Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy

Abstract

Aging is a major risk factor for most chronic disorders, for which cellular senescence is one of the central hallmarks. Senescent cells develop the pro‐inflammatory senescence‐associated secretory phenotype (SASP), which significantly contributes to organismal aging and age‐related disorders. Development of senotherapeutics, an emerging class of therapeutic agents to target senescent cells, allows to effectively delay aging and alleviate chronic pathologies. Here we report preliminary outputs from screening of a natural medicinal agent (NMA) library for senotherapeutic candidates and validated several agents with prominent potential as senomorphics. Rutin, a phytochemical constituent found in a number of plants, showed remarkable capacity in targeting senescent cells by dampening expression of the full spectrum SASP. Further analysis indicated that rutin restrains the acute stress‐associated phenotype (ASAP) by specifically interfering with the interactions of ATM with HIF1α, a master regulator of cellular and systemic homeostasis activated during senescence, and of ATM with TRAF6, part of a key signaling axis supporting the ASAP development toward the SASP. Conditioned media produced by senescent stromal cells enhanced the malignant phenotypes of prostate cancer cells, including in vitro proliferation, migration, invasion, and more importantly, chemoresistance, while rutin remarkably downregulated these gain‐of‐functions. Although classic chemotherapy reduced tumor progression, the treatment outcome was substantially improved upon combination of a chemotherapeutic agent with rutin. Our study provides a proof of concept for rutin as an emerging natural senomorphic agent, and presents an effective therapeutic avenue for alleviating age‐related pathologies including cancer.

Neuroprotective Effects of Bioactive Molecules Derived from Tobacco as Potential Therapeutic Candidates for Alzheimer Disease

“…This innovative cell line, equipped with a fluorescent sensor that reports NF-κB activity, allows for the real-time visualization of neuroinflammatory responses in vitro. By using this system, we have been able to model the complex neurodegenerative processes triggered by amyloid-beta peptides, akin to those seen in Alzheimer's disease, and assess the potential neuroprotective effects of bioactive molecules derived from tobacco, such as rutin (15). Looking ahead, the NPC-NFκB-mCherry cell line holds promise for integration into more complex tissue models, such as brain organoids (31).…”

“…Nicotine, a principal constituent of tobacco, has been shown to ameliorate neural damage and elicit anti-inflammatory responses in glial cells (12). Furthermore, non-nicotine compounds present in tobacco, including rutin, chlorogenic acid, and solanine, have been recognized for their antioxidative, antiinflammatory, and neuroprotective properties (6,(13)(14)(15). These insights offer a fresh perspective on assessing the economic value and potential applications of tobacco.…”

Importância Do Diagnóstico Diferencial Da Síndrome De Charles Bonnet Na Presença De Alucinações Visuais

“…Nesse contexto, a rutina, um fitonutriente disponível nos vegetais, tem a capacidade de regular a atividade celular, combater os efeitos negativos da inflamação e do envelhecimento citopatológico, além de ajustar negativamente o estresse celular agudo. Ela pode ser uma alternativa para incrementar terapias contra doenças relacionadas ao envelhecimento e potencializar os tratamentos oncológicos (Dobrzynska et al, 2020;Liu et al, 2024(a)).…”

“…De acordo com pesquisas desenvolvidas in vitro e in vivo em animais, os benefícios da rutina ocorrem devido a capacidade que esse flavonóide tem de combater o perfil doentio de algumas células e suprimir malignidades de células anormais, mutantes, envelhecidas ou cancerígenas. Tal mecanismo é observado por intermédio da promoção da autofagia, também pela regulação negativa do perfil inflamatório, invasibilidade, proliferação e divisão celular descontrolada, metastização, angiogênese e resistência a quimioterápicos (Dobrzynska et al, 2020, Farha et al, 2022Liu et al, 2024(a)).…”

Healthy aging: Linking causal mechanisms with holistic outcomes

“…There are several natural products with senomorphic properties including polyphenols and flavonoids. Here, Liu et al (2023) screened a natural medicinal agent library and describe rutin, a phytochemical with potent senomorphic activity against senescent cells and the senescence-associated secretory phenotype (SASP), as well as improving the efficacy of chemotherapeutic treatments.…”