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. Cell Death Discov. 2024 Oct 28;10(1):454. doi: 10.1038/s41420-024-02220-y. Xanthohumol overcomes osimertinib resistance via governing ubiquitination-modulated Ets-1 turnover. Ma Y(1)(2), Wang R(1), Liao J(1), Guo P(1), Wang Q(2), Li W(3). Author information: (1)Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China. (2)NHC key laboratory of translantional research on transplantation medicine, Department of Transplant Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China. (3)Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China. weililx@csu.edu.cn. Non-small cell lung cancer (NSCLC) is a prevalent and fatal malignancy with a significant global impact. Recent advancements have introduced targeted therapies like tyrosine kinase inhibitors (TKIs) such as osimertinib, which have improved patient outcomes, particularly in those with EGFR mutations. Despite these advancements, acquired resistance to TKIs remains a significant challenge. Hence, one of the current research priorities is understanding the resistance mechanisms and identifying new therapeutic targets to improve therapeutic efficacy. Herein, we identified high expression of c-Met in osimertinib-resistant NSCLC cells, and depletion of c-Met significantly inhibited the proliferation of osimertinib-resistant cells and prolonged survival in mice, suggesting c-Met as an attractive therapeutic target. To identify effective anti-tumor agents targeting c-Met, we screened a compound library containing 641 natural products and found that only xanthohumol exhibited potent inhibitory effects against osimertinib-resistant NSCLC cells. Moreover, combination treatment with xanthohumol and osimertinib sensitized osimertinib-resistant NSCLC cells to osimertinib both in vitro and in vivo. Mechanistically, xanthohumol disrupted the interaction between USP9X and Ets-1, and inhibited the phosphorylation of Ets-1 at Thr38, promoting its degradation, thereby targeting the Ets-1/c-Met signaling axis and inducing intrinsic apoptosis in osimertinib-resistant NSCLC cells. Overall, the research highlights the critical role of targeting c-Met to address osimertinib resistance in NSCLC. By demonstrating the efficacy of xanthohumol in overcoming resistance and enhancing therapeutic outcomes, this study provides valuable insights and potential new strategies for improving the clinical management of NSCLC. © 2024. The Author(s). DOI: 10.1038/s41420-024-02220-y PMCID: PMC11519634 PMID: 39468027 Conflict of interest statement: The authors declare no competing interests. 2. Int J Mol Sci. 2024 Oct 13;25(20):11015. doi: 10.3390/ijms252011015. Synergistic Proliferation Effects of Xanthohumol and Niflumic Acid on Merkel and Glioblastoma Cancer Cells: Role of Cell Membrane Interactions. Stompor-Gorący M(1), Włoch A(2), Sengupta P(2), Nasulewicz-Goldeman A(3), Wietrzyk J(3). Author information: (1)Department of Pathophysiology, Institute of Medical Sciences, University of Rzeszów, Warzywna 1a, 35-310 Rzeszów, Poland. (2)Department of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, 50-375 Wrocław, Poland. (3)Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland. The objective of our research was to determine the effects of xanthohumol (XN), a flavonoid isolated from hops (Humulus lupulus), and the anti-inflammatory drug niflumic acid (NA), separately and in combination with each other, on the proliferation of human cancer cells. Additionally, so as to understand the mechanism underlying the anticancer properties of the tested compounds, their effects on the biophysical parameters of a model membrane were assessed. The cells were incubated with XN and NA at various concentrations, either individually or in combination with each other. Cell proliferation was quantified using the sulforodamine B (SRB) assay. In addition, the IC50 values for niflumic acid and xanthohumol applied separately were determined by cell proliferation tests for the following human cancer cell lines: 5637 (urinary bladder carcinoma), A-431 (epidermoid carcinoma), UM-SCC-17A (head and neck squamous carcinoma), SK-MEL-3 (melanoma), MCC13 (Merkel cell cancer), and A172 (glioblastoma), in comparison with the mouse normal fibroblasts (BALB/3T3 clone A31). The results show that the two-compound combinations of XN and NA significantly decreased the proliferation of cancer cells in a dose-dependent manner, and the effects were stronger than the additive responses to XN and NA individually. The membrane studies revealed a synergistic effect on the membrane rigidity when using the mixture of XN and NA, which may explain the observed increase in anticancer activity for the combined XN and NA. Our results suggest that NSAIDs, such as niflumic acid, may be a promising strategy for co-application with xanthohumol as anticancer drugs. DOI: 10.3390/ijms252011015 PMCID: PMC11508127 PMID: 39456799 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest. 3. EXCLI J. 2024 Aug 28;23:1068-1070. doi: 10.17179/excli2024-7656. eCollection 2024. Opening avenue for the targeted treatment of lung cancer using xanthohumol loaded nanostructured lipid carriers. Singh S(1), Saxena S(2), Sharma H(1), Gupta G(3)(4), Dua K(5)(6), Singh SK(6)(7). Author information: (1)School of Biosciences and Engineering, Lovely Professional University, Phagwara, Punjab, India. (2)Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India. (3)Center of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates. (4)Center for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India. (5)Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia. (6)Faculty of Health, Australian Research Center in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia. (7)School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India. DOI: 10.17179/excli2024-7656 PMCID: PMC11483262 PMID: 39421029 Conflict of interest statement: The authors declare no conflict of interest. 4. Materials (Basel). 2024 Sep 30;17(19):4827. doi: 10.3390/ma17194827. Application of Response Surface Methodology to Design and Optimize Purification of Acetone or Aqueous Acetone Extracts of Hop Cones (Humulus lupulus L.) Using Superparamagnetic Iron Oxide Nanoparticles for Xanthohumol Isolation. Żuk N(1), Pasieczna-Patkowska S(2), Flieger J(1). Author information: (1)Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4A, 20-093 Lublin, Poland. (2)Faculty of Chemistry, Department of Chemical Technology, Maria Curie-Skłodowska University, Pl. Maria Curie-Skłodowskiej3, 20-031 Lublin, Poland. Iron oxide nanoparticles (IONPs) are an ideal sorbent for magnetic dispersion extraction due to their superparamagnetic properties and developed and active surface. This work aims to use IONPs, obtained by chemical co-precipitation, to purify 100% acetone and 50% acetone extracts from hop cones (Humulus lupulus L.) obtained by ultrasonic-assisted solvent extraction. The extracts were purified from bitter acids (i.e., humulones, lupulones) to isolate xanthohumol. The sorption conditions were optimized depending on the composition of the extraction mixture, specifically the mass of IONPs and the time needed to achieve effective sorption using response surface methodology (RSM). An analysis of variance (ANOVA) was performed to assess the adequacy of the developed model, and a good agreement was found between the experimental data and the proposed model. The polynomial equation describing the model is highly significant (p < 0.05), with a precision of Adeq (above 4). This indicates the usefulness of the polynomial regression model for prediction in experimental design. The final products of the purification for 100% acetone extracts and 50% acetone contain 40.58 ± 2.84 µg mL-1 and 57.64 ± 0.83 µg mL-1 of xanthohumol, respectively. The use of 50% acetone extract provides more favorable conditions due to the smaller amount of nanoparticles required for extract purification and a higher recovery of xanthohumol. The development of a reliable multivariate model allowed for the optimization of the extract purification process, resulting in high-purity xanthohumol from natural sources. DOI: 10.3390/ma17194827 PMCID: PMC11477801 PMID: 39410398 Conflict of interest statement: The authors declare no conflicts of interest. 5. Int J Mol Sci. 2024 Sep 27;25(19):10433. doi: 10.3390/ijms251910433. Biotransformation of Xanthohumol by Entomopathogenic Filamentous Fungi. Łój D(1), Janeczko T(1), Bartmańska A(1), Huszcza E(1), Tronina T(1). Author information: (1)Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wroclaw, Poland. Xanthohumol (1) is a major prenylated flavonoid in hops (Humulus lupulus L.) which exhibits a broad spectrum of health-promoting and therapeutic activities, including anti-inflammatory, antioxidant, antimicrobial, and anticancer effects. However, due to its lipophilic nature, it is poorly soluble in water and barely absorbed from the gastrointestinal tract, which greatly limits its therapeutic potential. One method of increasing the solubility of active compounds is their conjugation to polar molecules, such as sugars. Sugar moiety introduced into the flavonoid molecule significantly increases polarity, which results in better water solubility and often leads to greater bioavailability. Entomopathogenic fungi are well known for their ability to catalyze O-glycosylation reactions. Therefore, we investigated the ability of selected entomopathogenic filamentous fungi to biotransform xanthohumol (1). As a result of the experiments, one aglycone (2) and five glycosides (3-7) were obtained. The obtained (2″E)-4″-hydroxyxanthohumol 4'-O-β-D-(4‴-O-methyl)-glucopyranoside (5) has never been described in the literature so far. Interestingly, in addition to the expected glycosylation reactions, the tested fungi also catalyzed chalcone-flavanone cyclization reactions, which demonstrates chalcone isomerase-like activity, an enzyme typically found in plants. All these findings undoubtedly indicate that entomopathogenic filamentous fungi are still an underexploited pool of novel enzymes. DOI: 10.3390/ijms251910433 PMCID: PMC11477118 PMID: 39408760 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.