Immunomodulatory effect from ethanol extract and ethyl acetate fraction of Curcuma heyneana Valeton and Zijp: Transient receptor vanilloid protein approach.

This study aims to discover the immunomodulatory potential of the ethanol extract (EE) and the ethyl acetate fraction (EAF) of Curcuma heyneana Valeton and Zijp (Indonesian name: temu giring) rhizome using mice models. The affinity of the curcuminoid (curcumin, dimethoxy-, and bisdemethoxy-) through the Transient Receptor Potential Vanilloid 1 (TRPV1) was determined using Mollegro molecular docking in silico. The curcuminoid concentration of the EE and EAF of C. heyneana rhizome were determined using thin-layer chromatography densitometry. In vivo studies in mice models were conducted using the carbon clearance method to determine the phagocytosis index, and the number of leukocytes in the blood and spleen. Forty mice were divided into eight groups, including negative control (given 1% CMC-Na), positive control (given Stimuno Forte® suspension at a dose of 6.5 mg/kg BW), three groups given the EAF of C. heyneana rhizome extract at a dose of 125 mg/kg BW, 250 mg/kg BW, and 500 mg/kg BW, respectively, and three groups were given EE of temu giring rhizome extract with doses of 125 mg/kg BW, 250 mg/kg BW, and 500 mg/kg BW, respectively. E.E. and E.A.F. of C. heyneana (temu giring) rhizome extract contained dimethoxy curcumin (0.176 ± 0.01 and 4.53 ± 0.02 %b/b) greater than another curcuminoid, bisdemetoxy curcumin and curcumin. EE at 125 mg/kg BW and EAF dose at 500 mg/kg B W. of temu giring rhizome have immunostimulant activity with a phagocytosis index value of >1 compared to the negative control (p < 0.05). Additionally, both increase the number of lymphocytes, monocytes, and neutrophil cells in peripheral blood and spleen compared to the negative control (p < 0.05). Their activity was seen as similar to the positive control. Therefore, the EE of C. heyneana rhizome has immunostimulant activity, and the EAF of C. heyneana rhizome has immunosuppressant activity at 125 mg/kg BW and immunostimulant at a higher dose. The activity of temu giring as an immunomodulator was associataed with its affinity to TRPV1.

Ginger extract and its compound, 6-shogaol, attenuates painful diabetic neuropathy in mice via reducing TRPV1 and NMDAR2B expressions in the spinal cord.

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 ß-cells. Prolonged induction of TRPV-1 is related to the expression of N-methyl-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, 6-shogaol, 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.

Antihyperalgesia potency of Zingiber officinale var. Rubrum in inflammatory and neuropathy-induced chronic pain condition in mice.

Chronic inflammation and neuropathic pain are classified into chronic pain. Until now there are so many drugs that have been used for chronic pain but the effectiveness still lower. One of the plants that are commonly used for medicine in Indonesia is red ginger (Zingiber officinale var. rubrum). This study was aimed to analyze the component of red ginger oil and proved its antihyperalgesia potency in chronic pain using two models, inflammatory pain and neuropathy pain. Forty-eight mice were divided into 2 groups i.e. inflammatory and neuropathy. Each group was divided into 6 subgroups (@4 mice) i.e. for inflammatory model (sham, negative control, red ginger oil doses 100, 200, 400 and 600 mg/kg) and for neuropathy model (sham, negative control, red ginger oil doses 100, 200, 400 and 600 mg/kg). Inflammatory model was induced using Completed Freud's Adjuvant (CFA) 40 ml intraplantar. Neuropathy model was induced using Partial Sciatic Nerve Ligation (PSNL). At day-7, all groups were given orally treatment, once daily for seven days. The latency time toward thermal stimulus and plantar thickness were measured at day 0,1,3,5,7,8,10,12 and 14 after induction. Quality of red ginger oil was standardized by Indonesia standard (SNI 06-1312-1998). The red ginger oil compound was identified by GC/MS. The result showed that red ginger oil was qualified based on SNI 06-1312-1998. Red ginger oil 200 mg/kgBW and 400mg/kgBW administration in mice gave the best result in prolong the latency time toward thermal stimulus using hot plate and significantly different with inflammatory and neuropathy group. From GC/MS analysis, camphene was known as the highest compound of red ginger oil that might be important for its antihyperalgesia effect. The conclusion of this study that red ginger oil have antihyperalgesia activity in mice with chronic pain and could be developed further to be antihyperalgesia.