Abstract Cereus jamacaru DC. (Cactaceae) is used in folk medicine for treating pain and inflammation. However, the therapeutic potential of C. jamacaru extracts has not been assessed experimentally. This study aimed to characterize the effect of both aqueous (CAECJ) and ethanolic (CEECJ) extracts of C. jamacaru in mouse models of pain and inflammation. CAECJ and CEECJ were chemically characterized by qualitative methods. Toxicity of extracts was evaluated in vitro against J774.A1 macrophages and in vivo by monitoring mice for 14 days following a single oral treatment at 2000 mg/kg. The antinociceptive activity of the extracts was assessed in models of pain in mice: acetic acid-induced writhing test, formalin test, hot plate test, and glutamate-induced nociception assay. The anti-inflammatory activity of the extracts was assessed following zymosan-induced peritonitis and in the model of arthritis induced by Complete Freund’s Adjuvant (CFA). Phytochemical analyses revealed alkaloids, condensed tannins, flavonoids, and anthraquinones in both extracts; saponins were present in CEECJ only. Neither extract was cytotoxic in vitro or induced toxicity in mice. Both extracts reduced nociception in all models of nociception without impairing motor function. Both extracts reduced leucocyte migration during experimental peritonitis and reduced paw edema during experimental arthritis. The effects of the extracts can be both due to anti-inflammatory and centrally-mediated mechanisms. This paper corroborates the traditional use of C. jamacaru extracts and demonstrates their therapeutic potential in the development of new analgesic and anti-inflammatory drugs with a good safety profile. DC Cactaceae (Cactaceae inflammation However C experimentally (CAECJ (CEECJ methods J774A1 JA J774 A1 J A J774.A 1 200 mgkg mg kg mg/kg acidinduced acid test glutamateinduced glutamate assay antiinflammatory anti inflammatory zymosaninduced zymosan Freunds Freund s CFA. CFA . (CFA) alkaloids tannins flavonoids only function centrallymediated centrally mediated mechanisms profile J774A J77 20 (CFA J7 2

Abstract Humankind has always been fascinated by venomous animals, as their toxic substances have transformed them into symbols of power and mystery. Over the centuries, researchers have been trying to understand animal venoms, unveiling intricate mixtures of molecules and their biological effects. Among venomous animals, Latrodectus Walckenaer, 1805 (widow spiders) have become feared in many cultures worldwide due to their extremely neurotoxic venom. The Latrodectus genus encompasses 32 species broadly spread around the globe, 14 of which occur in the Americas. Despite the high number of species found in the New World, the knowledge on these spiders is still scarce. This review covers the general knowledge on Latrodectus spp. from the Americas. We address widow spiders’ taxonomy; geographical distribution and epidemiology; symptoms and treatments of envenomation (latrodectism); venom collection, experimental studies, proteome and transcriptome; and biotechnological studies on these Latrodectus spp. Moreover, we discuss the main challenges and limitations faced by researchers when trying to comprehend this neglected group of medically important spiders. We expect this review to help overcome the lack of information regarding widow spiders in the New World.