The Euphorbiaceae family is a rich source of bioactive terpenoids. Among its genera, Jatropha is a conspicuous producer of diterpenes and includes approximately 175 species, many of which have medicinal uses. To date, 140 diterpenes from Jatropha (JTDs) have been reported. Given their structural diversity and notable biological activities, this work aims to highlight the pharmaceutical potential of JTDs. To achieve this goal, an extensive literature review was conducted, encompassing studies on structural elucidation through NMR and pharmacological assays, both in vitro and in vivo. Based on 132 selected papers, a thorough discussion is presented on the biosynthesis, extraction, isolation, and structural characterization of JTDs, including a compilation of their ¹³C NMR chemical shifts. The review also covers their synthetic production and biological effects. Additionally, an in silico analysis predicting the drug-likeness of 141 JTDs was carried out. Notably, the occurrence of macrocyclic diterpenes has doubled in the past decade, and the summary of their NMR data provides a useful resource for future research. Furthermore, 21 distinct pharmacological activities were identified, with potent cytotoxic effects targeting new molecular pathways being particularly significant. Recent advances highlight the contributions of modern approaches in organic synthesis and the pharmacological evaluation of natural products. The drug-likeness analysis identified JTD classes and compounds with favorable physicochemical and ADMET features for pharmaceutical development. In light of these findings, the use of nanotechnology is proposed as a future direction for continued research on JTDs, a fascinating class of natural compounds. This work opens up new avenues for the study of Euphorbiaceae species, particularly the Jatropha genus and its bioactive compounds.

Chronic pain significantly impacts quality of life and is often accompanied by inflammation, a natural bodily response that can become harmful when excessive. The orofacial region is commonly affected, making effective treatment crucial. However, current drugs often cause undesirable side effects, highlighting the need for new pharmacological alternatives. 4-hydroxycoumarin (4-HC), a natural compound, has shown promising antinociceptive and anti-inflammatory effects, but studies confirming its specific properties are limited. In silico analyses suggest that 4-HC exhibits favorable pharmacokinetic characteristics, not interacting with P-glycoprotein and successfully crossing the blood–brain barrier. Molecular docking studies indicate that its effects may be mediated through NMDA_R or by inhibiting iNOS. Our study assessed the antinociceptive and anti-inflammatory effects of 4-HC in animal models at doses of 25, 50, and 75 mg/kg. 4-HC significantly reduced abdominal contortions induced by acetic acid and decreased nociceptive rubbing in orofacial pain models induced by formalin, glutamate, and capsaicin. Interactions with opioid receptors were not observed, suggesting that 4-HC’s antinociceptive effect does not involve this pathway. Additionally, 4-HC reduced paw edema induced by carrageenan and significantly decreased leukocyte migration and TNF-α levels. These findings highlight the therapeutic potential of 4-HC and warrant further investigation into its mechanisms.

The Euphorbiaceae family is renowned for its diverse array of compounds, primarily diterpenes, which exhibit multiple biological activities. In Brazil, the genera Jatropha, Cnidoscolus, Sapium, and Stillingia are predominantly found in the Northeast region. Despite their significant pharmacological potential, the chemical profiles of these species remain underexplored. In this context, chemotaxonomic is a tool to identify potential markers and bioactive structures within a given taxon. In order to analyze the chemical patterns among the diterpenes present in the four selected Euphorbiaceae genera, Phylogenetic Reconstruction and Self-Organizing Maps (SOMs) were applied. Two data sets were constructed: one containing 308 diterpenes structures and their 363 botanical occurrences, and a genetic data set encompassing ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) sequences of the selected species. The reconstruction exhibits a close relationship between Jatropha and Cnidoscolus, although it was not able to distinguish Sapium and Stillingia. In other hand, SOMs classified the diterpenes in two groups: the first containing benzene-derived compounds and the second encompassing mainly the tigliane-type, which stands out as a chemical signature. Both groups contain substances with significant cytotoxic activity. This study may guide the discovery of new cytotoxic compounds and provide new insights into the systematics of the Euphorbiaceae family.

Orofacial pain impairs quality of life, and current therapies, limited in efficacy and associated with adverse effects, drive the search for new treatments. Thiophene derivatives exhibit remarkable therapeutic properties, including antinociceptive and anti-inflammatory activities, with recent studies demonstrating superior activity compared to commercial drugs, highlighting their relevance in the design of novel agents. This study investigated the antinociceptive effect of the thiophene derivative 2-[(4-diethylamino-benzylidene)-amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbonitrile (7CN03) and its possible mechanisms of action. In vivo tests were performed on male mice (n = 6 per group), and nociception was induced by formalin, capsaicin, and glutamate 1 h after treatment. Facial rubbing was used as a parameter to measure nociceptive behavior. 7CN03 exhibited significant action during the neurogenic phase of the formalin test at different doses (1 mg/kg, 0.1 mg/kg, and 0.01 mg/kg), reducing nociceptive behavior by up to 56%. During the inflammatory phase, the 1 mg/kg dose exerted an antinociceptive effect, reducing nociceptive behavior by 32% (p < 0.05). In the glutamate test, 7CN03 blocked nociception by up to 90% (p < 0.001), and in the capsaicin test, it reduced nociceptive behavior by up to 74%. Molecular docking studies predicted higher binding affinity of 7CN03 for µ-opioid (-97.00 Kcal/mol), TRPV1 (-87.79 Kcal/mol), and NMDA (-104.86 Kcal/mol) receptors when compared with cocrystallized ligands. The findings suggest that the evaluated thiophene derivative exhibits an orofacial antinociceptive effect, with a mechanism of action likely mediated by opioid, transient receptor potential vanilloid, and glutamatergic receptors.

Chronic pain significantly impacts quality of life and is often accompanied by inflammation, a natural bodily response that can become harmful when excessive. The orofacial region is commonly affected, making effective treatment crucial. However, current drugs often cause undesirable side effects, highlighting the need for new pharmacological alternatives. 4-hydroxycoumarin (4-HC), a natural compound, has shown promising antinociceptive and anti-inflammatory effects, but studies confirming its specific properties are limited. In silico analyses suggest that 4-HC exhibits favorable pharmacokinetic characteristics, not interacting with P-glycoprotein and successfully crossing the blood-brain barrier. Molecular docking studies indicate that its effects may be mediated through NMDA_R or by inhibiting iNOS. Our study assessed the antinociceptive and anti-inflammatory effects of 4-HC in animal models at doses of 25, 50, and 75 mg/kg. 4-HC significantly reduced abdominal contortions induced by acetic acid and decreased nociceptive rubbing in orofacial pain models induced by formalin, glutamate, and capsaicin. Interactions with opioid receptors were not observed, suggesting that 4-HC’s antinociceptive effect does not involve this pathway. Additionally, 4-HC reduced paw edema induced by carrageenan and significantly decreased leukocyte migration and TNF- α levels. These findings highlight the therapeutic potential of 4-HC and warrant further investigation into its mechanisms.