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. 2022 Jul 29;14(15):3137.
doi: 10.3390/nu14153137.

The Efficacy of Camelina sativa Defatted Seed Meal against Colitis-Induced Persistent Visceral Hypersensitivity: The Relevance of PPAR α Receptor Activation in Pain Relief

Elena Lucarini  1 , Laura Micheli  1 , Eleonora Pagnotta  2 , Alessandra Toti  1 , Valentina Ferrara  1 , Clara Ciampi  1 , Francesco Margiotta  1 , Alma Martelli  3   4   5 , Lara Testai  3   4   5 , Vincenzo Calderone  3   4   5 , Roberto Matteo  2 , Serafino Suriano  6 , Antonio Troccoli  6 , Nicola Pecchioni  6 , Clementina Manera  3 , Lorenzo Di Cesare Mannelli  1 , Carla Ghelardini  1
Affiliations

The Efficacy of Camelina sativa Defatted Seed Meal against Colitis-Induced Persistent Visceral Hypersensitivity: The Relevance of PPAR α Receptor Activation in Pain Relief

Elena Lucarini et al. Nutrients. .

Abstract

Brassicaceae are natural sources of bioactive compounds able to promote gut health. Belonging to this plant family, Camelina sativa is an ancient oil crop rich in glucosinolates, polyunsaturated fatty acids, and antioxidants that is attracting renewed attention for its nutraceutical potential. This work aimed at investigating the therapeutic effects of a defatted seed meal (DSM) of Camelina sativa on the colon damage and the persistent visceral hypersensitivity associated with colitis in rats. Inflammation was induced by the intrarectal injection of 2,4-dinitrobenzenesulfonic acid (DNBS). The acute administration of Camelina sativa DSM (0.1-1 g kg-1) showed a dose-dependent pain-relieving effect in DNBS-treated rats. The efficacy of the meal was slightly enhanced after bioactivation with myrosinase, which increased isothiocyanate availability, and drastically decreased by pre-treating the animals with the selective peroxisome proliferator-activated receptor alpha (PPAR α) receptor antagonist GW6471. Repeated treatments with Camelina sativa DSM (1 g kg-1) meal counteracted the development, as well as the persistence, of visceral hyperalgesia in DNBS-treated animals by reducing the intestinal inflammatory damage and preventing enteric neuron damage. In conclusion, Camelina sativa meal might be employed as a nutraceutical tool to manage persistent abdominal pain in patients and to promote gut healing.

Keywords: 2,4-dinitrobenzenesulfonic acid; Camelina sativa; PPAR α receptor; enteric nervous system; inflammatory bowel diseases; mast cell; visceral pain.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The effect of Camelina sativa DSM acute administration on visceral pain associated with colitis in rats before and after bio-activation with myrosinase enzyme (Myr). (A) Experimental scheme: the behavioural test was performed 30 min after the oral administration of the Camelina sativa DSM (0.1–1 g kg−1 p.o.). Camelina sativa DSM was bioactivated by adding 30 μL mL−1 of myrosinase (32 U mL−1) 15 min before the administration. (B) Visceral sensitivity was assessed in animals by measuring the extent of the abdominal withdrawal response (AWR) to colorectal distension, carried out by applying an increasing distending stimulus on the colon walls (0.5–3 mL). Each value represents the mean ± SEM of six animals per group. ** p < 0.01 vs. vehicle. ^ p < 0.05 and ^^ p < 0.01 vs. DNBS + vehicle.
Figure 2
Figure 2
The involvement of H2S and Kv7 potassium channels in the acute pain-relieving effects of Camelina sativa DSM. (A) Experimental scheme: the behavioural test was performed 30 min after the oral administration of the Camelina sativa DSM (0.1–1 g kg−1 p.o.). Visceral sensitivity was assessed in animals by measuring the extent of the abdominal withdrawal response (AWR) to colorectal distension, carried out by applying an increasing distending stimulus on the colon walls (0.5–3 mL). (B) Oxidized glutathione (GSSG) (20 mg kg−1) was orally administered in concomitance with Camelina sativa DSM (1 g kg−1), and the test was performed after 30 min. (C) The Kv7 potassium channel blocker XE991 (1 mg kg−1) was intraperitoneally administered in concomitance with Camelina sativa DSM (1 g kg−1), and the test was performed after 30 min. Each value represents the mean ± SEM of six animals per group. * p < 0.05 and ** p < 0.01 vs. vehicle. ^ p < 0.05 and ^^ p < 0.01 vs. DNBS + vehicle. ° p < 0.05 vs. DNBS + Camelina sativa DSM.
Figure 3
Figure 3
The contribution of PPAR-α receptor activation to the acute pain-relieving effect of Camelina sativa DSM. (A) Experimental scheme: the behavioural test was performed 30 min after the oral administration of the Camelina sativa DSM (0.1–1 g kg−1 p.o.). (B) Visceral sensitivity was assessed in animals by measuring the extent of the abdominal withdrawal response (AWR) to colorectal distension, carried out by applying an increasing distending stimulus on the colon walls (0.5–3 mL). The PPAR-α receptor antagonist GW6471 (2 mg kg−1) was intraperitoneally administered in concomitance with Camelina sativa DSM (1 g kg−1), and the test was performed after 30 min. Each value represents the mean ± SEM of six animals per group. * p < 0.05 and ** p < 0.01 vs. vehicle. ^^ p < 0.01 vs. DNBS + vehicle. ° p < 0.05 and °° p < 0.01 vs. DNBS + Camelina sativa DSM.
Figure 4
Figure 4
The involvement of PPAR-Ƴ, CB1, and CB2 receptor in the acute pain-relieving effect of Camelina sativa DSM. Visceral sensitivity was assessed in animals by measuring the extent of the abdominal withdrawal response (AWR) to colorectal distension, carried out by applying an increasing distending stimulus on the colon walls (0.5–3 mL). (A) The PPAR-Ƴ receptor antagonist G3335 (2 mg kg−1) was intraperitoneally administered in concomitance with Camelina sativa DSM (1 g kg−1), and the test was performed after 30 min. (B) CB1 and CB2 receptor antagonists (SR141716A and MC21, respectively; 10 mg kg−1) were intraperitoneally administered in concomitance with Camelina sativa DSM (1 g kg−1), and the test was performed after 30 min. Each value represents the mean ± SEM of six animals per group. * p < 0.05 and ** p < 0.01 vs. vehicle. ^ p < 0.05 and ^^ p < 0.01 vs. DNBS + vehicle.
Figure 5
Figure 5
The effects of the repeated administration of Camelina sativa DSM in DNBS-treated rats. (A) Experimental scheme: Camelina sativa DSM (1 g kg−1) was administered once daily in the DNBS-treated animals, starting from the day of DNBS injection and continuing the daily treatment for 14 consecutive days. Body weight (B) and visceral pain threshold (C) were assessed on Days 8 (acute inflammatory phase) and 15 (post-inflammatory phase), 24 h after the last administration. Visceral sensitivity was assessed by measuring the extent of the abdominal withdrawal response (AWR) to colorectal distension (0.5–3 mL). Each value represents the mean ± SEM of six animals per group. * p < 0.05 and ** p < 0.01 vs. vehicle. ^ p < 0.05 vs. DNBS + vehicle.
Figure 6
Figure 6
The effects of the repeated treatment with Camelina sativa DSM on colon damage induced by DNBS in rats. Camelina sativa DSM (1 g kg−1) was administered once daily in the DNBS-treated animals, starting from the day of DNBS injection for 14 consecutive days; then tissues were collected (Day 15). The column graphs report the colon macroscopic (A) and microscopic (B) damage score; Representative pictures of haematoxylin–eosin-stained sections of full-thickness colon (C). Original magnification: 4× and 10×. Each value represents the mean ± SEM of six animals per group. ** p < 0.01 vs. vehicle. ^ p < 0.05 vs. DNBS + vehicle.
Figure 7
Figure 7
The effects of the repeated treatment with Camelina sativa DSM on submucosal mast cell infiltration caused by DNBS. Camelina sativa DSM (1 g kg−1) was administered once daily in the DNBS-treated animals, starting from the day of DNBS injection for 14 consecutive days, and then tissues were collected. The column graph displays the mean mast cell density per area of colonic wall (cells/field) (A). The panel shows pictures captured from submucosa of mast cell granules stained in purple with GIEMSA (B). Each value represents the mean ± SEM of six animals per group. ** p < 0.01 vs. vehicle. ^^ p < 0.01 vs. DNBS. Original magnification: 40×.
Figure 8
Figure 8
The neuroprotective effects of Camelina sativa DSM on the colonic myenteric plexus of DNBS-treated rats. Camelina sativa DSM (1 g kg−1) was administered once daily in the DNBS-treated animals, starting from the day of DNBS injection for 14 consecutive days, and then tissues were collected. The immunolabeling quantification of PGP 9.5 (A) and GFAP (B) with relative immunofluorescence images showing the expression of PGP 9.5 (green), GFAP (red), and DAPI (blue) in the myenteric plexus of the colon (C). The quantitative analysis of PGP9.5- and GFAP-related immunofluorescence intensity (arbitrary unit) was performed by collecting independent fields (4–6 for each animal) from the myenteric plexi. Results were expressed as a percentage of the control group (vehicle-treated animals). Each value represents the mean ± SEM of six animals per group. * p < 0.05 vs. vehicle. ** p < 0.01 vs. vehicle. ^ p < 0.05 vs. DNBS + vehicle. Original magnification: 40×.
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