Anti-allodynic Effects of Obtusifolin and Gluco-Obtusifolin against Inflammatory and Neuropathic Pain

Abstract

Inflammatory pain and neuropathic pain are major health issues that represent considerable social and economic burden worldwide. In this study we investigated the potential of obtusifolin and gluco-obtusifolin, two anthraquinones found in the seeds of the widely used traditional Chinese medical botanical Cassia obtusifolia, to reduce neuropathic and inflammatory pain. The potential analgesic effects of obtusifolin and gluco-obtusifolin were evaluated by mice formalin test and complete Freund's adjuvant (CFA)-induced nociceptive behaviors in rats. Chronic constriction injury (CCI), L5 spinal nerve ligation (L5 SNL), diabetes, and chemotherapeutics inducing allodynia were used to test whether repeated treatment with obtusifolin and gluco-obtusifolin ameliorated neuropathic pain. Finally, we explored whether obtusifolin and gluco-obtusifolin altered the degree of neuroinflammation in rat spinal cord after CFA administration and CCI induction. Obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reduced licking/biting time in dose-dependent manner in phase 2 of formalin-induced behavior in mice. Furthermore, repeated administration of obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reversed mechanical allodynia induced by CFA, CCI, L5 SNL, diabetes, and oxaliplatin in a dose-dependent manner in rats. Levels of activated nuclear factor-kappa B (NF-κB) and proinflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α)) in lumbar spinal cord were elevated in rats following CFA treatment and CCI induction, and obtusifolin and gluco-obtusifolin significantly inhibited these effects. Our results demonstrate that obtusifolin and gluco-obtusifolin produce significant antinociceptive action in rodent behavioral models of inflammatory/neuropathic pain, and that this activity is associated with modulation of neuroinflammation in spinal cord.

Hepatoprotective effects of Cassia semen ethanol extract on non-alcoholic fatty liver disease in experimental rat

“…Although several pharmacological activities of anthraquinones have been reported (He et al. 2014; Kwon et al. 2018; Paudel et al.…”

Changes in Plasma Lipid Levels and Antioxidant Activities in Rats after Supplementation of Obtusifolin

“…high-density lipoprotein cholesterol LDL-C: low-density lipoprotein cholesterol MDA: malondialdehyde NO: nitric oxide SOD: superoxide dismutase TC: total cholesterol TG: triglyceride seeds of C. obtusifolia, has been reported to exhibit antinociceptive action and ameliorate the memory impairment in mice [14,15]. Additionally, obtusifolin may have an antihyperlipidemia effect, as suggested by a previous study showing that an intraperitoneal injection of obtusifolin reduces blood lipid levels in diabetic rats induced by streptozocin [16].…”

“…As an anthraquinone from C. obtusifolia seeds, the safety and effective dose of obtusifolin have been studied by a wide body of documents. For example, previous in vivo studies have shown that obtusifolin, administered by intraperitoneal injection at a daily dose of 2 mg/kg body weight for 7 consecutive days, produces significant antinociceptive action in rodent behavioral models of inflammatory/neuropathic pain [14]. Obtusifolin administered orally at 2 mg/kg significantly reverses scopolamine-induced cognitive impairments [15].…”

A Potential Herbal Adjuvant Combined With a Peptide-Based Vaccine Acts Against HPV-Related Tumors Through Enhancing Effector and Memory T-Cell Immune Responses

“…On the basis of the chemical profile of H. diffusa Willd, we screened 10 compounds from different chemotypes ( Table S1). Some of them have been shown to modulate immune responses (37)(38)(39)(40)(41). Moreover, all 10 of these compounds can be found in the plasma after intraperitoneal injection of H. diffusa Willd water extract (36).…”