4.1 Analysis of field development trends

As shown in Fig. 1, the document-coupling analysis identifies multiple thematic clusters revolving around cell-death mechanisms, with ‘apoptosis’ prominently featured across quadrants in conjunction with ‘cells,’ ‘in vitro,’ and ‘nf-kappa-b. The bottom-left grouping, which includes “traditional Chinese medicine,” suggests that certain publications emphasize TCM formulations while maintaining relatively lower centrality and impact, possibly reflecting specialized or preliminary explorations of how TCM‐based compounds induce cell death. By contrast, apoptosis‐related terms associated with higher centrality and impact underscore the essential, widespread investigation of programmed cell death in cancer research. In Fig. 2, themes are plotted based on their development density and relevance: “apoptosis,” “expression,” and “activation” occupy the Basic Themes quadrant, indicating their foundational role in elucidating how Chinese patent drugs trigger signaling cascades within cancer cells. Meanwhile, “oxidative stress,” “cell death,” and “injury” appear in the Emerging or Declining Themes quadrant, implying that these areas either represent nascent directions requiring further investigation or are increasingly absorbed into more specific mechanistic discussions such as ferroptosis.TCM-focused terms (e.g., ‘traditional Chinese medicine’) cluster near the center, highlighting ongoing work that addresses both mechanistic depth (e.g., ‘nf-kappa-b’) and preclinical validation (‘in vitro’). The keyword timeline in Fig. 3 provides further insight into how these concepts have evolved over time: early research predominantly emphasized apoptosis and cytotoxicity, while more recent publications show an increasing frequency of terms such as “ferroptosis,” “autophagy,” and “signaling pathway,” implying a growing appreciation for diverse regulatory networks through which Chinese patent drugs might modulate tumor cell fate. The appearance of broader immunological and metabolic terms (e.g., “inflammation,” “gut microbiota,” “iron”) also suggests that investigators are examining cell death in a broader physiological context, in line with expanding interest in tumor microenvironment and holistic treatment strategies. Taken together, these trends reflect a field that—while grounded in fundamental apoptosis research—is steadily branching out to incorporate a wider spectrum of regulated cell death mechanisms and sophisticated experimental techniques, thereby refining our understanding of how Chinese patent drugs may enhance cancer therapy.

Fig. 1

Cluster analysis of documents by coupling

Fig. 2

Strategic diagram: thematic development and positioning

Fig. 3

Trend topics and their temporal evolution

4.2 Bibliometric analysis of country

As shown in Fig. 4, China overwhelmingly dominates the citation landscape, amassing a substantially higher number of citations than other nations, with the United States, Germany, Korea, and Japan following at considerable distance. This citation pattern underscores China’s pivotal role in the investigation of Chinese patent drugs aimed at inducing programmed cell death. Cultural and institutional investment in traditional Chinese medicine research may partly explain the magnitude of Chinese outputs in this field, a conclusion further reinforced by the temporal trends shown in Fig. 5, where China’s publication growth accelerates rapidly after 2010 and surpasses other major contributors by an expansive margin. Although the United States and select European countries (e.g., Germany) continue to maintain steady output levels, the gap widens each year, suggesting that Chinese institutions lead in both sheer volume and impact within this specialized research domain. Collaboration patterns, depicted in Fig. 6, illustrate strong international networks linking China to the United States, Taiwan, Japan, and various European countries, reflecting a globalization of research interests and the dispersal of Chinese patent drug investigations beyond domestic settings. Notably, this network showcases hub-like roles for both China and the United States, hinting at extensive scientific exchange and potential co‐financing or cross‐institutional partnerships. Korea, Australia, and Singapore also appear as increasingly visible collaborators, suggesting a broader regional interest in harnessing the therapeutic potential of Chinese herbal formulations for oncological applications. Taken together, this geographic distribution of citations, publications, and collaborations highlights both the rapid ascent of Chinese research institutions in traditional medicine–based cancer therapies and the importance of multinational efforts to validate, standardize, and innovate upon these compounds. The conspicuous leadership of China, however, does not diminish the contributions of other countries; rather, it underscores the field’s expanding global influence, where longstanding knowledge of Chinese patent drugs merges with advanced translational research to shape emerging paradigms in cancer cell‐death modulation.

Fig. 4

Most cited countries in the field

Fig. 5Fig. 6

Global collaboration network of countries

4.3 Bibliometric analysis of keywords

As shown in Fig. 7, the overall frequency of key terms such as “apoptosis,” “activation,” and “traditional Chinese medicine” has soared over the past two decades, underscoring the centrality of regulated cell-death mechanisms in research on Chinese patent drugs for cancer therapy. Early on, “apoptosis” dominated the literature, but more recent years reveal a broadening scope, as “expression,” “inhibition,” and “autophagy” gain traction. Simultaneously, ‘in vitro’ studies remain prevalent, reflecting the importance of laboratory-based validation before transitioning to clinical contexts. The co‐occurrence network in Fig. 8 highlights “apoptosis” as a prominent hub linked with “cells,” “proliferation,” and “nf‐kappa‐b,” suggesting that researchers are probing both mitochondrial and immune signaling pathways to elucidate how Chinese patent drugs initiate tumor cell death. “Traditional Chinese medicine” clusters closely with “expression” and “invasion,” indicating a convergence of pharmacological exploration and molecular studies that map natural compounds to distinct cancer pathways. According to Fig. 9, “apoptosis” stands out with the highest occurrence count, followed by “expression,” “activation,” and “cells,” illustrating a consistent focus on death‐inducing processes, gene‐regulatory events, and experimental verifications. Meanwhile, “cancer,” “in‐vitro,” and “growth” remain integral to the thematic landscape, pointing to sustained efforts in mechanistic assays and proliferation studies. “Proliferation” and “inhibition” likewise occupy considerable positions on this list, reinforcing that cell‐cycle disruption is a shared focal point. In Fig. 10, the mapped keyword clusters reveal at least three distinct groupings: one rich in references to oxidative stress, injury, and cell‐death; another featuring in‐vitro, nf‐kappa‐b, and TCM terms; and a third centered on apoptosis, activation, and expression. This partitioning underscores a thematic interplay wherein TCM formulations may induce multiple regulated cell‐death pathways, from classical mitochondrial apoptosis to more recent autophagy and ferroptosis paradigms. The green cluster around oxidative stress suggests interest in reactive‐oxygen‐species‐mediated cytotoxicity, while the red cluster focused on in‐vitro experimentation underscores the heavy reliance on laboratory models for screening and mechanistic elucidation. These keyword trajectories and co‐occurrence patterns reflect a dynamic research field that, while anchored by apoptosis, increasingly investigates alternative pathways, advanced in‐vitro strategies, and multifaceted TCM interventions to optimize cell‐death induction in cancer cells. Notably, the term ‘Multi-Target Therapy’ bridges several clusters, underscoring a growing research focus on exploiting the broad pharmacodynamic spectrum of Chinese patent drugs to synchronously modulate multiple regulated cell-death pathways.

Fig. 7

Temporal changes in keyword frequency

Fig. 8

Keyword co-occurrence network

Fig. 9

Ranking of the most relevant keywords

Fig. 10

Clusters of co-occurring keywords

4.4 Bibliometric analysis of journal

As shown in Fig. 11, the Journal of Ethnopharmacology leads all sources in number of documents, reflecting the enduring importance of ethnopharmacological perspectives in unveiling how Chinese patent drugs may induce programmed cell death in cancer cells. Frontiers in Pharmacology and Evidence-Based Complementary and Alternative Medicine follow closely, suggesting strong editorial focus on integrative or complementary approaches, where traditional Chinese compounds are often investigated alongside modern biochemical and pharmaceutical methodologies. Phytomedicine and Biomedicine & Pharmacotherapy also rank highly, underscoring a growing interest in plant‐derived or combinatorial therapeutics that target cancer at the molecular level. By concentrating publications in these journals, researchers are able to bridge ethnomedical traditions with cutting‐edge experimental science, thereby illuminating diverse mechanisms—such as modulating apoptotic pathways, regulating oxidative stress, or impeding tumor growth. This pattern is further corroborated in Fig. 12, where Journal of Ethnopharmacology emerges as the most frequently cited source, implying broad acknowledgment that traditional pharmacology provides a foundational framework for exploring the cell‐death–promoting effects of Chinese patent drugs. Meanwhile, Biomedicine & Pharmacotherapy, International Journal of Molecular Sciences, and Frontiers in Pharmacology each record hundreds of local citations, highlighting a synergy between fundamental mechanistic studies and translational efforts to refine Chinese herbal formulas for clinical oncology. The noticeable citations in PLOS ONE and Cancer Research reveal ongoing efforts to disseminate these findings in broader, high‐impact venues, possibly in an attempt to standardize TCM approaches and highlight reproducibility. Together, these journal trends point to the field’s multidimensional character: investigations are anchored in ethnopharmacological roots, yet advanced through interdisciplinary platforms that emphasize molecular mechanisms and evidence‐based validation. The dominance of the Journal of Ethnopharmacology in both publication count and citation frequency reinforces the pivotal role of culturally informed pharmacological insight, suggesting that ongoing collaboration between ethnopharmacologists and molecular oncologists may pave the way for future breakthroughs in harnessing Chinese patent drug therapies for programmed cell death in cancer.

Fig. 11

Most relevant journals by publication count

Fig. 12

Most frequently cited journals

4.5 Analysis of cooperation models

As shown in Fig. 13, China serves as the primary collaboration hub, forging extensive research linkages with North America, Western Europe, and select Asia-Pacific countries in the study of Chinese patent drugs that induce programmed cell death in cancer cells. These cross‐regional connections suggest that both developed and emerging economies are eager to validate, refine, and adapt traditional Chinese formulations for modern oncological applications. Notably, collaborations often involve broad‐spectrum research teams, encompassing pharmacology, molecular biology, and clinical science, indicating that multidisciplinary efforts are essential to translate laboratory findings into viable therapeutic interventions. At the same time, Fig. 14 reveals that most corresponding authors hail from China, reinforcing China’s leading position in both single‐country (SCP) and multi‐country (MCP) publications. While Chinese‐affiliated authors clearly dominate in terms of sheer output, the United States, Korea, Germany, and Japan make meaningful contributions, frequently entering multi‐institutional collaborations that pool expertise and resources. This pattern of authorship confirms a willingness among global research teams to leverage China’s deep ethnopharmacological heritage alongside cutting‐edge Western biomedical approaches, thereby accelerating progress in targeted cancer therapies. The increasing presence of Australia, India, and other nations in the MCP category also signifies a growing diversity of institutional perspectives. Such broad engagement potentially facilitates rigorous evaluation of Chinese patent drugs across varied experimental systems, patient populations, and regulatory environments. From a thematic standpoint, cross‐border partnerships appear to focus on refining mechanistic understanding—elucidating how these compounds modulate apoptotic and autophagic pathways—while simultaneously exploring clinical efficacy and safety. In doing so, they integrate high‐throughput screening, genomic profiling, and immunological assays, echoing a larger shift within oncology research toward precision medicine. Consequently, this network of collaborations fosters not only the standardization and global recognition of these therapeutic agents but also the development of novel combination strategies that may extend beyond classical apoptosis to incorporate complementary treatment modalities.

Fig. 13

World map of collaborations

Fig. 14

Corresponding authors’ country distribution

4.6 Analysis of the volume of literature published

As indicated in Table 1, the cumulative number of published articles on Chinese patent drugs that promote programmed cell death in cancer cells has expanded dramatically from just 2 papers in 1998 to a total of 4073 by 2024. During the initial phase (1998–2002), publication outputs were minimal, hovering in single to low double digits (2 to 12 articles per year), suggesting that the research focus in this era was only beginning to recognize the potential synergy between traditional Chinese formulations and targeted oncological therapies. From 2003 to 2008, the field experienced modest yet steady growth, reaching 44 annual publications in 2008; this period likely reflects gradual interest in elucidating the underlying mechanisms—particularly apoptosis—that make these compounds attractive for cancer treatment. A second inflection point emerges between 2009 and 2014, when annual publications rose from 54 to 141, which may be attributed to broader acceptance of complementary and alternative therapies in mainstream scientific discourse, as well as the advent of more sophisticated laboratory techniques capable of dissecting cellular pathways. The transition from 2015 to 2019 marks another significant surge, with articles climbing from 163 to 300 per year, consistent with expanding global collaborations and deeper mechanistic insights into regulated cell death processes (e.g., autophagy, ferroptosis). Notably, the jump between 2019 and 2023—rising from 300 to 416 articles—coincides with the COVID‑19 pandemic, a period during which research into traditional Chinese medicine (TCM) overall saw increased funding and attention, potentially boosting publications on TCM-derived cancer therapeutics as well. By 2024, the number of articles soars to 551, reflecting a culmination of factors including heightened cross‐disciplinary collaborations, technological advances in screening bioactive compounds, and continuing interest in combining TCM with standard anticancer regimens. The overall trajectory suggests that initial skepticism has given way to robust scientific inquiry, with many groups now viewing Chinese patent drugs as a complementary avenue to enhance the precision and efficacy of cancer treatments through targeted induction of programmed cell death.

Table 1 Annual number of publications on Chinese patent drugs promoting programmed cell death in Cancer cells (1998–2024)