Akademik Veri Yönetim Sistemi
16th National and 2nd International Congress of Histology and Embryology (NICHE2024), Sakarya, Türkiye, 26 - 28 Eylül 2024, ss.1
Introduction: Psoriasis is a chronic autoimmune disease marked by scaly, erythematous
skin plaques, driven by abnormal keratinocyte-immune cell interactions, leading
to inflammation and keratinocyte hyperproliferation. Current treatments provide
temporary symptom relief but have serious side effects. More effective
treatments are needed in the long term. Recent studies implicate NLRP3
inflammasome activation and Nrf2/Keap1/SIRT1 signaling disruptions in disease
progression, highlighting the potential of novel anti-inflammatory and
immunosuppressive strategies targeting these pathways.
Objective: This study aimed to investigate the potential therapeutic effects of
combined anti-inflammatory Bergenin (BER) and immunosuppressive mesenchymal
stem cells (MSCs) on NLRP3 inflammasome complex and Nrf2/Keap1/SIRT1 axis in an
imiquimod (IMQ)-induced psoriasis-like mouse model.
Material &Method: A total of 48 BALB/c mice were divided into the following groups:
Control, Saline+Vaseline (SAL+VAS), BER, MSCs, IMQ, IMQ+BER, IMQ+MSCs, and
IMQ+BER+MSCs. The psoriasis-like mice model was established by applying topical
IMQ to the back and ear skin for 7 days. In addition to macroscopic
observations, the Psoriasis Area Severity Index (PASI) score was used to assess
the severity and extent of psoriasis. Histological and biochemical changes in
the skin and spleen were examined using histochemical staining (H&E, Masson
Trichrome, and PAS), and epidermis and dermis volume alterations were
determined using the Cavalieri method. Immunohistochemistry was employed to
assess the immunoreactivity intensities of NLRP3 inflammasome components, Nrf2,
Keap1, and SIRT1 using ImageJ. Inflammatory cytokines levels (TNF-a,
IL-1β, IL-17A, IL-22 ve IL-23) were analyzed
using ELISA.
Results: Histopathological
and stereological data revealed that the IMQ+BER, IMQ+MSCs, and IMQ+BER+MSCs
treatment groups, compared to the IMQ group, exhibited: i) lower PASI scores, ii)
reduced keratinocyte hyperproliferation, parakeratosis, and Munro micro abscess
formation, iii) reduced immune cell infiltration and vascularized areas in the
dermis, iv) reduced increases in epidermal and dermal volume, and v)
significantly reduced splenomegaly and white pulp area expansion in the spleen.
BER and MSCs treatments significantly decreased the intensities of NLRP3, ASC,
Caspase-1, IL-1b, Nrf2, and Keap1 in the skin, as well as cytokines levels linked to
psoriasis, while also significantly increasing SIRT1 intensity compared to the
IMQ group.
Conclusion: In summary, the combined treatments of BER and MSCs were shown to
suppress the NLRP3 inflammasome and Keap1/Nrf2 signaling pathways, while
alleviating psoriasis symptoms in the psoriasis model by enhancing SIRT1
activation. This study demonstrates that the potent anti-inflammatory and
anti-psoriatic effects of BER, combined with the immunomodulatory activity of MSCs,
may represent a promising therapeutic approach for psoriasis.
Keywords: Psoriasis,
Bergenin, Mesenchymal Stem Cell, NLRP3 Inflammasome, Nrf2, SIRT1
Acknowledgement: This research was supported by VAN YYU Scientific Research Projects
Unit within the scope of the doctoral project numbered TDK-2022-10132.