Worldwide, there are plants known as psychoactive plants that naturally contain psychedelic active components. They have a high concentration of neuroprotective substances that can interact with the nervous system to produce psychedelic effects. Despite these plants' hazardous potential, recreational use of them is on the rise because of their psychoactive properties. Early neuroscience studies relied heavily on psychoactive plants and plant natural products (NPs), and both recreational and hazardous NPs have contributed significantly to the understanding of almost all neurotransmitter systems. Worldwide, there are many plants that contain psychoactive properties, and people have been using them for ages. Psychoactive plant compounds may significantly alter how people perceive the world.
1. Braz J Med Biol Res. 2024 Nov 4;57:e13914. doi: 10.1590/1414-431X2024e13914. eCollection 2024. Esculetin attenuates cerebral ischemia-reperfusion injury and protects neurons through Nrf2 activation in rats. Zhang Z(1), Zhang J(1), Shi R(1), Xu T(1), Wang S(1), Tian J(1). Author information: (1)Brain Disease Department, The First Affiliated Hospital of Hebei University of Traditional Chinese Medicine, Shijiazhuang, Hebei, China. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a key transcription factor in the antioxidant response and is associated with various chronic diseases. The aim of this study was to explore the action of esculetin, a natural dihydroxy coumarin, on attenuating middle cerebral artery occlusion (MCAO) and reperfusion, and whether its effect is dependent on Nrf2 activation, as well as nuclear factor-kappa B (NF-κB) inhibition. Two doses of esculetin (20 and 40 mg/kg) were tested on rats with MCAO reperfusion. Neurological deficiency, oxidative stress, and pathological analyses were performed to evaluate its effect. An in vitro analysis was also used to confirm whether its action was dependent on the Nrf2/HO-1/NQO-1 pathway. Compared with MCAO reperfusion rats, esculetin improved infarct volume and increased normal-shaped neuron cells by decreasing tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β levels. The oxidative stress parameter malondialdehyde (MDA) decreased and the activity of superoxide dismutase (SOD) and glutathione/glutathione disulfide (GSH/GSSG) ratio increased after esculetin treatment. Moreover, esculetin inhibited NF-κB activation induced by MCAO. In vitro, hypoxia/reoxygenation (H/R) impaired the viability of rat neuron cells and esculetin showed a neuron protection effect on cells. Nrf2 inhibitor Brusatol inhibited the activation of Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase 1 (NQO-1) caused by esculetin and abolished its protection effect. Esculetin protected cerebral neurons from ischemia-reperfusion injury by inhibiting NF-κB and Nrf2/HO-1/NQO-1 activation. DOI: 10.1590/1414-431X2024e13914 PMCID: PMC11540255 PMID: 39504067 [Indexed for MEDLINE] 2. Antioxidants (Basel). 2024 Sep 26;13(10):1170. doi: 10.3390/antiox13101170. Esculetin Combats Multidrug-Resistant Salmonella Infection and Ameliorates Intestinal Dysfunction via the Nrf2 Pathway. Xu W(1)(2), Ding W(2), Jia L(3), Zhu K(3), Luo Q(1). Author information: (1)Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing 100730, China. (2)College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. (3)National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. The increasing incidence of multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium (S. Tm), known for causing invasive enteric infections, presents a significant public health challenge. Given the diminishing efficacy of existing antibiotics, it is imperative to explore novel alternatives for the treatment of MDR S. Tm infections. Here, we identified esculetin (EST), a natural coumarin abundant in dietary foods and herbs, as a compound exhibiting broad-spectrum antibacterial properties against a range of MDR bacteria. Our findings demonstrate that EST effectively inhibited the proliferation and expansion of MDR S. Tm in both in vitro experiments and animal models. Specifically, EST significantly downregulated the type 3 secretion system-1 (T3SS-1) virulence expression of MDR S. Tm, thereby preventing its invasion into intestinal epithelial cells. In S. Tm-infected mice, we observed cecal injury characterized by the upregulation of inflammatory cytokines, a reduction in goblet cell numbers, a decreased expression of tight junction proteins, and microbial dysbiosis. Conversely, EST treatment ameliorated these pathological changes induced by S. Tm infection and reduced oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, thereby improving intestinal barrier function. These results suggest that dietary coumarins or a targeted plant-based diet may offer a promising strategy to counteract MDR bacteria-induced enteric diseases. DOI: 10.3390/antiox13101170 PMCID: PMC11504508 PMID: 39456424 Conflict of interest statement: The authors declare no conflicts of interest. 3. Front Pharmacol. 2024 Sep 13;15:1404172. doi: 10.3389/fphar.2024.1404172. eCollection 2024. The possible anti-tumor actions and mechanisms of active metabolites from Cortex Fraxini. Cai B(1), Cai T(2), Feng Z(1), Zhu H(1). Author information: (1)Department of Anorectal Surgery, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China. (2)Department of Nephrology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Wuxi, China. Cortex Fraxini is a traditional Chinese herb that is widely available, inexpensive, and has low toxicity. Modern pharmacological studies have demonstrated that the active metabolites in Cortex Fraxini, including esculin, esculetin, and fraxetin, exert anti-tumor activities by regulating genes and proteins involved in cancer cell proliferation, apoptosis, invasion, and migration. Additionally, these metabolites play a pivotal role in the regulation of several tumor-associated signaling pathways, including the PI3K/Akt, MAPK/ERK, JAK/STAT3, and Wnt/β-catenin pathways. Due to their pro-apoptotic and anti-proliferative properties in vitro and in vivo, Cortex Fraxini and its active metabolites may be considered as potential candidates for the treatment of tumor. The aim of this review is to highlight the anti-tumor biological activities and underlying mechanisms of action of the active metabolites of Cortex Fraxini, with a view to providing a reference for their further development and application in the treatment of tumors. Copyright © 2024 Cai, Cai, Feng and Zhu. DOI: 10.3389/fphar.2024.1404172 PMCID: PMC11427270 PMID: 39346560 Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 4. Pharm Dev Technol. 2024 Oct;29(8):886-898. doi: 10.1080/10837450.2024.2407854. Epub 2024 Oct 1. Preparation and characterisation of esculetin-loaded nanostructured lipid carriers gels for topical treatment of UV-induced psoriasis. Khalil RM(1), Abdelhameed MF(2), Abou Taleb S(1), El-Saied MA(3), Shalaby ES(1). Author information: (1)Pharmaceutical Technology Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, Egypt. (2)Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt. (3)Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. SIGNIFICANCE: As an inflammatory and autoimmune skin condition, psoriasis affects 2-3% of people worldwide. Psoriasis requires prolonged treatments with immunosuppressive medications which have severe adverse effects. Esculetin (Esc) is a natural medication that has been utilised to treat psoriasis. OBJECTIVE: The goal of this work is to improve Esc's solubility by developing novel Esc nanostructured lipid carriers (NLCs) for treating psoriasis and increasing the residence time on the skin which infers better skin absorption. METHODS: The particle size, zeta potential and entrapment efficiency (EE) of Esc NLCs were assessed. Incorporating NLCs into gum Arabic gel preparation enhances their industrial applicability, absorption and residence time on the skin. Esc NLC gels were evaluated by in vitro release and in vivo effectiveness on a rat model of UV-induced psoriasis. RESULTS: Esc NLCs showed high EE reaching more than 95% and reasonable particle size ranging between (53.86 ± 0.38 to 236.3 ± 0.11 nm) and were spherical. The release study of Esc NLCs gel demonstrated a fast release of Esc denoting enhanced bioavailability. Compared to free Esc, Esc NLCs gel (F2) could considerably lower the level of CD34 and TNF-α in the skin. The results were validated through histopathological analysis. CONCLUSION: As Esc NLCs gel (F2) has strong anti-inflammatory properties, our results showed that it presented a significant potential for healing psoriasis. DOI: 10.1080/10837450.2024.2407854 PMID: 39315459 [Indexed for MEDLINE] 5. J Biochem Mol Toxicol. 2024 Oct;38(10):e23861. doi: 10.1002/jbt.23861. The protective effects of esculetin against Doxorubicin-Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways. Kizir D(1), Yeşilkent EN(1), Öztürk N(1), Karağaç MS(1), Isıyel M(1), Tosun H(1), Karadaş H(1), Ceylan H(1), Karaman M(1), Demir Y(2). Author information: (1)Faculty of Science, Department of Molecular Biology and Genetics, Atatürk University, Erzurum, Türkiye. (2)Department of Pharmacy Services, Nihat Delibalta Göle Vocational High School, Ardahan University, Ardahan, Türkiye. Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX-induced hepatotoxicity in rat livers. Forty-eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX-induced expression of Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3, and Casp9 while increasing the DOX-induced expression of Foxo3. These findings suggest that esculetin, with its antioxidant and anti-inflammatory effects, might be a therapeutic option for protecting against DOX-induced hepatotoxicity. © 2024 Wiley Periodicals LLC. DOI: 10.1002/jbt.23861 PMID: 39305037 [Indexed for MEDLINE]