JB-001

The incidence of cancer has escalated at a distressing pace, creating an urgent demand for advancements and breakthroughs in medical interventions. Amidst the multitude of approaches for diagnosing and managing cancer, fluorescence imaging, photodynamic therapy, and photothermal therapy have emerged as key approaches due to their unique advantages. Herein, two new xanthene-based probes, namely, JB-1 and JB-2, with D-π-A conjugated structures, are reported. JB-1 and JB-2 each feature electron-donating and electron-accepting groups attached to tetraphenylethene or triphenylamine conjugate skeletons, respectively. The restriction of intramolecular rotation in JB-1 results in an absorption wavelength greater than 638 nm and strong emission at the first near-infrared window at 750 nm, with a 117 nm red-shift compared to ICG. In contrast, JB-2 exhibits an emission peak at 971 nm in the second near-infrared region, with an absorption beyond 691 nm. JB-2 also features a fluorescent shoulder peak at 1204 nm, offering a superior resolution for in vivo bioimaging. Furthermore, JB-2 demonstrates excellent photothermal and photodynamic effects for both in vitro and in vivo cancer therapy. This study highlights the potential for designing multifunctional xanthene dyes for dual-mode cancer treatment and bioimaging.

Icariin and icaritin, the major active components of Epimedii Genus, are considered as promising drugs with anti-inflammatory, anti-aging and neuroprotective effects. Our previous studies have demonstrated that icariin and icaritin can protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP⁺)-induced neurotoxicity on dopaminergic neurons via insulin-like growth factor-1 receptor (IGF-1 receptor) signaling. In the present study, we aimed to evaluate the role of IGF-1 receptor signaling in mediating the anti-inflammatory effects of icariin and icaritin against lipopolysaccharide (LPS)-induced neuroinflammation as well as their biological regulation effects in midbrain primary astrocytes. Our results showed that both icariin and icaritin significantly inhibited LPS-induced mRNA expressions of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β). Pre-treatment with IGF-1 receptor antagonist JB-1 could significantly block the anti-inflammatory effects of icariin and icaritin on LPS-induced up-regulations of TNF-α, IL-1β, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Under basal conditions of astrocytes, icariin and icaritin treatment alone increased the phosphorylation of ERK1/2 and AKT, which could be blocked by JB-1. Moreover, the mRNA expressions of glutamate transptor-1 (GLT-1) and glutamate-aspartate transporter (GLAST) could be up-regulated by icariin and icaritin in a time-dependent manner via IGF-1 receptor. Taken together, our results suggest for the first time that both icariin and icaritin exert regulatory effects in astrocytes under basal conditions and after an inflammatory challenge via IGF-1 receptor signaling pathway.