A pharmaco-metabolomics study of Glycyrrhiza glabra, Boswellia sarca, and Acacia nilotica in acute allergic dermatitis

Abstract

Acute allergic contact dermatitis is an inflammatory skin condition characterized by swollen, itchy lesions. This study aimed to evaluate the soothing and wound-healing effects of fixed and volatile oils of Boswellia sarca, as well as extracts of Glycyrrhiza glabra and Acacia nilotica, on acute contact dermatitis in rats. Phytochemical analysis revealed the presence of flavonoids, tannins, saponins, triterpenoids, alkaloids, and cardiac glycosides in Acacia nilotica and, Glycyrrhiza glabra extracts, with Boswellia sarca showing a dominance of volatile oils. The study included a normal group and six acute allergic dermatitis groups induced by subcutaneous histamine injection. One group served as a positive control without treatment, while five groups were treated topically at inflamed sites with Boswellia sarca oils, Glycyrrhiza glabra, and Acacia nilotica extracts, alongside betamethasone as a standard treatment. The effects were evaluated through inspection, serum levels of ICAM-1, LTB4, and ILβ-4, as well as histopathological and immunohistochemical analyses. GC/MS analysis identified Incensole acetate (50.12%) and Incensole (32.44%) as major compounds in BS fixed oil, with significant terpenoids and volatile components. Metabolomic profiling using LC-MS/MS highlighted diverse secondary metabolites in Acacia nilotica and, Glycyrrhiza glabra, including polyphenolic acids, flavonoids, and amino acids, showcasing their therapeutic potential. All topical treatments reduced ICAM-1 and LTB4 levels to varying degrees and exhibited better histopathological and immunohistochemical results compared to the untreated positive control group. Among the treatments, Boswellia oils and, Glycyrrhiza glabra extracts demonstrated the most effective soothing and curative effects on allergic dermatitis. Boswellia sarca oils and, Glycyrrhiza glabra extract showed the best soothing and curative effects against allergic dermatitis.

Keywords: Acacia nilotica; Boswellia sarca; Glycyrrhiza glabra; Acute dermatitis; Histamine.

Fig. 1

TIC of volatile and fixed oil of BS

Fig. 2

Profiles of listed compounds by LC-MSMS of AN and GG extract

Fig. 3

Evaluation of allergic reaction: A Normal control, B, C Positive control, D Betamethasone, E BS volatile oil, F, G BS fixed oil, H, I GG extract, J–L AN extract. Red arrows point to sites of inflammation in the form of redness, oedema, itching and injuries

Fig. 4

Results of ICAM-1 + SE, N = 5, ANOVA test was used to compare means, followed by the Tukey–Kramer multiple comparisons test. P ≤ 0.05. @Significant difference from negative control group,*Significant difference from positive control group, Significant difference from Betamethasone group, #Significant difference from Volatile oil of Frakisence group,&Significant difference from Fixed oil of Frakisence group

Fig. 5

Results of Leukotriene B4 + SE, N = 5, ANOVA test was used to compare means, followed by the Tukey–Kramer multiple comparisons test. P ≤ 0.05. @Significant difference from negative control group,* Significant difference from positive control group, Significant difference from Betamethasone group, #Significant difference from Volatile oil of Frakisence group,&Significant difference from Fixed oil of Frakisence group

Fig. 6

Results of IL 4 + SE, N = 5, ANOVA test was used to compare means, followed by the Tukey–Kramer multiple comparisons test. P ≤ 0.05. @Significant difference from negative control group,#Significant difference from Volatile oil of Frakisence group,&Significant difference from Fixed oil of Frakisence group

Fig. 7

Normal control group: High power view showing a average keratinized epidermis (black arrow), average pilo-sebaceous units (blue arrows), and average collagen distribution (red arrow), b average pilo-sebaceous units (black arrow), average collagen distribution (red arrow), and average muscles (blue arrows), c average muscles (black arrow), and average subcutis (blue arrow) with average blood vessels (red arrow) (H&E X 400)

Fig. 8

Positive control group: High power view showing a markedly dilated congested deep blood vessel (black arrow) with deep inflammatory infiltrate composed mainly of mast cells (blue arrow), b markedly dilated congested deep blood vessel (blue arrow) with mild peri-vascular edema (red arrow) and inflammatory infiltrate composed mainly of mast cells (green arrow), c moderate peri-adnexal inflammatory infiltrate (black arrow) composed mainly of mast cells (blue arrow) (H&E X 400)

Fig. 9

Betamethasone group: High power view showing a average keratinized epidermis (black arrow), with moderate superficial inflammatory infiltrate composed mainly of mast cells (blue arrows), b mildly dilated congested deep blood vessel (blue arrow), mild edema (red arrow), and mild deepinflammatory infiltrate composed mainly of mast cells (green arrows) (H&E X 400)

Fig. 10

BS volatile oil: High power view showing a intact keratinized epidermis (black arrow), with mild superficial (blue arrows) and peri-adnexal (red arrow) inflammatory infiltrate composed mainly of mast cells (green arrow), b mild peri-adnexal(blue) and deep inflammatory infiltrate composed mainly of mast cells (red arrow), and average deep blood vessel (green arrow) (H&E X 400)

Fig. 11

BS fixed oil: High power view showing a intact keratinized epidermis (black arrow), with mild superficial (blue arrows) and peri-adnexal inflammatory infiltrate (red arrow), b mildly dilated congested deep blood vessel (blue arrow) with peri-vascular inflammatory infiltrate composed mainly of mast cells (red arrow) (H&E X 400)

Fig. 12

GG extract: High power view showing a intact keratinized epidermis (black arrow), mild superficial (blue arrows) and peri-adnexal inflammatory infiltrate (red arrow), b mild deep inflammatory infiltrate composed mainly of mast cells (blue arrows) (H&E X 400)

Fig. 13

AN extract: High power view showing a intact keratinized epidermis (black arrow), moderate superficial (blue arrow) and peri-adnexal inflammatory infiltrate (red arrow), b moderate peri-adnexal(blue arrow) and deep intra-muscular inflammatory infiltrate (red arrow) with mildly dilated congested blood vessel (green arrow) (H&E X 400)

Fig. 14

Normal Control: Skin showing o mast cells in superficial dermis, and 2 mast cells/HPF in peri-adnexal area (red arrows) (Toluidine blue stain X 400)

Fig. 15

Positive Control: Skin showing 7 mast cells/HPF in peri-adnexal area (red arrows) and 6 mast cells/HPF in deep subcutis are (yellow arrows) (Toluidine blue stain X 400)

Fig. 16

Betamethasone group: Skin showing 3 mast cells/HPF in superficial dermis (red arrow) and 3 in peri-adnexal area (yellow arrows) (Toluidine blue stain X 400)

Fig. 17

BS volatile oil: Skin showing 1 mast cells/HPF in superficial dermis (red arrow) and 2 in peri-adnexal area (black arrow) (Toluidine blue stain X 400)

Fig. 18

BS fixed oil: Skin showing 2 mast cells/HPF in peri-adnexal area (red arrow) and 4 mast cells/HPF in deep subcutis area (black arrow) (Toluidine blue stain X 400)

Fig. 19

GG extract: Skin showing no mast cells in superficial dermis, and 4 mast cells/HPF in peri-adnexal area (red arrows) (Toluidine blue stain X 400)

Fig. 20

AN extract: Skin showing 5 mast cells/HPF in peri-adnexal area (red arrows), and 2 mast cells/HPF in deep subcutis area (black arrows) (Toluidine blue stain X 400)