Clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway
Ethnopharmacological relevance Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platel...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier Ireland
2023
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| Online Access: | http://psasir.upm.edu.my/id/eprint/107035/ http://psasir.upm.edu.my/id/eprint/107035/1/Clinacanthus%20nutans%20aqueous%20extract%20exerts%20anti-allergic%20activity%20in%20preclinical%20anaphylactic%20models%20via%20alternative%20IgG%20pathway.pdf |
| _version_ | 1848864855702896640 |
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| author | Kow, Audrey Siew Foong Khoo, Leng Wei Tan, Ji Wei Abas, Faridah Lee, Ming-Tatt Ahmad Israf, Daud Shaari, Khozirah Tham, Chau Ling |
| author_facet | Kow, Audrey Siew Foong Khoo, Leng Wei Tan, Ji Wei Abas, Faridah Lee, Ming-Tatt Ahmad Israf, Daud Shaari, Khozirah Tham, Chau Ling |
| author_sort | Kow, Audrey Siew Foong |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Ethnopharmacological relevance
Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of β-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (1H-NMR) metabolomics approach.
Aim of the study
As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE.
Material & methods
The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot.
Results
IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model.
Conclusion
Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy. |
| first_indexed | 2025-11-15T13:55:27Z |
| format | Article |
| id | upm-107035 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T13:55:27Z |
| publishDate | 2023 |
| publisher | Elsevier Ireland |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1070352024-10-17T03:51:59Z http://psasir.upm.edu.my/id/eprint/107035/ Clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway Kow, Audrey Siew Foong Khoo, Leng Wei Tan, Ji Wei Abas, Faridah Lee, Ming-Tatt Ahmad Israf, Daud Shaari, Khozirah Tham, Chau Ling Ethnopharmacological relevance Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of β-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (1H-NMR) metabolomics approach. Aim of the study As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE. Material & methods The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot. Results IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model. Conclusion Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy. Elsevier Ireland 2023-03-01 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/107035/1/Clinacanthus%20nutans%20aqueous%20extract%20exerts%20anti-allergic%20activity%20in%20preclinical%20anaphylactic%20models%20via%20alternative%20IgG%20pathway.pdf Kow, Audrey Siew Foong and Khoo, Leng Wei and Tan, Ji Wei and Abas, Faridah and Lee, Ming-Tatt and Ahmad Israf, Daud and Shaari, Khozirah and Tham, Chau Ling (2023) Clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway. Journal of Ethnopharmacology, 303 (116003). ISSN 0378-8741; ESSN: 1872-7573 https://linkinghub.elsevier.com/retrieve/pii/S037887412201042X 10.1016/j.jep.2022.116003 |
| spellingShingle | Kow, Audrey Siew Foong Khoo, Leng Wei Tan, Ji Wei Abas, Faridah Lee, Ming-Tatt Ahmad Israf, Daud Shaari, Khozirah Tham, Chau Ling Clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway |
| title | Clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway |
| title_full | Clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway |
| title_fullStr | Clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway |
| title_full_unstemmed | Clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway |
| title_short | Clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway |
| title_sort | clinacanthus nutans aqueous extract exerts anti-allergic activity in preclinical anaphylactic models via alternative igg pathway |
| url | http://psasir.upm.edu.my/id/eprint/107035/ http://psasir.upm.edu.my/id/eprint/107035/ http://psasir.upm.edu.my/id/eprint/107035/ http://psasir.upm.edu.my/id/eprint/107035/1/Clinacanthus%20nutans%20aqueous%20extract%20exerts%20anti-allergic%20activity%20in%20preclinical%20anaphylactic%20models%20via%20alternative%20IgG%20pathway.pdf |