Analgesic, Antioxidant, Anti-Inflammatory, and Wound-Treating Actions of Bitter Apricot Kernel Extract

Apricot (Prunus armeniaca L.) kernels have been widely employed in phytomedicine for treating different ailments. This study aims to unveil the phytochemical composition by HPLC-ESI-MS, in vitro antioxidant activity, and examine certain pharmacological effects of the hydro-ethanolic extract from bitter apricot kernels (BAK). Obtained results indicated that the BAK extract presents a content of 4.58 ± 0.15 mg GAE/g extract of TPA and 1.68 ± 0.09 mg QUE/g extract of TFA, respectively. HPLC-ESI-MS analysis discovered the presence of 17 phenolic compounds including phenolic acids and flavonoids like 3,4-dihydroxybenzoic acid, gallic acid, caffeic acid, (+)-catechin, epicatechin, and others, with associated antioxidant power. Regarding the studied potential pharmacological effects, notable analgesic activity at a dosage of 100 mg/kg BW was recorded with 63.46% protection. In the anti-inflammatory test, significant inhibition was observed after 6 hours of treatment (77.4%) compared to untreated animals. Moreover, the daily application of ointment formulated with 10% BAK extract resulted in a remarkable healing of wounds and burns in rats. These findings underscore the increasing evidence supporting the potential use of apricot kernel extracts in treating various diseases.


Introduction
Plants have been utilized historically as medicinal remedies for a range of ailments and health disorders.As a potent remedy for numerous ailments, medicinal plants and their by-products continue to hold a signifcant position in modern medicine [1].In recent years, consumers have increasingly expressed concerns regarding the inclusion of synthetic additives, namely, antioxidants butylated hydroxytoluene (BHT) and butylated hydroxy-anisole (BHA) in food.Research has indicated that these commonly used antioxidants can induce DNA damage [2].
Consequently, there has been a signifcant focus on exploring natural sources of efective antioxidant compounds.In this line, recently, extensive eforts have been made to identify compounds with potential antioxidant properties that could serve as suitable replacements for synthetic additives in food, cosmetic, and pharmaceutical industries.Plant species are rich in bio-functional components, such as vitamins, favonoids, carotenoids, and phenolic acids.Tese elements, commonly found in the human diet, have shown robust antioxidant activities [3].
Plants have long been recognized for their potential to alleviate pain and discomfort through their analgesic properties.A wide range of plant species have been studied for their analgesic properties because of their diverse phytochemical substance, which includes phenolics, alkaloids, and terpenoids [4,5].Te analgesic efcacy of these plantderived compounds has been demonstrated in various preclinical and clinical studies [6].Tese bio-based substances exert their analgesic efects through diverse mechanisms, including modulation of neurotransmitter pathways, anti-infammatory actions, and inhibition of pain mediators.Te exploration of plant-based analgesics continues to be an active area of research, with the aim of developing safer and more efective pain management strategies that harness the therapeutic potential of nature's pharmacopeia [7,8].
Infammation is a physiological response of tissue blood vessels to an inciting agent, marked by the infux of fuids and cells into the interstitial spaces.Tis infammatory process is distinguished by cardinal signs, including heat, redness, pain, and loss of function [9].While the causes of infammation may vary, the underlying mechanisms remain consistent across diverse etiologies.Numerous studies have substantiated that in various regions across the world, plants are extensively employed in traditional medicine to alleviate various infammatory disorders [10][11][12][13][14].
Burns continue to be regarded as one of the most challenging medical conditions, impacting individuals across all age groups in both developed and developing countries [15].Wound treatment is a complex and intricate biological process that comprises four essential steps: homeostasis, proliferation, infammation, and maturation.Each phase is important for the complete healing and regeneration of injured tissue, contributing to the successful healing of wounds [16].Several factors can contribute to the delay in the wound repair process, encompassing the size and severity of the wound, the individual's overall health status, and the presence of underlying medical conditions.Additionally, oxidative stress assumes a signifcant role in impeding healing and exacerbating tissue damage [17].
Te apricot species (Prunus armeniaca L.) of the Rosaceae family is not widely distributed because it can only grow in selected areas with ideal environmental conditions.It is native to China and Japan, although it is grown in Morocco and other temperate to subtropical regions around the world [18].Apricot kernels have earned considerable acclaim for their therapeutic potential, and these seeds have been utilized in the treatment of various diseases, including bronchitis, asthma, emphysema, constipation, nausea, leprosy, leukoderma, and pain [19].Furthermore, bitter apricot kernels (BAK) have also demonstrated efcacy in addressing diverse skin conditions [20] and exhibited several pharmacological efects, such as antimicrobial, antioxidant, antiasthmatic, anticancer, antianalgesic, and antiinfammatory activities [21,22].
Ostensibly, no published investigations examine the phytochemicals and pharmacological activities of Moroccan cultivar apricot kernels.Te current study aims to assess the phytochemical profle, anti-infammatory, analgesic, antioxidant, and wound treatment properties of the BAK hydroethanolic extract, aiming to enhance our understanding of its potential therapeutic benefts and explore its applications across diverse domains.

Plant Material.
Apricot fruits (Prunus armeniaca L.) of the Maoui variety were obtained from the Sefrou region Morocco (33 °40′13.6″N 4 °51′28.7″W) in June 2022.Te studied plant was recognized by Pr.Amina Bari, a Botanist from Sidi Mohamed Ben Abdellah University (USMBA), and the voucher specimen was under the following code: RPA 001 VM 226 SL.Te stones were removed from the fruits, and the kernels were extracted and dried for one week at ambient temperature.Finally, the kernels were stranded into a fne powder utilizing an electric mixer and the powder was kept at 4 °C until used.
2.3.Extract Preparation.10 g of BAK powder was saturated in 100 mL of 70% ethanol-water (v/v) for 48 h with continuous agitation at 200 rpm.After fltration with Whatman flter paper (no.1), the obtained fltrate was dried (yield: 6.25% of BAK), and the resultant extract was kept at 4 °C for further experiments [23].

Determination of Total Phenolic Amount (TPA).
Te method outlined by Amin et al. was used to calculate the TPA of the examined extract [24].For the experiment, 500 μL of Folin-Ciocalteu reagent was mixed with 100 μL of the diluted sample, and then, 400 μL of sodium carbonate (7.5% w/v) was added to the obtained mixture.Te absorbance was measured at 760 nm after two hours of incubation in the dark at room temperature.TPA was estimated by making a calibration curve with gallic acid (y � 3.0533x + 0.045; R 2 � 0.99), and it was calculated as milligrams of gallic acid equivalent per gram of extract (mg GAE/g extract).

Determination of Total Flavonoid Amount (TFA).
Te TFA was determined using the aluminum chloride colorimetric method previously described by Bahorun et al. [25] with some changes.To test, 1.5 mL of the BAK extract was mixed with 1.5 mL of 2% AlCl 3 .Following a 30-minute incubation in the dark, the absorbance was measured at 430 nm.Te TFA was calculated with a calibration curve prepared with quercetin (y � 41.129x + 0.1506; R 2 � 0.99) and expressed as milligrams of quercetin equivalent per gram of extract (mg QUE/g extract).Te antioxidant efect of the hydro-ethanolic extract was measured with the free radical scavenging method using stable 2,2′-diphenyl-1-picrylhydrazyl radical solution (DPPH at 150 μM) and prepared in ethanol with an absorbance of 0.700 ± 0.01 at 517 nm [26].To begin the test, a sequence of dilutions (2-fold) was created across 10 test tubes.Subsequently, 50 μL of diverse concentrations of the BAK extract was introduced into 825 μL of the DPPH solution.After 20 minutes without light at room temperature, the absorbance was measured at 517 nm.Ascorbic acid served as the standard solution.Equation ( 1) was used to determine the percentage of DPPH radical inhibition.Te DPPH inhibition concentration at 50% (IC 50 ) was determined by examining the graph indicating the extract's inhibition percentage and expressed in milligrams of extract per mL (mg/mL): where Abc represents the absorbance of the control and Abs represents the absorbance of the BAK extract or ascorbic acid.

Antioxidant Reducing Power Assay (RP).
Te ferric reducing antioxidant power of the BAK extract was estimated following the protocol of Oyaizu [27].Briefy, a sample of 0.2 mL was mixed with 0.5 mL of phosphate bufer solution (0.2 M, pH 6.6) and 0.5 mL of potassium ferricyanide (1%) (w/v).After 20 minutes in a 50 °C water bath, 0.5 mL of trichloroacetic acid (10%) (w/v) was supplemented, and the formulation was centrifuged at 3000 rpm for 10 minutes.Next, 0.5 mL of the supernatant was mixed with 0.5 mL of water distillated and 0.1 mL of a FeCl 3 solution (0.1%) (w/v), and the absorbance of the mixture was determined at 700 nm.Te resulting data were expressed as efective concentrations.From the graph, the median effective concentration (EC 50 ) was calculated and expressed as milligrams of extract per mL (mg/mL).).Tey had unrestricted access to tap water and food throughout the duration of the experiment.Te ethical protocols followed in this study were approved by our institution's animal protection committee, in accordance with the guidelines outlined in the ethical approval registration under the number L.20.USMBA-SNAMOPEQ 2020-03.

Analgesic Activity.
To assess potential peripheral effects stemming from the hydro-ethanolic of BAK extract, the acetic acid-induced writhing test was implemented in accordance with the methodology detailed by Okun and Liddon [28].A total of ffteen mice, comprising both sexes and weighing between 20 and 25 g, were utilized for the study and systematically divided into three groups, each consisting of fve mice (n � 5): Group 1: normal saline solution, 0.9% NaCl (control) Group 2: diclofenac, 25 mg/kg of body weight (b.wt) (analgesic standard) Group 3: hydro-ethanolic BAK extract, 100 mg/kg b.wt Tirty minutes after the administration of tested substances, each mouse received an intraperitoneal injection of 0.1 mL/10 g b.wt of a 0.7% acetic acid solution.Subsequently, the mice were positioned within transparent observation boxes for the purpose of scrutinizing writhing responses, encompassing manifestations such as contraction of abdominal musculature, trunk twisting, back arching, hind limb extension, and torsion to one side resulting in the mouse's belly contacting the foor, during 30 minutes.All mice's writhes were counted within a period of thirty minutes, and the formula below (2) was utilized to calculate the protection percentage (%) against writhing.
where Mc represents the abdominal contraction's mean number in the control group and Mt represents the standard group or BAK extract-treated group.
2.6.3.Anti-Infammatory Activity.BAK extract was tested for anti-infammatory efects following the procedure outlined previously [29].Fifteen Wistar rats weighing between 200 and 230 g were used for the study and separated into three equal groups, each group consisting of fve rats (n � 5): Group 1: normal saline solution, 0.9% NaCl (control) Group 2: indomethacin 10 mg/kg b.wt (standard) Group 3: hydro-ethanolic BAK extract (100 mg/kg) Advances in Pharmacological and Pharmaceutical Sciences Tirty minutes after the administration of the tested compounds, all rats received a subcutaneous injection of carrageenan (0.5%) in their right paw, with a volume of 0.1 mL to induce edema.A digital Vernier caliper (Moge, PRC) was used to measure each rat's paw thickness (in millimeters) at 2, 3, 4, 5, and 6 hours.Te paw thickness measurement is commonly used as a reliable indicator of infammation in experimental studies [30].Te percentage of infammation inhibition (PI) was calculated as follows: Te mean diameter of the paw before injection was represented by D0 and after the injection of carrageenan at a given time by Dt.

Wound Healing
(1) Preparation of Ointment.Te process elucidated by Mssillou et al. [31] was followed in order to prepare the ointment.Nine grams of Vaseline ® (Unilever, UAE) was mixed with one gram of hydro-ethanolic extract of BAK.Te mixtures were transferred to glass beakers placed in a water bath at 50 °C and were stirred continuously until thoroughly mixed.Up to use, the ointment was kept at 4 °C.
(2) Wound Healing Activity.Wound healing activity of the studied extract was evaluated on both male and female Wister rats following the protocol as described by Mssillou et al. [31].Briefy, the rats were separated into three groups, each group contained three rats, and then, the animal's dorsum hair was shaved and anesthetized by intraperitoneal injection with Pentobarbital (50 mg/kg b.wt).In order to create a deep second-degree burn, a metal cylinder with 3 cm in diameter and heated at 100 °C was used.Te ointments were applied daily to the whole wound surface for 21 days starting 24 hours after the burns were performed.
Group 1: Vaseline ® (control) Group 2: Biafne ® 1% (standard) Group 3: Ointment formulated with 10% of BAK hydro-ethanolic extract Te results were taken daily for three weeks.All rats were kept under standard laboratory conditions [32] and obtained the same food and drink during the study period.ImageJ software was used to analyze the obtained images, and equation ( 4) was utilized to measure the rate of contraction of the wound surfaces (Wc).
Te wound's size on the frst day was represented by Ws0 and on each specifc day by Ws1.

Statistical Analysis. Statistical analysis, including
Dunnett's multiple comparisons and one-way ANOVA tests, was performed by GraphPad Software Inc. (version 9.2.0.332,San Diego, CA, USA).Results were presented as a mean standard deviation.

Results and Discussion
3.1.Characterization of BAK Extract.Polyphenols, natural compounds found in plants, are renowned for their various properties, such as antibacterial, anti-infammatory, and antioxidant activities.Apricots have been discovered to contain substantial levels of polyphenols, as well as their subclass, favonoids [33].Te results obtained for TPA and TFA of the BAK hydro-ethanolic extract were 4.58 ± 0.15 mg GAE/g extract and 1.68 ± 0.09 mg QUE/g extract, respectively.Te obtained results are higher than those carried out by Gomaa [34] who found that the TPA and TFA of the ethanolic extract of sweet apricot kernels were to be 1.004 ± 0.6 mg GAE/g extract and 0.468 ± 0.1 mg QUE/g extract, respectively.Moreover, Yigit et al. observed that the TPA in the water extract of bitter apricot kernels was measured at 0.4 ± 0.1 μg GAE/mL [35].Conversely, a notably higher TPA value of 7.9 ± 0.2 μg GAE/mL was documented for the sweet apricot kernels.In addition, the study carried out by Sochor et al. [36] on 21 new apricot genotypes revealed that the total polyphenol levels were varied from 41 to 170 mg GAE/100 g FW.TPA and total antioxidant capacity have previously been shown to be afected by genotype variation in fresh apricot fruit [37], almond [38], hybrid berry, and blackberry [39].
Te BAK hydro-ethanolic extract was subjected to HPLC-ESI-MS analysis to determine its phenolic compound composition.Table 1 provides a comprehensive summary of the identifed phenolic compounds, detailing their retention times, molecular formulas, and name of tentatively identifed compounds.Sixteen phenolic compounds were identifed, encompassing phenolic acids and favonoids, among others.Phenolic acids are found in diverse plant tissues, such as fruits, leaves, roots, and vegetables [40].Tis study identifed several phenolic acids, including 3,4-dihydroxybenzoic acid, gallic acid, syringic acid, and vanillic acid, in the provided extract.Among these, 3,4-dihydroxybenzoic acid was found to be the predominant phenolic acid, with a concentration of 345.18 ± 3.19 μg/g extract.Additionally, favonoid compounds such as naringenin, catechin, luteolin, and epicatechin were detected and quantifed in the extract, with catechin being the most abundant favonoid component at 153.10 ± 0.82 μg/g extract.Tese compounds have been largely reported in the literature for their antioxidant capacity [41].Furthermore, hydroxycinnamic acids, such as cafeic acid, ferulic acid, and p-coumaric acid commonly found in numerous medicinal plants and functional foods, have been documented to ofer expansive health benefts, notably anti-infammatory and antiviral efects [42].Catechin is a bio-valuable phytochemical that has shown promising results in enhancing overall health and treating a variety of ailments and health disorders.It can modulate the Nrf2 and NFkβ pathways, which explain its antioxidative 4 Advances in Pharmacological and Pharmaceutical Sciences efects and anti-infammatory properties [43].It was reported that protocatechuic acid (3,4-dihydroxybenzoic acid) efectively reduced nitric oxide production in microglial cells stimulated with lipopolysaccharide, indicating its efectiveness as an anti-infammatory agent [44].Cafeic acid stands as the predominant phenolic acid prevalent in fruits, whereas ferulic acid exists in esterifed form within the cell walls of the seed coat, bran, and fruits [45].p-Coumaric acid, also known as 4-hydroxycinnamic acid, has shown promising pharmacological efects, encompassing antiproliferative, nephroprotective, neuroprotective, antioxidant, and antimicrobial properties, alongside various other biological attributes [46].Moreover, rutin, also known as quercetin-3-rutinoside, is widely contained in various plants, such as passion fowers, buckwheat, and apples.It has been extensively investigated for its pharmacological properties, including analgesic, anticancer, antiinfammatory efects, and wound healing activity [47].Te phenolic profle of wild apricot kernel skins was previously investigated by Qin et al. [48], who identifed approximately 35 polyphenol compounds, comprising phenolic acids, favonoids, and anthocyanins.Salicylic acid and gentisic acid were the most quantitatively substantial among the total phenolic acids, measuring at 31.34 and 38.92 mg/100 g, respectively.Prior research investigated by Mandalari et al. [49] reported that catechin, epicatechin, kaempferol-3-O-rutinoside, quercetin-3-O-rutinoside, and kaempferol-3-O-glucoside were the major favonoids in almond skins.Furthermore, hydroxybenzoic acids including vanillic, chlorogenic, p-hydroxybenzoic, and trans-pcoumaric acids were identifed.In addition, the study performed by Al Juhaimi et al. [50] revealed that gallic acid, (+)-catechin, 3,4-dihydroxybenzoic acid, apigenin-7glucoside, syringe, cafeic acid, 1,2-dihydroxybenzene, rutin, and quercetin were the main phenolics detected in wild apricot kernel samples, and some of these phenolic compounds were reduced a cause to the roasting process in microwave at 720 W.

Antioxidant Activity.
Te antioxidant activity of the selected extract was evaluated using the DPPH scavenging capacity and the RP assays, and they were expressed as IC 50 and EC 50 , respectively.Te studied BAK extract showed a moderate efect (Figure 1), as it was active against the DPPH radical with an IC 50 value of 1.17 ± 0.06 mg/mL (A).Indeed, this antioxidant activity of the studied extract is lower than that of ascorbic acid (IC 50 � 0.043 ± 0.001 mg/ mL) (P ≤ 0.0001), since lower IC 50 value indicates a more potent antioxidant efect.Furthermore, the RP assay fndings (B) demonstrated that hydro-ethanolic BAK extract has a lower potential to reduce iron (EC 50 � 10.44 ± 0.08 mg/mL) when compared to the ascorbic acid (EC 50 � 0.08 ± 0.01 mg/mL) (P ≤ 0.0001).Earlier work realized by Qin et al. [48] highlighted the antioxidant efect of apricot skin extracts.Tese extracts exhibited signifcant results of DPPH free radical scavenging capacity (IC 50 � 13.77 ± 0.98 μg/mL), reducing activity (EC 50 � 3.05 ± 0.78 μg/mL), and ABTS scavenging capacity (IC 50 � 0.24 ± 0.23 μg/mL).Furthermore, Gomaa's fndings revealed that the ethanolic extract of sweet apricots and bitter almond kernels displayed remarkable levels of radical scavenging activity, with values of 51% and 62%, respectively [34].Te remarkable antioxidant capacity of BAK extract can be credited to the chemical features of the polyphenols.Tese encompass multiple hydroxyl groups, their specifc arrangement, and the inclusion of supplementary substituents like double bonds, glycosylation, and conjugation.Tese elements function as reducing agents, singlet oxygen quenchers, hydrogen donors, and scavengers of free radicals [51].Other works revealed a signifcant link between TPA and antioxidant property in apricots, peaches, nectarines, and plum fruits [52,53].Furthermore, various phenolic acids and favonoids from the apricot kernel extracts, such as cafeic, gallic, gentisic, and salicylic acids, along with quercitrin and kaempferol, have demonstrated potent antioxidant activity against DPPH, ABTS, and superoxide radicals [48].Using the acetic acid-induced writhing procedure on mice, the hydro-ethanolic extract of BAK was tested for its peripheral antinociceptive activity.
According to the results in Table 2, oral use of the tested BAK extract at 100 mg/kg b.wt showed a signifcant analgesic action (P ≤ 0.001) with a protection percentage of 63.46% in contrast to the control group (group 2).A protection percentage of 93.30% was observed for the group administered with diclofenac sodium at an amount of 25 mg/kg b.wt against writhing produced by glacial acetic acid.Te fndings are consistent with those disclosed previously by Badr et al. [54] who mentioned that apricot kernel extract had a signifcant analgesic activity on tested rats when administered orally.Furthermore, the outcomes obtained by Ramadan et al. [55] demonstrated that ethanolic extracts given orally (at 100 mg/kg b.wt) exhibited a notable analgesic efect, providing 68.99% protection against writhing induced by glacial acetic acid.Moreover, there were no instances of mortality or toxic symptoms observed in animals orally administered the ethanolic extract of apricot kernels, and the LD 50 was determined to be higher than 10 g/kg b.wt.Te mechanism underlying the analgesic efect appears to be rooted in the inhibition of endogenous substance release, specifcally those that activate pain nerve endings.Tis intricate process is likely mediated peripherally, suggesting that the alleviation of pain is intricately tied to the regulation of signaling molecules at the site of pain perception.By intervening in the periphery, this proposed mechanism aims to fnely tune the modulation of pain-inducing substances, ofering a potential avenue for targeted therapeutic interventions focused on mitigating pain at its source [56].

Anti-Infammatory Activity.
Trough intraperitoneal injection of carrageenan, rats' paw edema was employed to test the in vivo anti-infammatory property of the studied BAK extract.Figure 2 illustrates the changes in edema observed in the rats' hind paws in millimeters after administration of physiological water, standard antiinfammatory medication (indomethacin), and the BAK extracts.All rats exhibited comparable levels of edema at the beginning of the experiment.After four hours, rats administered the hydro-ethanolic extract showed less thickness on their infamed paws (P ≤ 0.05).After six hours, in comparison with the control group, both the hydroethanolic BAK extract and standard groups exhibited a signifcant reduction in the thickness of the infamed rat paws with 77.4% and 80.8%, respectively.Tese results align with previous fndings by Ramadan et al. [55], who demonstrated that the infamed rat paw thickness was signifcantly decreased when the ethanolic extracts of apricot kernels were orally administrated.In addition, the current fndings align with the earlier research conducted by Badr et al. [54], which demonstrated strong anti-infammatory activity in rats through the use of the extract derived from apricot kernels in a histamine-induced paw edema model.Previous investigation of Kim et al. [57] on the therapeutic efect of the topical application of apricot kernel extract on dry eye found that the expression level of TNF-α in mice treated with apricot kernel extract was signifcantly reduced, and the infammatory reaction in the mice with dry eye decreased as well.Te research done by Esposito et al. [58] highlighted that the acute infammatory response is characterized by edema resulting from enhanced vascular permeability, resulting in the leakage of fuid and infltration of leukocytes.During the initial phase of infammation, histamine, serotonin, and bradykinin play a role, while prostaglandins, primarily induced by cyclooxygenase (COX)-2 in the infamed tissue, sustain the late phase of infammation.6 Advances in Pharmacological and Pharmaceutical Sciences synthesis of proinfammatory cytokines and COX-2, and to reduce prostaglandin synthesis [21].

Wound Healing.
Te wound-treating property of BAK extracts was tested through the experimental second-degree burns in Wistar rats.Te obtained results during the 1st, 5th, 10th, 15th, and 21st days are presented in Figures 3 and 4. Te topical application of the studied extract and the standard medication (Biafne ® 1%) on wounds demon- strated that the wound healing process progressed signifcantly faster than the control group (Vaseline ® ).Moreover, after one week of topical application of the prepared BAK extract ointment, all dead tissues were eliminated, and the lesion's size was reduced, and after three weeks of its topical application, signifcant healing activity was recorded, which induced complete tissue repair and wound closure (97 ± 0.9%).On the other hand, in the nontreated group (only Vaseline ® ), wounds in the rats did not heal totally at the end of treatment.Abdulsamad et al. [59] indicated that apricot seed extract showed excellent healing of eye corneal ulcers of pigeons.Te important healing efect observed for the studied extract could be explained by the fact that the kernels of bitter apricots are rich in bioactive compounds, namely, alkaloids, favonoids, phenolic acids, and tannins [60,61].Earlier fndings demonstrated the benefcial efects of apricot kernels in the acceleration of the wound-treating process of burned skin in Wistar rats [62], and this study indicated the presence of signs of wound healing as neovascularization and the beginning of reepithelialization, as well as a complete epidermal epithelialization and increased fbrosis in the dermis of sections from the group treated with apricot kernels.Furthermore, numerous reports in the literature about the usage of medicinal plant extracts as an efective treatment to promote wound healing [31,[63][64][65][66].
Several physiological processes are involved in the healing efect, including hemostatic and infammatory mechanisms, cell migration and proliferation, wound contraction, protein synthesis, and tissue remodeling or reconstitution.Moreover, many studies have shown the involvement of   Advances in Pharmacological and Pharmaceutical Sciences 7 phytochemicals in these diferent mechanisms that contribute to the healing process [67,68].

Conclusion
Te discoveries unveiled by this investigation reinforce the belief in multifaceted medicinal properties harbored within apricot kernels, holding promise for human health improvement.Several bioactive polyphenols were identifed in the BAK extract and exhibited remarkable antioxidant activity, notable potential in alleviating pain and infammation, and demonstrating signifcant efcacy in treating burns and expediting the healing process.Delving deeper into the mechanisms underpinning these pharmacological efects could open doors to pioneering treatments leveraging the therapeutic potential of apricot seeds.However, to validate these fndings, further exploration involving elevated doses, varied administration routes, and extended durations remains imperative.Moreover, a comprehensive assessment encompassing bioactive constituent's toxicity should be meticulously run.Furthermore, cautious consideration regarding potential impacts on blood parameters is paramount before contemplating the utilization of BAK extracts.

Figure 1 :
Figure 1: Antioxidant activity of bitter apricot kernel extract using DPPH (a) and RP (b) assays.
Male and female Swiss mice (25-30 g) and Wistar rats (200-230 g) were provided from the Animal Breeding Center of the Faculty of Sciences Dhar El-Mahraz, USMBA, Fez, Morocco.Animals in this study were housed in a controlled setting with a temperature of 26 ± 2 °C and a 12-hour photoperiod (12 L/ 12 D 2.6.Pharmacological Activities 2.6.1.Experimental Animal's Protocol.

Table 1 :
Identifed compounds in hydro-ethanolic extracts of bitter apricot kernels.

Table 2 :
Te analgesic activity of hydro-ethanolic extract of bitter apricot kernels.Values reported are means ± standard deviations of fve animals from each group.Signifcant values are defned at * * * P ≤ 0.001 compared to the control group. a