Chrysophanol Relieves Cognition Deficits and Neuronal Loss Through Inhibition of Inflammation in Diabetic Mice

Abstract

Patients with diabetes mellitus are easy to experience diabetic encephalopathy (DE) and other cognition dysfunction, whereas the neural alterations in developing this disease are unknown yet. Chrysophanol (CHR) is one of traditional Chinese medicine which was reported to show protective effects in cognition dysfunction and inflammatory in previously studies. In this current study, whether CHR protects learning and memory dysfunctions induced by diabetes disease or not and underlying mechanisms were studied. DE model was induced by streptozotocin (STZ, i.p.) in ICR mice. CHR was administrated 3 days after STZ treated mice which was confirmed with diabetes for consecutive 6 days. Learning and memory function was tested by Morris water maze after the CHR injection. The morphology of neuronal cells in hippocampus CA3 region was stained by HE-staining. ELISA and Western blot assay were used to determine the levels of pro-inflammation cytokines (IL-1β, IL-4, IL-6, TNF-α) in hippocampus. Here, we demonstrated that mice harboring diabetes mellitus induced by STZ exhibit high blood glucose, learning and memory deficits detected by Morris water maze behavior tests. Application with CHR right after developing diabetes disease rescues partial blood sugar increasing, learning and memory deficits. The data also indicated that the death rate of neurons and the number of astrocytes in hippocampus CA3 region was significantly improved in diabetic mice. Moreover, the underlying mechanisms of CHR's protective effect are likely associated with anti-inflammation by downregulating the expression of pro-inflammation cytokines (IL-1β, IL-4, IL-6, TNF-α) in hippocampus and inhibiting the over-activation of astrocytes in hippocampus CA3 region. Therefore, application with CHR contributes to the learning and memory deficits induced by diabetes disease via inhibitory expressions of inflammatory in hippocampus region.

Chrysophanol attenuates airway inflammation and remodeling through nuclear factor‐kappa B signaling pathway in asthma

“…We here found that CHR dose‐dependently inhibited the infiltration of inflammatory cells and reduced the generation of proinflammatory IL‐4, IL‐5, IL13, TNF‐α, and iNOS in the asthmatic lung. Although the inhibitory effects of CHR on IL‐4 expression have been found in other experimental disease models (Chu et al, ; Lin et al, ), we demonstrated such antitype 2 inflammation effects of CHR in asthmatic mice for the first time.…”

Chrysophanol: a review of its pharmacology, toxicity and pharmacokinetics

“…Therefore, chrysophanol was expected to be used for thrombosis and atherosclerotic diseases . In addition, in diabetic mice, chrysophanol could improve neuronal mortality and the number of astrocytes in the hippocampal CA3 region by down‐regulating the expression of pro‐inflammation cytokines . Moreover, chrysophanol enhanced the mRNA and protein expression of low‐density lipoprotein receptor, HMG‐CoAR and CYP7A1 and significantly decreased mRNA and protein expression of ACAT2 in liver cell Bel‐7402 .…”

“…Male C57BL mice 0.1 mg/kg In vivo [12] Promotes lead excretion and reducing peroxide content Adult Kunming mice 10.0 mg/kg In vivo [14] Reduces the expression of cleaved caspase-3 and enhances the activity of SOD and MnSOD Male C57BL mice 0.1-10 mg/kg In vivo [15] Inhibition of inflammation in the hippocampus Male wild-type ICR mice 10 mg/kg In vivo [66] Antioxidant and anti-inflammatory Murine BV2 cells 0-50 lM In vitro [51] Inhibition of Drp1-dependent mitochondrial fission BV-2 murine microglial cells…”

Antidiabetic potential of anthraquinones: A review

“…In high glucose‐induced hyperglycemic mice, chrysophanol (0.18 mg/kg bw) reduced blood glucose by 42.3% after a 2‐hr postadministration period (Choi et al, ). More recently, treatment with chrysophanol at 10 mg/kg bw (HED: 0.81 mg/kg bw) for 11 days reduced FBG by 45% and ameliorated diabetic‐associated inflammatory complications in STZ‐induced diabetic mice (Chu et al, ). Therefore, despite the scanty information, the beneficial role of chrysophanol in an animal model and the potent PTP 1B inhibition are of interest and need further extensive studies to explore the antidiabetic effect of chrysophanol.…”