The chemical analysis of Euphorbia bicolor (Euphorbiaceae) latex and its analgesic and antiproliferative properties

People with intense pain arising from disease or traumatic injuries are most commonly treated with opioids. Despite substantial advances in pain research and treatment, the negative side effects of opioids, such as addiction, physical dependency, and tolerance, remain a significant challenge to long-term pain management. On the other hand, globally breast cancer is one of the most frequently diagnosed cancers in women and is the second leading cause of cancer-related deaths in the USA. Both pain therapeutics and breast cancer treatments are accompanied by debilitating side effects. For that reason, the search for plant-derived natural compounds that could be used as pain and breast cancer therapeutics with better efficacy and lesser side effects has been enhanced. The present research investigated the pain relieving and antiproliferative properties of Snow-on-the-prairie, Euphorbia bicolor (Euphorbiaceae), a plant native to the south-central United States. Analgesic activity of the latex extract was tested in two distinct somatosensory systems of rat models of inflammatory and pain. Estrogenic and antiestrogenic activities were evaluated by employing a steroid-regulated yeast system and antiproliferative activity was assessed on estrogen receptor (ER) positive and negative breast carcinomas. Eleven bioactive latex phytochemicals were identified by UPLC-ESI-MS/MS. Injection of latex extract in rat hindpaw or orofacial region significantly induced long-lasting non-opioid analgesia in both male and female rats, in part via transient receptor potential V1 ion channels (TRPV1), pain-generating ion channels present in the peripheral nervous system. Furthermore, TRPV1-mediated analgesia occurred in part via modulating cytokines/chemokines, as well as downregulating the oxidative stress markers advanced oxidation protein products (AOPP), NADPH oxidase 4 protein (NOX4), and reactive oxygen species (ROS). E. bicolor latex extract and its phytochemicals induced different degrees of estrogenic and antiestrogenic activities in the steroid-regulated yeast system and the extract and its phytochemicals resiniferatoxin and rutin significantly reduced the growth of ER-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231 and MDA-MB-468) breast carcinomas. This is the first study on the phytochemical analyses and biological properties of E. bicolor latex extract. Overall, the results indicate that latex phytochemicals could contribute to the development of novel, non-opioid pain relieving and antiproliferative drugs.