Investigating the Neuroprotective and Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

Rhodiola rosea L. Extract, a Known Adaptogen, Evaluated in Experimental Arthritis.

Rhodiola rosea L. extract (RSE) is mostly known for its adaptogen properties, but not for its antiarthritic activities, therefore monotherapy and combination with low-dose methotrexate (MTX) was studied. The collagen-induced arthritis (CIA) model was used to measure the functional score, and the change in hind paw volume (HPV). Both parameters had significant antiarthritic effects. Based on these preliminary results, an adjuvant arthritis (AA) model was further applied to assess another parameters. The experiment included these animal groups: healthy controls, untreated AA, AA administered with RSE (150 mg/kg b.w. daily, p.o.), AA administered by MTX (0.3 mg/kg b.w. twice a week, p.o.), and AA treated with the combination of RSE+MTX. The combination of RSE+MTX significantly reduced the HPV and increased the body weight. The combination significantly decreased HPV when compared to MTX monotherapy. The plasmatic levels of inflammatory markers (IL-6, IL-17A, MMP-9 and CRP) were significantly decreased by MTX+RSE treatment. The RSE monotherapy didn't influence any of the inflammatory parameters studied. In CIA, the RSE monotherapy significantly decreased the arthritic parameters studied. In summary, the combination of RSE and sub-therapeutic MTX was significantly effective in AA by improving inflammatory and arthritic parameters.

Medicinal Plants, Phytochemicals and Regulation of the NLRP3 Inflammasome in Inflammatory Bowel Diseases: A Comprehensive Review.

Ongoing research explores the underlying causes of ulcerative colitis and Crohn's disease. Many experts suggest that dysbiosis in the gut microbiota and genetic, immunological, and environmental factors play significant roles. The term "microbiota" pertains to the collective community of microorganisms, including bacteria, viruses, and fungi, that reside within the gastrointestinal tract, with a particular emphasis on the colon. When there is an imbalance or disruption in the composition of the gut microbiota, it is referred to as dysbiosis. Dysbiosis can trigger inflammation in the intestinal cells and disrupt the innate immune system, leading to oxidative stress, redox signaling, electrophilic stress, and inflammation. The Nod-like Receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key regulator found in immunological and epithelial cells, is crucial in inducing inflammatory diseases, promoting immune responses to the gut microbiota, and regulating the integrity of the intestinal epithelium. Its downstream effectors include caspase-1 and interleukin (IL)-1ß. The present study investigated the therapeutic potential of 13 medicinal plants, such as Litsea cubeba, Artemisia anomala, Piper nigrum, Morus macroura, and Agrimonia pilosa, and 29 phytocompounds such as artemisitene, morroniside, protopine, ferulic acid, quercetin, picroside II, and hydroxytyrosol on in vitro and in vivo models of inflammatory bowel diseases (IBD), with a focus on their effects on the NLRP3 inflammasome. The observed effects of these treatments included reductions in IL-1ß, tumor necrosis factor-alpha, IL-6, interferon-gamma, and caspase levels, and increased expression of antioxidant enzymes, IL-4, and IL-10, as well as regulation of gut microbiota. These effects could potentially provide substantial advantages in treating IBD with few or no adverse effects as caused by synthetic anti-inflammatory and immunomodulated drugs. However, additional research is necessary to validate these findings clinically and to develop effective treatments that can benefit individuals who suffer from these diseases.

Anti-Inflammatory, Antioxidant, and Other Health Effects of Dragon Fruit and Potential Delivery Systems for Its Bioactive Compounds.

Dragon fruit (Hylocereus genus) has the potential for the prevention of diseases associated with inflammatory and oxidative processes. We aimed to comprehensively review dragon fruit health effects, economic importance, and possible use in delivery systems. Pubmed, Embase, and Google Scholar were searched, and PRISMA (Preferred Reporting Items for a Systematic Review and Meta-Analysis) guidelines were followed. Studies have shown that pitaya can exert several benefits in conditions such as diabetes, dyslipidemia, metabolic syndrome, cardiovascular diseases, and cancer due to the presence of bioactive compounds that may include vitamins, potassium, betacyanin, p-coumaric acid, vanillic acid, and gallic acid. Moreover, pitaya has the potential to be used in food and nutraceutical products as functional ingredients, natural colorants, ecologically correct and active packaging, edible films, preparation of photoprotective products, and additives. Besides the importance of dragon fruit as a source of bioactive compounds, the bioavailability is low. The development of delivery systems such as gold nanoparticles with these compounds can be an alternative to reach target tissues.

Curcumin-Based Nanomedicines in the Treatment of Inflammatory and Immunomodulated Diseases: An Evidence-Based Comprehensive Review.

Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Despite CUR's numerous beneficial effects on human health, it has limitations, such as poor absorption. Nano-based drug delivery systems have recently been applied to improve CUR's solubility and bioavailability and potentialize its health effects. This review investigated the effects of different CUR-based nanomedicines on inflammatory and immunomodulated diseases. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR databases were searched, and the Scale for Assessment of Narrative Review Articles (SANRA) was used for quality assessment and PRISMA guidelines. Overall, 66 studies were included comprising atherosclerosis, rheumatoid arthritis (RA), Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), inflammatory bowel diseases (IBD), psoriasis, liver fibrosis, epilepsy, and COVID-19. The available scientific studies show that there are many known nanoformulations with curcumin. They can be found in nanosuspensions, nanoparticles, nanoemulsions, solid lipid particles, nanocapsules, nanospheres, and liposomes. These formulations can improve CUR bioavailability and can effectively be used as adjuvants in several inflammatory and immune-mediated diseases such as atheroma plaque formation, RA, dementia, AD, PD, MS, IBD, psoriasis, epilepsy, COVID-19, and can be used as potent anti-fibrotic adjuvants in fibrotic liver disease.

Ginkgo biloba in the Aging Process: A Narrative Review.

Neurodegenerative diseases, cardiovascular disease (CVD), hypertension, insulin resistance, cancer, and other degenerative processes commonly appear with aging. Ginkgo biloba (GB) is associated with several health benefits, including memory and cognitive improvement, in Alzheimer's disease (AD), Parkinson's disease (PD), and cancer. Its antiapoptotic, antioxidant, and anti-inflammatory actions have effects on cognition and other conditions associated with aging-related processes, such as insulin resistance, hypertension, and cardiovascular conditions. The aim of this study was to perform a narrative review of the effects of GB in some age-related conditions, such as neurodegenerative diseases, CVD, and cancer. PubMed, Cochrane, and Embase databases were searched, and the PRISMA guidelines were applied. Fourteen clinical trials were selected; the studies showed that GB can improve memory, cognition, memory scores, psychopathology, and the quality of life of patients. Moreover, it can improve cerebral blood flow supply, executive function, attention/concentration, non-verbal memory, and mood, and decrease stress, fasting serum glucose, glycated hemoglobin, insulin levels, body mass index, waist circumference, biomarkers of oxidative stress, the stability and progression of atherosclerotic plaques, and inflammation. Therefore, it is possible to conclude that the use of GB can provide benefits in the prevention and treatment of aging-related conditions.

Anthocyanins: Metabolic Digestion, Bioavailability, Therapeutic Effects, Current Pharmaceutical/Industrial Use, and Innovation Potential.

In this work, various concepts and features of anthocyanins have been comprehensively reviewed, taking the benefits of the scientific publications released mainly within the last five years. Within the paper, common topics such as anthocyanin chemistry and occurrence, including the biosynthesis of anthocyanins emphasizing the anthocyanin formation pathway, anthocyanin chemistry, and factors influencing the anthocyanins' stability, are covered in detail. By evaluating the recent in vitro and human experimental studies on the absorption and bioavailability of anthocyanins present in typical food and beverages, this review elucidates the significant variations in biokinetic parameters based on the model, anthocyanin source, and dose, allowing us to make basic assumptions about their bioavailability. Additionally, special attention is paid to other topics, such as the therapeutic effects of anthocyanins. Reviewing the recent in vitro, in vivo, and epidemiological studies on the therapeutic potential of anthocyanins against various diseases permits a demonstration of the promising efficacy of different anthocyanin sources at various levels, including the neuroprotective, cardioprotective, antidiabetic, antiobesity, and anticancer effects. Additionally, the studies on using plant-based anthocyanins as coloring food mediums are extensively investigated in this paper, revealing the successful use of anthocyanins in coloring various products, such as dietary and bakery products, mixes, juices, candies, beverages, ice cream, and jams. Lastly, the successful application of anthocyanins as prebiotic ingredients, the innovation potential of anthocyanins in industry, and sustainable sources of anthocyanins, including a quantitative research literature and database analysis, is performed.

Lupinus albus Protein Components Inhibit MMP-2 and MMP-9 Gelatinolytic Activity In Vitro and In Vivo.

Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and 9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of 15 mg·kg-1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor was found to comprise a large fragment from δ-conglutin and, to a lower extent, small fragments of ß-conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in a dose-dependent manner in colon cancer cells, with an IC50 of 10 µg·mL-1 without impairing gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities when administered orally and significantly reduced colitis symptoms, along with a very significant inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9 activity in the digestive system.

From Diospyros kaki L. (Persimmon) Phytochemical Profile and Health Impact to New Product Perspectives and Waste Valorization.

Persimmon (Diospyros kaki L.) fruit's phytochemical profile includes carotenoids, proanthocyanidins, and gallic acid among other phenolic compounds and vitamins. A huge antioxidant potential is present given this richness in antioxidant compounds. These bioactive compounds impact on health benefits. The intersection of nutrition and sustainability, the key idea behind the EAT-Lancet Commission, which could improve human health and decrease the global impact of food-related health conditions such as cancer, heart disease, diabetes, and obesity, bring the discussion regarding persimmon beyond the health effects from its consumption, but also on the valorization of a very perishable food that spoils quickly. A broad option of edible products with better storage stability or solutions that apply persimmon and its byproducts in the reinvention of old products or even creating new products, or with new and better packaging for the preservation of food products with postharvest technologies to preserve and extend the shelf-life of persimmon food products. Facing a global food crisis and the climate emergency, new and better day-to-day solutions are needed right now. Therefore, the use of persimmon waste has also been discussed as a good solution to produce biofuel, eco-friendly alternative reductants for fabric dyes, green plant growth regulator, biodegradable and edible films for vegetable packaging, antimicrobial activity against foodborne methicillin-resistant Staphylococcus aureus found in retail pork, anti-Helicobacter pylori agents from pedicel extracts, and persimmon pectin-based emulsifiers to prevent lipid peroxidation, among other solutions presented in the revised literature. It has become clear that the uses for persimmon go far beyond the kitchen table and the health impact consumption demonstrated over the years. The desired sustainable transition is already in progress, however, mechanistic studies and clinical trials are essential and scaling-up is fundamental to the future.

Phenolic Compounds Impact on Rheumatoid Arthritis, Inflammatory Bowel Disease and Microbiota Modulation.

Non-communicable chronic diseases (NCDs) are nowadays the principal cause of death, especially in most industrialized nations. These illnesses have increased exponentially with the consumption of diets very high in fat and sugar, not to mention stress and physical inactivity among other factors. The potential impact of suboptimal diets on NCDs' morbidity and mortality rates brings to the forefront the necessity for a new way of improving dietary habits. The literature provides extensive scientific work that presents evidence that phenolic compounds from diets have antioxidant, anti-inflammatory and antiproliferative activities that impact human health. Gut microbiota modulation by some phenolic compounds leads to favorable changes in abundance, diversity, and in the immune system. However, polyphenol's limited bioavailability needs to be overcome, highlighting their application in new delivery systems and providing their health benefits in well-established ways such as health maintenance, treatment or adjuvant to conventional pharmacological treatments. In this context, novel dietary approaches, including new food supplements, have emerged to prevent diseases and preserve health.

Anti-inflammatory Effects of Persimmon (Diospyros kaki L.) in Experimental Rodent Rheumatoid Arthritis.

Persimmon (Diospyros kaki L.) fruits are used in traditional medicine largely due to their claimed beneficial effects on human health. The aim of this work was to evaluate the anti-inflammatory activity of a persimmon extract in rats with collagen-induced arthritis (CIA). CIA was induced in Wistar rats through an intradermal injection of an emulsion of bovine type II collagen (CII) in complete Freund's adjuvant (FCA). Macroscopic evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged rats, and the severity of CIA progressed for 35 days. Radiographs revealed focal resorption of bone, with osteophyte formation in the tibiotarsal joint and soft tissue swelling. The histopathologic features included erosion of the cartilage at the joint margins. The persimmon extract showed an anti-inflammatory effect given the significant reduction in both the edema volume and radiological alterations attributed to CIA in the bone. We demonstrate that the administration of persimmon extract attenuates the degree of chronic inflammation and tissue damage characteristic of CIA in rats, most probably by the potent antioxidant characteristics of the extract.

Reduction of inflammation and colon injury by a Pennyroyal phenolic extract in experimental inflammatory bowel disease in mice.

PURPOSE: Little is known about the pharmacological effects of the phenolic compounds of Pennyroyal (Mentha pulegium). This Mediterranean aromatic plant, used as a gastronomic spice and as food preservative by the food industry has been studied mainly due to its essential oil antibacterial properties, composed primarily by monoterpenes. With this work, we aimed to evaluate the effects of a phenolic extract of pennyroyal in the impairment of inflammatory processes in Inflammatory Bowel Diseases (IBD) and in the potential inhibition of progression to colorectal cancer (CRC). METHODS: To that purpose, we evaluated the effect of pennyroyal extract administration in a model of TNBS-induced colitis in mice and further determined its effect on human colon carcinoma cell proliferation and invasion. RESULTS: The phenolic extract of pennyroyal exhibited antioxidant properties in in vitro assays and administration of the extract in a rat model of carrageenan-induced paw oedema led to significant anti-inflammatory effects. Further results evidenced a beneficial effect of the phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells, effects not previously described, to our knowledge. A reduction in several markers of colon inflammation was observed following administration of the extract to colitis-induced mice, including functional and histological indicators. A successful inhibition of cancer cell invasion and proliferation was also observed in in vitro studies with HT-29 cells. Furthermore, the extract also led to a reduced expression of iNOS/COX-2 in the colon of colitis-induced mice, both being crucial mediators of intestinal inflammation. CONCLUSIONS: Taking into consideration the central role of inflammation in the pathophysiology of CRC and the recognised connection between inflammatory events and cancer, these results enlighten the relevance of the phenolic constituents of pennyroyal as important pharmacological sources in the investigation of new treatment options for patients with inflammatory bowel diseases.

Phytosomes with Persimmon (Diospyros kaki L.) Extract: Preparation and Preliminary Demonstration of In Vivo Tolerability.

Persimmon (Diospyros kaki L.), a fruit rich in phenolic compounds (PCs), has been considered effective in mitigating oxidative damage induced by an excess of reactive oxygen species. Due to large molecular weight and intrinsic instability in some physiological fluids, PCs' passage through biological membranes is very limited. Carriers like phytosomes are promising systems to optimize oral absorption of encapsulated extracts. This work prepared and fully characterized phytosomes containing bioactive phenolic extracts from persimmon in terms of size, surface charge, encapsulation efficiency and stability over six months. These phytosomes were orally dosed to Wistar rats during a 15-day period. Afterwards, haematological and biochemical analyses were performed. Monodisperse phytosomes were successfully prepared, with size less than 300nm (PI < 0.3) and high encapsulation efficiency (97.4%) of PCs. In contrast to free extract, extract-loaded phytosomes had higher antioxidant activity after 6 months storage. Oral administration of extract-loaded phytosomes and free extract did not lead to lipidic profile changes and were within referenced normal ranges, as well as glycaemia levels and urine parameters. The results highlighted the potential of persimmon PCs as food supplements or pharmacological tools, suggesting a promising and safe phytosomal formulation containing bioactive agents of persimmon that could lead to health benefits.

Reduction of Inflammation and Colon Injury by a Spearmint Phenolic Extract in Experimental Bowel Disease in Mice.

Background: Inflammatory Bowel Diseases (IBD) encompasses both Crohn's Disease and Ulcerative Colitis, known to be connected to an enlarged risk for developing colorectal cancer (CRC). Spearmint (Mentha spicata L.) is a Mediterranean plant used as an aromatic agent, and studies have mainly focused on the essential oil suggesting an anti-inflammatory activity. This work aimed to perform a preliminary screening of the in vivo anti-inflammatory effects of a spearmint phenolic extract in an acute inflammation model, in a chronic inflammation model of colitis, and also study the effects in vitro on a colon cancer model. Methods: Spearmint extract was administered to rats of a paw oedema model (induced by carrageenan) and to mice from a TNBS-induced colitis model in parallel with studies using HT-29 CRC cells. Results: Administration of the extract led to reduced paw inflammation, reduction of colon injury and inflammation, with attenuation of histological markers, and reduction of iNOS expression. It repressed the in vitro movement of HT-29 cells in a wound healing assay. Conclusions: These findings suggest that spearmint extract exhibits acute and chronic anti-inflammatory activity and is able to inhibit migration of cancer cells, suggesting a potential role in the supplementary therapy of IBD patients.

Combination of hyaluronic acid and PLGA particles as hybrid systems for viscosupplementation in osteoarthritis.

Hyaluronic acid (HA) is commonly used through intra-articular administration for viscosupplementation in osteoarthritis and other disorders. HA is generally supplied as an injection commonly reported as painful, with strong limitations after treatment. In this study, an alternative delivery system was constructed based on HA hydrogel and poly(lactic-co-glycolic acid) (PLGA) particles with oleic acid. Development studies included the determination of particle toxicity, hemolytic activity, in vitro and in vivo anti-inflammatory activity using macrophages and a murine model, respectively. This study showed that empty PLGA particles presented a mean size of 373 nm, while particles containing HA and oleic acid showed a marked particle size increase. The HA association efficiency was of 73.6% and 86.2% for PLGA particles without and with oleic acid, respectively. The in vitro HA release from PLGA particles revealed a sustained profile. Particles showed a good in vitro cell compatibility and the risk of hemolysis was less <1%, ensuring their safety. The in vivo anti-inflammatory study showed a higher inhibition for HA-loaded PLGA particles when compared to HA solution (78% versus 60%) and they were not different from the positive control, clearly suggesting that this formulation may be a promising alternative to the current HA commercial dosage form.

Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities.

Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD.

Protective effects of a blueberry extract in acute inflammation and collagen-induced arthritis in the rat.

Here we investigated the anti-inflammatory effect of a blueberry extract in the carrageenan-induced paw edema model and collagen-induced arthritis model, both in rats. Along with the chemical characterization of the phenolic content of the fruits and extract, the antioxidant potential of the extract, the cellular antioxidant activity and the effects over neutrophils' oxidative burst, were studied in order to provide a mechanistic insight for the anti-inflammatory effects observed. The extract significantly inhibited paw edema formation in an acute model the rat. Our results also demonstrate that the standardized extract had pharmacological activity when administered orally in the collagen-induced arthritis model in the rat and was able to significantly reduce the development of clinical signs of arthritis and the degree of bone resorption, soft tissue swelling and osteophyte formation, consequently improving articular function in treated animals.

Enantioselective assay for therapeutic drug monitoring of eslicarbazepine acetate: no interference with carbamazepine and its metabolites.

As add-on therapy, phase III clinical trials of eslicarbazepine acetate (ESL) conducted in patients with refractory partial-onset seizures have shown good efficacy, safety, and tolerability, even in patients taking carbamazepine (CBZ) at baseline (approximately 60% of the enrolled patients). Thus, considering the pharmacological disadvantages of CBZ and the similar efficacy spectrum of CBZ and ESL, switching to ESL may be successful in many patients. As ESL is a prodrug almost instantaneously converted to S-licarbazepine (S-Lic; approximately 95%), an interest in therapeutic drug monitoring (TDM) of S-Lic is likely to develop in the future. This study investigated the plasma concentrations of S-Lic and R-licarbazepine (R-Lic) enantiomers in patients under CBZ long-term treatment to assess the potential interference of CBZ or its metabolites in the enantioselective TDM of ESL (using S-Lic concentrations). A chiral high-performance liquid chromatography assay with ultraviolet detection (HPLC-UV) previously developed and validated by our research group was used. Twenty-four patients admitted to the Coimbra University Hospital and supposedly receiving CBZ long-term treatment were identified. Blood samples were collected from patients and serum CBZ concentrations were measured by the usual TDM protocol. Aliquots of plasma from such patients were also submitted to a chiral HPLC-UV analysis. The bioanalytical data indicated that S-Lic and R-Lic were not present at detectable concentrations in plasma samples of the CBZ-treated patients. The chromatograms generated by the analysis of patient plasma samples, when compared with those obtained from blank plasma samples spiked with S-Lic and R-Lic, clearly showed the absence of interferences at the retention times of both Lic enantiomers. These data support the usefulness of the chiral HPLC-UV method used for the enantioselective TDM of ESL (using S-Lic) for programs in which switching from CBZ to ESL is implemented.