Objective:. Daphnegiravone D (DGD), a prenylated flavonoid from Daphne giraldii Nitsche, a plant whose roots and stem are used in Chinese medicine, exerts an inhibitory effect on liver cancer cells. The protein kinase ataxia telangiectasia-mutated and Rad3-related (ATR) is an important component of the DNA damage response, and its inhibition enhances the sensitivity of some cancer cells to DNA-damaging drugs. Oxaliplatin (OXA) is a third-generation, platinum-based anticancer drug that exerts its inhibitory effects on liver cancer cells by inhibiting DNA synthesis. Owing to the fact that most patients develop drug resistance, finding novel treatments for liver cancer is urgent. In a previous study, DGD was shown to exert anti-tumor effects as a potential ATR kinase inhibitor. This study investigated the mechanism of action of DGD and its combination with OXA in liver cancer. Methods:. HepG2 and Hep3B cells were used to evaluate the inhibitory effects of DGD on liver cancer. Cellular thermal shift assay, co-immunoprecipitation, and western blotting were used to confirm the impact of DGD on DNA damage. The methyl thiazolyl tetrazolium (MTT) assay was performed, and the resulting data were used to calculate drug synergy scores. Acridine orange/ethidium bromide staining, Annexin V/propidium iodide staining, reactive oxygen species–related staining, and western blotting were performed to assess the efficacy of the combination of DGD and OXA. An in vivo tumor xenograft model in nude mice was used to investigate the efficacy of this combination. Hematoxylin–eosin staining and immunohistochemistry were performed to observe the condition of tissues in vivo. Results:. DGD inhibited liver cancer cells by affecting the formation of the ATR-ATRIP complex and downregulating the activator protein TopBP1. We found that DGD and OXA showed synergistic growth-inhibitory effects in liver cancer cells in vitro. DGD and OXA showed synergistic growth-inhibitory effects in liver cancer cells in vitro and showed lower cytotoxicity toward L-02 cells than an equi-effective higher concentration of OXA under the tested conditions in normal liver cells. The combination was associated with enhanced apoptosis, mitochondrial dysfunction, and oxidative stress. Further experiments suggested that DGD may enhance OXA-induced DNA damage, at least partly in association with suppression of ATR-related signaling. Consistent with the above results, DGD enhanced the antitumor efficacy of OXA in vivo without causing overt additional toxicity under the present experimental conditions. Conclusion:. Our findings indicate that DGD enhances the antitumor activity of OXA against liver cancer, with the in vitro synergistic effect being associated, at least partly, with suppression of ATR-related signaling, enhanced DNA damage, and oxidative stress. DGD also improved the antitumor efficacy of OXA in the xenograft model without overt additional toxicity.
Ophiocordyceps sinensis (Berk) Sacc. (O. sinensis; Family: Clavicipitaceae; synonym: Cordyceps sinensis) is a fungus that is revered in ancient Tibetan folklore as a “miraculous species that becomes a worm in winter and a grass in summer” and renowned as the “elixir of life gifted” by the snow-capped region. Its evolutional awareness and utilization span both traditional Chinese medicine practices and modern biomedical research, rendering it a quintessential example of symbiotic entomo-fungal biological resource development. Extensive research on the biological characteristics, active constituents, pharmacological effects, and underlying mechanisms of O. sinensis has generated significant breakthroughs in recent years. From “heavenly elixir” to a vital tonic in imperial cuisine, and from its symbiotic life cycle to its current prominence in modern pharmacological research and clinical applications, this fungus has nurtured both the cultural legends and survival wisdom of the Plateau ancestors and reflected the long journey of contemporary scientific exploration and industrialization. This review traces the journey of O. sinensis from traditional empirical applications to scientific validation, focusing on its biological characteristics, extraction and separation techniques for key bioactive constituents, and its pharmacological effects and molecular mechanisms in antitumor activity, immunomodulation, renoprotection, antioxidant properties, and anti-aging effects, and summarizes the current status of its clinical applications. Furthermore, this review examines the challenges confronting current research on O. sinensis, including resource conservation and sustainable utilization, quality control and standardization, differences between artificially cultivated and wild-harvested specimens, further elucidating its mechanisms of action and outlining prospects for future research directions.
Natural products with vasodilatory properties are increasingly recognized for treating hypertension, angina, and heart failure owing to their efficacy, accessibility, and favorable safety profiles, rendering them viable therapeutic alternatives. Following a systematic search of the NCBI PubMed and CNKI databases, 227 natural compounds with potent vasodilatory activity were identified. This review delineates the vasodilatory effects of major phytochemical classes—specifically flavonoids, saponins, phenols, and alkaloids—and evaluates preclinical evidence supporting their therapeutic application. Furthermore, potential vasodilatory mechanisms are elucidated, encompassing endothelium-dependent regulation of smooth muscle tone, fluid homeostasis, oxidative stress mitigation, and antagonism of the renin-angiotensin-aldosterone system. These mechanisms clarify the pharmacological basis of natural vasodilators, offering researchers and clinicians enhanced strategies for managing cardiovascular diseases.
Traditional Chinese Medicine(TCM)is an important part of the national healthcare systems and has the potential for transferability to other systems,with promising results for chronic pain,neurological disorders,and other condi-tions[1-2].However,its credibility depends on the alignment of its holistic,individualized paradigm with international standards for trial design and reporting,careful formula-tion of relevant research questions,and movement toward patient and public involvement(PPI)and open science[3].In the following sections,we expand on these points.
