Progress 01/01/22 to 12/31/22
Outputs
Target Audience:During the period covered by this 2nd annual report, this project has provided research/experiential learning opportunities/laboratory instruction to 2 medical students and 3 undergraduate students through formal educational programs, namely (i) Year 2 Medical Student Research for medical students, and (ii) Undergraduate Research Scholar Program and Pi2 Program for undergraduate students. Two of the five trainees are racial and ethnic minorities. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Through animal studies, we provided training in behavior, molecular biology, surgery, animal handling, data analysis, interpretation and presentation to two senior research associates for their professional development in the field of bioactive compounds in pain research. How have the results been disseminated to communities of interest?We published our work in 3 peer-referred journals. Paper #1: Shen et al. Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation. Journal of Nutritional Biochemistry. 2022 Feb;100:108904. doi: 10.1016/j.jnutbio.2021.108904. Paper #2: Shen CL et al. Gingerol-enriched ginger supplementation mitigates neuropathic pain via mitigating intestinal permeability and neuroinflammation: gut-brain connection. Frontiers in Pharmacology. 2022. Jul 8;13:912609. doi: 10.3389/fphar.2022.912609. Paper #3: Wang/Shen (corresponding author). Ginger root extract improves GI health in diabetic rats by improving intestinal integrity and mitochondrial dysfunction. Nutrients. 2022 Oct 19;14(20):4384. doi: 10.3390/nu14204384. In addition, we published two invited review articles. Review #1: Shen et al. Bioactive compounds for neuropathic pain: an update on preclinical studies and future perspectives. Journal of Nutritional Biochemistry. 2022; 104:108979. doi: 10.1016/j.jnutbio.2022.108979. Review #2: Shen et al. Bioactive compounds for fibromyalgia-like symptoms: a narrative review and future perspectives. International Journal of Environment Research and Public Health, Special Issue: "Individual Difference in Pain in Various Populations". 2022, 19(7):4148. Although we are still generating more data through upcoming animal studies in 3rd year grant period, the results so far suggest that this research project will impact the emerging field of neuropathic pain management through natural food ingredients (ginger root and its bioactive compounds) affecting the gut-brain-axis. What do you plan to do during the next reporting period to accomplish the goals?We plan to finish the bench work and data analysis for non-targeted fecal metabolites in both male and female studies. We plan to finish bench work and data analysis for all mRNA expression in collected tissues (amygdala, frontal cortex, spinal cord, DRG, and colon) of female study. We will conduct immunohistochemistry (IHC) or Western blotting to confirm the findings of mRNA expression at the protein level in colon or other available tissues of both male and female studies. We plan to submit 3-4 abstracts for presentation at national or international conferences. Finally, we aim to publish 2-3 manuscripts to address GEG dose-response and sex differences in the outcome measures.
Impacts
What was accomplished under these goals?
We have conducted two animal studies to deliver gingerols-enriched ginger (GEG) via oral gavage inanimals with neuropathic pain. Male animal study There were 5 groups including sham+vehicle (corn oil), spinal nerve ligation (spinal nerve ligation, SNL, neuropathic pain model)+vehicle (corn oil), SNL+200 mg GEG/BW, SNL+400 mg GEG/BW, and SNL+600 mg GEG/BW for 4-week periods. We assessed behavioral outcomes (SA 1) and collected tissues for mRNA expression of neuroinflammation (SA 3) in frontal cortex, amygdala, spinal cord, dorsal root ganglion (DRG), and colon. The cecum feces were collected for gut microbiome and non-targeted metabolites (hydrophobic and hydrophilic) analysis. All behavioral outcomes (SA 1), assessed by von Frey test, vocalization measurements, open field test (OFT), elevated plus maze test (EPM), and grimace test were completed with statistical analysis. In terms of gut health (SA 2), (1) statistical analysis of gut microbiome data is completed; (2) the laboratory work on fecal metabolites is currently being conducted at TTU core facility; (3) intestinal barrier integrity was assessed by completion of mRNA expression analysis of tight junction protein (i.e., claudin-1, claudin-3, occuldin, and zonulin) in variety of tissues and urinary lactulose/mannitol concentrations; and (4) intestinal inflammation was assessed by completion of mRNA expression analysis of TNF-α, NF-kB, and IL-1β in colon. Regarding NP-associated neuroinflammation (SA 3), we have completed the mRNA gene expression analysis of glial activation biomarkers, mitochondrial function parameters (fission, fusion, biogenesis, respiratory chain complex, and oxidative stress), and proinflammatory cytokine/chemokine signaling in all collected tissues. Female animal study Similar to the Male Study, there were 5 groups [sham+vehicle (corn oil), spinal nerve ligation (SNL, pain model)+vehicle (corn oil), SNL+200 mg GEG/BW, SNL+400 mg GEG/BW, and SNL+600 mg GEG/BW for 4-week periods] in the Female Study. We have completed animal feeding experiment, data collection of pain-associated behavior outcomes, collection of specimens (feces, tissues), and data analysis of gut microbiome. The remaining laboratory work (non-target fecal metabolites, mRNA expression, IHC) and follow-up statistical analyses will be conducted/completed in the Year 3. Effect of GEG supplementation: (1) Pain hypersensitivity. Pain mechanosensitivity was assessed by von Frey test and by paw compression test (reflex thresholds). Compared to the SNL vehicle group, after 4 weeks of GEG intervention, all GEG doses (200, 400, and 600 mg/kg body weight) significantly mitigated SNL-induced mechanical hypersensitivity regardless of sex. (2) Emotional pain responses. Emotional pain responses were assessed by measuring audible and ultrasound vocalization evoked by innocuous or noxious stimuli. In the male study, the magnitude of decrease of SNL-induced emotional responses was greater in the 200 mg/BW GEG group than in the other GEG groups (400 and 600 mg/kg BW). A similar trend in GEG effects on emotional pain responses was observed in the female animals with NP. (3) Spontaneous pain behavior. Quantification of spontaneous pain was done with the Rodent Grimace Test (RGT). After 4 weeks of GEG intervention, compared to the SNL vehicle group, the SNL male animals with GEG supplementation showed significantly decreased spontaneous pain behavior, reflected in lower scores of orbital tightening, nose budge, ears position, and whiskers changes, in a GEG-dose dependent manner. (4) Pain-associated anxiety. Pain-associated anxiety behaviors were assessed by OFT and EPM. After 4 weeks of GEG intervention, in both male and female, the low dose of GEG (200 mg/kg BW) decreased pain-associated anxiety behaviors, as shown by increased duration/frequency in the center of OFT and by increased distance travelled and duration in the open-arms of EPM. (5) Gut microbiom. Based on alpha-diversity analysis (Pielou's evenness and Faith's phylogenetic diversity indices), we observed a statistically significant drop in species evenness and richness in groups treated with GEG of both male and female animals with NP (Wilcoxon signed-rank test, P < 0.05). SNL induction resulted in the loss of some of the microbiome species. These taxa belonged to several phyla, such as Proteobacteria (e.g., Sutterella stercoricanis) and Firmicutes. This effect of GEG was more pronounced in female rats, than in male rats. To answer Q2, we used a similar approach as for Q1 and examined the increase/decrease of species in GEG groups in both sexes vs. SNL using LOCOM. First, it is remarkable that certain species are consistently altered by GEG treatments in both sexes. This was the case for ASVs of Rikenella, Muribaculaceae, Clostridia UCG-014, and Mucispirillum schaedleri, RF39, which were decreased in GEG treated animals (both sexes) vs. SNL. In contrast, ASVs of the following taxa were increased in GEG treated animals (both sexes) vs. SNL: Bacteroides, UBA1819, and Hungatella. Second, we observed distinct patterns between sexes and their response to GEG treatments. For example, an Anaerotruncus ASV was only decreased in male rats. Flavonifractor and Anaerofustis stercorihominis were only increased in male rats. Parasutterella and Odoribacter were decreased in female rats only, while Victivallis was increased. Third, a few taxa showed a dose-response with GEG treatments, such as RF39 and UCG-009, Parasutterella, Hungatella, and Rikenella. (6) mRNA in in brain, spinal cord, DRG, and colon. Tight junction: claudin-3 in collected tissues. GEG supplementation increased the mRNA expression of claudin-3 in the amygdala, DRG, colon, but not in frontal cortex and spinal cord. Pro-inflammatory cytokines: NF-kB, TNF-α, IL-1β, and IL-6. GEG supplementation suppressed SNL-induced gene expression of NF-kB, TNF-α, and IL-1β in the above tissues. Glial activation: IBA-1, CD11B, and GFAP. GEG supplementation at high doses (400 and 600 mg/kg BW GEG) significantly increased gene expression of IBA-1 (frontal cortex and spinal cord) and GFAP (frontal cortex), but it significantly decreased gene expression of CD11b (frontal cortex, amygdala, spinal cord, DRG, and colon), IBA-1 (amygdala and colon), CD11b (), and GFAP (amygdala, DRG, and colon). Mitochondrial fission: DRP1 and FIS1. GEG supplementation significantly increased mRNA expression of DRP1 in frontal cortex and amygdala, while it significantly decreased DRP1 mRNA expression in colon. In terms of FIS1, SNL induction significantly decreased the mRNA expression levels of FIS1 in colon, while GEG at 200 mg/kg BW reversed such this decrease. Mitochondrial fusion: MFN1 and MFN2. GEG supplementation significantly decreased MFN1 (amygdala, spinal cord, DRG, and colon) and MFN2 (amygdala, spinal cord, DRG, and colon), but significantly increased the mRNA expression MFN1 in frontal cortex. Mitochondrial biogenesis: PINK1, PGC-1α, NRF1, and TFAM. GEG supplementation significantly suppressed SNL-induced mRNA expression of PINK1 in frontal cortex, spinal cord, DRG, and colon. Although SNL did not affect PINK1 mRNA expression in amygdala, GEG supplementation significantly increased PINK1 mRNA expression level in amygdala. GEG supplementation significantly increased SNL-suppressed mRNA expression of PGC1a in all collected tissues (frontal cortex, amygdala, spinal cord, DRG, and colon). GEG supplementation significantly increased mRNA expression of NRF1 (frontal cortex, amygdala, and spinal cord) and TFAM (frontal cortex and spinal cord), while it significantly reduced SNL-induced NRF1 mRNA expression in colon. Mitochondrial respiratory chain complexes: complex I and complex III. GTP supplementation significantly increased mRNA expression of complex I (fontal cortex, amygdala, spinal cord, DRG, and colon) and complex III (frontal cortex, amygdala, spinal cord, DRG, and colon).
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
" Shen CL, Wang R, Ji G, Elmassry MM, Zabet-Moghaddam M, Vellers H, Hamood AN, Gong X, Mirzaei P, Sang S, Neugebauer V. Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation. Journal of Nutrition Biochemistry. 2022 Feb;100:108904. doi: 10.1016/j.jnutbio.2021.108904.
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
" Wang R, Santos JM, Dufour JM, Stephens ER, Miranda JM, Washburn RL, Hibler T, Kaur G, Lin D, Shen CL (corresponding author). Ginger root extract improves GI health in diabetic rats by improving intestinal integrity and mitochondrial dysfunction. Nutrients. 2022 Oct 19;14(20):4384. doi: 10.3390/nu14204384.
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
" Shen CL, Wang R, Yakhnitsa V, Santos J, Watson C, Kiritoshi T, Ji C, Hamood A, Neugebauer V. Gingerol-enriched ginger supplementation mitigates neuropathic pain via mitigating intestinal permeability and neuroinflammation: gut-brain connection. Frontiers in Pharmacology. 2022. Jul 8;13:912609. doi: 10.3389/fphar.2022.912609. eCollection 2022.
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
" Shen CL, Castro L, Fang C-Y, Castro M, Sherali S, White S, Wang R, Neugebauer V. Bioactive compounds for neuropathic pain: an update on preclinical studies and future perspectives. Journal of Nutritional Biochemistry. 2022; 104:108979. doi: 10.1016/j.jnutbio.2022.108979. Online ahead of print.
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
" Shen CL, Schuck A, Tompkins C, Dunn DM, Neugebauer V. Bioactive compounds for fibromyalgia-like symptoms: a narrative review and future perspectives. International Journal of Environment Research and Public Health, Special Issue: Individual Difference in Pain in Various Populations . 2022, 19(7):4148.
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Progress 01/01/21 to 12/31/21
Outputs
Target Audience:This project has provided research/experiential learning opportunities/laboratory instruction to 2 medical students and 3 undergraduate students through formal educational programs, namely (i) Medical Student Summer Research Program and Year 2 Medical Student Research for medical students, and (ii) Undergraduate Research Scholar Program and Pi2 Program for undergraduate students. Two of the five trainees are racial and ethnic minorities. Changes/Problems:The major changes of this project include: A change in the method of GEG delivery from dietary supplementation to oral gavage, which has been approved by TTUHSC IACUC full board meeting. Based on our pilot study, we learned that oral gavage avoids the GEG taste issue. Replace lipopolysaccharide binding protein (LBP) in plasma samples test with urinary lactulose and mannitol ratio test for intestinal permeability assessment (SA 3). We tried to quantify the levels of lipopolysaccharide binding protein (LBP) in plasma samples to access the intestinal barrier integrity. However, the concentrations of LBP in plasma was below the detectable limits, suggesting the LBP method may not be sensitive enough to detect such subtle change due to SNL or GEG supplementation. This change has been approved by TTUHSC IACUC full board meeting. Replace Conditioned Place Preference (CPP)/Conditioned Place Aversion (CPA) tests that require animal training/learning with Grimace test for ongoing pain-associated behavioral outcomes in SA 1. This change has been approved by TTUHSC IACUC full board meeting. Ongoing pain will be assessed as pain scores in freely moving rats using facial grimace chart (Sotocinal et al 2011), which has been used successfully in neuropathic pain models (Akintola et al 2017).Method:Rats are acclimated to the testing room for 1 hour before the beginning of the experiment. Animals are placed in individual Plexiglas cages with bedding from animal's home cage to make the environment as stress-free as possible. Animals are acclimated to the cage for 5 to 10 minutes before pictures are taken with a digital camera (4 pictures at 20-second intervals to increase reliability). If the animal was grooming, actively sniffing or rearing, then the next available picture is used for scoring. Images are taken from multiple angles. For consistency, the same individuals score all the images in a blinded manner. Five facial parameters (action units) are scored: orbital tightening (eye lid fissure), nose bulge, cheek bulge, ear position, and whisker change. Each action unit is scored 0 (not present), 1 (moderately visible), or 2 (severe) on the basis of criteria described previously (Sotocinal et al 2011). An initial grimace score of each photograph is calculated by averaging the scores of the 5 action units, and a mean grimace score is obtained from the 4 images. Scores from the blinded investigators are averaged for the final result. All above changes will have no significant impact on either the overall goal of the project or the rate of expenditure. Instead, Grimace test will provide a less invasive/stressful approach for the involved animals, than CPP/CPA test. References: Akintola T, Raver C, Studlack P, Uddin O, Masri R, Keller A. The grimace scale reliably assesses chronic pain in a rodent model of trigeminal neuropathic pain.Neurobiol Pain. 2017 Aug;2:13-17. PMID: 29450305 Sotocinal, S.G., Sorge, R.E., Zaloum, A., Tuttle, A.H., Martin, L.J., Wieskopf, J.S.,Mapplebeck, J.C., Wei, P., Zhan, S., Zhang, S., McDougall, J.J., King, O.D., Mogil,J.S., 2011. The Rat Grimace Scale: a partially automated method for quantifying painin the laboratory rat via facial expressions. Mol. Pain 755. What opportunities for training and professional development has the project provided?Through animal studies, we provided training to two senior research associates for their professional development in the field of bioactive compounds in pain research. How have the results been disseminated to communities of interest?We published our pilot study (Shen et al. Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation) in the Journal of Nutritional Biochemistry (JNB), special issue: precision nutrition-individual nutrient needs for optimal health throughout the lifespan this year (doi: 10.1016/j.jnutbio.2021.108904). JNB has impact factor of 6.048 and open access to all communities of interest. In addition, one review manuscript (Shen et al. Bioactive compounds for neuropathic pain: an update on preclinical studies and future perspectives) is currently under review by the JNB. Although we are still generating more data through upcoming animal studies in our 2nd and 3rd year grant periods, the results so far suggest that this research project will impact the emerging field of neuropathic pain management through natural food ingredients (ginger root and its bioactive compounds) affecting the gut-brain-axis. What do you plan to do during the next reporting period to accomplish the goals?We plan to conduct two animal studies; one animal study on male rats and another on female rats. A total of 50 (male SD rats) will be divided into 5 groups (n=10 per group): Sham+vehicle, SNL+vehicle, SNL+200 mg/kg GEG, SNL+400 mg/kg GEG, and SNL+600 mg/kg GEG for 4 weeks. We will perform sensory and affective behaviors (SA 1) while animals are alive. Collected tissues from animals will be used to perform SA 2: gut health; SA 3: neuroinflammation via mRNA expression, protein expression, ELSIA, or IHC, in the amygdala (right), spinal cord (lumbar enlargement), dorsal root ganglion (DRG), and GI. SA 4: gut microbiota composition and fecal metabolites). In SA 3, we will use the following approaches: (1) due to the limited amount of tissue (e.g. amygdala-right, DRG), mRNA gene expression using RT-PCR will be our first priority; and (2) if adequate tissue samples are available, we will perform IHC and/or protein expression to confirm the findings of mRNA expression. We will analyze the amygdala (right-side, because of hemispheric lateralization of pain processing), spinal cord (lumbar enlargement, site of afferent input from nerve injury), and DRG (L5+L6, site of afferent input from nerve injury).
Impacts
What was accomplished under these goals?
We conducted the following two animal studies: STUDY 1 Gingerol-enriched ginger root extract (GEG) was delivered to male SD rats via diet. The groups assignment included wild type control, sham, spinal nerve ligation (SNL, pain model), SNL+0.375%GEG, SNL+0.75%GEG, and SNL+1.125%GEG for 4-week feeding periods. Unexpectedly, GEG administration through the diet turned out to be problematic because the animals did not like the taste of GEG; we lost all animals (n=6) from the SNL+1.125% GEG group, 1 animal from the SNL+0.75%GEG group, and 1 animal from the SNL+0.375%GEG group within a week after SNL. Despite that, we still completed the 4-week intervention period, performed behavioral assessment (SA 1), conducted intestinal permeability test (SA 3), and collected tissues for mRNA expression of neuroinflammation (SA 3) in colon, amygdala (right and left), spinal cord (lumbar enlargement), and ileum. Preliminary findings: (1) GEG supplementation mitigated pain hypersensitivity. Pain mechanosensitivity was assessed by von Frey test and by tissue compression (spinal reflexes). According to the results of von Frey test, compared to the SNL group, both SNL+0.375% GEG and SNL+0.75% GEG groups showed reduced pain sensitivity as early as 1-week post-operation and sustained through 4 weeks, as shown by increased mechanical thresholds. At the end of the study (4 weeks after supplements started), the order of pain sensitivity was SNL group > SNL+0.75%GEG group > SNL+0.37%%GEG group > sham group = control group. The findings of spinal reflexes were similar to those in von Frey test. (2) GEG supplementation decreased NP-induced audible vocalizations. At the baseline, there were no differences in audible vocalization among all groups, regardless of different stimuli conditions, including innocuous mechanical stimuli, innocuous ultrasound stimuli, noxious mechanical stimuli, and noxious ultrasound stimuli. GEG supplementation significantly reduced SNL-induced emotional responses under all statuses. (3) GEG supplementation decreased NP-induced spontaneous pain. Quantification of spontaneous pain was assessed by Grimace test. At the baseline, there were no any differences in any facial expressions. At the end of study, GEG supplementation significantly reduced SNL-induced nose bulge, whiskers change, and ear position of SNL-operated rats. (4) GEG supplementation tended to improve intestinal integrity. We evaluated intestinal permeability by analyzing urinary lactulose and mannitol levels. SNL procedure increased intestinal permeability as shown in increased ratio of lactulose/mannitol ratio. GEG supplementation had a trend in lowering the ratio of lactulose/mannitol, an indicator of intestinal permeability. (5) The expression levels of tight junction, mitochondrial, and inflammation genes in CNS (amygdala), PNS (spinal cord), and GI (colon only, not ileum) were modified by GEG supplementation. SNL procedure increased the expression levels of neuroinflammation-related genes. Amygdala: SNL operation tended to increase mRNA expression of zonulin (tight junction) (0.05<p<0.1), while GEG supplementation tended to suppress zonulin mRNA expression in the amygdala (0.05<p<0.1). SNL procedure significantly induced mRNA expression levels of (i) mitochondria associated genes [dynmin-related protein 1 (Drp 1) for mitochondrial fission; mitofusin 1 (Mfn1) and mitofusion 2 (Mfn2) for mitochondrial fusion; p62 and parkin-mediated mitophagy 1 (Pink1) for mitophagy; nuclear factor erythroid 2 p45-related factor 2 (Nrf2) for mitochondrial biogenesis], and (ii) inflammatory gene (nuclear factor kappa B, NF-κB). GEG supplementation suppressed those SNL-induced gene expressions (zonulin, Mfn1, Mfn2, P62, Pink1, Nrf2, and NF-κB) in the amygdala of SNL-treated animals. Additionally, GEG supplementation significantly suppressed the mRNA expression of GFAP (glial fibrillary acidic protein) in the amygdala of SNL-treated rats (p<0.05). Spinal cord: SNL procedures induced increased mRNA expression levels of mitochondria associated genes (Mfn1 and Nrf2) in the spinal cord of rats. GEG supplementation suppressed the mRNA expression of FIS1 and NF-κB of the spinal cord. Colon: SNL operation resulted in the increased mRNA expression levels of claudin and occludin (tight junction) (p<0.05), while GEG supplementation tended to suppress mRNA expression in the colon (0.05<p<0.1). SNL procedure induced the mRNA expressions of (i) mitochondria associated genes (Drp 1, Fis1, Pink1, and Nrf2), and (ii) inflammatory gene (TNF-α, NF-kB, and IL-1β). GEG supplementation suppressed those SNL-induced gene expressions (namely, Drp1, Fis1, Nrf2, TNF-α, NF-kB, and IL-1β) in the colon of SNL-treated animals. In addition, GEG supplementation resulted in a reduction of GFAP mRNA gene expression in the colon of SNL-treated animals. Ileum: Neither SNL procedure nor GEG supplementation significantly impacted mRNA expression levels in the ileum of animals. We learned that animals did not consume GEG in the diet possibly because of the taste. Thus, we designed STUDY 2 to deliver GEG at 200 and 400 mg GEG/kg BW via oral gavage. The results of STUDY 2 confirmed the acceptance of GEG by study animals. Besides the sham group (receiving surgical procedure only) as we proposed in the USDA proposal, we included wild type animals as an additional control group for STUDY 1. Based on the results of behavioral assessment and tissue mRNA expression levels, there was no statistically significant difference in the above described behavioral or mRNA outcomes between the wild-type group and the sham group. Thus, in the future animal studies, we will not include wild-type animals. Since mRNA expression levels of proposed genes in the ileum of animals were not affected by SNL procedure or GEG supplementation compared to those in the colon of animals, our follow-up animal GEG oral gavage feeding studies will focus on the colon tissues. STUDY 2: GEG was delivered to male SD rats via oral gavage. The group assignments included normal+400 group (normal+400 mg GEG/kg BW), SNL (SNL+corn oil as vehicle at 200 mg corn oil/BW), SNL+200 group (SNL+200 mg GEG/kg BW), and SNL+400 (SNL+400 mg GEG/kg BW) (n=3 per group) for 3 weeks. The purpose of this pilot study was to evaluate the acceptability of GEG via oral gavage by the SNL-operated animals. The GEG-treated animals significantly reduced the SNL-induced hypersensitivity, in a dose-dependent pattern. The order of mechanical thresholds was normal+400 group > SNL+400 group > SNL+200 group > SNL group.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Shen CL, Wang R, Ji G, Elmassry MM, Zabet-Moghaddam M, Vellers H, Hamood AN, Gong X, Mirzaei P, Sang S, Neugebauer V. Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation. Journal of Nutritional Biochemistry, Special Issues: Precision nutrition individual nutrient needs for optimal health throughout the lifespan. 2021 Nov 5:108904. doi: 10.1016/j.jnutbio.2021.108904. JNB IF: 6.048, open access.
- Type:
Journal Articles
Status:
Under Review
Year Published:
2022
Citation:
Shen CL, Castro L, Fang C-Y, Castro M, Sherali S, White S, Wang R, Neugebauer V. Bioactive compounds for neuropathic pain: an update on preclinical studies and future perspectives. Submitted to Journal of Nutritional Biochemistry on 9/23/2021, under review. Received favorable comments from reviewers. Plan to submit revision in the end of December 2021.
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