Purpose The optimal health benefits of curcumin are limited by its low solubility in water and corresponding poor intestinal absorption. Cyclodextrins (CD) can form inclusion complexes on a molecular basis with lipophilic compounds, thereby improving aqueous solubility, dispersibility, and absorption. In this study, we investigated the bioavailability of a new γ-cyclodextrin curcumin formulation (CW8). This formulation was compared to a standardized unformulated curcumin extract (StdC) and two commercially available formulations with purported increased bioavailability: a curcumin phytosome formulation (CSL) and a formulation of curcumin with essential oils of turmeric extracted from the rhizome (CEO). Methods Twelve healthy human volunteers participated in a double-blinded, cross-over study. The plasma concentrations of the individual curcuminoids that are present in turmeric (namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin) were determined at baseline and at various intervals after oral administration over a 12-h period. Results CW8 showed the highest plasma concentrations of curcumin, demethoxycurcumin, and total curcuminoids, whereas CSL administration resulted in the highest levels of bisdemethoxycurcumin. CW8 (39-fold) showed significantly increased relative bioavailability of total curcuminoids (AUC₀₋₁₂) in comparison with the unformulated StdC. Conclusion The data presented suggest that γ-cyclodextrin curcumin formulation (CW8) significantly improves the absorption of curcuminoids in healthy humans.

Chronic microglial activation is a prominent feature of many chronic neurodegenerative diseases, including Parkinson’s and Alzheimer’s disease. To investigate the effects of chronic microglial activation on cerebellar structure and motor function throughout the lifespan, the transgenic GFAP-IL6 mouse model was used. The aim of the study was to examine inflammatory markers and neuronal degeneration while simultaneously characterizing the motor performance of GFAP-IL6 mice at 3, 6, 14, and 24 months of age in comparison to WT (C57BL/6) mice. In respect to markers of neuroinflammation in the cerebellum, increased numbers of Iba1⁺ microglia were observed as early as at 3 months of age. In addition, TNF-α levels proved to be significantly higher in the GFAP-IL6 compared to WT mice at all time points. A difference in cerebellar volume between the GFAP-IL6 and WT mice was observed later in life, starting at 6 months and increasing to a loss of about 50% in aged (24 months old) GFAP-IL6 mice. Synaptic deficits were also assessed by using pre- (synaptophysin) and post-synaptic (PSD95) markers. While synaptophysin levels remained unchanged, PSD95 levels decreased in the aging GFAP-IL6 mice compared to their WT littermates from 14 months onward. To assess the effect of microglia activation and neurodegeneration on behavior, a variety of motor function tests, semi-quantitative cerebellar ataxia score, accelerod, beam walking, and open field tests were performed. An age-dependent difference between the genotypes was observed in many of the motor function tests. For example, reduced performance on the accelerod and higher ataxia scores were observed at 6 months of age, followed by the beam walking test showing differences at 14 months of age. In summary, this study constitutes a comprehensive, age-dependent examination of inflammatory, synaptic and neurodegenerative changes in the brains of GFAP-IL6 mice leading to a deterioration in motor performance. The results also indicate that early chronic microglia activation in the GFAP-IL6 mouse leads to observable cerebellar volume loss and motor deficits later in life.

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds—cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis’s bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis’s sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis’s complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis’s full therapeutic potential within the realm of natural plant-based medicine.

This study aims to investigate the combined anti-inflammatory activity of ginger and turmeric extracts. By comparing the activities of individual and combined extracts in lipopolysaccharide and interferon-γ-induced murine RAW 264.7 cells, we demonstrated that ginger-turmeric combination was optimal at a specific ratio (5:2, w/w) in inhibiting nitric oxide, tumour necrosis factor and interleukin 6 with synergistic interaction (combination index < 1). The synergistic inhibitory effect on TNF was confirmed in human monocyte THP-1 cells. Ginger-turmeric combination (5:2, w/w) also upregulated nuclear factor erythroid 2–related factor 2 activity and heme oxygenase-1 protein expression. Additionally, 6-shogaol, 8-shogaol, 10-shogaol and curcumin were the leading compounds in reducing major proinflammatory mediators and cytokines, and a simplified compound combination of 6-s, 10-s and curcumin showed the greatest potency in reducing LPS-induced NO production. Our study provides scientific evidence in support of the combined use of ginger and turmeric to alleviate inflammatory processes.

Nitric oxide is now universally recognized as an extracellular signaling molecule. Nitric oxide, produced in one cell, diffuses across the extracellular space and acts with targets in an adjoining cell. In this study, we present proof that hydrogen peroxide – like nitric oxide – acts as a true first (intercellular) messenger for a multitude of pro-inflammatory ligands. RAW 264.7 macrophages were activated with three different ligands, lipopolysaccharide, interferon-gamma or advanced glycation end products in the presence of increasing concentrations of (hydrogen peroxide scavenging) catalase. As inflammatory readouts, nitric oxide and tumor necrosis factor were determined. We hypothesize that hydrogen peroxide travels between cells propagating the signal, then a certain percentage of the readout should be inhibited by catalase in a concentration-dependent manner. The experiment showed concentration-dependent inhibition of nitric oxide and tumor necrosis factor-α production in response to all three ligands/ligand combinations (interferon-gamma, lipopolysaccharide, and chicken egg albumin-derived advanced glycation end product) in the presence of increasing concentration of catalase. For example, catalase inhibited 100% of nitric oxide and 40% of tumor necrosis factor-α production at its highest concentration. Our results suggest that hydrogen peroxide travels through cell membranes into the extracellular space and enters and activates adjacent cells. Like nitric oxide, we suggest that it is a ubiquitous first messenger, able to transmit cell-to-cell pro-inflammatory signals such as nitric oxide and tumor necrosis factor-α. In a therapeutic setting, our data suggest that compounds acting as hydrogen peroxide scavengers might not even need to enter the cell to act as anti-inflammatory drugs.