The Metabolomic Profile of the Essential Oil from Zanthoxylum caribaeum (syn. chiloperone) Growing in Guadeloupe FWI using GC × GC-TOFMS

The essential oil (EO) from the leaves of Zanthoxylum caribaeum (syn. Chiloperone) (Rutaceae) was studied previously for its acaricidal, antimicrobial, antioxidant, and insecticidal properties. In prior studies, the most abundant compound class found in leaf oils from Brazil, Costa Rica, and Paraguay was terpenoids. Herein, essential oil from the leaves of Zanthoxylum caribaeum (prickly yellow, bois chandelle blanc (FWI), peñas Blancas (Costa Rica), and tembetary hu (Paraguay)) growing in Guadeloupe was analyzed with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS), and thirty molecules were identified. A comparison with previously published leaf EO compositions of the same species growing in Brazil, Costa Rica, and Paraguay revealed a number of molecules in common such as β-myrcene, limonene, β-caryophyllene, α-humulene, and spathulenol. Some molecules identified in Zanthoxylum caribaeum from Guadeloupe showed some antimetabolic effects on enzymes; the in-depth study of this plant and its essential oil with regard to metabolic diseases merits further exploration.


Introduction
Medicinal plants contribute significantly to primary health care due to cultural traditions [1] and the lack of access to and affordability of pharmaceuticals. In addition, natural products are potential sources of new and selective agents for the treatment of important tropical diseases [2][3][4]. Nowadays, the search for effective molecules for chronic disease treatments, such as metabolic disorders, has increased, and plants may offer innovative approaches to treat and prevent diseases [5].
Zanthoxylum is a genus of Rutaceae, a widely studied family having a worldwide distribution mainly in tropical and subtropical regions. Many species of the Zanthoxylum genus have been extensively studied due to their large role in the traditional medicine of various cultures [6][7][8]. These species have demonstrated larvicidal, antiinflammatory, analgesic, antinociceptive, antioxidant, antibiotic, hepatoprotective, antiplasmodial, cytotoxic, antiproliferative, anthelminthic, antiviral, anticonvulsant, and antifungal properties [9]. The extracts and essential oils (EOs) derived from these plants have been used to test for these properties. For example, canthin-6-ones in Zanthoxylum chileperone (prickly yellow, bois chandelle blanc (FWI), peñas Blancas (Costa Rica), and tembetary hu (Paraguay)) grown in Paraguay was assessed for the treatment of mice with Chagas disease. An extract of Zanthoxylum chileperone stem bark demonstrated antiTrypanosomacruzi activity [7]. The reported variety of beneficial properties in the Zanthoxylum species has motivated past studies

Essential oil
The fresh leaves (751 g) were washed with distilled water, chopped, and hydrodistilled for 2 h 20 min using a Clevenger hydrodistillation apparatus coupled with a microwave reactor (ETHOS X, Milestone ® , Sorisole, Italy). This setup allowed for heating at 100°C with a power of 1700 watts. The essential oil was collected and then stored under refrigeration and in the dark at an average temperature of 4°C until it was analyzed.

Essential Oil
The fresh leaves (751 g) were washed with distilled water, chopped, and hydrodistilled for 2 h 20 min using a Clevenger hydrodistillation apparatus coupled with a microwave reactor (ETHOS X, Milestone ® , Sorisole, Italy). This setup allowed for heating at 100 • C with a power of 1700 watts. The essential oil was collected and then stored under refrigeration and in the dark at an average temperature of 4 • C until it was analyzed.

HS-SPME-GC × GC-TOFMS
The ZC essential oil (20 µL) was added to 20 mL headspace vials (VWR, CA), and the vials were capped with magnetic screw caps containing septa (Canadian Life Sciences, CA, Canada). Headspace solid-phase microextraction (HS-SPME) was accomplished using an automated SPME module (Gerstel, Linthicum, MD, USA). A tri-mode fibre (50/30 µm DVB/CAR/PDMS; divinylbenzene/carboxen on polydimethylsiloxane, Millipore Sigma, St. Louis, MO, USA) was used to extract the headspace above the EO samples. The fibre was initially conditioned according to the manufacturer's guidelines. The EO samples were incubated at 60 • C for 5 min to allow for the volatile organic compounds (VOCs) to partition into the headspace. The headspace was extracted for 20 min while the sample was heated at 60 • C. Fibre desorption was achieved by maintaining 250 • C at the septumless head (SLH) of the Cooled Injection System-Programmable Temperature Vaporizing (CIS-PTV) inlet (Gerstel) for 180 s. The GC × GC-TOFMS system consisted of an Agilent 7890 (Agilent Technologies, Palo Alto, CA, USA) gas chromatograph and a Pegasus 4D TOFMS (LECO, St. Joseph, MI, USA) with a quad jet liquid nitrogen-cooled thermal modulator. The first dimension (1D) column was a 5% phenyl polysilphenylene-siloxane phase (Rtx ® -5MS; 60 m × 0.25 mm i.d.; 0.25 µm film thickness) connected with a SilTiteTM µ-Union (Trajan Scientific and Medical, Victoria, Australia) to a second dimension (2D) trifluoropropylmethylpolysiloxane-type phase (Rtx-200; 1.6 m × 0.25 mm i.d.; 0.25 µm film thickness). All columns were from the Restek Corporation (Restek Corp., Bellefonte, PA, USA). The 2D column was installed in a separate oven located inside the main GC oven. The carrier gas was helium at a corrected constant flow rate of 2 mL/min, and the injector operated in the splitless mode. The main oven temperature program was 40 • C (3 min hold) with a ramp of 3.5 • C/min to 190 • C (no hold) and a final ramp of 15 • C/min to 290 • C (12 min hold). The secondary oven was programmed with a constant +5 • C offset relative to the primary oven. The modulation period was 2.50 s (0.40 s hot pulse and 0.85 s cold pulse) with a +15 • C offset relative to the secondary oven. Mass spectra were acquired in the range of m/z 40-800 for 200 spectra/s. The ion source temperature was set at 200 • C, and the transfer line temperature was set at 240 • C. The detector voltage was run at an offset of −200 V relative to the tuning potential, and the ionization electron energy (EI source) was set at 70 eV. Samples were acquired using LECO ChromaTOF ® software version 4.72.0.0(LECO, St. Joseph, MI, USA). The data were processed using LECO ChromaTOF ® software version 4.71.0.0(LECO, St. Joseph, MI, USA). The expected peak width settings in the 1D and 2D were 12.5 s and 0.16 s, respectively. The peaks were detected from the raw chromatogram using a minimum signal-to-noise (S/N) ratio value of 100 with a minimum sub-peak S/N of 6. The minimum match required to combine sub-peaks was 600. The identities of the peaks were tentatively assigned based on mass spectral similarity matches (>700) against library spectra and temperature-programmed retention index matches (±15 RI window; when available in PubChem). The retention indices (RIs) were calculated using n-alkanes from C7-C22 in a separate analysis under the same extraction and GC × GC-TOFMS conditions. Mass-spectral library searches were performed against the NIST/EPA/NIH Mass Spectral Library (NIST 17) and Wiley Registry of Mass Spectral Data (9th edition). The peak areas were integrated with unique m/z. The filtering scripts for the GC × GC-TOFMS data [34] automatically and rapidly identified the chemical classes of interest.

HS-SPME-GC × GC-TOFMS Analysis and Comparison
The goal of this study was to compare the volatile metabolite profile of the essential oil of yellow prickly ash (Z. caribaeum) grown in Guadeloupe (Figure 1) to the ZC essential oils from other regions. Herein, GC × GC-TOFMS was used to facilitate the detection of the previously identified Z. caribaeum VOCs and the uncharacterized VOCs of potential interest. Automated filtering scripts for the GC × GC-TOFMS data were applied to the obtained chromatograms to classify the chemical families. GC × GC-TOFMS chromatograms could be read similarly to a contour map. The colors emerge at the reader based on the color scale on the left of the image. Dark blue denotes the baseline or background, while red denotes high intensity (i.e., amount). Each peak or "blob" that the reader sees represents one compound on the two-dimensional plot. A chromatogram with script bubbles is provided in Figure 2. Filtering scripts are able to classify four major chemical families: alcohols, aldehydes, ketones, and terpenoids. The large band in the middle of the chromatogram is 2undecanone, a ketone in such high abundance that detection yields a large streak. Other ketones, alcohols, aldehydes, and terpenoids were present in the essential oil but in far lesser amounts. Terpenoids were the most common compound class detected with the GC × GC-TOFMS, and were subject to further exploration. A number of terpenoids were tentatively identified based on the MS and RI matches, and a labelled extracted ion chromatogram is shown in Figure 3. Filtering scripts are able to classify four major chemical families: alcohols, aldehydes, ketones, and terpenoids. The large band in the middle of the chromatogram is 2-undecanone, a ketone in such high abundance that detection yields a large streak. Other ketones, alcohols, aldehydes, and terpenoids were present in the essential oil but in far lesser amounts. Terpenoids were the most common compound class detected with the GC × GC-TOFMS, and were subject to further exploration. A number of terpenoids were tentatively identified based on the MS and RI matches, and a labelled extracted ion chromatogram is shown in Figure 3.
ketones, and terpenoids. The large band in the middle of the chromatogram is 2undecanone, a ketone in such high abundance that detection yields a large streak. Other ketones, alcohols, aldehydes, and terpenoids were present in the essential oil but in far lesser amounts. Terpenoids were the most common compound class detected with the GC × GC-TOFMS, and were subject to further exploration. A number of terpenoids were tentatively identified based on the MS and RI matches, and a labelled extracted ion chromatogram is shown in Figure 3. The essential oil of the fresh leaves of ZC was recovered in a 0.06% yield, and the terpenoid compounds are displayed in Table 1. Thirty terpenoids were tentatively identified and numbered according to their retention orders in Figure 3 and Table 1. The relative amounts of each terpenoid are provided as a percentage of the total identified terpenoid peak areas.  The essential oil of the fresh leaves of ZC was recovered in a 0.06% yield, and the terpenoid compounds are displayed in Table 1. Thirty terpenoids were tentatively identified and numbered according to their retention orders in Figure 3 and Table 1. The relative amounts of each terpenoid are provided as a percentage of the total identified terpenoid peak areas.  The essential oil of the fresh leaves of ZC was recovered in a 0.06% yield, and the terpenoid compounds are displayed in Table 1. Thirty terpenoids were tentatively identified and numbered according to their retention orders in Figure 3 and Table 1. The relative amounts of each terpenoid are provided as a percentage of the total identified terpenoid peak areas.  The essential oil of the fresh leaves of ZC was recovered in a 0.06% yield, and the terpenoid compounds are displayed in Table 1. Thirty terpenoids were tentatively identified and numbered according to their retention orders in Figure 3 and Table 1. The relative amounts of each terpenoid are provided as a percentage of the total identified terpenoid peak areas.  The essential oil of the fresh leaves of ZC was recovered in a 0.06% yield, and the terpenoid compounds are displayed in Table 1. Thirty terpenoids were tentatively identified and numbered according to their retention orders in Figure 3 and Table 1. The relative amounts of each terpenoid are provided as a percentage of the total identified terpenoid peak areas. The three most abundant compounds of the thirty identified terpenoids were βcaryophyllene (33.23%), cis-carvyl acetate (18.88%), and β-damascenone (10.78%). Other identified terpenoids ranged from 0.03% to 5.20% of the total terpenoid peak area. Onethird of the identified terpenoids are common with ZC's leaves' EO from different tropical countries (Paraguay [10], Costa Rica [15], and Brazil [11][12][13][14]16]). Limonene and βcaryophyllene were present in ZC's leaves' EO in all regions. Limonene was reported with a low yield of 0.3% and 0.42% in the EO species located in Paraguay [10] and Brazil [12], whereas this molecule was one of the most abundant compounds identified in the species from Costa Rica with a yield of 16.7% [15]. Unlike the current work, β-caryophyllene was reported with a low yield of 0.5% by Guy et al. [10] (Paraguay) and an approximate 4% yield in species located in Costa Rica [15] and Brazil [11,13,14]. β-myrcene, α-humulene, α-selinene, and spathulenol were also reported many times in the EOs from these three different countries. Caryophyllene oxide molecules occurred at least once in ZC's leaves' EO located in Paraguay. In the current work, nearly twenty molecules are either not listed elsewhere or present in another form, i.e., a different oxidation state or a different isomer. α-muurolene was identified as Γ-muurolene in the species located in Brazil [11,13,14], and 3-eudesmen-11-ol was identified as eudesm-11-en-1-ol by Souza et al. [16]. This comparison shows that the same species has a very high variability in its composition across origins.

Antimetabolic effects of some molecules
Several studies have shown the biological properties of ZC extracts [35], but very few were interested in the antimetabolic properties of the essential oils extracted from the The three most abundant compounds of the thirty identified terpenoids were βcaryophyllene (33.23%), cis-carvyl acetate (18.88%), and β-damascenone (10.78%). Other identified terpenoids ranged from 0.03% to 5.20% of the total terpenoid peak area. Onethird of the identified terpenoids are common with ZC's leaves' EO from different tropical countries (Paraguay [10], Costa Rica [15], and Brazil [11][12][13][14]16]). Limonene and βcaryophyllene were present in ZC's leaves' EO in all regions. Limonene was reported with a low yield of 0.3% and 0.42% in the EO species located in Paraguay [10] and Brazil [12], whereas this molecule was one of the most abundant compounds identified in the species from Costa Rica with a yield of 16.7% [15]. Unlike the current work, β-caryophyllene was reported with a low yield of 0.5% by Guy et al. [10] (Paraguay) and an approximate 4% yield in species located in Costa Rica [15] and Brazil [11,13,14]. β-myrcene, α-humulene, α-selinene, and spathulenol were also reported many times in the EOs from these three different countries. Caryophyllene oxide molecules occurred at least once in ZC's leaves' EO located in Paraguay. In the current work, nearly twenty molecules are either not listed elsewhere or present in another form, i.e., a different oxidation state or a different isomer. α-muurolene was identified as Γ-muurolene in the species located in Brazil [11,13,14], and 3-eudesmen-11-ol was identified as eudesm-11-en-1-ol by Souza et al. [16]. This comparison shows that the same species has a very high variability in its composition across origins.

Antimetabolic effects of some molecules
Several studies have shown the biological properties of ZC extracts [35], but very few were interested in the antimetabolic properties of the essential oils extracted from the The three most abundant compounds of the thirty identified terpenoids were βcaryophyllene (33.23%), cis-carvyl acetate (18.88%), and β-damascenone (10.78%). Other identified terpenoids ranged from 0.03% to 5.20% of the total terpenoid peak area. Onethird of the identified terpenoids are common with ZC's leaves' EO from different tropical countries (Paraguay [10], Costa Rica [15], and Brazil [11][12][13][14]16]). Limonene and βcaryophyllene were present in ZC's leaves' EO in all regions. Limonene was reported with a low yield of 0.3% and 0.42% in the EO species located in Paraguay [10] and Brazil [12], whereas this molecule was one of the most abundant compounds identified in the species from Costa Rica with a yield of 16.7% [15]. Unlike the current work, β-caryophyllene was reported with a low yield of 0.5% by Guy et al. [10] (Paraguay) and an approximate 4% yield in species located in Costa Rica [15] and Brazil [11,13,14]. β-myrcene, α-humulene, α-selinene, and spathulenol were also reported many times in the EOs from these three different countries. Caryophyllene oxide molecules occurred at least once in ZC's leaves' EO located in Paraguay. In the current work, nearly twenty molecules are either not listed elsewhere or present in another form, i.e., a different oxidation state or a different isomer. α-muurolene was identified as Γ-muurolene in the species located in Brazil [11,13,14], and 3-eudesmen-11-ol was identified as eudesm-11-en-1-ol by Souza et al. [16]. This comparison shows that the same species has a very high variability in its composition across origins.

Antimetabolic effects of some molecules
Several studies have shown the biological properties of ZC extracts [35], but very few were interested in the antimetabolic properties of the essential oils extracted from the The three most abundant compounds of the thirty identified terpenoids were βcaryophyllene (33.23%), cis-carvyl acetate (18.88%), and β-damascenone (10.78%). Other identified terpenoids ranged from 0.03% to 5.20% of the total terpenoid peak area. Onethird of the identified terpenoids are common with ZC's leaves' EO from different tropical countries (Paraguay [10], Costa Rica [15], and Brazil [11][12][13][14]16]). Limonene and βcaryophyllene were present in ZC's leaves' EO in all regions. Limonene was reported with a low yield of 0.3% and 0.42% in the EO species located in Paraguay [10] and Brazil [12], whereas this molecule was one of the most abundant compounds identified in the species from Costa Rica with a yield of 16.7% [15]. Unlike the current work, β-caryophyllene was reported with a low yield of 0.5% by Guy et al. [10] (Paraguay) and an approximate 4% yield in species located in Costa Rica [15] and Brazil [11,13,14]. β-myrcene, α-humulene, α-selinene, and spathulenol were also reported many times in the EOs from these three different countries. Caryophyllene oxide molecules occurred at least once in ZC's leaves' EO located in Paraguay. In the current work, nearly twenty molecules are either not listed elsewhere or present in another form, i.e., a different oxidation state or a different isomer. α-muurolene was identified as Γ-muurolene in the species located in Brazil [11,13,14], and 3-eudesmen-11-ol was identified as eudesm-11-en-1-ol by Souza et al. [16]. This comparison shows that the same species has a very high variability in its composition across origins.

Antimetabolic effects of some molecules
Several studies have shown the biological properties of ZC extracts [35], but very few were interested in the antimetabolic properties of the essential oils extracted from the The three most abundant compounds of the thirty identified terpenoids were βcaryophyllene (33.23%), cis-carvyl acetate (18.88%), and β-damascenone (10.78%). Other identified terpenoids ranged from 0.03% to 5.20% of the total terpenoid peak area. Onethird of the identified terpenoids are common with ZC's leaves' EO from different tropical countries (Paraguay [10], Costa Rica [15], and Brazil [11][12][13][14]16]). Limonene and βcaryophyllene were present in ZC's leaves' EO in all regions. Limonene was reported with a low yield of 0.3% and 0.42% in the EO species located in Paraguay [10] and Brazil [12], whereas this molecule was one of the most abundant compounds identified in the species from Costa Rica with a yield of 16.7% [15]. Unlike the current work, β-caryophyllene was reported with a low yield of 0.5% by Guy et al. [10] (Paraguay) and an approximate 4% yield in species located in Costa Rica [15] and Brazil [11,13,14]. β-myrcene, α-humulene, α-selinene, and spathulenol were also reported many times in the EOs from these three different countries. Caryophyllene oxide molecules occurred at least once in ZC's leaves' EO located in Paraguay. In the current work, nearly twenty molecules are either not listed elsewhere or present in another form, i.e., a different oxidation state or a different isomer. α-muurolene was identified as Γ-muurolene in the species located in Brazil [11,13,14], and 3-eudesmen-11-ol was identified as eudesm-11-en-1-ol by Souza et al. [16]. This comparison shows that the same species has a very high variability in its composition across origins.

Antimetabolic effects of some molecules
Several studies have shown the biological properties of ZC extracts [35], but very few were interested in the antimetabolic properties of the essential oils extracted from the leaves. Some molecules identified in this article were studied for their interesting The three most abundant compounds of the thirty identified terpenoids were βcaryophyllene (33.23%), cis-carvyl acetate (18.88%), and β-damascenone (10.78%). Other identified terpenoids ranged from 0.03% to 5.20% of the total terpenoid peak area. One-third of the identified terpenoids are common with ZC's leaves' EO from different tropical countries (Paraguay [10], Costa Rica [15], and Brazil [11][12][13][14]16]). Limonene and β-caryophyllene were present in ZC's leaves' EO in all regions. Limonene was reported with a low yield of 0.3% and 0.42% in the EO species located in Paraguay [10] and Brazil [12], whereas this molecule was one of the most abundant compounds identified in the species from Costa Rica with a yield of 16.7% [15]. Unlike the current work, β-caryophyllene was reported with a low yield of 0.5% by Guy et al. [10] (Paraguay) and an approximate 4% yield in species located in Costa Rica [15] and Brazil [11,13,14]. β-myrcene, α-humulene, α-selinene, and spathulenol were also reported many times in the EOs from these three different countries. Caryophyllene oxide molecules occurred at least once in ZC's leaves' EO located in Paraguay. In the current work, nearly twenty molecules are either not listed elsewhere or present in another form, i.e., a different oxidation state or a different isomer. α-muurolene was identified as Γ-muurolene in the species located in Brazil [11,13,14], and 3-eudesmen-11-ol was identified as eudesm-11-en-1-ol by Souza et al. [16]. This comparison shows that the same species has a very high variability in its composition across origins.

Manool Antioxidant
Metabolites 2022, 12, x FOR PEER REVIEW 10 of 14 Table 2. Antimetabolic activities of molecules present in Zanthoxylum caribaeum essential oil from Guadeloupe.

β-Caryophyllene
Paraguay [10] Brazil [11][12][13][14] Antiinflammatory and antitumor cis-Carvyl acetate Currently unknown β-Damascenone Currently unknown Carvone Antidiabetic and obesity prevention β-Ionone Anticancer, antitumor, antiinflammatory, antibacterial, antifungal, and antileishmanial Limonene Paraguay [10] Costa Rica [15] Brazil [12] Antidiabetic, antioxidant, and anticarcinogenic Safranal Antioxidant, antidiabetic, and antihyperglycemic Spathulenol Paraguay [10] Brazil [11][12][13][14]16] antidiabetic α-Copaen-11-ol Antidiabetic Manool Antioxidant A recent review conducted by Francomano et al. showed the great biological potential of β-caryophyllene [36]. It is a selective phytocannabinoid agonist of the type 2 receptor CB2, one of the two classical cannabinoid receptors. Among its various biological activities, β-caryophyllene exerts an antiinflammatory action via inhibiting the main inflammatory mediators, such as inducible nitric oxide synthase, interleukin 1 beta, interleukin-6, tumor necrosis factor-alfa, and so on [37]. Several in vitro and in vivo studies have suggested that treatments with β-caryophyllene improved the phenotype of A recent review conducted by Francomano et al. showed the great biological potential of β-caryophyllene [36]. It is a selective phytocannabinoid agonist of the type 2 receptor CB2, one of the two classical cannabinoid receptors. Among its various biological activities, β-caryophyllene exerts an antiinflammatory action via inhibiting the main inflammatory mediators, such as inducible nitric oxide synthase, interleukin 1 beta, interleukin-6, tumor necrosis factor-alfa, and so on [37]. Several in vitro and in vivo studies have suggested that treatments with β-caryophyllene improved the phenotype of animals used to model various inflammatory pathologies, such as nervous system diseases (Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and stroke), atherosclerosis, and tumors (colon, breast, pancreas, lymphoma, melanoma, and glioma cancer). Further insights and clinical trials are required for future human applications. To our knowledge, there are no biological studies investigating cis-carvyl acetate and βdamascenone, but compounds with similar structures, carvone and β-ionone respectively, have interesting biological properties. Bouyahya et al. reviewed the health benefits and pharmacological properties of carvone [38]. This molecule has also demonstrated an antidiabetic effect through its role in the prevention of obesity and metabolic problems associated with high-fat diets. This effect is achieved by improving glycoprotein component abnormalities and controlling glucose metabolism. The potential of β-ionone and related compounds as anticancer agents was reviewed by Ansari et al. [39]. Antitumor activities of β-ionone were demonstrated in melanoma, breast cancer, and chemical-induced rat carcinogenesis. Prostate-specific G protein-coupled receptor (PSGR) activation with its ligand, β-ionone, could suppress prostate cancer cell growth in both in vitro and in vivo models, according to the study by Xie and co-workers [40]. Due to its ability to selectively kill tumor cells and its anti-metastatic and apoptosis induction properties obtained with in vitro and in vivo studies, this molecule and its related compounds could be considered novel candidates in chemopreventive and chemotherapeutic strategies for overcoming cancerous diseases. Along with these potential applications, antiinflammatory, antibacterial, antifungal, and antileishmanial properties were also reported [41].
Although other molecules are present in lower proportions in our study, they have created great interest due to their effects on metabolism. For example, Murali et al. studied the antidiabetic effect of D-limonene in streptozotocin-induced diabetic rats [42]. This molecule was reported to have a number of pharmacological effects, including antioxidant, chemopreventive, and anticarcinogenic properties. A 100 mg/kg body weight D-limonene dose shows more effect on increasing plasma glucose and glycosylated hemoglobin levels. Glucose 6-phosphatase and fructose 1, 6-bisphosphatase enzyme activities were increased, while glucokinase activity was decreased along with liver glycogen in diabetic rats. These results suggest the potential antihyperglycemic activity of D-limonene. Safranal, only identified in ZC's leaves' EO from Guadeloupe, was reported for its antioxidant properties and ability to improve chemically-induced diabetes [43].This compound modulates antioxidant gene expression and upregulates mitochondrial antioxidant genes, leading to a lower mitochondrial oxygen radical generation. This may, in part, induce an improvement in hyperglycemia, hyperlipidemia, and oxidative stress in an experimental model of diabetes [44]. By modulating oxidative stress in streptozotocin-diabetic rats, safranal may also be effective in the treatment of diabetes [45]. Samini et al. reported that safranalmighthave antihyperglycemic effects without hepatic and renal toxicities in alloxan-diabetic rats [44]. Molecular docking studies showed spathulenoland α-copaen-11-ol, compounds identified in Cinnamomum travancoricum leaves' essential oil, play an active role in antidiabetic activity through α-amylase, α-glucosidase, insulin receptors, and insulin secretion protein, GLP-1 [46]. According to Ravera et al., manool could serve as an exogenous antioxidant to prevent oxidative damage in photoreceptors, a risk factor for degenerative retinal diseases. The molecular docking study confirmed that the OxPhos machinery is ectopically expressed in the outer rod segments and that the F1Fo-ATP synthase enzyme is a target of manool, which inhibited the outer segments' ATP synthesis by binding to the F1 moiety with high affinity [47].

Conclusions
This is the first time that the yellow prickly ash, or Zanthoxylum caribaeum (syn. chiloperone), leaves' essential oil from Guadeloupe is reported in the literature. Its metabolite profile was determined to be similar in composition to the same species located in Brazil, Costa Rica, and Paraguay. Numerous compounds were detected, and thirty terpenoids were tentatively identified using GC × GC-TOFMS. Among them, eight of the identified terpenoids pressented antimetabolic properties in the literature. Two of the identified terpenoids have no reported activity, but their structural analogs exhibit antimetabolic effects. GC × GC-TOFMS facilitated a rapid and simple method for profiling the volatile metabolome of yellow prickly. These results suggest the biological potential of Zanthoxylum caribaeum, and provide a preliminary metabolite profile for further study on the essential oil from Guadeloupe. Future work on the metabolomics of the yellow prickly ash should follow this protocol to maximize the number of identifiable VOC metabolites.

Data Availability Statement:
The data presented in this study are available in article.