Curcumin (CCM) is one of the most frequently explored plant compounds with various biological actions such as antibacterial, antiviral, antifungal, antineoplastic, and antioxidant/anti-inflammatory properties. The laboratory data and clinical trials have demonstrated that the bioavailability and bioactivity of curcumin are influenced by the feature of the curcumin molecular complex types. Curcumin has a high capacity to form molecular complexes with proteins (such as whey proteins, bovine serum albumin, β-lactoglobulin), carbohydrates, lipids, and natural compounds (e.g., resveratrol, piperine, quercetin). These complexes increase the bioactivity and bioavailability of curcumin. The current review provides these derivatization strategies for curcumin in terms of biological and physico-chemical aspects with a strong focus on different type of proteins, characterization methods, and thermodynamic features of protein–curcumin complexes, and with the aim of evaluating the best performances. The current literature review offers, taking into consideration various biological effects of the CCM, a whole approach for CCM-biomolecules interactions such as CCM-proteins, CCM-nanomaterials, and CCM-natural compounds regarding molecular strategies to improve the bioactivity as well as the bioavailability of curcumin in biological systems.

Curcumin is among the most well-studied natural substances, known for its biological actions within the central nervous system, its antioxidant and anti-inflammatory properties, and human health benefits. However, challenges persist in effectively utilising curcumin, addressing its metabolism and passage through the blood–brain barrier (BBB) in therapies targeting cerebrovascular diseases. Current challenges in curcumin’s applications revolve around its effects within neoplastic tissues alongside the development of intelligent formulations to enhance its bioavailability. Formulations have been discovered including curcumin’s complexes with brain-derived phospholipids and proteins, or its liposomal encapsulation. These novel strategies aim to improve curcumin’s bioavailability and stability, and its capability to cross the BBB, thereby potentially enhancing its efficacy in treating cerebrovascular diseases. In summary, this review provides a comprehensive overview of molecular pathways involved in interactions of curcumin and its metabolites, and brain vascular homeostasis. This review explores cellular and molecular current aspects, of curcumin-based effects with an emphasis on curcumin’s metabolism and its impact on pathological conditions, such as neurodegenerative diseases, schizophrenia, and cerebral angiopathy. It also highlights the limitations posed by curcumin’s poor bioavailability and discusses ongoing efforts to surpass these impediments to harness the full therapeutic potential of curcumin in neurological disorders.

Galium verum is a well-known medicinal plant which is used in various pathologies. G. verum extracts are characterized here using chromatography, where among the rich pool of phenolic acids of flavonoids two known anti-stress modulators, chlorogenic acid and rutin are identified in high quantities. Additionally, the extracts are characterized using a series of in vitro assays (EPR, DPPH, TPC and TEAC). Considering the chemical findings, the potential beneficial effects of the G. verum extract are explored here in a living organism exposed to stress induced oxidative damages. Thus, the biochemical-modulatory and antioxidant roles of two doses of G. verum extract are examined in animals exposed to acute restraint and dark stress (S). The animals were divided in groups [control, S, SG1 (exposed to 25 mg G. verum extract), SG2 (50 mg extract)]. Increased levels of lipid peroxidation (TBARS from 4.43 to 8.06 nmol/mL), corticosterone from 0.43 to 1.96 μg/dL and epinephrine from 44.43 to 126.7 μg/mL, as well as decreased antioxidant enzymes activities (SOD/CAT) were observed in the S group. The G. verum extract afforded a near-normal equilibrium within the biochemical parameters of animals exposed to RS, by reducing oxidative damage (TBARS at a 3.73 nmol/mL; CS at 0.90 μg/dL; EP at 63.72 μg/mL) and by restoring the antioxidant balance.

The allicin pleiotropic effects, which include anti-inflammatory, anti-oxidant, anti-tumoral, and antibacterial actions, were well demonstrated and correlated with various molecular pathways. The immunostimulatory mechanism of allicin has not been elucidated; however, there is a possible cytokine stimulation from immunoglobulin release caused by allicin. In this study, when Wistar female rats and CD19+ lymphocytes were treated with three different doses of allicin, immunoglobulins, glutathione, and oxidative stress markers were assayed. Molecular docking was performed between S-allylmercaptoglutathione (GSSA)—a circulating form of allicin in in vivo systems formed by the allicin interaction with glutathione (GSH)—and scavenger receptors class A and B from macrophages, as well as CD19+ B lymphocytes. Our data demonstrated a humoral immunostimulatory effect of allicin in rats and direct stimulation of B lymphocytes by S-allyl-mercapto-glutathione, both correlated with decreased catalase (CAT) activity. The molecular docking revealed that S-allyl-mercapto-glutathione interacting with Colec12, MARCO (class A), and SCARB1 (class B) scavenger receptors in in vitro tests demonstrates a direct stimulation of immunoglobulin secretion by GSSA in CD19+ B lymphocytes. These data collectively indicate that GSSA stimulates immunoglobulin secretion by binding on scavenger receptors class B type 1 (SCARB1) from CD19+ B lymphocytes.

Alzheimer’s disease (AD) is known as the primary and most common cause of dementia in the middle-aged and elderly population worldwide. Chemical analyses of B. pendula leaf extract (BPE), performed using spectrophotometric and chromatographic methods (LC/MS), revealed high amounts of polyphenol carboxylic acids (gallic, chlorogenic, caffeic, trans-p-coumaric, ferulic, and salicylic acids), as well as flavonoids (apigenin, luteolin, luteolin-7-O-glucoside, naringenin, hyperoside, quercetin, and quercitrin). Four groups of Wistar rats were used in this experiment (n = 7/group): control (untreated), Aβ_1-42 (2 μg/rat intracerebroventricular (i.c.v.), Aβ_1-42 + BPE (200 mg/Kg b.w.), and DMSO (10 μL/rat). On the first day, one dose of Aβ_1-42 was intracerebroventricularly administered to animals in groups 2 and 3. Subsequently, BPE was orally administered for the next 15 days to group 3. On the 16th day, behavioral tests were performed. Biomarkers of brain oxidative stress Malondialdehyde (MDA), (Peroxidase (PRx), Catalase (CAT), and Superoxid dismutase (SOD) and inflammation (cytokines: tumor necrosis factor -α (TNF-α), Interleukin 1β (IL-1β), and cyclooxygenase-2 (COX 2)) in plasma and hippocampus homogenates were assessed. Various protein expressions (Phospho-Tau (Ser404) (pTau Ser 404), Phospho-Tau (Ser396) (pTau Ser 396), synaptophysin, and the Nuclear factor kappa B (NFkB) signaling pathway) were analyzed using Western blot and immunohistochemistry in the hippocampus. The results show that BPE diminished lipid peroxidation and neuroinflammation, modulated specific protein expression, enhanced the antioxidant capacity, and improved spontaneous alternation behavior, suggesting that it has beneficial effects in AD.

The present work shows the biochemical and structural fundamentals for the stress induced anxiety and stress adjustment response of the CA3 hippocampus area. Adult male Wistar rats were repeatedly exposed to a 3 h day restraint stress, for either 3 or 6 days. The concentration of corticosterone and testosterone in the CA3 hippocampus area was divergent, while oxidative stress was progressively increased during the stress exposure. The mitochondrial lysis in the CA3 neurons confirmed the oxidative stress events. Immunohistochemical findings showed that oligodendrocytes (OCs) proliferation and neuroglobin (Ngb) expression were stimulated, whereas MeCP2 expression was decreased as a balance reaction in stress exposure under corticosterone signaling. Remarkably, ultrastructural changes such as mitochondrial lysis, endoplasmic reticulum swelling, and perivascular lysis with platelets adherence to endothelium in the CA3 area were seen in the 6th day of restraining. The anxiety-like behavior was noticed 6 days later after stress exposure. These results suggest that the duration of the exposure, but not the intensity of the stress, is the key factor in the stress-buffering function by the CA3 hippocampus area via up-regulation of the Ngb-OCs bionome. The imbalance of the Ngb-OCs communication may be involved in the development of CA3-dependent anxious behavior.