Endogenous Plant signals and human Health: Molecular mechanisms, ecological functions, and therapeutic Prospects

Abstract

Endogenous plant signals, including phytohormones, secondary metabolites, and volatile organic compounds, play pivotal roles in plant growth, defense, and ecological interactions. Signals are crucial in plant responses to both biotic and abiotic stressors, as well as in the biosynthesis of therapeutic compounds. Jasmonic acid, salicylic acid, and ethylene are crucial signaling molecules that regulate internal and external communication, including herbivore defense and microbial interactions. Volatile organic compounds further enable plant–plant communication and ecological resilience. Increasing evidence links these signaling pathways to the production of compounds with antioxidant, anti-inflammatory, and anticancer properties in humans, bridging plant ecology with human health. This narrative review was conducted through integrative thematic synthesis of peer-reviewed literature published between 2015 and 2025, using databases such as PubMed, Scopus, and ScienceDirect. Articles were selected based on their relevance to the molecular mechanisms, ecological roles, and therapeutic implications of endogenous plant signals. Emphasis was placed on interdisciplinary studies spanning molecular biology, pharmacology, and systems ecology. This review explores recent advancements in plant signals' molecular and ecological roles, emphasizing their importance in sustainable agriculture, drug discovery, and functional foods. Signaling networks' complexity necessitates interdisciplinary strategies involving molecular biology, systems ecology, and pharmacology, which can be harnessed through biotechnology and systems-based research for therapeutic and ecological innovations.

Graphical abstract

Highlights

• •This study explores endogenous plant signals and their roles in human health promotion.
• •It links plant defense signaling to bioactive compound biosynthesis.
• •Highlights volatile compounds in plant communication and therapy.
• •Reviews signal transduction pathways regulating phytochemical production.
• •Emphasizes interdisciplinary insights bridging ecology, medicine, and biotechnology.

1. Introduction

Plants, as sessile organisms, have evolved sophisticated signaling systems to perceive, respond to, and interact with their environment. These endogenous plant signals, such as phytohormones, secondary metabolites, and volatile organic compounds, play crucial roles in regulating plant growth, development, and defense mechanisms [1]. Volatile organic compounds, especially terpenoids, facilitate plant communication and response to climate change [2]. Plants utilize physical barriers and chemical defences, such as secondary metabolites and volatile organic compounds, to combat herbivory and infection (Fig. 1). These reactions entail intricate signaling cascades that activate hormones such as jasmonic acid, salicylic acid, and ethylene [3]. Microbial signals significantly influence plant growth and development. Beneficial microorganisms synthesize phytohormones, including auxins and cytokinins, along with other signaling molecules such as N-acyl-l-homoserine lactones and volatile organic compounds, which can influence plant immunity, gene expression, metabolism, and growth [4]. These signals are pivotal in enabling plants to adapt to their environment, mediate interactions with other organisms, and maintain ecological balance. Communication between plants through airborne volatiles improves defence mechanisms against herbivores [5]. These signaling pathways entail complex interactions and cross-communication, enabling plants to assimilate various inputs and implement suitable developmental responses. For instance, ethylene, a crucial hormone in plant development, regulates responses to environmental challenges and interactions with other organisms. Its regulatory role in multi-organismal interactions can result in community-level impacts, including relationships with commensals and resistance to secondary invaders [6]. Plant communication includes not just volatile compounds but also subterranean signaling, allelopathy, and photosensory signals [7]. Diverse signaling pathways are essential in plant defense, invasive exotic plant species, and trophic relationships. Beyond their ecological importance, these signaling pathways have significant implications for human health, as they govern the biosynthesis of numerous bioactive compounds with therapeutic potential [8] (Fig. 1). Recent advances in plant molecular biology, metabolomics, and ecological research have revealed that many phytochemicals produced in response to internal or external stimuli not only confer survival advantages to plants but also exert potent biological effects in humans [9]. Compounds such as salicylic acid, paclitaxel, artemisinin, and cannabidiol are well-known examples of plant-derived molecules whose biosynthesis is tightly regulated by endogenous signals. These substances often exhibit antioxidant, anti-inflammatory, anticancer, neuroprotective, and immunomodulatory properties, making them attractive candidates for drug discovery and therapeutic development [10]. Moreover, plant communication which is mediated by VOCs, root exudates, and microbial signaling demonstrates a complex web of interspecies interactions that influence plant metabolism and secondary compound biosynthesis [11]. Understanding these signaling pathways not only enriches our ecological knowledge but also offers new biotechnological avenues for enhancing the yield of bioactive phytochemicals. By exploring the origins and functions of these signals, researchers can uncover novel approaches to drug discovery, sustainable agriculture, and holistic healthcare solutions.

Fig. 1.

Effects of Endogenous Plant Signaling. Adapted, and modified from Ref. [99] (Created in https://BioRender.com).

The exploration of plant-derived compounds for therapeutic applications has gained global attention in recent years. However, most biomedical research has focused on isolated bioactive molecules, often overlooking the dynamic signaling mechanisms by which these compounds are synthesized in nature. Endogenous signals within plants, such as phytohormones, secondary metabolites, and volatile organic compounds, play central roles in plant physiology and ecological adaptation. Despite their critical importance, the integrated ecological and biomedical relevance of these signals remains poorly understood.

Conventional phytochemical research has predominantly aimed at identifying and extracting compounds with pharmacological activity. Approaches in plant biotechnology, synthetic biology, and molecular pharmacognosy have improved yield and bioactivity of select compounds. However, these efforts rarely contextualize these molecules within the complex plant signaling pathways that govern their production in response to environmental stimuli. Additionally, efforts in sustainable agriculture and ecological conservation have begun leveraging these signaling systems to enhance plant resilience and reduce dependence on synthetic agrochemicals.

This review proposes an integrative framework that examines endogenous plant signals not only from a botanical or agricultural perspective but also through the lens of human health and therapeutic innovation. By mapping the molecular mechanisms of signal transduction and ecological interactions onto translational outcomes, such as antioxidant, anti-inflammatory, and anticancer activities, we aim to reveal how endogenous signaling cascades can be repurposed for drug discovery and functional food development.

This review is unique in bridging plant molecular signaling, ecological function, and therapeutic relevance in a unified discussion. It offers an interdisciplinary synthesis of current literature, covering phytohormones, secondary metabolites, and volatile organic compounds as mediators of ecological communication and human health outcomes. Our objective is to highlight how understanding these pathways opens new avenues for biotechnology, sustainable agriculture, and pharmacological innovation. Through this approach, we advocate for a systems-level understanding of plant-derived therapeutics, rooted in the evolutionary logic of endogenous signaling networks.

2. Methodology

This narrative review was conducted through an integrative and qualitative synthesis of current literature to explore the molecular mechanisms, ecological roles, and therapeutic potentials of endogenous plant signals. A comprehensive literature search was performed using electronic databases including PubMed, Scopus, and ScienceDirect. Keywords such as “endogenous plant signals,” “phytohormones,” “secondary metabolites,” “volatile organic compounds,” “plant defense mechanisms,” and “therapeutic phytochemicals” were used in various combinations to identify relevant peer-reviewed articles, reviews, and book chapters published primarily between 2015 and 2025. Sources were selected based on their relevance, scientific rigor, and contribution to advancing the understanding of plant signaling pathways and their intersection with human health. Special attention was given to interdisciplinary studies that integrate molecular biology, plant physiology, pharmacology, and ecological interactions. The collected literature was thematically analyzed to identify key concepts, trends, and translational implications. Findings were structured to reflect a coherent narrative that bridges plant science and biomedical research.

3. Discussion and comparative insights

The role of endogenous plant signals has been well-studied across different disciplines. However, their integrative impact on human health through ecological functions requires comparative evaluation with existing literature to identify translational potential. Strengthening this understanding requires deeper mechanistic insights and interdisciplinary characterization. Table 1 provides a concise summary of major endogenous plant signals, illustrating their roles in plant physiology and their translational relevance to human health.

Table 1.

Endogenous plant signals: Physiological roles and human health implications.

Endogenous Signal	Major Role in Plants	Human Health Effects	Example Sources	References
Jasmonic Acid	Defense against herbivores and pathogens; regulation of secondary metabolism	Indirect role via increased artemisinin production; supports anticancer and antimalarial therapy	Artemisia annua	[13,32]
Salicylic Acid	Systemic acquired resistance; redox homeostasis; thermogenesis	Precursor to aspirin; anti-inflammatory, antipyretic, and cardioprotective properties	Willow bark (Salix spp.)	[16,33]
Ethylene	Fruit ripening; senescence; response to mechanical stress	Ethylene inhibitors used in postharvest medicine; links to anti-aging research	Climacteric fruits (e.g., banana)	[34,35]
Auxin	Cell elongation; apical dominance; root initiation	Limited direct effects; synthetic analogs explored in cancer inhibition and regenerative biology	Arabidopsis thaliana, legumes	[36,37]
Abscisic Acid	Stress adaptation; stomatal closure; seed dormancy	Studied for anti-inflammatory and anti-diabetic effects via modulation of PPARγ	Grapevine, maize, tomato	[38,39]
Flavonoids	UV protection; pollinator attraction; pathogen resistance	Antioxidant, anti-inflammatory, cardioprotective, and neuroprotective functions	Citrus, berries, tea	[40]
Terpenoids	Volatile signaling; defense against herbivores and pathogens	Anticancer (e.g., taxol), antimalarial (e.g., artemisinin), antimicrobial	Taxus spp., Artemisia spp.	[[18], [19], [20]]
Alkaloids	Herbivore deterrence; antimicrobial defense	Analgesic (e.g., morphine), anticancer (e.g., vincristine), antimalarial (e.g., quinine)	Papaver somniferum, Cinchona spp.	[41,42]
Phenolics	Structural defense (lignin); UV screening; antioxidant support	Reduce oxidative stress; prevent cardiovascular and neurodegenerative diseases	Green tea, cocoa, grapes	[22,23]
Volatile Organic Compounds	Inter-plant communication; attraction of predators; microbial interaction	Inhaled aromatherapy agents with stress-relief, antimicrobial, or anticancer potential	Lavender, peppermint, eucalyptus	[29,43]

The bioactivity of jasmonic acid (JA) in regulating defense and secondary metabolism has been reported in prior studies [12,13]. In our discussion, we align this with its ecological roles and draw comparisons to JA-induced artemisinin production for antimalarial therapy, which is consistent with He et al. [14]. Advanced metabolomic profiling of JA-treated plants has demonstrated a correlation with increased sesquiterpene lactone content, confirming its regulatory influence on secondary metabolism [15].

Salicylic acid (SA)-mediated immunity in plants is comparable to human anti-inflammatory pathways activated by aspirin. This aligns with Dempsey & Klessig [16], who emphasized the role of SA in systemic acquired resistance and its pharmacological significance in cardiovascular diseases. Transcriptomic analyses have shown SA upregulates defense genes like PR1, PR5, and WRKY70, confirming its molecular activity during plant-pathogen interactions [17].

The production and therapeutic relevance of terpenoids such as taxol and artemisinin are documented by Boncan et al. [18] and Kamran et al. [19]. Our findings echo these by showing how stress-induced terpenoid pathways in plants may correlate with anti-cancer and anti-microbial benefits in humans. This is further supported by Siddiqui et al. [20]. Biosynthetic pathways such as the MEP and MVA routes are tightly regulated by stress-induced transcription factors (e.g., MYC2, WRKYs), as demonstrated by Ren et al. [21].

When comparing phenolic compounds, our synthesis reinforces findings by Misra et al. [22], which highlighted their role in oxidative stress mitigation. This is expanded by Singh & Yadav [23], whose review documented phenolics’ preventive roles in neurodegeneration and cardiovascular disorders. Functional characterizations via metabolite profiling and antioxidant assays consistently show elevated phenolic content under UV or biotic stress.

The plant–microbe–insect interaction matrix emphasizes ecological specificity of metabolite biosynthesis. This complements findings by Noman et al. [24], who documented microbial induction of plant chemical defenses, and Chamkhi et al. [25], who highlighted microbial elicitors in stimulating secondary metabolites. Several studies have shown endophyte-mediated enhancement of alkaloid and flavonoid biosynthesis via signaling cross-talk involving jasmonate and ethylene [26,27]. Table 2 compares matrix of plant–microbe–insect interactions, signaling cascades involved, associated secondary metabolites, and ecological outcomes.

Table 2.

Plant–microbe–insect interaction matrix.

S/N	Interaction type	Signaling cascade	Secondary metabolite	Ecological outcome
1	Symbiosis (Rhizobia)	Nod factor - Cytokinin	Isoflavonoids	Nitrogen fixation
2	Defense (Herbivory)	Jasmonic acid, Ethylene	Alkaloids, Flavonoids	Insect deterrence
3	Attraction (Pollinators)	Terpenoids, VOCs	Nectar volatiles	Pollination
4	Antagonism (Pathogens)	Salicylic acid, ROS	Phenolics, Phytoalexins	Disease resistance
5	Endophytic colonization	JA/ET/SA cross-talk	Terpenoids, Lignans	Enhanced growth & immunity

Our ecological framing of volatile organic compounds mirrors results by Zhou & Jander [28] and Razo-Belman & Ozuna [29], confirming their dual functions in communication and defense. These comparisons validate the hypothesis that ecological stressors not only direct biosynthesis but also enhance the therapeutic profiles of plant compounds. VOC profiling techniques such as GC-MS have linked specific compound profiles (e.g., linalool, methyl salicylate) with plant defense phenotypes [30].

In line with Jalota et al. [31], we also compared elicitor-based enhancement of phytochemical yields in medicinal plants, reinforcing the role of ecological triggers and metabolic engineering in optimizing bioactivity. Future characterization strategies should include CRISPR-based modulation of biosynthetic genes and isotope-labeled flux analysis for quantitative pathway mapping.

This integrative approach across plant biology, pharmacology, and systems ecology underscores the translational significance of comparative frameworks, offering a holistic understanding of how endogenous plant signals can inform sustainable therapeutic innovation.

3.1. Classification and functional diversity of plant signaling molecules

Endogenous plant signals encompass a diverse array of biochemical messengers that regulate plant physiology, stress responses, and ecological interactions. These signals can be broadly categorized into three main groups: phytohormones, secondary metabolites, and volatile organic compounds (VOCs) [44]. Each group plays distinct yet often overlapping roles in maintaining homeostasis, coordinating development, and mediating environmental responses. These dynamic roles highlight the dual nature of endogenous signals as mediators of both internal regulation and external communication. Table 3 is a summary of key bioactive phytochemicals, their chemical classes, source plants, signaling pathways, and bioactivities.

Table 3.

Bioactive phytochemicals.

S/N	Phytochemicals	Class	Source plant	Signaling pathway	Bioactivity
1	Artemisinin	Terpenoid	Artemisia annua	Jasmonic acid	Antimalarial, anticancer
2	Salicylic Acid	Phenolic acid	Salix spp.	Salicylic acid	Anti-inflammatory, antipyretic
3	Paclitaxel	Terpenoid	Taxus brevifolia	Jasmonic acid	Anticancer
4	Resveratrol	Polyphenol	Grapes, Berries	SA/JA cross-talk	Antioxidant, anti-aging
5	Epicatechin	Flavonoid	Cocoa, Green tea	ROS-mediated	Cardioprotective
6	Quinine	Alkaloid	Cinchona spp.	Ethylene/JA	Antimalarial
7	Morphine	Alkaloid	Papaver somniferum	Auxin/JA	Analgesic
8	Linalool	VOCs (Monoterpene alcohol)	Lavender	Ethylene	Anti-anxiety, antimicrobial
9	Anthocyanins	Flavonoid	Blueberries, Black rice	MYB-bHLH	Neuroprotective
10	Abscisic Acid	Phytohormone	Tomato, Grapevine	ABA	Anti-inflammatory, anti-diabetic

3.1.1. Phytohormones

Phytohormones are small organic molecules that serve as central regulators of plant growth, differentiation, and adaptive responses. Phytohormone networks exhibit extensive crosstalk, enabling plants to fine-tune responses to complex and dynamic environments [1]. Key phytohormones include:

• i.Jasmonates (JAs): Involved in plant defense against herbivores and pathogens, as well as regulation of senescence, reproduction, and secondary metabolite biosynthesis [12]. JA signaling also integrates with other pathways to balance growth-defense trade-offs.
• ii.Salicylic acid (SA): A major mediator of systemic acquired resistance (SAR), SA is critical for plant immunity, especially against biotrophic pathogens. It also modulates redox homeostasis and thermogenesis [45,46].
• iii.Ethylene: Regulates fruit ripening, abscission, senescence, and responses to mechanical stress and pathogen attack. Ethylene signaling often synergizes or antagonizes other hormone pathways [47].
• iv.Auxins, Cytokinins, Gibberellins, Abscisic Acid, and Brassinosteroids: These classic phytohormones govern key aspects of development, cell division, seed dormancy, and environmental stress tolerance [48].

3.1.2. Secondary metabolites

Secondary metabolites are specialized compounds not directly involved in primary metabolic processes but essential for ecological fitness. These metabolites are often tightly regulated by hormonal signaling and environmental cues and serve as key reservoirs of bioactive compounds with therapeutic potential in humans [10]. They include:

• i.Phenolics (e.g., flavonoids, tannins): Possess antioxidant, UV-protective, and antimicrobial properties. Often synthesized in response to abiotic or biotic stress [49].
• ii.Alkaloids: Nitrogen-containing compounds with diverse pharmacological activities, including analgesic, anticancer, and antimicrobial effects [50].
• iii.Terpenoids: The largest class of secondary metabolites; involved in plant defense, signaling, and attraction of pollinators or natural enemies of herbivores [51].
• iv.Saponins and Glycosides: Contribute to plant defense by disrupting cell membranes of pests and pathogens [52].

3.1.3. Volatile organic compounds (VOCs)

VOCs are low molecular weight, lipophilic compounds that easily vaporize and play vital roles in plant communication and defense. VOCs function not only as external messengers but also as internal modulators of metabolism, stress signaling, and development [53]. Major VOC classes include terpenes, alcohols, aldehydes, and esters. Their major functions are as follows:

• i.Plant-Plant Communication: VOCs released from damaged or stressed plants can prime neighboring plants for enhanced resistance, a phenomenon known as “priming” [54].
• ii.Plant-Insect Interactions: Certain VOCs attract pollinators or predatory insects that defend the plant against herbivores, exemplifying indirect plant defense mechanisms [28].
• iii.Microbial Interactions: VOCs also mediate interactions with soil microbiota, influencing microbial colonization, competition, and signaling [44].

3.2. Molecular mechanisms of signal transduction

The transmission of endogenous plant signals involves a sophisticated network of molecular mechanisms that enable plants to perceive environmental and developmental cues, transduce them into cellular responses, and coordinate appropriate physiological outcomes. The perception and transduction of endogenous plant signals involve tightly regulated molecular pathways that allow plants to sense their environment and activate precise physiological responses. Signal transduction typically proceeds through a four-step process: signal perception, amplification, transcriptional regulation, and cellular response (Fig. 2). Below, we delineate these steps using concrete examples of phytohormone and volatile-mediated pathways.

Fig. 2.

Endogenous plant signal transduction.

3.2.1. Signal perception: receptor-ligand specificity

Signal recognition begins with the interaction of signaling molecules with their respective receptors, which are typically located on the plasma membrane or within intracellular compartments. These receptors exhibit high ligand specificity. Key examples include:

• i.Auxins bind to the TIR1/AFB family of F-box proteins, which serve as co-receptors in conjunction with AUX/IAA proteins [55]. This interaction promotes ubiquitination and degradation of AUX/IAA repressors, liberating ARF transcription factors to modulate auxin-responsive genes [56].
• ii.Jasmonic acid (JA) is perceived via the COI1–JAZ co-receptor complex. JA-Ile binding induces the ubiquitination and degradation of JAZ repressors, thereby activating MYC transcription factors involved in defense and secondary metabolism [57].
• iii.Salicylic acid binds to Nonexpressor of PR Genes 1 (NPR1), a redox-sensitive regulator that modulates transcription of pathogenesis-related (PR) genes after its monomerization and translocation to the nucleus [58].
• iv.Ethylene perception is initiated by membrane-bound receptors such as ETR1, which, upon ethylene binding, relieve the repression exerted by CTR1, leading to activation of the downstream transcription factor EIN3 [59].

3.2.2. Signal amplification: secondary messengers and kinase cascades

Once recognized, these signals trigger secondary messengers like calcium ions, reactive oxygen species, and nitric oxide, which amplify the signal and activate downstream kinases, particularly MAPKs as follows:

• i.Calcium ions (Ca²⁺): Bind to calcium sensors like calmodulin (CaM) or calcium-dependent protein kinases (CDPKs), which phosphorylate downstream effectors [60].
• ii.Reactive oxygen species (ROS): Act as both signaling molecules and stress indicators; for example, H₂O₂ triggers the activation of MAPKs and transcription factors [61].
• iii.Mitogen-Activated Protein Kinase (MAPK) cascades: These involve a sequential activation of MAPKKKs → MAPKKs → MAPKs. For instance, in JA signaling, MPK6 phosphorylates transcription factors like MYC2, enhancing expression of defense-related genes [62].

3.2.3. Transcriptional regulation

These pathways culminate in transcriptional regulation through the activation of signal-responsive transcription factors (e.g., MYB, WRKY, bZIP), which control the expression of genes involved in defense and secondary metabolite biosynthesis [63]. These cascades of activation or repression of specific transcription factors are:

• i.WRKYs: Central to SA-mediated defense signaling.
• ii.MYBs and bHLHs: Regulate secondary metabolite biosynthesis including anthocyanins and alkaloids [64].
• iii.NACs and ERFs: Participate in abiotic stress responses and ethylene signaling.

Post-translational modifications (e.g., phosphorylation, ubiquitination) of these transcription factors fine-tune the strength and duration of transcriptional responses [65].

3.2.4. Metabolic reprogramming and cellular response

Signal-induced transcription leads to upregulation of biosynthetic genes encoding enzymes such as:

• i.Phenylalanine ammonia-lyase (PAL): A gateway enzyme in the phenylpropanoid pathway.
• ii.Chalcone synthase (CHS): Initiates flavonoid biosynthesis.
• iii.DXS and HMGR: Key regulators of the MEP and MVA pathways, respectively, leading to terpenoid biosynthesis.

This reprogramming not only enables defense against pathogens or herbivores but also facilitates the accumulation of therapeutically relevant phytochemicals such as resveratrol, paclitaxel, and artemisinin. Complex crosstalk exists between signaling pathways such as JA–SA antagonism and ABA–ethylene synergy, ensuring that plants balance growth, defense, and adaptation depending on environmental context [66]. This dynamic regulation is further modulated by epigenetic mechanisms, including histone modifications and small RNAs (e.g., miRNAs targeting TFs or biosynthetic genes) [67].

3.3. Bioactive phytochemicals as mediators of human health

Bioactive phytochemicals derived from plant signaling pathways hold immense promise for human health. Diverse phytochemicals, such as polyphenols, alkaloids, and saponins, influence numerous signaling pathways associated with cancer, including apoptosis, proliferation, invasion, and metastasis [68]. These compounds, often produced as part of the plant's defense mechanism, have demonstrated remarkable therapeutic properties [10]. For instance, paclitaxel, a product of plant secondary metabolism, has revolutionized cancer treatment due to its ability to inhibit cell division [69]. Botanical derivatives such as phenolic chemicals, flavonoids, and alkaloids demonstrate anticancer effects via regulating proliferative and apoptotic processes [70]. Examples include paclitaxel from (Taxus brevifolia), which stabilizes microtubules and inhibits mitosis, and resveratrol, which activates p53-mediated apoptosis [51,71]. Flavonoids like epicatechin and anthocyanins can help mitigate cardiovascular disease by lowering lipids, enhancing nitric oxide availability, preventing hypertension, improving endothelial function, and reducing vascular inflammation, restoring vascular homeostasis, and thus preventing atherosclerosis [40]. Plant compounds, including polyphenols, alkaloids, and terpenoids, can modulate gut microbiota, enhancing beneficial bacteria growth, influencing microbial composition, and contributing to biotransformation into bioactive metabolites, influencing systemic health [72,73]. Similarly, artemisinin, derived from the jasmonate-inducible pathways in Artemisia annua, has become a cornerstone in malaria therapy [14]. Numerous plant chemicals, frequently chromophoric, are incorporated into stress adaptation systems and can influence mitochondrial and calcium signaling in animals [74]. Compounds originating from the shikimate and phenylpropanoid pathways exhibit a variety of therapeutic qualities, including anti-inflammatory and anti-aging actions [75]. Prominent therapeutic substances such as salicylic acid and cannabidiol may indicate their evolutionary roles in plants regarding stress adaptation and the preservation of dissipative homeostasis [76]. Salicylic acid, the precursor to aspirin, rooted in plant defense signaling is notable for various immunomodulatory roles in human [77]. These findings highlight the promise of plant-derived chemicals in the creation of innovative medicines. The mechanisms of action of these phytochemicals are often linked to their ecological functions. Compounds that protect plants from pathogens and environmental stressors frequently exhibit analogous effects in human cells, such as antioxidant, anti-inflammatory, and antimicrobial activities [78,79]. This ecological parallel underscores the potential of endogenous plant signals as a rich source of bioactive molecules for drug development. Moreover, advancements in understanding how these signals regulate the biosynthesis of phytochemicals open new avenues for enhancing their production. Biotechnological approaches, including metabolic engineering and elicitor-based strategies, are increasingly employed to optimize the yield of these valuable compounds, bridging ecological insights with practical applications in medicine [80]. Functional foods and nutraceuticals incorporate phytochemicals like polyphenols, carotenoids, and glucosinolates for health benefits, prevention of chronic diseases, improved gut health, and natural antioxidants [81].

Recent studies have emphasized the intricate regulatory mechanisms that control the manufacture of therapeutic chemicals in plants. For instance, transcription factors are essential in regulating the expression of critical enzymes involved in the generation of secondary metabolites [73]. These regulatory networks react to many environmental inputs and phytohormones, precisely adjusting the timing and intensity of gene expression within pathways [82]. Moreover, microbial elicitors have demonstrated the capacity to stimulate the production of bioactive chemicals in medicinal plants, such as terpenoids, phenolic acids, and flavonoids [25]. The connection between endophytes and host plants entails intricate signaling pathways, with chemicals serving as intermediaries between the two species [83]. These regulatory processes and plant-microbial interactions offer significant insights for augmenting the synthesis of pharmaceutically vital chemicals in medicinal plants [25].

3.4. Translational implications: from ecological interactions to therapeutic innovation

The interplay between plant ecology and human medicine offers a unique perspective on drug discovery and therapeutic innovation. Many plant-derived medicines have ecological origins, stemming from the interactions between plants and their biotic and abiotic environments. For example, plant-microbe interactions often trigger the production of antimicrobial compounds, which can be repurposed as human antibiotics [84]. Similarly, the production of volatile organic compounds in response to herbivory provides insights into stress signaling pathways that may be harnessed for human health benefits [85]. Recent research underscores the complex interactions of plants, insects, and bacteria within ecosystems, highlighting their significance for the discovery of medicinal plants. Relationships among plants, insects, and microbes entail complex chemical communication and defence strategies, affecting ecosystem dynamics [24]. These interactions may result in the bioaccumulation or alteration of phytochemicals in insects, potentially generating new therapeutic molecules [86]. Volatile organic compounds are essential in plant-insect communication, with related microbial communities influencing these interactions [87]. An interdisciplinary methodology integrating evolutionary ecology, molecular biology, and ethnopharmacology is suggested to enhance medicinal plant research, utilising traditional knowledge alongside contemporary biodiversity science [88]. This comprehensive viewpoint regards medicinal plants as possible symbiotic allies that have impacted human health and society, rather than simply chemical resources for exploitation, presenting new opportunities for biodiscovery and pharmaceutical progress. Case studies, such as the development of anti-cancer drugs from endophyte-infected plants, demonstrate the potential of cross-disciplinary collaborations in translating ecological knowledge into medical advancements [89]. This bridge between ecology and medicine underscores the importance of viewing plant signals not merely as botanical phenomena but as foundational elements with broad applications in healthcare and pharmacology.

3.5. Challenges and knowledge gaps

Despite the promising applications of endogenous plant signals in agriculture and medicine, several critical challenges and knowledge gaps must be addressed to fully harness their potential. These challenges span biological complexity, technological limitations, regulatory hurdles, and environmental sustainability. Addressing these issues through interdisciplinary and integrative approaches is essential for translating scientific insights into real-world impact.

• i.Complexity of Plant Signaling Networks: One of the foremost challenges is the intrinsic complexity of plant signaling pathways. These networks involve redundant and overlapping functions among signaling molecules, crosstalk between pathways (e.g., JA-SA, ABA-ethylene) that can yield context-dependent outcomes, as well as spatiotemporal dynamics, where signaling responses vary by tissue type, developmental stage, or environmental condition [90]. Deciphering these interactions requires advanced computational modeling, high-throughput omics technologies, and systems biology approaches [91]. Moreover, functional validation using gene editing tools (e.g., CRISPR/Cas) remains underutilized in non-model and medicinal plants [59].
• ii.Limited Understanding of Signal-Driven Metabolite Biosynthesis: Although it is known that plant signals regulate the biosynthesis of key phytochemicals, the exact regulatory nodes and transcriptional controls remain unclear for many bioactive compounds. There is a need to map the transcriptional and metabolic networks that link signal perception to secondary metabolite production [92]. Identifying rate-limiting enzymes and master regulators involved in compound biosynthesis is very critical. Additionally, there is limited understanding of epigenetic and non-coding RNA involvement [93]. Bridging these gaps would enable more precise metabolic engineering strategies for enhancing therapeutic compound yields.
• iii.Challenges in Biotechnological Production and Scalability: Efforts to enhance phytochemical production using elicitors, transformed root cultures, and microbial consortia have shown promise but are often limited by variability in metabolite yield under in vitro versus in vivo conditions [31]. Similarly, scalability issues in bioreactors and field-level implementation are critical. Moreover, instability of elicitor responses across different plant genotypes or environmental settings do exist [94]. Optimizing cultivation protocols, improving bioreactor design, and developing robust bioinformatic pipelines for strain and elicitor selection are critical next steps [95].
• iv.Sustainable Sourcing and Biodiversity Conservation: The growing demand for plant-derived therapeutics raises concerns about overharvesting, threatening biodiversity and ecological balance. Sustainable practices include in vitro propagation, tissue culture, synthetic biology, agroecological principles, ethical bioprospecting, and environmental stewardship [96]. Integrating environmental stewardship with phytochemical sourcing is vital for long-term viability.
• v.Regulatory and Translational Barriers: Plant-derived compounds face regulatory challenges due to lack of standardized quality control, inconsistent regional frameworks, and limited clinical data on bioavailability, pharmacokinetics, and toxicity [97,98]. To improve medical translation, establish safety and efficacy guidelines, expand clinical trials and real-world evidence, and collaborate academic, industry, and regulatory bodies for efficient development pipelines.

4. Future research directions

To overcome current limitations and unlock the full potential of endogenous plant signals, future research should prioritize:

• i.Multi-omics integration (transcriptomics, proteomics, metabolomics, microbiomics) to map comprehensive signaling and metabolic networks.
• ii.Synthetic biology and gene editing to optimize biosynthetic pathways and signaling circuits in medicinal plants.
• iii.Plant–microbe–insect interaction studies to explore ecological drivers of bioactive compound variation.
• iv.Computational modeling and AI tools for predicting compound biosynthesis and bioactivity.
• v.Transdisciplinary frameworks that merge ethnobotany, molecular biology, ecology, and pharmacology for innovation in both drug discovery and sustainable agriculture.

5. Conclusion

Endogenous plant signals form the biochemical foundation of plant life, regulating growth, development, defense, and ecological interactions. These signaling molecules ranging from phytohormones and secondary metabolites to volatile organic compounds are not only vital for plant survival but also represent a treasure trove of bioactive compounds with profound implications for human health. By mediating the biosynthesis of phytochemicals with antioxidant, anti-inflammatory, anticancer, and neuroprotective properties, plant signaling pathways serve as a bridge between ecology and medicine. Their applications extend from sustainable crop protection and enhanced agricultural resilience to the discovery and development of novel therapeutics and functional foods. Importantly, the ecological functions of these compounds often mirror their pharmacological effects in humans, underscoring the deep evolutionary interconnectedness between plant defense strategies and human physiological responses. Despite these promising insights, the complexity of plant signaling networks, limitations in our understanding of biosynthetic regulation, and challenges related to sustainable sourcing and translational application present significant hurdles. Addressing these issues requires a holistic and interdisciplinary approach, integrating molecular biology, systems ecology, pharmacology, biotechnology, and traditional knowledge. Looking forward, advances in omics technologies, synthetic biology, and computational modeling offer unprecedented opportunities to decode, manipulate, and apply plant signaling systems for global benefit. As the world faces unprecedented challenges, from emerging health crises to environmental degradation, the study of endogenous plant signals emerges as a beacon of hope. Bridging the gap between ecology and medicine is not merely an academic endeavor; it is a call to action for a more harmonious and sustainable future where the wisdom of nature informs the progress of humanity. By harnessing the biochemical wisdom of plants, we move toward a future where ecological balance and human well-being are not separate goals, but deeply intertwined pursuits.

CRediT authorship contribution statement

Esther Ugo Alum: Writing – review & editing, Writing – original draft, Methodology, Investigation, Conceptualization. David Chukwu Obasi: Writing – review & editing, Project administration, Methodology, Investigation, Conceptualization. Jacinta Nnennaya Abba: Writing – review & editing, Resources, Methodology, Investigation. Ugonna Cassandra Aniokete: Writing – review & editing, Resources, Methodology, Investigation, Formal analysis. Prince Nkemakolam Okoroh: Writing – review & editing, Resources, Methodology, Investigation, Data curation. Okechukwu Paul-Chima Ugwu: Writing – review & editing, Writing – original draft, Validation, Software, Methodology. Daniel Ejim Uti: Writing – review & editing, Writing – original draft, Visualization, Supervision, Software, Methodology, Investigation.

Consent to participate

Not applicable.

Ethics approval

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Funding support

No funding was received.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

Data will be made available on request.