Ginger Extract and its Compound, 6-shogaol, Attenuates Painful Diabetic Neuropathy in Mice via Reducing TRPV1 and NMDAR2B Expressions in the Spinal Cord
FAJRIN, Fifteen Aprila
NUGROHO, Agung Endro
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Ethnopharmacological relevance: In silico data revealed that the active compound of ginger (Zingiber oﬃcinale Roscoe), 6-shogaol, has strong aﬃnity toward transient receptor potential vanilloid-1 (TRPV-1). TRPV-1 is expressed in nervous tissue and pancreatic β-cells. Prolonged induction of TRPV-1 is related to the expression of Nmethyl-D-aspartate receptor subunit 2B (NMDAR2B). However, there are no data on TRPV-1 and NMDAR2B expressions in nervous tissue after 6-shogaol or ginger extract treatment nor pancreatic islet morphology and insulin expression in mice model of painful diabetic neuropathy (PDN). Aim of the study: This study aimed to investigate the mechanism of action of ginger extract and its compound, 6shogaol, on pancreatic islets as well as on expressions of TRPV-1 and NMDAR2B in the spinal cord of streptozotocin (STZ)-induced mice model of PDN. Materials and methods: Sixty-four 5–6 weeks old male-Balb/C mice were induced with 110 mg/kgBW STZ i.p., while eight mice were used as control group. Mice with blood glucose level ≥200 mg/d, that suﬀered hyperalgesia and allodynia were classiﬁed as PDN mice. Hot plate and von Frey ﬁlament tests were performed once a week until termination. At day 28 after considered as PDN, ginger extracts, 6-shogaol or gabapentin as control treatment were given once daily for 21 days until day 49, except for the diabetic control group. Upon termination, mice’ pancreas were ﬁxed, processed as paraﬃn sections and stained with hematoxylin eosin. Total volume of pancreatic islets was estimated using Cavalieri methods. Immunohistochemistry on pancreatic sections were performed to observe insulin expression. mRNA was extracted from lumbar segments of the spinal cord, followed by cDNA preparation and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to measure the expressions of TRPV1 and NMDAR2B. The mean diﬀerences between groups were analyzed using one-way analysis of variance (ANOVA) with p < 0.05 considered statistically signiﬁcant. Results: Ginger extracts and 6-shogaol alleviated hyperalgesia and allodynia. The groups that received ginger extract 400 mg/kgBW or 6-shogaol 15 mg/kgBW had signiﬁcantly lower TRPV1 and NMDAR2B expressions in the spinal cord compared to the diabetic control group (p < 0.001;p < 0.05). However, no diﬀerences in volume of pancreatic islets (p > 0.05) nor insulin expression were observed in all PDN groups. Conclusion: Ginger extracts and its compound, 6-shogaol, reduced pain symptoms in PDN via its eﬀect on decreasing TRPV1 and NMDAR2B expressions in the spinal cord, with very limited eﬀect on pancreatic islets.
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