Yu-Ping Tang

Renal anemia (RA) is a common complication associated with chronic kidney diseases. Its pathological mechanism is attributed to the combined effects of insufficient production of erythropoietin by the kidneys, iron metabolism disorders, and chronic inflammatory conditions. The main pillars of medicine treatment for these aspects include erythropoiesis-stimulating agents, iron supplementation, and novel hypoxia-inducible factor prolyl hydroxylase inhibitors. Traditional Chinese medicine shows potential advantages across multiple targets in improving anemia and renal function in patients with RA. This review aims to systematically explain the current pathophysiological understanding of RA, examine the prevailing treatment approaches, and summarize the pharmacological mechanisms and research findings related to natural products and their active compounds used in RA treatment. This review is to provide new insights and references to support future in-depth research and clinical management of RA.

Rutin is a flavonoid glycoside with well-documented antioxidant and anti-inflammatory activities in preclinical models, but its oral bioavailability is poor due to extensive presystemic metabolism. Following oral administration, intact rutin reaches the colon largely unabsorbed, where gut microbiota convert it to quercetin aglycone, which is further metabolized to circulating conjugated metabolites and local phenolic acid derivatives. Accumulating evidence, derived predominantly from preclinical studies, suggests this metabolic activation can be usefully conceptualized as a microbiota-activated prodrug system. This challenges conventional formulation strategies that only increase parent compound exposure. In this review, we propose a metabolism-oriented conceptual framework for oral rutin delivery design. We compare nano-delivery systems and structural modifications strategies across pharmacokinetics, metabolic regulation, safety, manufacturability, and translational feasibility. Nano-delivery systems are functionally reclassified into four absorption, distribution, metabolism, excretion (ADME) -oriented categories based on their primary pharmacokinetic objectives. While numerous preclinical studies report improved bioavailability and efficacy, human metabolite-resolved pharmacokinetic data remain extremely limited, and no European Food Safety Authority (EFSA) -authorized health claims exist for rutin. This review provides a new conceptual framework for selecting oral rutin delivery strategies based on metabolic objectives rather than solely on improving solubility or systemic exposure.

Tetrahydrocarbazole (THCz) is a privileged scaffold validated by clinically approved drugs such as ondansetron, frovatriptan, and ramatroban and exhibits diverse bioactivities including antimicrobial, antitumor, antidiabetic, and neuroprotective effects. Despite extensive structure–activity relationship (SAR) studies, a systematic integration of findings across different therapeutic targets has been lacking. This review provides a comprehensive SAR dissection of THCz derivatives across key targets (bacterial sliding clamp, BTK, HDAC, AMPK, etc.), analyzing how modifications at key positions of the core scaffold (N-9, C-1, and C-6) influence potency and selectivity. Notably, we highlight four emerging design paradigms: pharmacophore hybridization, conformational constraint, cross-target SAR decoding, and precision intervention. By consolidating fragmented knowledge into a practical cross-target SAR matrix, this review offers a strategic framework for the rational design of next-generation THCz-based therapeutics.

In contemporary oncologic care, ionizing radiation (IR) is a crucial therapeutic modality for a wide range of cancers. However, a significant challenge in thoracic radiotherapy is the unavoidable exposure of adjacent lung tissue, which has a high intrinsic radiosensitivity. This often results in radiation-induced lung injury (RILI), a common and dose-limiting clinical complication. The pathogenesis of RILI is mechanistically associated with IR-induced cytosolic double-strand DNA (dsDNA) breaks, which strongly enhance the activation of the stimulator of interferon genes (STING) signaling pathway. Nevertheless, the persistent activation of this innate immune cascade leads to an excessive production of type I interferons (IFN-α/β) and numerous pro-inflammatory cytokines. We summarize the current evidence on the role of IR-stimulated cyclic GMP-AMP synthase (cGAS)-STING signaling in driving the pathological progression from radiation pneumonitis to pulmonary fibrosis. The elucidation of IR-mediated cGAS-STING signaling in RILI is crucial for developing innovative adjuvant strategies aimed at improving the therapeutic ratio of radiotherapy by simultaneously enhancing tumor cell kill and reducing normal lung injury. Additionally, this review discusses the emergence of cGAS-STING inhibitors as a promising new approach for managing RILI. We aim to provide a critical framework for exploring novel RILI management strategies and to inform the rational development of therapeutics targeting the cGAS-STING axis.