Diabetic neuropathy is a frequent complication of diabetes. Symptoms include neuropathic pain and sensory alterations—no effective treatments are currently available. This work characterized the therapeutic effect of bergenin in a mouse (C57/BL6) model of streptozotocin-induced painful diabetic neuropathy. Nociceptive thresholds were assessed by the von Frey test. Cytokines, antioxidant genes, and oxidative stress markers were measured in nervous tissues by ELISA, RT-qPCR, and biochemical analyses. Single (3.125–25 mg/kg) or multiple (25 mg/kg; twice a day for 14 days) treatments with bergenin reduced the behavioral signs of diabetic neuropathy in mice. Bergenin reduced both nitric oxide (NO) production in vitro and malondialdehyde (MDA)/nitrite amounts in vivo. These antioxidant properties can be attributed to the modulation of gene expression by the downregulation of inducible nitric oxide synthase (iNOS) and upregulation of glutathione peroxidase and Nrf2 in the nervous system. Bergenin also modulated the pro- and anti-inflammatory cytokines production in neuropathic mice. The long-lasting antinociceptive effect induced by bergenin in neuropathic mice, was associated with a shift of the cytokine balance toward anti-inflammatory predominance and upregulation of antioxidant pathways, favoring the reestablishment of redox and immune homeostasis in the nervous system. These results point to the therapeutic potential of bergenin in the treatment of painful diabetic neuropathy.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by impaired glycemic regulation and persistent hyperglycemia, which drives the onset of microvascular complications such as diabetic neuropathy and nephropathy. Chronic hyperglycemia activates oxidative stress pathways and alters gut microbiota composition, both of which contribute to disease progression. In this context, probiotics have emerged as promising therapeutic agents due to their ability to modulate oxidative stress, improve glycemic control, and influence gut microbial balance. This review summarizes preclinical and clinical evidence supporting the antioxidant potential of probiotics in DM management, with a focus on underlying mechanisms. Strains from the Lactobacillus and Bifidobacterium genera are the most extensively studied and have demonstrated hypoglycemic and antioxidant effects, including the enhancement of key antioxidant enzymes and reductions in lipid peroxidation and nitrosative stress markers. Probiotics have also shown beneficial effects in DM-associated complications, particularly diabetic neuropathy and nephropathy. While clinical data are still limited, recent findings underscore oxidative stress as a critical therapeutic target influenced by probiotic interventions. Overall, current evidence supports probiotics as a complementary strategy for managing DM and its complications, highlighting the need for further well-designed clinical trials exploring diverse strains, formulations, and dosing regimens.

Although the mouse model of incisional pain is broadly used, the mechanisms underlying plantar incision-induced nociception are not fully understood. This work investigates the role of Na_v1.8 and Na_v1.9 sodium channels in nociceptive sensitization following plantar incision in mice and the signaling pathway modulating these channels. A surgical incision was made in the plantar hind paw of male Swiss mice. Nociceptive thresholds were assessed by von Frey filaments. Gene expression of Na_v1.8, Na_v1.9, TNF-α, and COX-2 was evaluated by Real-Time PCR in dorsal root ganglia (DRG). Knockdown mice for Na_v1.8 and Na_v1.9 were produced by antisense oligodeoxynucleotides intrathecal treatments. Local levels of TNF-α and PGE₂ were immunoenzymatically determined. Incised mice exhibited hypernociception and upregulated expression of Na_v1.8 and Na_v1.9 in DRG. Antisense oligodeoxynucleotides reduced hypernociception and downregulated Na_v1.8 and Na_v1.9. TNF-α and COX-2/PGE₂ were upregulated in DRG and plantar skin. Inhibition of TNF-α and COX-2 reduced hypernociception, but only TNF-α inhibition downregulated Na_v1.8 and Na_v1.9. Antagonizing NF-κB and p38 mitogen-activated protein kinase (MAPK), but not ERK or JNK, reduced both hypernociception and hyperexpression of Na_v1.8 and Na_v1.9. This study proposes the contribution of the TNF-α/p38/NF-κB/Na_v1.8 and Na_v1.9 pathways to the pathophysiology of the mouse model of incisional pain.

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.