Wound healing is a tightly regulated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. When these phases are disrupted, wound repair can be delayed or become chronic. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, coordinate immune activation, cytokine expression, cell proliferation, and tissue repair. Medicinal plants and their bioactive compounds, such as flavonoids, alkaloids, tannins, and other phytoconstituents, have demonstrated significant anti-inflammatory, antioxidant, and immunomodulatory effects that modulate these pathways. Tannins contribute to repair through neutralization of reactive oxygen species (ROS), activation of antioxidant enzymes, and metal-chelating activity. Alkaloids, including tetrandrine, oxymatrine, and berberine, inhibit NF-κB signaling, thereby reducing pro-inflammatory cytokines such as IL-1β and TNF-α. Flavonoids regulate inflammatory mediators and enzymes, including COX and phospholipase A2, while also protecting against oxidative stress and stimulating fibroblast and keratinocyte proliferation—key steps in tissue regeneration. Collectively, these compounds accelerate wound closure by reducing oxidative stress and promoting cellular proliferation and migration. Thus, medicinal plants represent promising complementary approaches to wound management. Future research should focus on developing advanced drug delivery systems to enhance the stability, bioavailability, and targeted action of plant-derived compounds. Localized and biomaterial-based strategies show promise for sustained release at the wound site, and further preclinical and clinical studies are required to ensure their safety, reproducibility, and efficacy.

Extracts from medicinal plants are widely used in the treatment and prevention of different diseases. Micromeria frivaldszkyana is a Balkan endemic species with reported antioxidant and antimicrobial characteristics; however, its phytochemical composition is not well defined. Here, we examined the metabolome of M. frivaldszkyana by chromatography–mass spectrometry (GC-MS), ultra-performance liquid chromatography–mass spectrometry (UPLC-MS-MS), and inductively coupled plasma mass spectrometry (ICP-MS). Amino acids, organic acids, sugars, and sugar alcohols were the primary metabolites with the highest levels in the plant extract. Detailed analysis of the sugar content identified high levels of sucrose, glucose, mannose, and fructose. Lipids are primary plant metabolites, and the analysis revealed triacylglycerols as the most abundant lipid group. Potassium (K), magnesium (Mg), zinc (Zn), and calcium (Ca) were the elements with the highest content. The results showed linarin, 3-caffeoil-quinic acid, and rosmarinic acid, as well as a number of polyphenols, as the most abundant secondary metabolites. Among the flavonoids and polyphenols with a high presence were eupatorin, kaempferol, and apigenin—compounds widely known for their bioactive properties. Further, the acute toxicity and potential anti-inflammatory activity of the methanolic extract were evaluated in Wistar rats. No toxic effects were registered after a single oral application of the extract in doses of between 200 and 5000 mg/kg bw. A fourteen-day pre-treatment with methanolic extract of M. frivaldszkyana in doses of 250, 400, and 500 mg/kg bw induced anti-inflammatory activity in the 1st, 2nd, and 3rd hours after carrageenan injection in a model of rat paw edema. This effect was also present in the 4th hour only in the group treated with a dose of 500 mg/kg. In conclusion, M. frivaldszkyana extract is particularly rich in linarin, rosmarinic acid, and flavonoids (eupatorin, kaempferol, and apigenin). Its methanolic extract induced no toxicity in male Wistar rats after oral application in doses of up to 5000 mg/kg bw. Additionally, treatment with the methanolic extract for 14 days revealed anti-inflammatory potential in a model of rat paw edema on the 1st, 2nd, and 3rd hours after the carrageenan injection. These results show the anti-inflammatory potential of the plant, which might be considered for further exploration and eventual application as a phytotherapeutic agent.

Recently, compounds of plant origin have been the focus of increased scientific interest. Micromeria frivaldszkyana is a rare species endemic to Bulgaria, whose biological activity remains unknown. This article aims to evaluate the subchronic toxicity of Micromeria frivaldszkyana methanolic extract and its effect on cognition in rats. Following 90 days of oral administration, a histopathological evaluation of brain, kidney, and liver tissues was conducted. Additionally, serum levels of total bilirubin (TB), conjugated bilirubin (CB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CR), uric acid (UA), and urea (U) were measured. Cognitive function was studied after 7 d of treatment using activity cage test, along with tests for active memory, passive memory, anxiety, spatial and working memory, and explorative activity. The experiments showed no toxic effects of the extract in subchronic application. No adverse effects on brain function were observed after 14 days of treatment. While the extract increased the motor activity of the animals, it did not significantly improve the learning and memory processes. In conclusion, the methanolic extract of Micromeria frivaldszkyana in doses 250 and 500 mg/kg bw did not induce toxicity after 90-day treatment in rats. These doses did not significantly affect central nervous system (CNS) functions, although increased motor activity was observed after 14 days of treatment with the extract.

Type 1 diabetes mellitus is characterized with decreased microbial diversity. Gut microbiota is essential for the normal physiological functioning of many organs, especially the brain. Prebiotics are selectively fermentable oligosaccharides [xylooligosaccharides (XOS), galactooligosaccharides, etc.] that promote the growth and activity of gut microbes and influence the gut–brain axis. Aerobic exercise is a non-pharmacological approach for the control of diabetes and could improve cognitive functions. The potential beneficial effect of XOS and/or aerobic training on cognition, the lipid profile and oxidative stress markers of experimental rats were evaluated in this study. Male Wistar rats were randomly divided into three streptozotocin-induced diabetic groups and a control group. Some of the rats, either on a XOS treatment or a standard diet, underwent aerobic training. The results showed that the aerobic training independently lowered the total cholesterol levels compared to the sedentary diabetic rats (p = 0.032), while XOS lowers the malondialdehyde levels in the trained diabetic rats (p = 0.034). What is more the exercise, independently or in combination with XOS beneficially affected all parameters of the behavioral tests. We conclude that aerobic exercises alone or in a combination with the prebiotic XOS could ameliorate the dyslipidemia, oxidative stress, and cognitive abilities in experimental type 1 diabetic animals.

The genus Marrubium (Lamiaceae) is widely used in traditional medicine. While some representatives of the genus have been well investigated, the biological activity of others remains largely unknown. The aim of the current study was to assess the in vitro antioxidant potential and the effect on the reactivity of isolated rat gastric smooth muscles (SM) of aqueous extracts of Marrubium friwaldskyanum inflorescences, stems and leaves, and Marrubium peregrinum as a whole herb. The antioxidant activity was analyzed through multiple spectrophotometric and fluorometric assays. The effect on SM reactivity was determined by the treatment of excised gastric muscles of 10 male Whistar rats with the plant extracts alone or successive to 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide, ketanserin, verapamil, and acetylcholine. According to the obtained results, the M. friwaldskyanum leaf extract exhibited the greatest antioxidant potential, followed by the M. peregrinum one. The SM reactivity analysis revealed that the treatment with all four extracts induced a dose-dependent contractile response with predominant cholinergic character. However, activation of serotoninergic and/or dopaminergic pathways was also observed. Furthermore, when applied after verapamil, the extracts showed a SM relaxant effect. The discovered biological activity will serve as a basis for future analyses through which the therapeutic effect of the plants will be investigated.

Acetaminophen (APAP) overdose can result in potentially fatal acute liver failure, with free radical formation identified as a major mechanism of liver tissue damage. Micromeria frivaldszkyana (M. frivaldszkyana), a rare species endemic to Bulgaria, has demonstrated significant antioxidant activity. Male Wistar rats were treated orally for 7 days with saline; 250, 400, or 500 mg/kg of a water solution of dried methanolic extract of M. frivaldszkyana; 100 mg/kg rosmarinic acid (RA); or 125 mg/kg silymarin. Liver toxicity was induced by oral application of 2000 mg/kg APAP on the last day of treatment. Forty-eight hours later, blood and livers were collected for histological and biochemical analysis. The results revealed that treatment with 500 mg/kg of the dried methanolic extract significantly reduced the elevated levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and tumor necrosis factor-alpha in APAP overdose. The present results clearly demonstrate, for the first time, that pre-treatment with methanolic extract of M. frivaldszkyana results in significant hepatoprotective effects in the APAP-induced rat model of liver injury. The mechanism of this effect may involve cell membrane protection, decreased lipid peroxidation and DNA damage, and attenuation of aseptic inflammation. These effects can be attributed to the main compounds identified in the extract (linarin, chlorogenic acid, rutin, eupatorin, apigenin, RA).