For millennia, various cultures have utilized cannabis for food, textile fiber, ethno-medicines, and pharmacotherapy, owing to its medicinal potential and psychotropic effects. An in-depth exploration of its historical, chemical, and therapeutic dimensions provides context for its contemporary understanding. The criminalization of cannabis in many countries was influenced by the presence of psychoactive cannabinoids; however, scientific advances and growing public awareness have renewed interest in cannabis-related products, especially for medical use. Described as a \'treasure trove,\' cannabis produces a diverse array of cannabinoids and non-cannabinoid compounds. Recent research focuses on cannabinoids for treating conditions such as anxiety, depression, chronic pain, Alzheimer\'s, Parkinson\'s, and epilepsy. Additionally, secondary metabolites like phenolic compounds, terpenes, and terpenoids are increasingly recognized for their therapeutic effects and their synergistic role with cannabinoids. These compounds show potential in treating neuro and non-neuro disorders, and studies suggest their promise as antitumoral agents. This comprehensive review integrates historical, chemical, and therapeutic perspectives on cannabis, highlighting contemporary research and its vast potential in medicine.

Insulin resistance (IR) is the main cause of type 2 diabetes mellitus (T2DM). The specific targets and underlying mechanisms responsible for the ameliorative effects of the stilbenoid compounds found in fenugreek seeds for ameliorating IR require further study. Here, we were predicted by using the network pharmacology prediction, molecular docking and molecular dynamics simulation approach the targets in common and the potential mechanismsof three stilbenoid compounds (rhaponticin, desoxyrhaponticin, and rhapontigenin) in relation to T2DM and IR. The results showed that the compounds may improve IR through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Molecular docking studies revealed that they exhibit high binding affinity with the structural domains of peroxisome proliferator-activated receptor gamma (PPARG), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), PI3K, and AKT. These results suggest that PPARG and GAPDH may be the potential targets for these three compounds in the treatment of T2DM.Subsequently, experiments using the zebrafish T2DM model showed that the stilbenoid compounds had varying degrees of efficacy in improving IR through the PI3K/AKT/mTOR signaling pathway, and rhaponticin had the most promising effects. The findings implicate a potential mechanism of action for the three stilbenoid compounds in enhancing insulin resistance (IR) through modulation of the PI3K/AKT/mTOR pathway.

Piceatannol is a natural compound found in plants and can be derived from resveratrol. While resveratrol has been extensively researched for its effects and how the body processes it, there are concerns about its use. These concerns include its limited absorption in the body, the need for specific dosages, potential interactions with other drugs, lack of standardization, and limited clinical evidence to support its benefits. Interestingly, Piceatannol, another compound derived from resveratrol, has received less attention from researchers but appears to offer advantages. It has better bioavailability and seems to have a more favorable therapeutic profile compared to resveratrol. Surprisingly, no previous attempts have been made to explore or predict the metabolites of piceatannol when it interacts with the enzyme cytochrome P450. This study aims to fill that gap by predicting how piceatannol is metabolized by cytochrome P450 and assessing any potential toxicity associated with its metabolites. This research is interesting because it\'s the first of its kind to investigate the metabolic fate of piceatannol, especially in the context of cytochrome P450. The findings have the potential to significantly contribute to the field of piceatannol research, particularly in the food industry where this compound has applications and implications.
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Three undescribed compounds including two furosteroid glycosides (perfoloside and 22-O-methylperfoloside) and one stilbenedimer (perfolostilbene) together with 21 known compounds were isolated from the roots of Smilax perfoliata. The structural elucidation was established by extensive uses of HRMS, 1D and 2D spectroscopic techniques. The assignment of the stereocenters in perfolostilbene was based on NOESY data and ECD calculation. Among the isolates, two compounds showed marginal cytotoxic activity against KB and Hela cell lines while seven stilbenoids showed strong to weak antiacetylcholinesterase and antibutyrylcholinesterase activities with IC50 ranging between 2-197 µM.

Antimicrobial drugs have made outstanding contributions to the treatment of pathogenic infections. However, the emergence of drug resistance continues to be a major threat to human health in recent years, and therefore, the search for novel antimicrobial drugs is particularly urgent. With a deeper understanding of microbial habits and drug resistance mechanisms, various creative strategies for the development of novel antibiotics have been proposed. Stilbenoids, characterized by a C6-C2-C6 carbon skeleton, have recently been widely recognized for their flexible antimicrobial roles. Here, we comprehensively summarize the mode of action of stilbenoids from the viewpoint of their direct antimicrobial properties, antibiofilm and antivirulence activities and their role in reversing drug resistance. This review will provide an important reference for the future development and research into the mechanisms of stilbenoids as antimicrobial agents.

One new alkyl benzoquinone, paphionone (1), one new trans-stilbenoid, (E)-6,5\'-dihydroxy-2,3\'-dimethoxystilbene (2), and eight known stilbenoids and flavonoids (3-10) were isolated from the leaves and roots of Paphiopedilum exul (Orchidaceae). Their chemical structures were determined based on IR, ECD, MS and NMR analyses. Cytotoxicity of all isolated compounds towards human hepatocellular carcinoma (HepG2) cell line was examined in vitro by MTT assay. The para-hydroxybenzyl substituted stilbene 10 was potently cytotoxic to the cancer cells, with an IC50 value of 4.80 ± 1.10 μM (selectivity index = 20.83). All compounds were non-toxic to normal human embryo fibroblast (OUMS-36) cell line.

Grapevines encounter many different pathogens throughout their lifespans, including the bacterial pathogen Xylella fastidiosa, which causes Pierce\'s disease that results in vascular occlusion and eventual plant host death, the fungal pathogen Neofusicoccum parvum, which causes stem cankers that kill individual vines and reduce fruit yields, and the root knot nematode Meloidogyne incognita, which destroys root tissues that impacts host vigour. To date, little research has been conducted to examine how one infection could impact subsequent infections by the same or different pathogens despite this is important to ensure healthy vineyards. Therefore, grapevines initially infected with either X. fastidiosa, N. parvum, or M. incognita were subsequently infected with N. parvum eight weeks later to observe developing lesion lengths, which were assessed to determine grapevine resistance to infections. Collected data shows that when prior infections were present, the N. parvum lesions lengths were smaller. This suggests grapevines had induced resistance to combat infections. Further, defence-associated phenolics were measured by high-performance liquid chromatography to determine roles in observed resistance to the secondary N. parvum infections. Data shows that of the different phenolics examined, only stilbenoids were different due to infections, with lowered levels observed in plants that were infected compared with non-infected controls. These data provide insight into how infections by different pathogens could impact grapevine host resistance to new, subsequent pathogen infections.

Neuropsychiatric disorders are anticipated to be a leading health concern in the near future, emphasizing an outstanding need for the development of new effective therapeutics to treat them. Stilbenes, with resveratrol attracting the most attention, are an example of multi-target compounds with promising therapeutic potential for a broad array of neuropsychiatric and neurological conditions. This review is a comprehensive summary of the current state of research on stilbenes in several neuropsychiatric and neurological disorders such as depression, anxiety, schizophrenia, autism spectrum disorders, epilepsy, traumatic brain injury, and neurodegenerative disorders. We describe and discuss the results of both in vitro and in vivo studies. The majority of studies concentrate on resveratrol, with limited findings exploring other stilbenes such as pterostilbene, piceatannol, polydatin, tetrahydroxystilbene glucoside, or synthetic resveratrol derivatives. Overall, although extensive preclinical studies show the potential benefits of stilbenes in various central nervous system disorders, clinical evidence on their therapeutic efficacy is largely missing.

A grapevine shoot extract (GSE) was obtained using ultrasound-assisted extraction and characterized. The main phenolic constituents were identified as stilbenoids. Among them, trans-resveratrol and trans-ε-viniferin stood out. The GSE was administered to an isoproterenol-induced myocardial injury animal model. The extract alleviated the associated symptoms of the administration of the drug, i.e., the plasma lipid profile was improved, while the disturbed plasma ion concentration, the cardiac dysfunction markers, the DNA laddering, and the necrosis of myocardial tissue were diminished. This effect could be related to the anti-oxidative potential of GSE associated with its antioxidant properties, the increased levels of endogenous antioxidants (glutathione and enzymatic antioxidants), and the diminished lipid peroxidative markers in the heart. The results also revealed angiotensin-converting enzyme (ACE)-inhibitory activity, which indicated the potential of GSE to deal with cardiovascular disease events. This work suggests that not only trans-resveratrol has a protective role in heart function but also GSE containing this biomolecule and derivatives. Therefore, GSE has the potential to be utilized in the creation of innovative functional ingredients.

Three new stilbenoids, namely two rare plant-derived phenanthrenes denominated Cajananthrenes A and B (1, 2) and one bibenzyl named Cajanbenzyl (3), together with a diphenyl ether derivative designated Cajanether (4), as well as five other known compounds (5-9) were isolated from the ethanolic extract of the leaves of Cajanus cajan. Their structures were determined through extensive spectroscopic analysis including UV, IR, NMR (1D and 2D) and HRESIMS as well. A plausible biogenesis pathway was proposed for the biosynthesis of compounds 1-3. Compounds 1 and 2 displayed moderate anti-inflammatory activity as evident from the inhibitory effect on NO production in LPS-stimulated RAW 264.7 macrophages with IC50 values of 73.6 and 44.6 μM respectively.