Calcipotriol

Yang Z, et al. Cytokine, 2023, 171, 156382.

Calcipotriol has demonstrated potential as a therapeutic agent in mitigating osteoarthritis (OA). Recent studies have explored its molecular mechanisms, revealing its ability to alleviate chondrocyte ferroptosis, a process implicated in OA progression. In vitro experiments using quantitative reverse-transcription polymerase chain reaction, western blotting, and immunofluorescence analysis indicated that calcipotriol reduces reactive oxygen species and lipid peroxidation levels in chondrocytes. This is achieved through the inhibition of GPX4, a key enzyme in ferroptosis, by suppressing the transforming growth factor-β1 (TGF-β1) signaling pathway.
In vivo studies, employing a destabilized medial meniscus model, demonstrated that intra-articular calcipotriol injection effectively mitigates cartilage degradation, as evidenced by hematoxylin and eosin staining, safranin O-Fast green staining, and micro-computed tomography analysis. Furthermore, calcipotriol treatment led to a reduction in the expression of catabolic markers such as MMP13 and ADAMTS5, while promoting the expression of anabolic markers like SOX9, col2a1, and Aggrecan. These findings suggest that calcipotriol has therapeutic potential in OA by modulating chondrocyte ferroptosis and cartilage homeostasis.

Zheng M, et al. Toxicology and Applied Pharmacology, 2024, 491, 117078.

Calcipotriol has demonstrated significant antifibrotic effects in the treatment of chronic pancreatitis. Recent research has elucidated its mechanism of action, showing that it inhibits the transcription of COL1A1 and COL1A2 in pancreatic stellate cells (PSCs) through modulation of the RUNX1/CBFβ complex. The study found that TGF-β1-induced RUNX1 expression in PSCs is regulated by the TGF-β1/pSmad3 signaling pathway, which promotes the formation of a pSmad3/RUNX1/CBFβ complex that activates COL1 gene transcription. However, calcipotriol effectively downregulates RUNX1 production and disrupts the formation of the RUNX1/CBFβ complex, thereby abrogating the synthesis of COL1A1/1A2. These findings suggest that calcipotriol's ability to inhibit the RUNX1-mediated fibrotic pathway presents a promising therapeutic approach for the management of fibrosis in chronic pancreatitis.

Kim H, et al. Biomedicine & Pharmacotherapy, 2022, 154, 113553.

Calcipotriol has shown promising results in overcoming immune evasion in glioblastoma multiforme (GBM) by modulating immune responses and reprogramming the immunosuppressive tumor microenvironment. In both in vivo and in vitro studies, calcipotriol administration significantly reduced GBM tumor growth. The treatment was found to enhance the activation of CD8+ T cells and natural killer (NK) cells, with elevated production of IFN-γ and granzyme B, crucial for antitumor immunity. Conversely, regulatory T cells (Tregs), known for their role in suppressing immune responses, were notably reduced in calcipotriol-treated subjects. A key mechanism identified was the elevation of CD127 expression in CD4+ T cells, suggesting enhanced T-cell priming. The depletion of CD4+ T cells, but not NK or CD8+ T cells, abrogated the antitumor efficacy of calcipotriol, pointing to the critical role of the calcipotriol/TSLP/CD4+T axis in activating immune responses.

Camillo L, et al. Journal of Photochemistry and Photobiology, 2022, 12, 100158.

Calcipotriol has demonstrated significant potential in counteracting photoaging caused by ultraviolet B (UVB) radiation. In a study using primary human dermal fibroblasts (HDFs), treatment with calcipotriol (100 nM) prior to UVB exposure reduced reactive oxygen species (ROS) production and DNA damage. This resulted in lower activation of the p53/p21 pathway, promoting enhanced cell cycle progression, reduced senescence, and improved cellular viability. Additionally, calcipotriol treatment, alongside nicotinamide, mitigated the harmful effects of UVB on skin cells by preventing the activation of senescence markers and promoting cellular proliferation. These findings highlight calcipotriol's potential as an effective agent in protecting skin from UV-induced damage and preventing the onset of photoaging.