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. J Ethnopharmacol. 2024 Oct 30:119011. doi: 10.1016/j.jep.2024.119011. Online ahead of print. Traditional Chinese Herbal Formula, Fuzi-Lizhong Pill, Produces Antidepressant-like Effects in Chronic Restraint Stress Mice through Systemic Pharmacology. Zhao F(1), Piao J(1), Song J(1), Geng Z(1), Chen H(1), Cheng Z(1), Cui R(2), Li B(3). Author information: (1)Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, P.R. China, 130041; Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, P.R. China, 130041; Jilin Provincial Key Laboratory on target of traditional Chinese medicine with anti-depressive effect, Changchun, P.R. China, 130041. (2)Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, P.R. China, 130041; Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, P.R. China, 130041; Jilin Provincial Key Laboratory on target of traditional Chinese medicine with anti-depressive effect, Changchun, P.R. China, 130041. Electronic address: cuiranji@jlu.edu.cn. (3)Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, P.R. China, 130041; Engineering Laboratory for Screening of Antidepressant Drugs, Jilin Province Development and Reform Commission, Changchun, P.R. China, 130041; Jilin Provincial Key Laboratory on target of traditional Chinese medicine with anti-depressive effect, Changchun, P.R. China, 130041. Electronic address: libingjin@jlu.edu.cn. ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi-Lizhong Pill (FLP) is a well-validated traditional Chinese medicine (TCM) formula that has long been used in China for gastrointestinal disease and adjunctive therapy for depression. In our previous study, we reported that the principal herb of FLP, Aconitum carmichaelii Debx. (Fuzi), exhibits antidepressant-like effects. However, there have been no reports on whether FLP produces antidepressant-like effects and its potential molecular mechanisms. AIM OF THE STUDY: We aim to demonstrate the antidepressant-like effects of FLP in chronic restraint stress (CRS) mice and to explore the associated molecular mechanisms. MATERIALS AND METHODS: The active components and probable molecular targets of FLP, as well as the targets related to depression, were identified through network pharmacology. A protein-protein interaction (PPI) network was generated using the overlapping targets, followed by the visualization as well as identification of the core targets associated with the antidepressant-like action of FLP. Subsequently, KEGG and GO enrichment analyses were conducted. UHPLC-MS/MS was employed to further detect the active compounds in FLP. Molecular docking was applied to assess the connections between the active components as well as the core targets. The efficacy of FLP in treating depression and its molecular mechanisms were examined using western blotting, ELISA, 16S rRNA sequencing, HE staining, Nissl staining, and Golgi-Cox staining in a CRS-induced mouse model. RESULTS: Network pharmacology and UHPLC-MS/MS analyses indicated that the active compounds of FLP comprised taraxerol, songorine, neokadsuranic acid B, ginkgetin, hispaglabridin B, quercetin, benzoylmesaconine and liquiritin. KEGG pathway analysis implicated that the PI3K/Akt/mTOR as well as MAPK signaling pathways are closely related to the therapeutic effects of FLP on depression. Molecular docking analysis demonstrated that the main components of FLP bind to PI3K, AKT, mTOR, BDNF and MAPK. FLP significantly decreased immobility in mice that were elevated by CRS in the FST and the TST. FLP also significantly increased sucrose preference in mice after CRS in the SPT. FLP upregulated proteins associated with BDNF-TrkB and PI3K/Akt/mTOR signaling and downregulated proteins associated with MAPK signaling. Serum levels of CORT, IL-6, IL-1β, and TNF-α in CRS mice were significantly decreased following treatment with FLP. In addition, FLP ameliorated CRS-induced gut microbiota dysbiosis as demonstrated by 16S rRNA sequencing analysis. FLP ameliorated CRS-induced intestinal inflammation and neuronal damage. Finally, antidepressant-like effects and concomitant increases in dendritic spine density induced by FLP administration were also reduced after rapamycin treatment. CONCLUSION: These results demonstrate that FLP has antidepressant-like effects in mice exposed to CRS that involve activation of the PI3K/Akt/mTOR signaling pathway, increase in spinogenesis, inhibition of the MAPK signaling pathway, decrease in inflammation, and amelioration of gut microbiota dysbiosis. These findings provide novel evidence for the clinical application of FLP on depression. Copyright © 2024. Published by Elsevier B.V. DOI: 10.1016/j.jep.2024.119011 PMID: 39486672 Conflict of interest statement: Declaration of Competing Interest The authors declare that there are no conflicts of interest regarding the publication of this manuscript. 2. Int J Mol Sci. 2024 Sep 15;25(18):9952. doi: 10.3390/ijms25189952. Rhododendron luteum Sweet Flower Supercritical CO(2) Extracts: Terpenes Composition, Pro-Inflammatory Enzymes Inhibition and Antioxidant Activity. Łyko L(1), Olech M(1), Gawlik U(2), Krajewska A(3), Kalemba D(3), Tyśkiewicz K(4), Piórecki N(5)(6), Prokopiv A(7), Nowak R(1). Author information: (1)Department of Pharmaceutical Botany, Medical University of Lublin, ul. Chodźki 1, 20-093 Lublin, Poland. (2)Department of Biochemistry and Food Chemistry, University of Life Sciences, ul. Skromna 8, 20-704 Lublin, Poland. (3)Institute of Natural Products and Cosmetics, Lodz University of Technology, ul. Stefanowskiego 4/10, 90-924 Łódź, Poland. (4)Supercritical Extraction Department, Łukasiewicz Research Network-New Chemical Syntheses Institute, ul. Tysiąclecia Państwa Polskiego 13a, 24-110 Puławy, Poland. (5)Bolestraszyce Arboretum and Institute of Physiography, Bolestraszyce 130, 37-722 Wyszatyce, Poland. (6)Institute of Physical Culture Sciences, Medical College, University of Rzeszow, ul. Cicha 2A, 35-326 Rzeszow, Poland. (7)Department of Botany, Botanical Garden, Ivan Franko National University of Lviv, 79005 Lviv, Ukraine. Terpenes are plant secondary metabolites known for their anti-inflammatory and antioxidant activities. According to ethnobotanical knowledge, Rhododendron luteum Sweet was used in traditional medicine against inflammation. The present study was conducted to determine the triterpene profile and antioxidant and anti-inflammatory activity of supercritical CO2 (SC-CO2) extracts of Rhododendron luteum Sweet flower (RLF). An LC-APCI-MS/MS analysis showed the presence of eight pentacyclic triterpenes and one phytosterol in the extracts obtained with pure CO2 as well as CO2 with the addition of aqueous ethanol as a co-solvent. Among the compounds detected, oleanolic/ursolic acid, β-sitosterol and 3β-taraxerol were the most abundant. The extract obtained with pure SC-CO2 was additionally subjected to HS-SPME-GC-FID-MS, which revealed more than 100 volatiles, mainly eugenol, β-phenylethanol, dodecane, β-caryophyllene, estragole and (Z)- and (E)-cinnamyl alcohol, followed by δ-cadinene. The extracts demonstrated significant hyaluronidase inhibition and exhibited varying modes of lipoxygenase and xanthine oxidase inhibitory activities. The studies of RLF have shown that their SC-CO2 extracts can be a rich source of triterpenes with anti-inflammatory potential. DOI: 10.3390/ijms25189952 PMCID: PMC11432528 PMID: 39337440 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest. 3. In Silico Pharmacol. 2024 Sep 9;12(2):82. doi: 10.1007/s40203-024-00257-6. eCollection 2024. In silico analysis reveals α-amylase inhibitory potential of Taraxerol (Coccinia indica) and Epoxywithanolide-1 (Withania coagulans): a possible way to control postprandial hyperglycemia-induced endothelial dysfunction and cardiovascular events. Ravi L(1), Sadhana V(2), Jain P(3), Godidhar Raghuram SK(4), Vaithilingam M(4), Manjunathan R(5)(6), Krishnan AK(7), Kesavan MP(8). Author information: (1)Department of Food Technology, Faculty of Life and Allied Health Sciences, MS Ramaiah University of Applied Sciences, Bengaluru, Karnataka 560054 India. (2)Department of Chemistry, Atria Institute of Technology, Bangalore, Karnataka 560024 India. (3)Department of Biotechnology, Faculty of Life and Allied Health Sciences, MS Ramaiah University of Applied Sciences, Bengaluru, Karnataka 560054 India. (4)School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014 India. (5)Multi-Disciplinary Research Unit, Kottayam Government Medical College and Hospital, Kottayam, Kerala India. (6)Dr. ALM Postgraduate Institute of Basic Medical Science, University of Madras, Taramani Campus, Chennai, Tamil Nadu 600113 India. (7)Department of Life Sciences, Kristu Jayanti College (Autonomous), Bengaluru, Karnataka 560077 India. (8)Department of Chemistry, Hajee Karutha Rowther Howdia College, Uthamapalayam, Tamil Nadu 625533 India. Postprandial hyperglycemia (PPG) exacerbates endothelial dysfunction and impairs vascular function in diabetes as well in healthy people. Though synthetic drugs are available to regulate PPG, the severe gastrointestinal side effects of those medications have prompted the search for alternative treatments. Recently, some phytochemicals captured the attention because of their inhibitory effects on α-amylase to control diabetes. The aim of this study was to investigate and identify potential alpha-amylase inhibitors in C. indica and W. coagulans. This study also aims to understand one of the possible mechanisms of action of plants for their anti-diabetic activity. A total of 36 phytochemical ligands were subjected for protein-ligand docking analysis. Among the phytochemicals, Taraxerol and Epoxywithanolide-I demonstrated significant binding free energy of - 10.2 kcal/mol and - 11.9 kcal/mol respectively, which was higher than the reference acarbose with - 8.6 kcal/mol. These molecules were subjected for molecular dynamics simulation (MDS) analysis with alpha-amylase protein for a duration of 150 ns. Among the three complexes, Taraxerol and Epoxywithanolide-I complexes demonstrates strong potential as inhibitors of the target protein. MDS results were analyzed via root mean square deviation (RMSD), fluctuation of residues, potential energy, radii of gyration and solvent access surface area analysis. Taraxerol demonstrated a significantly low potential energy of - 1,924,605.25 kJ/mol, and Epoxywithanolide-I demonstrated - 1,964,113.3 kJ/mol of potential energy. RMSD plot shows that Epoxywithanolide-I has much higher stability than the other MDS complexes. Drugability and toxicity studies show that the test ligands are demonstrating strong potential as drug like molecules. The results of the study conclude that, Taraxerol of C. indica and Epoxywithanolide-I of W. coagulans are strong inhibitors of alpha-amylase enzyme and that, this is one of the possible mechanisms of action of the plants for their reported anti-diabetic activities. Further in-vitro analysis is in demand to prove the observed results. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. DOI: 10.1007/s40203-024-00257-6 PMCID: PMC11383901 PMID: 39262568 Conflict of interest statement: Conflict of interestThe authors confirm that there are no known conflicts of interest for this study. 4. Comb Chem High Throughput Screen. 2024 Jun 26. doi: 10.2174/0113862073288546240528085144. Online ahead of print. Revealing the Molecular Mechanism of Sageretia theezans in the Treatment of Hemorrhoids based on Network Pharmacology. Ji X(1), Huang J(1), Li Z(1), Luan X(1), Bai S(1), Zhu Z(1). Author information: (1)First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, People's Republic of China. OBJECTIVE: Sageretia theezans is one of the classic medicines in ancient times, which is commonly used to treat scabies, lacquer sores, acute and chronic pharyngitis, Tonsillitis, Cholecystitis, secondary infection of hemorrhoids, and other symptoms. However, the potential molecular mechanism of Sageretia theezans is still unclear. In this study, we explored the active compounds of Sageretia theezans in the treatment of hemorrhoids (HD), predicted the potential targets of drugs, and verified their functions through network pharmacology and in vivo and in vitro experiments. METHODS: First, we identified the active compounds and key targets of Sageretia theezans in treating HD through network pharmacology. The key signaling pathways related to the role of Sageretia theezans were analyzed. HUVEC Human umbilical vein endothelial cells were used to study the function of Sageretia theezans and its target in vitro. In addition, we also used the SD rat hemorrhoid model to explore the efficacy of Sageretia theezans in HD in vivo. RESULT: A total of 159 drug targets were obtained from the TCMSP, ETCM, and PubChem databases. Constructing a drug component target network; differential analysis using sequencing data identified 1046 differentially expressed genes. Intersecting drug targets and differentially expressed genes obtained four intersection targets (GOT1, SLC25A10, SUCLG1, CLEC4E). Perform single gene GSEA functional enrichment analysis on intersection targets, select KEGG and GO of the top 10 for display, and merge the results. In order to investigate the interaction between intersecting genes and differentially expressed genes, we conducted a PPI protein interaction analysis on 1046 differentially expressed genes. Finally, a network of Chinese medicine active molecule intersection genes was proposed, and the genes and their corresponding active molecules (Successful acid, Taraxerone, Taraxerol) were Macromolecular docking, respectively. The results showed that these four genes could be successfully docked with the responsive active molecules and had high binding affinity. In vivo, the low-dose treatment group of Sageretia theezans, the medium-dose treatment group of Sageretia theezans, and the high-dose treatment group of Bromelia can inhibit the proliferation of HUVECs cells. In vitro, the middle dose of Sageretia theezans has the best therapeutic effect on hemorrhoids, and the treatment of Sageretia theezans on hemorrhoids is correlated with the expression of GOT1, SLC25A10, SUCLG1, and CLEC4E. CONCLUSION: To sum up, Sageretia theezans can alleviate the symptoms of hemorrhoids and is related to the expression of GOT1, SLC25A10, SUCLG1, and CLEC4E. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. DOI: 10.2174/0113862073288546240528085144 PMID: 38934275 5. Curr Comput Aided Drug Des. 2024 Jun 5. doi: 10.2174/0115734099301866240527100128. Online ahead of print. Identification of Novel Inhibitors for ERα Target of Breast Cancer By In Silico Approach. Alagarsamy V(1), Sulthana MT(1), Narendhar B(1), Solomon VR(1), Gobinath M(2), Satishchandra A(1), Sangeetha D(1), Murugesan S(3). Author information: (1)Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy, 502 294, India. (2)Department of Pharmaceutical Chemistry, Swathi College of Pharmacy, SPSR Nellore, 524 320, Andhra Pradesh, India. (3)Department of Pharmacy, Birla Institute of Technology & Science, Pilani Campus, Pilani, 333 031, India. BACKGROUND: Estrogen alpha has been recognized as a perilous factor in breast cancer cell proliferation and has been proficiently treated in breast cancer chemotherapy with the development of selective estrogen receptor modulators (SERMs). OBJECTIVES: The major aim of this study was to identify the potential inhibitors against the most influential target ERα receptor by in silico studies of 115 phytochemicals from 17 medicinal plants using in silico molecular docking studies. METHODS: The molecular docking investigation was carried out by a genetic algorithm using the Auto Dock Vina program, and the validation of docking was also performed using molecular dynamic (MD) simulation by the Desmond tool of Schrödinger molecular modeling. The ADME( T) studies were performed by SWISS ADME and ProTox-II. RESULTS: The top ten highest binding energy phytochemicals identified were amyrin acetate (- 10.7 kcal/mol), uscharine (-10.5 kcal/mol), voruscharin (-10.0 kcal/mol), cyclitols (-10.0 kcal/mol), taraxeryl acetate (-9.9 kcal/mol), amyrin (-9.9 kcal/mol), barringtogenol C (-9.9 kcal/mol), calactin (-9.9 kcal/mol), 3-beta taraxerol (-9.8 kcal/mol), and calotoxin (-9.8 kcal/mol). A molecular docking study revealed that these phytochemical constituents showed higher binding affinity compared to the reference standard tamoxifen (-6.6 kcal/mol) towards the target protein ERα. The results of MD studies showed that all four tested compounds possess comparatively stable ligand-protein complexes with ERα target as compared to the tamoxifen- ERα complex. CONCLUSION: Among the ten compounds, phytochemical amyrin acetate (triterpenoids) formed a more stable complex as well as exhibited greater binding affinity than standard tamoxifen. ADMET studies for the top ten phytochemicals showed a good safety profile. Additionally, these compounds are being reported for the first time in this study as possible inhibitors of ERα for the treatment of breast cancer by adopting the concept of drug repurposing. Hence, these phytochemicals can be further studied and can be used as a parent core molecule to develop novel lead molecules for breast cancer therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. DOI: 10.2174/0115734099301866240527100128 PMID: 38847264