TRPC3

Magnoliae Officinalis Cortex, a commonly used Chinese medicinal herb, has a long history in traditional East Asian medicine and is widely employed in the treatment of gastrointestinal disorders, asthma, depression, and other ailments. However, the potential of volatile oil derived from the bark of Magnolia officinalis Cortex (MVO) in asthma treatment remains to be determined.

This study aimed to explore the therapeutic effect of MVO on asthma and to explore its pathway and molecular mechanism under cAMP signal background.

This study combined GC-MS with in vivo and in vitro experiments to elucidate the anti-asthmatic mechanism of MVO. An OVA-induced asthma model was established to evaluate the therapeutic effect of MVO via pulmonary function tests, H&E, BALF inflammatory cell counting, and ELISA. Fluo-4 AM, immunofluorescence and WB were further used to explore the underlying mechanism. In vitro, isolated tracheal rings were used as the object, and contraction models were constructed with KCl and acetylc holine to observe the relaxatory effect of MVO. Nifedipine (an L-type calcium channel blocker) and Pyr3 (a TRPC3 channel inhibitor) were used to intervene in the calcium signaling pathway, and the involvement of the cAMP pathway was analyzed by detecting cAMP level.

GC-MS analysis identified high concentrations of α-eudesmol, β-eudesmol, γ-eudesmol, and o-cymene in MVO. In vivo experiments showed that MVO reduced OVA-induced inflammatory cell infiltration and mucus secretion, improved pulmonary function, decreased Th2-type cytokines in BALF and serum IgE level, up-regulated the level of cAMP and the expressions of p-PKA/p-CREB in lung tissues, and inhibited NF-κB activation, reducing Ca²⁺ level and membrane localization in lung tissues. In vitro experiments showed that MVO could relax tracheal smooth muscle contractions induced by KCl and ACh in a dose-dependent manner. Application of nifedipine and Pyr3 confirmed that MVO exerted its relaxant effect by blocking L-VDCC and NSCC/TRPC channels.

MVO attenuated airway hyperresponsiveness by modulating the cAMP/PKA/CREB pathway, which subsequently suppressed NF-κB-driven inflammatory responses, while concurrently restoring cAMP/Ca²⁺ homeostasis. Significantly, our study demonstrated a novel dual-action therapeutic strategy targeting cAMP for asthma, bridging bronchodilatory and anti-inflammatory effects.

Celastrol, a terpenoid, has been shown to exert several beneficial properties in health and disease, particularly in obesity. Recent studies have demonstrated that orosensory detection of dietary fatty acids plays an important role in the pathogenesis of obesity. In the present report, we have studied the role of celastrol in the modulation of calcium signaling in Fluo-4/AM loaded mouse taste bud cells (mTBC) and fat taste perception in the mouse. Celastrol was found to induce increases in free intracellular calcium concentrations, [Ca²⁺]i, in mTBC. Celastrol seems to exert its action via bile acid TGR5 (Takeda-G-protein-receptor-5) receptor. Furthermore, U-73122, a phospholipase C (PLC) inhibitor, significantly curtailed celastrol-induced calcium signaling, suggesting that this agent triggers an increase from endoplasmic reticulum via inositol-tris-phosphate (IP₃) production. Celastrol-recruited Ca²⁺ from intracellular pool that triggered the opening of TRPC3 channels. We further employed thapsigargin (TG), known to trigger an increase in [Ca²⁺]i. Celastrol shared the TG-recruited Ca²⁺ pool. Celastrol was observed to share linoleic acid-triggered Ca²⁺ signaling in these cells. In two-bottle choice paradigm, celastrol increased the gustatory preference for linoleic acid. Our study might be helpful for considering the synthesis of celastrol analogues as fat taste modifiers with a potential in the management of obesity.

Wound healing is a complex, highly orchestrated process involving distinct yet overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Effective healing requires precise cellular and molecular interactions across these phases, with calcium signaling playing a pivotal role in modulating cellular responses such as migration, proliferation, and differentiation. Among the calcium channels involved, the Transient Receptor Potential Canonical (TRPC) family, particularly TRPC3, emerged as a key modulator of wound repair processes. In this review, we explore the dynamic contributions of TRPC3 to each phase of wound healing, highlighting its regulation of calcium fluxes and the downstream cellular responses critical for effective tissue repair. We will further discuss the altered role of TRPC3 in pathological conditions, such as chronic wounds and diabetic ulcers, where aberrant TRPC3 signaling disrupts normal wound healing, contributing to impaired resolution and fibrosis. By summarizing findings from recent studies, we underscore the potential of targeting TRPC3 as a therapeutic strategy to restore normal wound healing. Finally, we will discuss future directions in TRPC3‐targeted interventions, including the development of selective modulators and the use of TRPC3‐targeting therapy, to address unmet needs in wound care. This review aims to provide a comprehensive overview of TRPC3's multifaceted role in wound repair and its therapeutic potential in regenerative medicine.