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Evaluating the potential therapeutic effect of Rosa damascena Mill. essential oil on acetic acid-induced ulcerative colitis in rats

  • Dilek Özbeyli ORCID logo , Duygu Yiğit Hanoğlu ORCID logo , Özlem Tuğçe Çilingir-Kaya ORCID logo and Asli Aykac ORCID logo EMAIL logo
Published/Copyright: February 24, 2025
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Turkish Journal of Biochemistry
From the journal Turkish Journal of Biochemistry Volume 50 Issue 2

Abstract

Objectives

In this study, Rosa damascena Mill. essential oil (RDEO) was aimed to evaluate its potential anti-inflammatory and mitochondria-mediated anti-apoptotic effects in vitro and in vivo in acetic acid (AA)-induced ulcerative colitis (UC) rat model.

Methods

In the UC rat model, RDEO (100 μL/kg, p.o.) or sulfasalazine (100 mg/kg/p.o.) was administered to the treatment groups. After decapitation, the UC activity index, colon mass index, and macroscopic and microscopic damages were determined in rat colon tissue. TNF-α levels and MPO activity were measured to evaluate the effect of the inflammation in the colon. Changes in the expression levels of Bcl-2, Bax, casp-3, and casp-9 proteins, which are indicators of mitochondrial-mediated apoptosis were determined by the Western blot method.

Results

Our study results revealed that AA-induction caused a significant increase in colitis activity index (CAI), colon mass index (CMI), and macroscopic and microscopic damages in rat colon tissue. It shows that RDEO treatment has an effective curative effect by reducing AA-induced inflammation (TNF-α and MPO activity), CAI, CMI, pro-apoptotic protein (Bcl-2, Bax, Casp-3, and Casp-9), and morphological damages in rat colon tissue.

Conclusions

All these results suggest that RDEO may have suppressed changes in colon tissue due to its ability to reduce AA-induced inflammation and apoptosis. The results of this study showed that RDEO was beneficial in UC and, like other herbal anti-inflammatory agents, RDEO did not cause gastrointestinal side effects.

Keywords: Rosa damascena Mill.; ulcerative colitis; mitochondrial-mediated apoptosis; acetic acid; caspase

Introduction

Inflammatory bowel disease, also called IBD, is a gastrointestinal (GI) system of disease characterized by the activation of a recurrent inflammatory process accompanied by a wide range of symptoms, from abdominal pain to bloody diarrhea. The main causes of the disease include genetic factors, environmental factors, various microbial agents, and immune system defects, but unfortunately, the underlying causes remain unclear and the prevalence of the disease is increasing worldwide [1].

During the course of the disease, there are not only physical symptoms such as diarrhea and abdominal pain but also psychological symptoms such as anxiety and social isolation. In the pathological process of the disease, the inflammatory cascade is activated. In fact, IBD develops and progresses as a result of dysregulation in the levels of various inflammatory mediators, including cytokines and chemokines. Prolonged inflammation can lead to irreversible intestinal damage and colorectal cancer [2]. In the treatment of IBD, some expensive agents have been developed that target molecular mechanisms to reduce symptoms. Currently, there are very few effective and affordable treatment options for IBD which including ulcerative colitis (UC) patients [3], 4].

The mucosa of the intestinal tract is protected by a precise balance between epithelial cell proliferation and apoptosis. Epithelial cell apoptosis is a prominent occurrence at the onset of UC and plays an important role in the development of the disease [5]. UC disrupts the mucosal barrier, leading to the overproduction of inflammatory cytokines such as TNF-α and IL-1β [6]. Therefore, it is important to develop treatments that can maintain the integrity of the epithelial cell barrier and inhibit apoptosis.

Considering that herbal products or foods are sources of diet and new drugs in the treatment of various diseases, we can better realize the importance of research using various traditional medicinal plants. In the treatment of inflammation, herbal therapies have been used for almost hundreds of years. In the results of research using experimental models to study the effect of plant extracts on inflammation, it has been reported that plant extracts have the ability to reduce and even minimize inflammation [7], 8]. Natural components are thought to interfere with the pathogenesis of UC by exhibiting antioxidant, anti-inflammatory, and anti-apoptotic properties through signaling pathways [9]. Several natural compounds have been shown to suppress mitochondria-mediated apoptosis, which may be linked to their therapeutic effects on experimental animal models of UC [10].

Rosa damascena Mill. (Damask Rosa: DR), a plant belonging to the Rosaceae family is highly valued worldwide as a valuable source of aroma [11]. DR has been extensively cultivated in various areas, such as Turkey’s lakes region, Isparta, Burdur, and Afyonkarahisar [12], 13]. Numerous studies have reported that the antibacterial, antioxidant, anti-inflammatory, anticancer, analgesic, and relaxant properties of DR [13]. Rosa damascena essential oil (RDEO) contains citronellol, geraniol, methyl eugenol, and nonadecane in varying proportions. Previous research has highlighted the antioxidant and anti-inflammatory effects of RDEO, with more than 80 % of its content consisting of citronellol, trans-geraniol, and phenylethyl alcohol, in a liver sepsis model [14].

Experimental models in rodents using various agents have been developed to study the mechanisms involved in the pathogenesis of IBD [15]. Among these models, the acetic acid (AA) model of UC is widely used and shows histopathological and morphological similarities to human UC [16]. The lesions induced by intracolonic administration of AA are mucosal, acute, and non-transmural, making this simple, inexpensive, and reproducible model a suitable experimental model for studying UC [15], 16].

Despite studies reporting the potent antioxidant and anti-inflammatory effects of RDEO in various organs, there have been few reports on its potential therapeutic effect in colon tissue in UC. In a previous study, it has been shown that Rosa damascena Mill. essential oil and hydroalcoholic extract exert anti-inflammatory effects on AA-induced colitis in rats however, there is no information about the underlying mechanisms of this action [17]. Considering the previously published reports on the rat model of UC, this study aimed to evaluate the potential anti-inflammatory and mitochondria-mediated anti-apoptotic effects of RDEO in an AA-induced rat model of UC in vitro and in vivo.

Materials and methods

Analysis and identification of RDEO

Gas chromatography/mass spectrometry (GC/MS) analyses were carried out after diluting RDEO 1:2 (v/v) with n-hexane. It was used at a 1:1 dilution for GC/flame ionization detection (GC/FID) studies (i.e., as an undiluted stock solution). The GC analysis was carried out on an Agilent 6890 N GC. RDEO underwent simultaneous capillary GC and GC/MS analysis utilizing an Agilent GC-MS system (5,975; Agilent Technologies Inc., Santa Clara, CA). The research of simultaneous injections was conducted using an Agilent INNOWax GC column (HP, USA) (60 m, 0.25 mm; layer thickness, 0.25 mm). The FID temperature was set at 300 °C. The carrier gas was He2+, and the flow rate was 0.8 mL per minute. The GC oven was kept at a constant temperature of 60 °C for 10 min before being increased to 220 °C at a rate of 4 °C/min and subsequently decreased to 240 °C at a rate of 1 °C/min. The split ratio was adjusted to 40:1. The injector temperature was fixed at 250 °C. Mass spectra were acquired at 70 eV. The mass range was 35–450 m/z. The relative retention indices were compared with the n-alkane series to determine the RDEO components [11].

Animals

Rats (n=30, Sprague-Dawley males; 200–250 g) were obtained from the Experimental Animals Research and Implementation Centre of Marmara University (MU), Istanbul, Turkey. The protocols used for all animal procedures were approved by the Animal Research Ethics Committee of MU (Approval number: 64.2020.mar). There were three rats in each plastic cage, and the rats were housed in rooms with temperature, humidity, and light/dark cycles of 21–24 °C, 50–55 %, and 12 h/24 h, respectively.

Colitis rat model induction and treatment protocols

The experimental groups were divided into two main groups: the control groups (without AA-induction) and the model groups (with AA-induction) [1 mL of 5 % (v/v) AA in 0.9 % NaCl intrarectally (i.r.); Sigma-Aldrich, St. Louis, MO, USA] [18], 19].

  1. SS group: The first control group of rats received saline solution (1 mL of 0.9 % NaCl i.r. instead of AA. and distilled water p.o.)

  2. DR group: The second control group of rats received RDEO (100 μL/kg, p.o.)

  3. AA group: The first model groups of rats received injections of AA alone (1 mL of 5 % (v/v) in 0.9 % NaCl i.r.

  4. AA + DR group: The second model group of rats received AA (1 mL of 5 % (v/v) in 0.9 % NaCl i.r. + RDEO 100 μL/kg, p.o.) [20].

  5. AA + SL group: The third model group of rats received AA (1 mL of 5 % (v/v) in 0.9 % NaCl i.r. + sulfasalazine 100 mg/kg, p.o.) n=6 for each group [21].

After one day of fasting, the UC model was created by inserting the cannula into the rectal hole and pushing 8 cm under ether anesthesia. All rats were kept upside down for 30 s after administration to prevent any leakage of the applied solution. AA was administered to the rats only once, and a colitis pattern was induced at 2 h after administration [18].

The rats were treated at the same time of day for three days, with the total dose divided in half (twice-daily treatments). A total of 30 rats were used, with n=6 in each group. After the third day, the rats were euthanized [50 mg/kg/i.p., thiopental sodium (IE Ulagay, Istanbul, Turkey)] and the last 8 cm of the distal section of the colon was dissected for biochemical, histological, and molecular analysis.

Ulcerative colitis activity index and colon mass index

As reported in previous protocols, the UC Activity Index (CAI), often used to measure the severity of colitis, was reported based on changes in all significant bleeding and stool consistency indicators. As previously, the ulcerative CAI was followed by scores ranging from 0 to 3 (well-formed and non-bleeding pellet; pellet adherent to anus, with blood). The colon mass index (CMI), the ratio of colon weight to total body weight, was calculated to measure the degree of colonic oedema and severity of inflammation [22].

Quantification of TNF-α level

TNF-α levels were determined according to the manufacturer’s instructions using a commercial ELISA kit (cat.no: ab100785, Abcam, Cambridge, UK). The quantification of the TNF-α levels was expressed as pg/mL (double assay).

MPO activity

The homogenized tissue samples supernatants were sonicated in an ice bath after being added to 2.3 mL of reaction mixture containing 50 mM phosphate buffer, o-dianisidine, and 20 mM H2O2 solution. MPO activity that is expressed as U/g in tissue was determined as the absorbance of the resulting color was measured at 460 nm using a spectrometer (one assay) [15].

Assessment of histopathological and macroscopic changes in colonic tissues

For light microscopic investigations, colon tissues from all experimental groups were fixed in 10 % formaldehyde, then dehydrated in a series of alcohol solutions with progressively higher alcohol concentrations (70, 90, 96, and 100 %), cleared in xylene solution, and finally embedded in paraffin. The Leica rotary microtome (RM2125RT) was used to slice paraffin tissue blocks into 5 m slices, and they were subsequently mounted on slides made from glass and coated with H&E. The sections were examined with an Olympus BX51 light microscope, and photographs were taken with a digital camera system (Olympus DP72) connected to the photomicroscope. Using the macroscopic damage scale [0: none; 1: mucosal erythema; 2: mild (mucosal oedema, bleeding, or erosion); 3: moderate (oedema, ulceration, or erosion); 4: severe (oedema, erosion, bleeding ulcers, and necrosis)]. The macroscopic properties of the dissected colon tissues were assessed after they were cut longitudinally and washed with saline [23].

Mitochondrial apoptosis-related protein expression levels

Following the determination of the samples’ protein content with the Lowry method, immunoblotting was conducted as double blotting in the following manner: samples comprising a total of 100 g protein were separated via 12 % SDS electrophorese gel and afterward passed through membranes [24]. Membranes were handled for 14 h at + 4 °C with primary antibodies ((1:200 dilution for all) Bax (cat.no: sc-20067), Bcl-2 (cat. no: sc-7382), Casp-3 (cat. no: sc-56053), and Casp-9 (cat.no: sc-56076)) [25]. Protein bands visible on membranes treated with secondary antibody (rabbit monoclonal anti-goat IgG 1:1,000 dilution) for 1 h were visualized using NBT/BCIP (nitro blue tetrazolium and 5-bromo-4-chloro-3-indolyl- phosphate; Promega, Wisconsin, USA) [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47]. Image J software was used to perform semi-quantitative densitometric analyses of the membranes All antibodies for immunoblotting were obtained from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA).

Statistical analysis

All results were reported as mean±SEM, and differences between groups were examined using the Bonferroni post-hoc test following one-way (ANOVA) in GraphPad Prism 9 (San Diego, CA, USA). In the evaluation of the experimental outcomes, p<0.05 was judged significant.

Results

Components of the RDEO identified through content analysis

The constituents (percentages, %) of RDEO obtained from the GC/MS content analysis are shown in Table 1. The three components making up the largest percentage of the content were identified as follows: citronellol (29.5 %), geraniol (20.2 %), and nonadecane (16.5 %).

Table 1:

Compositional analysis of R. damascena essential oil.

RRI Compound name Relative percentage amounts (%) of the essential oil of Rosa damascena
1021 α–Pinene 0.6
1119 β–Pinene 0.1
1132 Sabinene 0.1
1172 Myrcene 0.1
1262 γ-Terpinene 0.1
1361 1-Hexanol 0.1
1368 cis-Rose oxide 0.1
1501 Pentadecane 0.4
1615 α-Guaiene 0.1
1624 Terpinene-4-ol 0.3
1629 β-Caryophyllene 0.2
1675 Citronellyl acetate 0.2
1702 Heptadecane 2.6
1704 α-Humulene 0.1
1717 α-Terpineol 0.2
1727 Heptadecene 0.1
1741 Neryl acetate 0.1
1744 Germacrene D 0.5
1747 δ–Guaiene 0.1
1757 Geranial 0.5
1771 Geranyl acetate 0.6
1777 Citronellol 29.5
1802 Octadecane 0.3
1816 Nerol 9.6
1826 iso-Geraniol 0.2
1847 2-Phenylethyl formate 0.3
1860 Geraniol 20.2
1903 Nonadecane 16.5
1923 Nonadecene 3.2
1944 Phenylethyl alcohol 1.1
2001 Eicosane 1.4
2022 Eicosene 0.3
2037 Methyl eugenol 1.6
2102 Heneicosane 5.5
2121 1-Tridecanol 0.1
2141 Tetracosene 0.1
2206 Eugenol 0.5
2302 Tricosane 0.9
2370 (2E,6E)-Farnesol 0.9
Total 99.4

  1. aRRI, relative retention indices (vs. n-alkanes in a polar column).

The ulcerative colitis activity index and the colon mass index

The feces of the rats in the control group were of normal fecal consistency. As expected, a remarkable increase in the CAI was observed in the AA-induced UC model group compared to the SS-group (p<0.001; Table 2). The CAI was found to be lower in the AA+DR and AA+SL groups compared to the AA-induction group (p<0.01–0.001; Table 2). CMI significantly increased in the AA-induced UC model group compared to the SS group (p<0.001). It was found that both DR and SL treatment significantly reduced the effect on CMI compared to AA-induction (p<0.001; Table 2).

Table 2:

Ulcerative colitis activity index and colon mass index in AA-induced colitis rat model.

Index SS DR AA AA + DR AA + SL
CAI 0.45 ± 0.2 0.9 ± 0.1 2.4 ± 0.2a 1.5 ± 0.2b 1.2 ± 0.1c
CMI 2.4 ± 0.1 2.5 ± 0.1 4.8 ± 0.2a 3.4 ± 0.2c 3.1 ± 0.1c

  1. ap<0.001 vs. control group, bp<0.01 and cp<0.001 vs. AA-induced colitis group. CAI, colitis activity index; CMI, colon mass index; SS, saline solution treated control group; DR, R osa D amascene Mill. essential oil treated control group; AA, Acetic acid induced colitis group; AA + DR, Rosa Damascena Mill. essential oil treated colitis group; SL, sulfasalazine treated colitis group.

TNF-α level and MPO activity

As a result of the TNF-α level and MPO activity evaluations performed in the rat colon tissue, a significant increase was found in both the TNF-α level and MPO activity of the AA-induction group compared to the SS-treated group (p<0.001; Figure 1A and B). It was found that DR or SL treatment administered to rats after AA-induction caused a significant decrease in TNF-α (p<0.01–0.001, respectively) level and MPO activity (p<0.05–0.001, respectively) compared with the AA-induction group.

Figure 1: TNF-α and MPO levels in tissue from the colon according to different treatments in acetic acid-induced rat ulcerative colitis model. ***p<0.001 vs. control group, +, ++, +++ p<0.05–0.001 vs. AA-induced colitis group. TNF-α: tumor necrosis factor-alpha, MPO: myeloperoxidase, SS: saline solution treated control group, DR: Rosa damascena essential oil treated control group, AA: acetic acidinduced colitis group, AA + DR: Rosa damascena essential oil treated colitis group, SL: sulfasalazine treated colitis group.
Figure 1:

TNF-α and MPO levels in tissue from the colon according to different treatments in acetic acid-induced rat ulcerative colitis model. ***p<0.001 vs. control group, +, ++, +++ p<0.05–0.001 vs. AA-induced colitis group. TNF-α: tumor necrosis factor-alpha, MPO: myeloperoxidase, SS: saline solution treated control group, DR: Rosa damascena essential oil treated control group, AA: acetic acidinduced colitis group, AA + DR: Rosa damascena essential oil treated colitis group, SL: sulfasalazine treated colitis group.

Macroscopic scores and histological results

It was determined that the total macroscopic score was higher in the AA-induction group (12.5 ± 0.15) than in the SS-treated group (1.56 ± 0.05), the DR-treated group (1.59 ± 0.03), the AA+DR-treated group (4.7 ± 0.15) and the AA + SL-treated group (2.73 ± 0.03) (Figure 2 and Table 3). Microscopic examination of the stained sections revealed that the SS-treated group had a regular histologic appearance (Figure 3A). Irregular epithelial lining, damaged glandular structures, dilation of blood vessels, and inflammation were noted in the AA-induced colitis group (Figure 3B). It was found that the abnormal histologic appearance of the colon tissues of the rats in the SL-treated AA-induced colitis groups improved with control-like features (Figure 3C). The DR-treated group showed similar morphological features to the SS-treated group (Figure 3D). It was found that the abnormal histological appearance of the colon tissues of the rats in the DR-treated AA-induced colitis groups improved with control-like features (Figure 3E).

Figure 2: Representative macroscopic images of the colon tissues from the different experimental groups: SS-treated group; AA-induced colitis group; AA + SL-treated colitis group; DR-treated group; AA + DR-treated colitis group.
Figure 2:

Representative macroscopic images of the colon tissues from the different experimental groups: SS-treated group; AA-induced colitis group; AA + SL-treated colitis group; DR-treated group; AA + DR-treated colitis group.

Table 3:

Microscopic scorings obtained from colon tissues in the rat model of AA-induced colitis.

Score Evaluation criteria Experimental groups
SS DR AA AA + DR AA + SL
Macroscopic Oedema 0.2 ± 0.05 0.2 ± 0.03 2.9 ± 0.2 1.3 ± 0.3 0.7 ± 0.03
Necrosis 0.4 ± 0.08 0.5 ± 0.05 3 ± 0.1 1.8 ± 0.35 0.7 ± 0.04
Inflammation 0.5 ± 0.06 0.5 ± 0.02 3 ± 0.14 0.8 ± 0.08 1 ± 0.06
Perforation 0.4 ± 0.004 0.3 ± 0.03 1.1 ± 0.1 0.3 ± 0.02 0.23 ± 0.03
Hemorrhage 0.06 ± 0.01 0.09 ± 0.04 2.5 ± 0.2 0.5 ± 0.04 0.1 ± 0.02
Total score 1.56 ± 0.05 1.59 ± 0.03 12.5 ± 0.15a 4.7 ± 0.15b 2.73 ± 0.03b

  1. ap<0.001 vs. control group, bp<0.001 vs. AA-induced colitis group. CAI, colitis activity index; CMI, colon mass index; SS, saline solution treated control group; DR, Rosa damascena essential oil treated control group; AA, acetic acid induced colitis group; AA + DR, Rosa damascena Mill. essential oil treated colitis group; SL, sulfasalazine treated colitis group.

Figure 3: Representative microscopic images of the colon tissues from the different experimental groups: (A) SS-treated group; (B) AA-induced colitis group; (C) AA+SL-treated colitis group; (D) DR-treated group; (E) AA + DR-treated colitis group. Arrow: irregular epithelial lining. Arrowhead: damaged glandular structures. Asterisk (*): neutrophil infiltration. Plus (+): dilated blood vessels.
Figure 3:

Representative microscopic images of the colon tissues from the different experimental groups: (A) SS-treated group; (B) AA-induced colitis group; (C) AA+SL-treated colitis group; (D) DR-treated group; (E) AA + DR-treated colitis group. Arrow: irregular epithelial lining. Arrowhead: damaged glandular structures. Asterisk (*): neutrophil infiltration. Plus (+): dilated blood vessels.

Mitochondria-mediated apoptosis results

Representative images obtained from electrophoresis and subsequent blotting procedures performed on rat colon tissues are given in Figure 4. The Bax/Bcl-2 ratio was significantly increased in AA-induced colitis rats compared with the SS-treated group (p<0.001). It was found that the AA+DR and AA+SL treatment groups significantly decreased the Bax/Bcl-2 ratio in the colon tissue when compared to the AA-induction group (p<0.01–0.001, respectively; Figure 4A). Casp-9 and -3 levels were significantly increased in the colon tissue of rats in the AA-treated group compared with the SS-treated group (p<0.01; Figure 4B and C). AA + DR and AA+SL treatment groups significantly decreased Casp-9 and -3 levels when compared with the AA-induced colitis group (for Casp-9, p<0.01–0.001, respectively; p<0.05 in both treatments for Casp-3).

Figure 4: Changes in the expression of some mitochondria-mediated apoptotic proteins determined by western blotting assay according to treatment in an acetic acid-induced rat ulcerative colitis model. **, ***p<0.01–0.001 vs. control group, +, ++, +++ p<0.05–0.001 vs. AA-induced colitis group. SS: saline solution treated control group, DR: Rosa damascena essential oil treated control group, AA: acetic acid induced colitis group, AA + DR: Rosa damascena essential oil treated colitis group, SL: sulfasalazine treated colitis group, n=3 double blotting. Bcl-2: B-cell lymphoma protein 2, Bax: B-cell lymphoma protein 2-associated X, Casp-3: Caspase-3, Casp-9: Caspase-9.
Figure 4:

Changes in the expression of some mitochondria-mediated apoptotic proteins determined by western blotting assay according to treatment in an acetic acid-induced rat ulcerative colitis model. **, ***p<0.01–0.001 vs. control group, +, ++, +++ p<0.05–0.001 vs. AA-induced colitis group. SS: saline solution treated control group, DR: Rosa damascena essential oil treated control group, AA: acetic acid induced colitis group, AA + DR: Rosa damascena essential oil treated colitis group, SL: sulfasalazine treated colitis group, n=3 double blotting. Bcl-2: B-cell lymphoma protein 2, Bax: B-cell lymphoma protein 2-associated X, Casp-3: Caspase-3, Casp-9: Caspase-9.

Discussion

In this study, the anti-inflammatory and antiapoptotic effects of RDEO were evaluated based on biochemical, histological, and molecular analyses. Our study results showed that AA-induction caused a significant increase in CAI, and CMI and caused macroscopic damage to colonic tissues. Our findings are consistent with the reports of a significant increase in CAI, CMI, and macroscopic damage in colon tissue after AA-induction, which has been highlighted by many studies [22], 27]. RDEO treatment provided significant protection against AA-induced colitis by reducing colonic macroscopic damage as well as reducing high CAI and CMI. The outcomes of our study demonstrate that RDEO has an effective curative effect on AA-induced rat colon tissue by lowering inflammation (TNF-a and MPO activity), CAI, CMI, pro-apoptotic protein (Bax, Casp-3, and Casp-9) expression levels and raising anti-apoptotic protein Bcl-2 expression levels. Moreover, the reversal of colon tissue damage by RDEO and thus the preservation of colon tissue demonstrates clearly its usefulness in AA-induced colitis in rats.

The drop-in body weight and the change in the length of the colon tissue, that is, the increase in the CMI, are two of the most basic indications in determining the severity of the inflammatory reaction [28], 29]. In the current study, the induction of UC by AA caused oedema, perforation, hemorrhage, necrosis, inflammation, and colonic tissue damage, which was well supported by histopathologic observations.

While the dried flowers of DR are used to relieve constipation, the water containing trace amounts of oil is used to relieve intestinal spasms [30]. Terpenes, which are commonly found in the essential oils of edible plants, have received great attention in research due to their therapeutic positive pharmacological properties, especially in GI diseases of the GI system. In the current study, the most abundant components detected in RDEO content analysis were citronellol, geraniol, and nonadecane, respectively. Citronellol has been reported to have anti-inflammatory effects [31]. Geraniol also ameliorated colitis by modulating different inflammatory pathways and cytokines [32], 33]. It has been shown that citronellol and geraniol are accountable for anti-inflammatory effects of RDEO [34], 35]. Our results also support this literature and show that these two active ingredients have a significant effect on the healing effect of the essential oil.

Results obtained with the induction of AA, an agent adopted to model UC in the rat, may mimic increased inflammatory mediators and epithelial damage very similar to that seen in human IBD [36]. Under normal conditions in the GI mucosa, there is a tight control in the balance between pro-inflammatory (TNF-α) and anti-inflammatory cytokines, just as there is a balance between pro- and anti-apoptotic proteins in the course of apoptosis [28], 36]. TNF-α and MPO are among the most important indicators of the body’s inflammatory status/response [37]. TNF-α, released primarily by activated macrophages, disrupts the colonic epithelial barrier, induces epithelial cell apoptosis, activates neutrophils, and is crucial in the pathogenesis of IBD. TNF-α and MPO are commonly used to evaluate the efficacy of therapeutic agents in the treatment of IBD disease [38]. There are studies in the literature reporting an increase in MPO activity and TNF-α as a result of analyzes performed in colon tissue in ulcerative colitis rat models induced by AA-induction. Consistent with other studies, we found that AA-induction increased MPO activity and TNF-α level in colon tissue [39], [40], [41]. In our study, MPO and TNF-α content were significantly decreased by the administration of DR treatment to rats with colitis, which indicates that DR has an anti-inflammatory effect on ulcerative rats. Our result showing that RDEO has a reducing effect on MPO activity in the colon which damaged by AA supports a previous study [17].

Some inflammatory mediators inhibit apoptosis by prolonging neutrophil survival time. In parallel with the increased neutrophil survival at sites of inflammation, there is improvement in the cell’s immune response. However, this may also cause tissue damage in some conditions. Unlike necrosis, cell apoptosis contributes to the reduction of immune cell-mediated tissue damage [42]. SL is an anti-inflammatory agent with proven efficacy in the treatment of UC [43]. It has also been proven that SL inhibits the apoptosis of immune cells [44]. The fact that apoptosis, which has an important role in the pathogenesis of IBD, causes deterioration in intestinal integrity and intestinal dysfunction, which may result in the activation of the inflammatory cascade [45], 46]. In this study, it was discovered that AA-induction raised the expression of Bax, Casp-3, and Casp-9 the mitochondrial proteins linked to apoptosis, while decreasing the expression of Bcl-2 in colon tissue. Our results are consistent with the results of AA-induced UC rat study results, which reported an increase in Bax, Casp-3 expression and a decrease in Bcl-2 expression [23], 47]. RDEO treatment administrated to the UC group effectively reversed the increase in pro-apoptotic protein expressions, the decrease in the expression of Bcl-2, one of the anti-apoptotic proteins, and the damage in the colon tissue.

Inhibiting the apoptosis of intestinal epithelial cells is critical for the treatment of UC and may be a target for research and the development of therapeutic agents. In recent years, there have been studies reporting that natural products inhibiting intestinal epithelial apoptosis with different anti-apoptotic mechanisms have curative effects on UC. One of these mechanisms is mitochondria-mediated apoptosis. Different apoptotic stimuli activate the mitochondria-dependent apoptotic pathway by stimulating the release of pro-apoptotic proteins such as Casp-3, -9, and Bax.

All these results suggest that RDEO may have suppressed changes in colon tissue due to its ability to reduce AA-induced inflammation and apoptosis. The results of this study found that RDEO was beneficial in UC and, like other herbal anti-inflammatory agents, RDEO did not cause GI side effects.

Corresponding Author: Prof. Dr. Asli Aykac, PhD, Department of Biophysics, Near East University, Near East Boulevard, Mersin 10, Türkiye, E-mail:

  1. Research ethics: All animal experimental protocols were approved by the Committee of Ethics and Animal Experimentation of the Marmara University, Istanbul, Turkey (protocol number: MUHDEK 64.2020.nov).

  2. Informed consent: Not applicable.

  3. Author contributions: A.A., and D.Ö. and conceived the study design. D.Y.H. was responsible for content analysis and identification of its components. A.A., and D.Ö. were responsible for animal experiments. A.A. was responsible for molecular, biochemical experiments and statistical analysis. Ö.T.Ç.K. was responsible for histological analysis. A.A., and D.Ö. wrote the original draft manuscript. A.A., D.Ö., Ö.T.Ç.K., and D.H.Y read, reviewed, edited and approved the final version of the manuscript.

  4. Use of LLM, AI and MLT: None declared.

  5. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships, which have or could be perceived to have influenced the work reported in this article.

  6. Research funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  7. Data availability: The authors confirm that the data supporting the findings of this study are available within the article. Data supporting the findings of this study are available from the corresponding author when necessary conditions.

References

1. McDowell, C, Farooq, U, Haseeb, M. Inflammatory bowel disease. In: StatPearls. Treasure Island, FL, USA: StatPearls Publishing; 2023.Search in Google Scholar

2. Caballero-Mateos, AM. Gut feelings: the psychological impact of inflammatory bowel disease. J Clin Med 2023;12:3867. https://doi.org/10.3390/jcm12123867.Search in Google Scholar PubMed PubMed Central

3. Wehkamp, J, Stange, EF. Recent advances and emerging therapies in the non-surgical management of ulcerative colitis. F1000Res 2018;7. F1000 Faculty Rev-1207. https://doi.org/10.12688/f1000research.15159.1.Search in Google Scholar PubMed PubMed Central

4. Zhou, Y, Wang, D, Yan, W. Treatment effects of natural products on inflammatory bowel disease in vivo and their mechanisms: based on animal experiments. Nutrients 2023;15:1031. https://doi.org/10.3390/nu15041031.Search in Google Scholar PubMed PubMed Central

5. Wan, Y, Yang, L, Jiang, S, Qian, D, Duan, J. Excessive apoptosis in ulcerative colitis: crosstalk between apoptosis, ROS, ER stress, and intestinal homeostasis. Inflamm Bowel Dis 2022;28:639–48. https://doi.org/10.1093/ibd/izab277.Search in Google Scholar PubMed

6. Saez, A, Herrero-Fernandez, B, Gomez-Bris, R, Sánchez-Martinez, H, Gonzalez-Granado, JM. Pathophysiology of inflammatory bowel disease: innate immune system. Int J Mol Sci 2023;24:1526. https://doi.org/10.3390/ijms24021526.Search in Google Scholar PubMed PubMed Central

7. Azab, A, Nassar, A, Azab, AN. Anti-inflammatory activity of natural products. Molecules 2016;21:1321. https://doi.org/10.3390/molecules21101321.Search in Google Scholar PubMed PubMed Central

8. El-Naggar, ME, Hussein, J, El-Sayed, S, Youssef, AM, El Bana, M, Latif, YA, et al.. Protective effect of the functional yogurt based on Malva parviflora leaves extract nanoemulsion on acetic acid-induced ulcerative colitis in rats. J Mat Res Technol 2020;9:14500–8. https://doi.org/10.1016/j.jmrt.2020.10.047.Search in Google Scholar

9. Cao, SY, Ye, SJ, Wang, WW, Wang, B, Zhang, T, Pu, YQ. Progress in active compounds effective on ulcerative colitis from Chinese medicines. Chin J Nat Med 2019;17:81–102. https://doi.org/10.1016/s1875-5364(19)30012-3.Search in Google Scholar

10. Liu, C, Zeng, Y, Wen, Y, Huang, X, Liu, Y. Natural products modulate cell apoptosis: a promising way for the treatment of ulcerative colitis. Front Pharmacol 2022;31:806148. https://doi.org/10.3389/fphar.2022.806148.Search in Google Scholar PubMed PubMed Central

11. Pellati, F, Orlandini, G, van Leeuwen, KA, Anesin, G, Bertelli, D, Paolini, M, et al.. Gas chromatography combined with mass spectrometry, flame ionization detection and elemental analyzer/isotope ratio mass spectrometry for characterizing and detecting the authenticity of commercial essential oils of Rosa damascena Mill. Rapid Commun Mass Spectrom 2013;27:591–602. https://doi.org/10.1002/rcm.6489.Search in Google Scholar PubMed

12. Baser, KHC, Altintas, A, Kürkçüoglu, M. A review of the history, ethnobotany, and modern uses of rose petals, rose oil, rose water, and other rose products. HerbalGram 2012;96:40–53.Search in Google Scholar

13. Nunes, HS, Miguel, MG. Rosa damascena essential oils: a brief review about chemical composition and biological properties. Trends Phytochem Res 2017;1:111–28.Search in Google Scholar

14. Dadkhah, A, Fatemi, F, Malayeri, MRM, Ashtiyani, MHK, Noureini, SK, Rasooli, A. Considering the effect of Rosa damascene essential oil on oxidative stress and COX-2 gene expression in liver of septic rats. Turk J Pharm Sci 2019;16:16–24.10.4274/tjps.galenos.2018.58815Search in Google Scholar PubMed PubMed Central

15. Karakoyun, B, Ertaş, B, Yüksel, M, Akakın, D, Çevik, Ö, Şener, G. Ameliorative effects of riboflavin on acetic acid-induced colonic injury in rats. Clin Exp Pharmacol Physiol 2018;45:563–72. https://doi.org/10.1111/1440-1681.12894.Search in Google Scholar PubMed

16. Yadav, V, Varum, F, Bravo, R, Furrer, E, Bojic, D, Basit, AW. Inflammatory bowel disease: exploring gut pathophysiology for novel therapeutic targets. Transl Res 2016;176:38–68. https://doi.org/10.1016/j.trsl.2016.04.009.Search in Google Scholar PubMed

17. Latifi, G, Ghannadi, A, Minaiyan, M. Anti-inflammatory effect of volatile oil and hydroalcoholic extract of Rosa damascena Mill. on acetic acid-induced colitis in rats. Res Pharm Sci 2015;10:514–22.Search in Google Scholar

18. Rashidian, A, Roohi, P, Mehrzadi, S, Ghannadi, AR, Minaiyan, M. Protective effect of Ocimum basilicum essential oil against acetic acid-induced colitis in rats. J Evid Based Compl Altern Med 2016;21:36–42. https://doi.org/10.1177/2156587215616550.Search in Google Scholar PubMed

19. Rashidian, A, Rashki, A, Abdollahi, A, Haddadi, NS, Chamanara, M, Mumtaz, F, et al.. Dapsone reduced acetic acid-induced inflammatory response in rat colon tissue through inhibition of NF-kB signaling pathway. Immunopharmacol Immunotoxicol 2019;41:607–13. https://doi.org/10.1080/08923973.2019.1678635.Search in Google Scholar PubMed

20. Hajhashemi, V, Ghannadi, A, Hajiloo, M. Analgesic and anti-inflammatory effects of Rosa damascena hydroalcoholic extract and its essential oil in animal models. Iran J Pharm Res (IJPR) 2010;9:163–8.Search in Google Scholar

21. Soliman, NA, Keshk, WA, Rizk, FH, Ibrahim, MA. The possible ameliorative effect of simvastatin versus sulfasalazine on acetic acid induced ulcerative colitis in adult rats. Chem Biol Interact 2019;298:57–65. https://doi.org/10.1016/j.cbi.2018.11.002.Search in Google Scholar PubMed

22. Soliman, SM, Wadie, W, Shouman, SA, Ainshoka, AA. Sodium selenite ameliorates both intestinal and extra-intestinal changes in acetic acid-induced colitis in rats. Naunyn-Schmiedeberg’s Arch Pharmacol 2018;391:639–47. https://doi.org/10.1007/s00210-018-1491-7.Search in Google Scholar PubMed

23. Mohamed, NI, Suddek, GM, El-Kashef, DH. Molsidomine alleviates acetic acid-induced colitis in rats by reducing oxidative stress, inflammation and apoptosis. Int Immunopharmacol 2021;99:108005. https://doi.org/10.1016/j.intimp.2021.108005.Search in Google Scholar PubMed

24. Lowry, OH, Rosebrough, NJ, Farr, AL, Randall, RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265–75. https://doi.org/10.1016/s0021-9258(19)52451-6.Search in Google Scholar

25. Aykaç, A, Gören, M, Cabadak, H. Altered ratio of proapoptotic and antiapoptotic proteins in different brain regions of female rats in model of post-traumatic stress disorder. TJB 2015;40:1–7. https://doi.org/10.5505/tjb.2015.50479.Search in Google Scholar

26. Yu, YR, Rodriguez, JR. Clinical presentation of Crohn’s, ulcerative colitis, and indeterminate colitis: symptoms, extraintestinal manifestations, and disease phenotypes. Semin Pediatr Surg 2017;26:349–55. https://doi.org/10.1053/j.sempedsurg.2017.10.003.Search in Google Scholar PubMed

27. Falcão, TR, de Araújo, AA, Soares, LAL, de Moraes Ramos, RT, Bezerra, ICF, Ferreira, MRA, et al.. Crude extract and fractions from Eugenia uniflora Linn leaves showed anti-inflammatory, antioxidant, and antibacterial activities. BMC Compl Alternative Med 2018;18:84. https://doi.org/10.1186/s12906-018-2144-6.Search in Google Scholar PubMed PubMed Central

28. Santana, MT, Cercato, LM, Oliveira, JP, Camargo, EA. Medicinal plants in the treatment of colitis: evidence from preclinical studies. Planta Med 2017;83:588–614. https://doi.org/10.1055/s-0043-104933.Search in Google Scholar PubMed

29. Bastaki, SMA, Amir, N, Adeghate, E, Ojha, S. Nerolidol, a sesquiterpene, attenuates oxidative stress and inflammation in acetic acid-induced colitis in rats. Mol Cell Biochem 2021;476:3497–512. https://doi.org/10.1007/s11010-021-04094-5.Search in Google Scholar PubMed

30. El Morsy, EM, Kamel, R, Ahmed, MA. Attenuating effects of coenzyme Q10 and amlodipine in ulcerative colitis model in rats. Immunopharmacol Immunotoxicol 2015;37:244–51. https://doi.org/10.3109/08923973.2015.1021357.Search in Google Scholar PubMed

31. Jayaganesh, R, Pugalendhi, P, Murali, R. Effect of citronellol on NF-kB inflammatory signaling molecules in chemical carcinogen-induced mammary cancer in the rat model. J Biochem Mol Toxicol 2020;34:e22441. https://doi.org/10.1002/jbt.22441.Search in Google Scholar PubMed

32. Soubh, AA, Abdallah, DM, El-Abhar, HS. Geraniol ameliorates TNBS-induced colitis: involvement of Wnt/β-catenin, p38MAPK, NFκB, and PPARγ signaling pathways. Life Sci 2015;136:142–50. https://doi.org/10.1016/j.lfs.2015.07.004.Search in Google Scholar PubMed

33. Medicherla, K, Sahu, BD, Kuncha, M, Kumar, JM, Sudhakar, G, Sistla, R. Oral administration of geraniol ameliorates acute experimental murine colitis by inhibiting pro-inflammatory cytokines and NF-κB signaling. Food Funct 2015;6:2984–95. https://doi.org/10.1039/c5fo00405e.Search in Google Scholar PubMed

34. Sadraei, H, Asghari, G, Emami, S. Inhibitor effect of Rosa damascena Mill. flower essential oil, geraniol, citronellol on rat ileum contraction. Res Pharm Sci 2013;8:17–23.Search in Google Scholar

35. Katsukawa, M, Nakata, R, Koeji, S, Hori, K, Takahashi, S, Inoue, H. Citronellol and geraniol, components of rose oil, activate peroxisome proliferator-activated receptor α and ã and suppress cyclooxygenase-2 expression. Biosci Biotechnol Biochem 2011;75:1010–2. https://doi.org/10.1271/bbb.110039.Search in Google Scholar PubMed

36. Sanchez-Munoz, F, Dominguez-Lopez, A, Yamamoto-Furusho, JK. Role of cytokines in inflammatory bowel disease. World J Gastroenterol 2008;14:4280–8. https://doi.org/10.3748/wjg.14.4280.Search in Google Scholar PubMed PubMed Central

37. González, R, Rodríguez, S, Romay, C, Ancheta, O, González, A, Armesto, J, et al.. Anti-inflammatory activity of phycocyanin extract in acetic acid-induced colitis in rats. Pharmacol Res 1999;39:55–9. https://doi.org/10.1006/phrs.1998.0409.Search in Google Scholar PubMed

38. Gautam, MK, Goel, S, Ghatule, RR, Singh, A, Nath, G, Goel, RK. Curative effect of Terminalia chebula extract on acetic acid-induced experimental colitis: role of antioxidants, free radicals and acute inflammatory marker. Inflammopharmacology 2013;21:377–83. https://doi.org/10.1007/s10787-012-0147-3.Search in Google Scholar PubMed

39. Becker, C, Watson, AJ, Neurath, MF. Complex roles of caspases in the pathogenesis of inflammatory bowel disease. Gastroenterology 2013;144:283–93. https://doi.org/10.1053/j.gastro.2012.11.035.Search in Google Scholar PubMed

40. Najafi, A, Motaghi, E, Hosseini, MJ, Ghasemi-Pirbaluti, M. The effect of sodium valproate on acetic acid-induced colitis in rats. Inflammopharmacology 2017;25:137–45. https://doi.org/10.1007/s10787-016-0304-1.Search in Google Scholar PubMed

41. Shen, J, Cheng, J, Zhu, S, Zhao, J, Ye, Q, Xu, Y, et al.. Regulating effect of baicalin on IKK/IKB/NF-kB signaling pathway and apoptosis-related proteins in rats with ulcerative colitis. Int Immunopharmacol 2019;73:193–200. https://doi.org/10.1016/j.intimp.2019.04.052.Search in Google Scholar PubMed

42. Ward, C, Dransfield, I, Chilvers, ER, Haslett, C, Rossi, AG. Pharmacological manipulation of granulocyte apoptosis: potential therapeutic targets. Trends Pharmacol Sci 1999;20:503–9. https://doi.org/10.1016/s0165-6147(99)01391-7.Search in Google Scholar PubMed

43. Bertolotto, M, Dallegri, F, Dapino, P, Quercioli, A, Pende, A, Ottonello, L, et al.. Sulphasalazine accelerates apoptosis in neutrophils exposed to immune complex: role of caspase pathway. Clin Exp Pharmacol Physiol 2009;36:1132–5. https://doi.org/10.1111/j.1440-1681.2009.05215.x.Search in Google Scholar PubMed

44. Oerlemans, R, Vink, J, Dijkmans, BA, Assaraf, YG, van Miltenburg, M, van der Heijden, J, et al.. Sulphasalazine sensitizes human monocytic/macrophage cells for glucocorticoids by upregulation of glucocorticoid receptor alpha and glucocorticoid induced apoptosis. Ann Rheum Dis 2007;66:1289–95. https://doi.org/10.1136/ard.2006.060509.Search in Google Scholar PubMed PubMed Central

45. Chelakkot, C, Ghim, J, Ryu, SH. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med 2018;50:1–9. https://doi.org/10.1038/s12276-018-0126-x.Search in Google Scholar PubMed PubMed Central

46. Saber, S, Khalil, RM, Abdo, WS, Nassif, D, El-Ahwany, E. Olmesartan ameliorates chemically-induced ulcerative colitis in rats via modulating NFκB and Nrf-2/HO-1 signaling crosstalk. Toxicol Appl Pharmacol 2019;364:120–32. https://doi.org/10.1016/j.taap.2018.12.020.Search in Google Scholar PubMed

47. Sedger, LM, McDermott, MF. TNF and TNF-receptors: from mediators of cell death and inflammation to therapeutic giants - past, present and future. Cytokine Growth Factor Rev 2014;25:453–72. https://doi.org/10.1016/j.cytogfr.2014.07.016.Search in Google Scholar PubMed

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/tjb-2024-0166).

Received: 2024-07-09
Accepted: 2025-01-02
Published Online: 2025-02-24

© 2025 the author(s), published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/tjb-2024-0166
Keywords for this article
Rosa damascena Mill.; ulcerative colitis; mitochondrial-mediated apoptosis; acetic acid; caspase
Creative Commons
BY 4.0

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Interaction of fetuin-A with obesity related insulin resistance and diabetes mellitus
  4. Research Articles
  5. Preanalytical errors in pediatric blood sampling: a systematic review of common challenges and risks
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  7. Investigation into drug resistance to cisplatin in cancer stem cell-enriched population in non-small cell lung cancer
  8. The cytotoxic and antiproliferative effect of Polygala saponin XLIV on the human colorectal carcinoma cell line
  9. Development of HEK293T cell reference materials for β-thalassemia genetic testing using prime editing
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  21. Assessment of blood collection competency in phlebotomists: a survey study
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