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

Shen, Chwan‐Li; Wang, Rui; Ji, Guangchen; Elmassry, Moamen M.; Zabet-Moghaddam, Masoud; Vellers, Heather L.; Hamood, Abdul N.; Gong, Xiao; Mirzaei, Parvin; Sang, Shengmin; Neugebauer, Volker

doi:10.1016/j.jnutbio.2021.108904

Cited by 47 publications

(34 citation statements)

References 123 publications

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“…Lumbar spinal nerve (L5) ligation in this model results in acute hypersensitivity within 1 week that persists for multiple weeks (Chung et al, 2004). The SNL model is well-established in our laboratories (Ji et al, 2017;Ji et al, 2018;Ji and Neugebauer, 2019;Navratilova et al, 2019;Presto et al, 2021;Shen et al, 2022b). In brief, rats were anesthetized with isoflurane (2%-3%; precision vaporizer, Harvard Apparatus) and the left L5 spinal nerve was surgically exposed and tightly ligated using 6-0 sterile silk.…”

Section: Animals and Treatmentsmentioning

confidence: 99%

“…Mechanical withdrawal thresholds of spinal nocifensive reflexes were measured on the left paw using Electronic von Frey Aesthesiometer (IITC Life Science, Woodland Hills, CA, United States) with a plastic tip in an exclusive testing area (catalog number 76-0488, Harvard Apparatus, Holliston, MA, United States) 1 day before-SNL and 1, 2, 3, and 4 weeks after respective treatments, as described in our previous studies (Ji et al, 2018;Shen et al, 2022b). The average of six measurements per subject, taken at least 30 s apart, was calculated.…”

Section: Assessment Of Mechanosensitivitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

“…We previously reported that GEG supplementation into the diet decreased mechanical hypersensitivity assessed in the von Frey test and favored microbiome composition and fecal metabolites (Shen et al, 2022b). Such beneficial effects of GEG may be due to its anti-inflammatory property as shown in the suppression of circulating cell-free mitochondrial DNA (Shen et al, 2022b). The current study advances this concept by investigating 1) if GEG supplementation would affect different NP-related behaviors, including sensory (mechanical withdrawal thresholds), emotional-affective (audible and ultrasonic vocalization), and spontaneous components, 2) if GEG supplementation would improve leaky gut, and 3) if GEG supplementation would suppress neuroinflammation in the colon (gut) and amygdala (brain).…”

Section: Introductionmentioning

confidence: 97%

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Gingerol-Enriched Ginger Supplementation Mitigates Neuropathic Pain via Mitigating Intestinal Permeability and Neuroinflammation: Gut-Brain Connection

Shen

Wang

Yakhnitsa³

et al. 2022

Front. Pharmacol.

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Objectives: Emerging evidence suggests an important role of the gut-brain axis in the development of neuropathic pain (NP). We investigated the effects of gingerol-enriched ginger (GEG) on pain behaviors, as well as mRNA expressions of inflammation via tight junction proteins in GI tissues (colon) and brain tissues (amygdala, both left and right) in animals with NP.Methods: Seventeen male rats were randomly divided into three groups: Sham, spinal nerve ligation (SNL, pain model), and SNL+0.375% GEG (wt/wt in diet) for 4 weeks. Mechanosensitivity was assessed by von Frey filament tests and hindpaw compression tests. Emotional responsiveness was measured from evoked audible and ultrasonic vocalizations. Ongoing spontaneous pain was measured in rodent grimace tests. Intestinal permeability was assessed by the lactulose/D-mannitol ratio in urine. The mRNA expression levels of neuroinflammation (NF-κB, TNF-α) in the colon and amygdala (right and left) were determined by qRT-PCR. Data was analyzed statistically.Results: Compared to the sham group, the SNL group had significantly greater mechanosensitivity (von Frey and compression tests), emotional responsiveness (audible and ultrasonic vocalizations to innocuous and noxious mechanical stimuli), and spontaneous pain (rodent grimace tests). GEG supplementation significantly reduced mechanosensitivity, emotional responses, and spontaneous pain measures in SNL rats. GEG supplementation also tended to decrease SNL-induced intestinal permeability markers. The SNL group had increased mRNA expression of NF-κB and TNF-α in the right amygdala and colon; GEG supplementation mitigated these changes in SNL-treated rats.Conclusion: This study suggests GEG supplementation palliated a variety of pain spectrum behaviors in a preclinical NP animal model. GEG also decreased SNL-induced intestinal permeability and neuroinflammation, which may explain the behavioral effects of GEG.

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Section: Animals and Treatmentsmentioning

confidence: 99%

Section: Assessment Of Mechanosensitivitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Gingerol-Enriched Ginger Supplementation Mitigates Neuropathic Pain via Mitigating Intestinal Permeability and Neuroinflammation: Gut-Brain Connection

Shen

Wang

Yakhnitsa³

et al. 2022

Front. Pharmacol.

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“…Our experiment confirmed that QBPF could improve the imbalance of Th17/Treg cells and regulate immune function. Additionally, through this experiment, we believe that the imbalance of intestinal and pulmonary microbiota may be one of the pathological mechanisms of COPD rats, and traditional Chinese medicine has a regulatory effect on microbiota in the gut and lung [115][116][117][118]. QBPF could treat COPD by regulating the intestinal and pulmonary microbiota, which provides a new idea and direction for exploring the potential biomarkers of COPD and the possible mechanism of QBPF in the prevention and treatment of COPD.…”

Section: There Exists Regulation Of Qbpf In Immune Homeostasis and In...mentioning

confidence: 99%

The treatment of Qibai Pingfei Capsule on chronic obstructive pulmonary disease may be mediated by Th17 / Treg balance and gut-lung axis microbiota

Jia

et al. 2022

Preprint

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Background: Chronic obstructive pulmonary disease (COPD), a prevalent, progressive respiratory disease, has become the third leading cause of death globally. Increasing evidence suggests that intestinal and pulmonary microbiota dysbiosis is associated with COPD. Researchers have shown that T helper (Th) 17/regulatory T (Treg) imbalance is involved in COPD. Qibai Pingfei Capsule (QBPF) is a traditional Chinese medicine used to treat COPD clinically in China. However, the effects of QBPF intervention on the Th17/Treg balance and microbiota in the gut and lung are still poorly understood. Methods: This study divided the rats into three groups (n=8): control, model, and QBPF group. After establishing the model of COPD for four weeks and administration of QBPF for two weeks, Th17 cells, Treg cells, their associated cytokines, transcription factors, and intestinal and pulmonary microbiota of rats were analyzed. Furthermore, the correlations between intestinal and pulmonary microbiota and between bacterial genera and pulmonary function and immune function were measured. Results: The results revealed that QBPF could improve pulmonary function and contribute to the new balance of Th17/Treg in COPD rats. Meanwhile, QBPF treatment could regulate the composition of intestinal and pulmonary microbiota and improve community structure in COPD rats, suppressing the relative abundance of Coprococcus_2 , Prevotella_9 , and Blautia in the gut and Mycoplasma in the lung, but accumulating the relative abundance of Prevotellaceae_UCG_003 in the gut and Rikenellaceae_RC9_gut_group in the lung. Additionally, gut–lung axis was confirmed by the significant correlations between the intestinal and pulmonary microbiota. Functional analysis of microbiota showed amino acid metabolism was altered in COPD rats in the gut and lung. Spearman correlation analysis further enriched the relationship between the microbiota in the gut and lung and pulmonary function and immune function in COPD model rats. Conclusions: Our study indicated that the therapeutic effects of QBPF may be achieved by maintaining the immune cell balance and regulating the gut-lung axis microbiota, providing references to explore the potential biomarkers of COPD and the possible mechanism of QBPF to treat COPD.

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Evaluation of dynamic effects of dietary medium-chain monoglycerides on performance, intestinal development and gut microbiota of broilers in large-scale production

Liu

Ruan

et al. 2023

Animal Nutrition

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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

Cited by 47 publications

References 123 publications

Gingerol-Enriched Ginger Supplementation Mitigates Neuropathic Pain via Mitigating Intestinal Permeability and Neuroinflammation: Gut-Brain Connection

Gingerol-Enriched Ginger Supplementation Mitigates Neuropathic Pain via Mitigating Intestinal Permeability and Neuroinflammation: Gut-Brain Connection

The treatment of Qibai Pingfei Capsule on chronic obstructive pulmonary disease may be mediated by Th17 / Treg balance and gut-lung axis microbiota

Evaluation of dynamic effects of dietary medium-chain monoglycerides on performance, intestinal development and gut microbiota of broilers in large-scale production

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