Ji-Hye Kang

Natural products have a long history of use as valuable therapeutic resources, and continue to provide structurally diverse bioactive compounds for pharmaceutical, biomedical, nutraceutical, and cosmetic applications

Polydeoxyribonucleotide (PDRN), a bioactive DNA fragment, has been known to promote anti‐inflammatory responses and wound healing primarily via adenosine A ₂ A receptor activation. However, low molecular weight PDRN can undergo rapid degradation, limiting its sustained therapeutic efficacy. In this study, we developed a scalable method to produce high‐purity, and low molecular weight PDRN ( c.a . 325 bp) from calf thymus DNA via physical fragmentation. To enhance its stability and delivery, PDRN was encapsulated in poly(lactic‐co‐glycolic acid) (PLGA) to form PDRN/PLGA nanoparticles, yielding uniform and spherical particles (336 ± 43 nm). These nanoparticles exhibited excellent colloidal stability and biodegradability (38.3% over 14 days), with sustained PDRN release (88.39% over 14 days). Moreover, the nanoformulation effectively protected PDRN from thermal, acidic, enzymatic, and UV degradation. The PDRN/PLGA nanoparticles, which exhibited no cytotoxicity or hemolysis, demonstrated superior anti‐inflammatory and wound‐healing efficacy compared to free PDRN. In an in vitro lipopolysaccharide (LPS)‐induced inflammatory wound model, they significantly accelerated wound closure compared to both LPS‐treated and untreated controls. These results suggest that nanoformulation effectively protects low molecular weight PDRN, thereby significantly enhancing its therapeutic activity and underscore the potential of PDRN/PLGA nanoparticles as a stable and effective platform for the regeneration of skin inflammation.

Macrophages play a central role in orchestrating inflammation and immune responses, with their polarization states (M1 or M2) exhibiting both pro- and anti-inflammatory, as well as anti-cancer functions. Inducible nitric oxide synthase (iNOS) plays a pivotal role in immune regulation through its impact on macrophage polarization. As a hallmark of M1 macrophages, iNOS drives pro-inflammatory responses, while its suppression favors anti-inflammatory M2 phenotypes. This dual role as both a biomarker and regulatory hub positions iNOS as a promising therapeutic target across diverse disease states. This review examines the roles of iNOS modulation in macrophage polarization across various disease models. Both synthetic and natural iNOS regulators have been shown to modulate iNOS activity, thereby reprogramming macrophages toward either inflammatory or reparative phenotypes. We categorize these regulators into those that directly inhibit enzymatic activity and those that indirectly modulate through signaling pathways. Additionally, recent preclinical and clinical studies on iNOS inhibitors are summarized, highlighting their therapeutic potential in inflammatory, metabolic, and oncologic diseases. Taken together, the evidence underscores the therapeutic relevance of iNOS regulation as a strategy to reprogram macrophage plasticity in disease-specific immune microenvironments.

Paclitaxel (PTX) is a widely used anticancer drug for ovarian cancer treatment, but its clinical application is limited by poor water solubility and dose-limiting toxicities. To overcome these challenges, we developed a thermoresponsive, multistep drug delivery system, pNIB/PTX, designed to improve PTX solubility and provide controlled drug release. The pNIB/PTX-3 complex exhibited an initial rapid drug release phase followed by sustained slow release, optimizing both short-term and long-term therapeutic efficacy. At physiological temperatures, the complex demonstrated a precisely controlled drug release mechanism driven by changes in the polymeric micelle structure. In vitro studies showed that pNIB/PTX-3 significantly enhanced therapeutic effects in human ovarian cancer cell lines HeyA8 and SKOV3ip1, compared to PTX alone. In orthotopic ovarian cancer mouse models, a single intraperitoneal injection of pNIB/PTX-3 led to a substantial reduction in tumor size and prolonged survival. This multistep, thermoresponsive delivery system shows strong potential as a promising therapeutic option for dose-dense ovarian cancer treatments, providing improved drug stability, controlled release, and minimized side effects.

The extract of Paspalum thunbergii, a native perennial herb in Korea belonging to the rice family, was investigated for its anti-inflammatory activity and the underlying mechanisms driving its effects. Fifteen chemical components of the P. thunbergii extract, including rosmarinic acid and isoquercitrin, were identified using LC-MS. The extract showed antioxidative activity through DPPH and ABTS cation radical scavenging activity. The P. thunbergii extract significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW 264.7 cells. The extract inhibited the expression of lipopolysaccharide-induced iNOS and COX-2, which are inflammation-related enzymes. To explore the underlying anti-inflammatory mechanism, the expression levels of signal proteins related to MAPK, NF-κB, JAK/STAT, and Wnt/β-catenin signaling were measured. As a result, the P. thunbergii extract inhibited the expression of p-p38, and p-JNK increased by LPS in RAW 264.7 cells. Additionally, it decreased the expression of LPS-induced p-IKKβ and p-NF-κB p65 and prevented the migration of p-NF-κB into the nucleus caused by LPS. Notably, p-JAK1, p-STAT3, Wnt 3α, β-catenin, and p-GSK-3β protein expressions were also inhibited. Therefore, the prominent anti-inflammatory activity of the P. thunbergii extract may be via the MAPK, NF-κB, JAK/STAT, Wnt/β-catenin signal pathway.