The potential of natural herbal plants in the treatment and prevention of non-small cell lung cancer: An encounter between ferroptosis and mitophagy.

Ethnopharmacological relevance: Chinese herbal medicine constitutes a substantial cultural and scientific resource for the Chinese nation, attracting considerable scholarly interest due to its intrinsic characteristics of "multi-component, multi-target, and multi-pathway" interactions. Simultaneously, it aligns accurately with the intricate and continuously evolving progression of non-small cell lung cancer (NSCLC). Furthermore, contemporary pharmacological studies indicate that natural herbaceous plants and their bioactive compounds exhibit a diverse array of biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects, among others. Additionally, these substances have been demonstrated to possess a degree of safety, particularly in terms of exhibiting comparatively lower levels of toxicity to the liver and kidneys when contrasted with conventional Western medicine. Thus, the development of herbal plants, which includes both single herbs and composite formulations, as well as their bioactive constituents, through the targeted regulation of ferroptosis and mitophagy, presents substantial potential and instills considerable hope for individuals diagnosed with NSCLC.

Aim of the review: This review aims to conduct a critical analysis of the ethnopharmacological applications of natural herbaceous plants in relation to ferroptosis and mitophagy in NSCLC. The objective is to evaluate the potential advantages of prioritizing specific phytochemical constituents found in these plants, which may serve as novel therapeutic candidates informed by ethnobotanical knowledge. Additionally, this study seeks to enhance the current pharmacological applications of natural herbaceous plants.

Methods: An investigation into natural herbal remedies for NSCLC was conducted, with a particular emphasis on the ferroptosis and mitophagy pathways. This study utilized traditional medical texts and ethnomedicinal literature as primary sources. Furthermore, relevant information related to ethnobotany, phytochemistry, and pharmacology is obtained from online databases, including PubMed and the China National Knowledge Infrastructure (CNKI), among others. "Traditional Chinese medicine compound preparations", "single herb extracts", "active compounds", "NSCLC", "ferroptosis", and "mitophagy" were used as keywords when searching the databases. Consequently, pertinent articles published in recent years were collected and analyzed.

Results: Given the complex etiology of NSCLC, treatment strategies that concentrate exclusively on ferroptosis or mitophagy often demonstrate limitations. In this regard, the utilization of herbal plants offers unique benefits in the management of NSCLC. The rationale can be summarized within the following two dimensions: Firstly, due to the molecular mechanisms of ferroptosis and mitophagy involving multiple signaling pathways (including PINK1/Parkin, HMGB1, system Xc^-/GPX4/GSH, FSP1/CoQ10/NAD (P) H, and so on), sometimes drugs with a single target are difficult to involve multiple pathways. Fortunately, there is an expanding body of evidence suggesting that various herbaceous plants and their bioactive compounds can affect multiple biological targets. Moreover, these compounds seem to interact with several targets associated with ferroptosis and mitophagy in NSCLC (such as NIX, BNIP3, FUNDC1, GPX4, FSP1, P53, Nrf2, LncRNA, and so on). Secondly, Herbaceous plants and their bioactive compounds have been shown to possess a favorable safety profile, particularly with respect to reduced hepatotoxicity and nephrotoxicity in comparison to conventional Western medicine. For example, Numerous compound formulations, such as Fangji Huangqi decoction, Mufangji decoction, Qiyu Sanlong decoction, and Fuzheng Kangai decoction, have been employed in China for millennia, and their clinical efficacy appears to be quite promising. Notably,In recent years, numerous researchers have sought to isolate active constituents from clinically effective compound formulations through the application of chemical methodologies. This endeavor has been driven by the necessity to tackle challenges related to complex ingredient compositions and sophisticated processing. These active compounds have been employed in cellular and animal studies to elucidate the molecular mechanisms underlying these formulations.

Conclusions: The Asian region has a long-standing historical tradition of employing natural herbaceous plants for traditional medicinal purposes. Phytochemical and pharmacological studies have shown that various compound preparations derived from traditional Chinese medicine, along with individual herb extracts and their active constituents, display a range of bioactive effects. These effects encompass anti-tumor, anti-inflammatory, antibacterial, and antioxidant properties, among others. Numerous traditional compound formulations originating from China have emerged as promising candidates for the development of pharmacological agents targeting NSCLC. It is noteworthy that a variety of compound formulations aimed at the ferroptosis and mitophagy pathways, which demonstrate unique therapeutic effects on NSCLC, are presently under extensive investigation by an increasing number of researchers. Therefore, it is imperative to consider in vitro mechanistic studies, in vivo pharmacological evaluations, and assessments of clinical efficacy. Furthermore, it is essential to conduct a comprehensive assessment of plant resources, implement quality control measures, and engage in toxicological research to ensure that the data is appropriate for further examination.