Mechanisms Involved in the Therapeutic Effect of Cannabinoid Compounds on Gliomas: A Review with Experimental Approach.

INTRODUCTION: Brain tumors have high morbidity and mortality rates, accounting for 1.4% of all cancers. Gliomas are the most common primary brain tumors in adults. Currently, several therapeutic approaches are used; however, they are associated with side effects that affect patients'quality of life. Therefore, further studies are needed to develop novel therapeutic protocols with a more favorable side effect profile. In this context, cannabinoid compounds may serve as potential alternatives. OBJECTIVE: This study aimed to review the key enzymatic targets involved in glioma pathophysiology and evaluate the potential interaction of these targets with four cannabinoid derivatives through molecular docking simulations. METHODS: Molecular docking simulations were performed using four cannabinoid compounds and six molecular targets associated with glioma pathophysiology. RESULTS: Encouraging interactions between the selected enzymes and glioma-related targets were observed, suggesting their potential activity through these pathways. In particular, cannabigerol showed promising interactions with epidermal growth factor receptors and phosphatidylinositol 3- kinase, while Δ-9-tetrahydrocannabinol showed remarkable interactions with telomerase reverse transcriptase. CONCLUSION: The evaluated compounds exhibited favorable interactions with the analyzed enzymatic targets, thus representing potential candidates for further in vitro and in vivo studies.

Biochemical aspects of the inflammatory process: A narrative review.

Inflammation is a protective response of the body potentially caused by microbial, viral, or fungal infections, tissue damage, or even autoimmune reactions. The cardinal signs of inflammation are consequences of immunological, biochemical, and physiological changes that trigger the release of pro-inflammatory chemical mediators at the local of the injured site thus, increasing blood flow, vascular permeability, and leukocyte recruitment. The aim of this study is to give an overview of the inflammatory process, focusing on chemical mediators. The literature review was based on a search of journals published between the years 2009 and 2023, regarding the role of major chemical mediators in the inflammatory process and current studies in pathogenesis, diagnosis, and therapy. Some of the recent contributions in the study of inflammatory pathologies and their mediators, including cytokines and chemokines, the kinin system, free radicals, nitric oxide, histamine, cell adhesion molecules, leukotrienes, prostaglandins and the complement system and their role in human health and chronic diseases.

Virtual Screening of Different Subclasses of Lignans with Anticancer Potential and Based on Genetic Profile.

Cancer is a multifactorial disease that continues to increase. Lignans are known to be important anticancer agents. However, due to the structural diversity of lignans, it is difficult to associate anticancer activity with a particular subclass. Therefore, the present study sought to evaluate the association of lignan subclasses with antitumor activity, considering the genetic profile of the variants of the selected targets. To do so, predictive models were built against the targets tyrosine-protein kinase ABL (ABL), epidermal growth factor receptor erbB1 (EGFR), histone deacetylase (HDAC), serine/threonine-protein kinase mTOR (mTOR) and poly [ADP-ribose] polymerase-1 (PARP1). Then, single nucleotide polymorphisms were mapped, target mutations were designed, and molecular docking was performed with the lignans with the best predicted biological activity. The results showed more anticancer activity in the dibenzocyclooctadiene, furofuran and aryltetralin subclasses. The lignans with the best predictive values of biological activity showed varying binding energy results in the presence of certain genetic variants.

Plectranthus Species with Anti-Inflammatory and Analgesic Potential: A Systematic Review on Ethnobotanical and Pharmacological Findings.

The use of medicinal plants to treat inflammatory conditions and painful processes has attracted the attention of scientists and health professionals due to the evidence that natural products can promote significant therapeutic benefits associated with fewer adverse effects compared to conventional anti-inflammatory drugs. The genus Plectranthus is composed of various plants with pharmacological potential, which are used to treat various diseases in traditional communities worldwide. The present study systematically reviewed Plectranthus species with anti-inflammatory and analgesic potential. To this end, a systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The search was conducted on the following databases: PubMed, ScienceDirect, SciVerse Scopus, and Web of Science. Different combinations of search terms were used to ensure more excellent article coverage. After the selection, a total of 45 articles were included in this review. This study identified twelve Plectranthus species indicated for the treatment of different inflammatory conditions, such as wounds, fever, bronchitis, abscess, asthma, hepatitis, labyrinthitis, tonsillitis, and uterine inflammation. The indications for pain conditions included headache, sore throat, heartburn, menstrual cramp, colic, toothache, stomachache, migraine, chest pain, abdominal pain, local pain, labor pain, and recurring pain. Among the listed species, ten plants were found to be used according to traditional knowledge, although only four of them have been experimentally studied. When assessing the methodological quality of preclinical in vivo assays, most items presented a risk of bias. The SR results revealed the existence of different Plectranthus species used to treat inflammation and pain. The results of this systematic review indicate that Plectranthus species have the potential to be used in the treatment of diseases with an inflammatory component, as well as in the management of pain. However, given the risk of biases, the experimental analysis of these species through preclinical testing is crucial for their safe and effective use.

Pharmacological applications of farnesol (C15H26O): a patent review.

Introduction: Farnesol (C15H26O) is a sesquiterpene alcohol found in essential oils. This substance is reported to have different pharmacological activities such as antimicrobial, antitumor and antioxidant effects, as well as actions in different body systems.Areas covered: This study aimed to analyze pharmaceutical patents containing this substance in their formulations. Patent search was carried out through the WIPO (World Intellectual Property Organization), LatiPat and INPI (National Institute of Industrial Property) electronic banks using the following descriptors and combinations: 'farnesol', 'pharmaceutical product', 'pharmacology' and 'pharmacy'.Expert opinion: Primary research identified 54 patents, from which 17 were selected for the final analysis after applying the inclusion criteria. The selected patents referred to products presenting different pharmaceutical activities of interest such as the prevention and treatment of diseases affecting the dermis, central nervous and cardiovascular systems, diseases caused by different microorganisms and cancers, among others. A minority of the articles included in this review reported the type of farnesol isomer that was investigated, this becoming a major limitation for the development of future pharmaceutical products. With the completion of this study, farnesol presents itself as a potential agent with pharmacological application both in the prevention and treatment of different diseases.

Toxicological and pharmacologic effects of farnesol (C15H26O): A descriptive systematic review.

The objective of the present study was to perform a systematic review (SR) composed of preclinical and clinical studies which investigated the toxicological and pharmacologic effects of farnesol [Molecular formula: C15H26O; IUPAC: (3,7,11-Trimethyl-2,6,10-dodecatrien-1-ol]. This SR was performed according to PRISMA guidelines. Literature research was performed using PubMed, MEDLINE, Scopus and Web of Science databases using the descriptor combinations: "farnesol and pharmacological effect" and "farnesol and toxicology". The inclusion criteria used were original articles from preclinical and clinical studies investigating the pharmacological and toxicological effects of farnesol, published between January 1960 and December 2017 which were written in English, Portuguese and Spanish. Primary research identified 414 articles, from which 76 articles were selected for final analysis following the inclusion criteria. After grouping, 51.32 and 22.37% of the articles investigated the antimicrobial and antitumor effect, respectively. Methodological biases have been observed both in pre-clinical studies with non-human animals and in clinical trials, mainly in group allocation and blinding. This SR is the first study developed to compile the studies concerning the pharmacological and toxicological effects of farnesol. This study concludes that farnesol possesses different pharmacological and toxicological features, which permit its use as an active or a coadjuvant drug.

Comparative study of alpha- and beta-pinene effect on PTZ-induced convulsions in mice.

Convulsions occur in response to a loss of balance between excitatory and inhibitory neurotransmitters, and the treatment for this condition consists in restore such lost balance. Many anticonvulsant drugs present side effects which may limit their use. This fact has stimulated the search for new sources of treatment from aromatic plants. Many monoterpenes commonly present in essential oils are known because of their anticonvulsant properties. The anticonvulsant effect of α- and ß-pinene, two structural isomers, is still little studied. Thus, the present work evaluated the anticonvulsant effect of α- and ß-pinene in pentylenetetrazole-induced convulsions model. Initially, the oral LD50 for α- and ß-pinene was estimated. Following the oral administration, a mild sedation was observed and no deaths were recorded; the LD50 estimated for both monoterpenes was greater than 2 000 mg/kg, p.o. Further, animals were orally treated with α-pinene (100, 200 and 400 mg/kg), ß-pinene (100, 200 and 400 mg/kg) and the equimolar mixture of α- and ß-pinene (400 mg/kg) and subjected to the pentylenetetrazole-induced convulsions model. In this model, only the dose of 400 mg/kg of the compounds was able to significantly decrease the seizure intensity. The latency of first convulsion was significantly increased by the mixture of α- and ß-pinene (400 mg/kg). In addition, ß-pinene and the mixture of the two monoterpenes, both at a dose of 400 mg/kg, significantly increased the time of death of animals. The treatment with ß-pinene and the equimolar mixture of the two monoterpenes significantly reduced hippocampal nitrite level and striatal content of dopamine (DA) and norepinephrine (NE). Taken together, the results suggest that α-pinene appears to be devoid of anticonvulsant action. This fact, however, seems to be dependent on the chemical structure of the compound, since pretreatment with the ß-pinene increased the time of death pf PTZ-treated mice, which seems to depend on the ability of the compound to reduce nitrite concentration and NE and DA content, during the pentylenetetrazole-induced seizure.

Murraya paniculata (L.) (Orange Jasmine): Potential Nutraceuticals with Ameliorative Effect in Alloxan-Induced Diabetic Rats.

Orange jasmine, Murraya paniculata (Rutaceae), is a plant from India widely used in folk medicine as antinociceptive, antiinflammatory, and antioxidant. Although oral hypoglycemic agents and insulin are the mainstays of treatment of diabetes mellitus (DM), there is a significant demand for new natural products to reduce the development of diabetic complications. Alloxan-induced diabetic rats were treated for 60 days with a hydroalcoholic extract of M. paniculata (MPE), at doses of 100, 200, and 400 mg/kg. MPE decreased glycemia and also cholesterol and triglyceride levels, starting 1 week after treatments, as compared with the same group before treatments. Glucose values were reduced toward normality after 1 week of treatment. MPE hypoglycemic effects were potentiated by glibenclamide and metformin. MPE also decreased fructosamine and glycated hemoglobin values. MPE reduced diabetes-induced morphological alterations of the kidney, pancreas, and liver. MPE acts similarly to glibenclamide and metformin, and its glucose-lowering action is partly a consequence of ATP-sensitive K+ channel inhibition. MPE may be a potential therapeutic alternative for the treatment of diabetes and its complications. Copyright © 2017 John Wiley & Sons, Ltd.

Caryocar coriaceum Wittm. (Pequi) fixed oil presents hypolipemic and anti-inflammatory effects in vivo and in vitro.

Caryocar coriaceum Wittm. (Pequi) is found in southern Ceará, where the fruit is used as food and in folk medicine as an anti-inflammatory, and to promote healing. However, little is known about the effects of repeated administration of its oil on the biochemical parameters of the blood. This work aimed to evaluate the effects Caryocar coriaceum fixed oil (OFCC); on the lipid profiles of healthy mice, on dyslipidemia induced by tyloxapol, and to study its anti-inflammatory effect both in vivo and in vitro. The results revealed significant reduction in total serum cholesterol and triglycerides, and an increase in HDL-C. The paw edema (induced by carrageenan) and myeloperoxidase (MPO), in polymorphonuclear culture cells, was reduced at all dose levels. Results demonstrated that Caryocar coriaceum's fix oil present anti-inflammatory activity and, for the first time describe the hypolipidemic effects, supporting its traditional use and suggest that present a potential cardioprotective effect.

Analgesic Potential of Essential Oils.

Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the pharmaceutical industry and academia. This review describes studies involving antinociceptive activity of essential oils from 31 plant species. Botanical aspects of aromatic plants, mechanisms of action in pain models and chemical composition profiles of the essential oils are discussed. The data obtained in these studies demonstrate the analgesic potential of this group of natural products for therapeutic purposes.

Eicosapentaenoic acid and docosahexaenoic acid exert anti-inflammatory and antinociceptive effects in rodents at low doses.

In the present study, we evaluated omega-3 polyunsaturated fatty acid (PUFA) (consisting of 20:5n-3 and 22:6n-3) properties on inflammation and nociception. Among the in vivo tests, writhing, formalin, and hot plate tests were conducted in mice, and carrageenan-induced paw edema, peritonitis, and Hargreaves tests were performed in rats. Following the carrageenan-induced edema, immunohistochemistry for tumor necrosis factor-α (TNF-α) was also carried out. We found that omega-3 PUFA treatment significantly decreased acetic acid-induced abdominal contortions as well as the first and second phases of the formalin test, which were reversed by naloxone. The carrageenan-induced rat paw edema was significantly reduced, along with neutrophil migration to the peritoneal cavity in the omega-3 PUFA treatment. In addition, there was a decrease in TNF-α immunostained cells in the inflamed paw with the omega-3 treatment compared with no omega-3. Withdrawal threshold in response to the thermal stimulation was significantly increased by the omega-3 treatment in the Hargreaves and hot plate tests. The in vitro studies (myeloperoxidase, lactate dehydrogenase, MTT cell viability and lipid peroxidation assays) were performed in human neutrophils. These studies showed that omega-3 treatment significantly decreased myeloperoxidase release, presented no cytotoxicity, and did not alter lipid peroxidation. Our study suggests that omega-3 PUFA anti-inflammatory and antinociceptive actions may involve inhibition of cyclooxygenases and microglial activation, leading to a reduced release of proinflammatory cytokines such as TNF-α, among other factors. The omega-3 PUFAs are potential candidates used alone or in combination with conventional nonsteroidal anti-inflammatory drugs, for the treatment of diseases where inflammation plays an important role.

Piperine decreases pilocarpine-induced convulsions by GABAergic mechanisms.

Piperine, an alkaloid present in the Piper genus, was shown to have an anticonvulsant activity, evaluated by the pilocarpine-induced model, in mice. Pilocarpine (350mg/kg, i.p.) was administered 30min after piperine (2.5, 5, 10 and 20mg/kg, i.p.) which significantly increased latencies to 1st convulsion and to death, and percentage of survivals. These parameters were also increased in the pilocarpine groups pretreated with atropine plus piperine (10 and 2.5mg/kg, respectively), as related to the pilocarpine group. However, they were not altered in the pilocarpine groups pretreated with memantine (a NMDA-type glutamate receptors blocker, 2mg/kg, p.o.) or nimodipine (a calcium channel blocker, 10mg/kg, p.o.), both associated with piperine (1 or 2.5mg/kg), as compared to the piperine plus pilocarpine group. Moreover, the pilocarpine group pretreated with diazepam (which binds to the GABAA receptor, 0.2 and 0.5mg/kg, i.p.) plus piperine (1 and 2.5mg/kg) significantly increased latency to the 1st convulsion, as related to the pilocarpine group, suggesting that the GABAergic system is involved with the piperine action. Furthermore, the piperine effect was blocked by flumazenil (2mg/kg, i.p.), a benzodiazepine antagonist. Untreated P350 animals showed decreased striatal DA and increased DOPAC and HVA levels that were not affected in the piperine plus pilocarpine groups. Piperine increased striatal levels of GABA, glycine and taurine, and reversed pilocarpine-induced increases in nitrite contents in sera and brain. Hippocampi from the untreated pilocarpine group showed an increased number of TNF-α immunostained cells in all areas, as opposed to the pilocarpine group pretreated with piperine. Taken together, piperine anticonvulsant effects are the result of its anti-inflammatory and antioxidant actions, as well as TNF-α reduction. In addition, piperine effects on inhibitory amino acids and on the GABAergic system may certainly contribute to the drug anticonvulsant activity.