptake. Given the role of endocannabinoids in inflammation and pain reduction, here we evaluated guineensine in mouse models of acute and inflammatory pain and endotoxemia. Significant dose-dependent anti-inflammatory effects (95.

Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake.

The extracellular effects of the endocannabinoids anandamide and 2-arachidonoyl glycerol are terminated by enzymatic hydrolysis after crossing cellular membranes by facilitated diffusion. The lack of potent and selective inhibitors for endocannabinoid transport has prevented the molecular characterization of this process, thus hindering its biochemical investigation and pharmacological exploitation. Here, we report the design, chemical synthesis, and biological profiling of natural product-derived -substituted 2,4-dodecadienamides as a selective endocannabinoid uptake inhibitor.

Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice.

High-content screening led to the identification of the N-isobutylamide guineensine from Piper nigrum as novel nanomolar inhibitor (EC50=290nM) of cellular uptake of the endocannabinoid anandamide (AEA). Noteworthy, guineensine did not inhibit endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) nor interact with cannabinoid receptors or fatty acid binding protein 5 (FABP5), a major cytoplasmic AEA carrier. Activity-based protein profiling showed no inhibition of serine hydrolases.

Endocannabinoid content in fetal bovine sera - unexpected effects on mononuclear cells and osteoclastogenesis.

The major endocannabinoids (ECs) arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) and related N-ethanolamines act as full and partial agonists at CB(1), CB(2), GPR55, PPAR and TRPV1 receptors to various degrees. These receptors are also expressed in immune cells like monocytes/macrophages where they regulate different cellular processes. In this study, potentially bioactive lipids in fetal bovine sera (FBS) were quantified by GC/MS.

Mechanisms of osteoclastogenesis inhibition by a novel class of biphenyl-type cannabinoid CB(2) receptor inverse agonists.

The cannabinoid CB(2) receptor is known to modulate osteoclast function by poorly understood mechanisms. Here, we report that the natural biphenyl neolignan 4'-O-methylhonokiol (MH) is a CB(2) receptor-selective antiosteoclastogenic lead structure (K(i) < 50 nM). Intriguingly, MH triggers a simultaneous G(i) inverse agonist response and a strong CB(2) receptor-dependent increase in intracellular calcium.

Antioxidant activity of butyl- and phenylstannoxanes derived from 2-, 3- and 4-pyridinecarboxylic acids.

In vitro antioxidant activity for 12 stannoxanes derived from Ph(3)SnCl (compounds 1-3), Ph(2)SnCl(2) (compounds 4-6), Bu(3)SnCl (compounds 7-9), and Bu(2)SnCl(2) (compounds 10-12), was assayed qualitatively by the chromatographic profile with 1,1-diphenyl-2-picrylhydrazil (DPPH) method and by two quantitative methods: the DPPH radical scavenging activity and Ferric-Reducing Antioxidant Power (FRAP) assays. The results were compared with those obtained with the starting materials 2-pyridine- carboxylic acid (I), 3-pyridinecarboxylic acid (II) and 4-pyridinecarboxylic acid (III), as well as with standard compounds, such as vitamin C and vitamin E, respectively. The in vitro antiradical activity with DPPH of diphenyltin derivative 5 showed a very similar behavior to vitamin C at a 20 microg/mL concentration, whereas according to the FRAP method, compound 8 was better.

Plant immunostimulants--scientific paradigm or myth?

In traditional medicine, numerous plant preparations are used to treat inflammation both topically and systemically. Several anti-inflammatory plant extracts and a few natural product-based monosubstances have even found their way into the clinic. Unfortunately, a number of plant secondary metabolites have been shown to trigger detrimental pro-allergic immune reactions and are therefore considered to be toxic.

Dysregulation of the Th1/Th2 cytokine profile is associated with immunosuppression induced by hypothalamic-pituitary-adrenal axis activation in mice.

Hypothalamic-pituitary-adrenal (HPA) axis activation-induced immunosuppression is associated with increased concentration of circulating corticosterone and impaired cellular immune responses. The purpose of this study was to investigate the effect of chronic HPA axis activation on the cellular immune response, Th1/Th2 cytokine profile, and concentration of corticosterone. Mice were divided into two groups: a control group comprised of healthy, untreated mice that received no stress, and an HPA axis-activated group that received stress through electric shock (ES).

Effect of Ginkgo biloba extract EGb 761 on the nonspecific and humoral immune responses in a hypothalamic-pituitary-adrenal axis activation model.

We evaluated the immune response of healthy control and stressed Wistar rats submitted to hypothalamic-pituitary-adrenal (HPA) axis activation. Rats were treated with Ginkgo biloba extract (EGb 761) orally (100 mg/kg per day for 7 days). EGb 761 stimulated the digestion index of peritoneal and alveolar macrophages (PM and AM) of stressed rats.