A structured literature search was performed to identify studies addressing the therapeutic potential of Arthrospira platensis (Gomont) Kützing ex Gomont, Cyanobacteriaceae in smooth muscle–related disorders. The databases PubMed, Scopus, Web of Science, and SciELO were searched for articles published between 2010 and 2025. Reference lists of retrieved articles and relevant reviews were also screened for additional studies. The literature search was performed in PubMed, Scopus, and Web of Science using the following keywords: “Arthrospira platensis,” “Spirulina platensis,” “smooth muscle,” “oxidative stress,” “antioxidant,” “inflammation,” “uterine contraction,” “vascular,” “intestinal,” “airway,” “pharmacology,” and “clinical trial.” Boolean operators (AND/OR) were applied to refine the search strategy.

Inclusion criteria were: (i) validated taxonomy of A. platensis; (ii) experimental data from in vitro or in vivo pharmacological models, or clinical trials; and (iii) publication in English. Exclusion criteria were: review articles, conference abstracts, studies lacking pharmacological data, or those using non-validated taxa.

The search initially retrieved 428 articles. After screening titles and abstracts, 252 articles were excluded, and 176 studies were included in the qualitative synthesis. The selection process is summarized in the PRISMA flowchart (Figure 2).

Asthma is a chronic, heterogeneous pulmonary disease marked by airway inflammation, remodeling, hyperresponsiveness, and variable airflow limitation, leading to symptoms such as coughing, wheezing, dyspnea, and chest tightness (Pelaia et al., 2021; Kardas et al., 2020). Affecting over 339 million people worldwide, it imposes a considerable social and economic burden (Zhang et al., 2025; GBD, 2021, 2025).

Airway smooth muscle (ASM) plays a central role in asthma pathophysiology. Once considered a passive contractile element, ASM is now recognized as a dynamic tissue with immunomodulatory, secretory, and remodeling capacities (Camoretti-Mercado et al., 2021; Van der Velden et al., 2013). In asthmatic individuals, ASM exhibits increased proliferation, hypertrophy, contractility, and cytokine secretion compared with non-asthmatic tissue (Ma et al., 2002; Chambers et al., 2003). ASM also releases inflammatory mediators—cytokines, chemokines, and extracellular matrix proteins—that amplify airway inflammation and remodeling (Lambrecht and Hammad, 2015a; Parikh et al., 2019).

From a mechanistic perspective, smooth muscle is the primary cell type responsible for generating tone and airway contraction in the lungs (Prakash, 2013). Upon stimulation by bronchoconstrictor agonists, there is an increase in intracellular calcium concentration ([Ca²⁺]ᵢ), triggering Ca²⁺–calmodulin binding, MLCK activation, and actin–myosin interactions that ultimately result in contraction (Zhu, 2011). Dysregulation of these calcium signaling pathways contributes to hypercontractility in asthma (Prakash et al., 2009; Bergantin, 2020; Sivaraman and Onyenwoke, 2021).

In summary, ASM is a key driver of asthma pathogenesis through its roles in bronchomotor regulation, inflammation, and remodeling. Understanding its functional plasticity is essential for developing targeted therapies.

The gastrointestinal (GI) tract is responsible for managing fluids and processing large quantities of solids and semi-solids that pass through the intestinal lumen. It also plays a central role in secretion, digestion, nutrient absorption, and waste elimination (Le et al., 2021; Ghishan and Kiela, 2012). In this context, GI smooth muscle (GISM) is primarily responsible for generating peristalsis, which facilitates efficient digestion, absorption, and excretion. These functions are regulated by the intrinsic electrical and mechanical properties of smooth muscle, through tonic contractions that maintain organ dimensions against luminal content (e.g., food bolus) and/or through the development of contractile force and muscle shortening (Bitar, 2003).

Contractility in gastrointestinal smooth muscle is a highly integrated process, wherein smooth muscle cells represent the final effectors of modulatory inputs from neurons, interstitial cells of Cajal (ICC), hormones, and paracrine substances (Sanders, 2008). These contractions generate the propulsive force needed to move digesta along the GI tract and ensure proper mixing with digestive enzymes, continuously exposing nutrients to the absorptive mucosal surface (Grundy et al., 1985). Therefore, alterations in GISM contractility are directly implicated in the pathophysiology of major gastrointestinal diseases and disorders. The fundamental basis of GI motility lies in the intrinsic ability of GISM to generate cyclic changes in resting membrane potential, which give rise to spontaneous and rhythmic contractions (Grundy et al., 1985). These contractions are tightly regulated by calcium (Ca²⁺) influx, which plays a key role in initiating GISM contraction.

In intestinal regions characterized by phasic motor patterns (small and large intestines), ICC-driven slow waves bring the membrane potential to the threshold of CaV1.2 channels, triggering action potentials (Morgan et al., 1981; Cannell and Lederer, 1987). In contrast, in areas such as the proximal stomach, the resting potential is near CaV1.2 activation, so depolarizing stimuli easily enhance tone (Sanders, 2008; Morgan et al., 1981). GI motility, especially in the ileum, has been studied with isometric transducers in response to electrical field stimulation (EFS), highlighting its key role in nutrient absorption (Nishiyama et al., 2017; Azuma et al., 2021).

Smooth muscle plays a critical role in the pathophysiology of infertility and erectile dysfunction (ED), as it is involved in essential physiological processes required for reproductive and sexual function. Consequently, impaired smooth muscle function may directly disrupt these processes, leading to difficulties in achieving conception or maintaining an erection (Hiremath et al., 2020; Souza et al., 2022). Male infertility is often characterized by a reduced sperm count. Studies have shown that this condition is not only associated with impaired sperm production but also with a decreased number of spermatozoa successfully transported through the male reproductive tract (Hiroshige et al., 2024).

The male reproductive tract is lined with smooth muscle that contracts rhythmically to propel sperm. This intrinsic activity ensures sperm movement, and although the autonomic nervous system does not directly trigger these contractile events, it plays a fundamental role in coordinating and modulating such contractions and other critical components of the sexual response (Klinge et al., 1994; Courtois et al., 2013).

A key contributing factor to infertility is erectile dysfunction (ED), defined as the consistent inability to achieve and/or maintain a penile erection sufficient for satisfactory sexual intercourse, affecting approximately 52% of men (Zhuang et al., 2024; Tchang et al., 2021).

Penile erection is a complex physiological process involving coordinated interactions among the nervous, vascular, and endocrine systems. Cavernosal smooth muscle, located in the erectile tissue of the penis, along with smooth muscle in the walls of small arteries and arterioles, plays a central role in erection. Sexual stimulation—triggered by auditory, visual, olfactory, or cognitive stimuli—is processed by the cerebral cortex and relayed through the parasympathetic pathways of the sacral plexus (Dean and Lue, 2005).

This neural activity stimulates the release of nitric oxide (NO) by non-adrenergic, non-cholinergic (NANC) nerve fibers or acetylcholine (ACh) by parasympathetic cholinergic neurons. NO enhances cyclic guanosine monophosphate (cGMP) synthesis and reduces intracellular calcium (Ca²⁺) levels, promoting relaxation of smooth muscle cells. Concurrently, compression of the submucosal venous plexus decreases venous outflow, allowing blood to be retained in the sinusoids of the corpora cavernosa, which progressively increases rigidity and results in full penile erection (Zhuang et al., 2024).

Therefore, smooth muscle is a critical component of the mechanisms underlying both infertility and erectile function. Research into agents capable of modulating smooth muscle activity represents a promising approach for the treatment of related disorders.

The uterus is structurally composed of three layers: the endometrium (luminal surface), the myometrium (smooth muscle layer), and the perimetrium (serosal surface) (Hong, 2023; Zhai et al., 2020; Ameer and Munakomi, 2022). The myometrium, the predominant layer, contains longitudinal and circular smooth muscle fibers and is responsible for uterine contractility, essential for menstruation, implantation, and parturition (Wray and Prendergast, 2019).

Among the most prevalent uterine smooth muscle disorders are leiomyoma (uterine fibroids) and adenomyosis, both associated with infertility and abnormal uterine bleeding (Bazot et al., 2001; Stewart et al., 2016; Ahmad et al., 2023). Leiomyomas are benign monoclonal tumors of smooth muscle origin with high prevalence, affecting over 70% of women (Wray and Prendergast, 2019).

Primary dysmenorrhea (PD), the most common gynecological disorder among women of reproductive age, is characterized by cyclic pelvic pain in the absence of underlying pelvic pathology (Itani et al., 2022; Smith et al., 2024). Its pathogenesis is closely linked to elevated levels of prostaglandins—particularly PGF2α—triggered by lysosomal destabilization and increased phospholipase A2 (PLA₂) activity following the premenstrual drop in progester-one (Dikensoy et al., 2008; Guimarães and Póvoa, 2020). These prostanoids enhance myometrial contractility and vasoconstriction, resulting in ischemia and pain sensitization (Xie et al., 2020; Dawood, 2006).

Oxidative stress also contributes to PD, and conventional treatments (NSAIDs, hormonal contraceptives) may be ineffective or cause adverse effects (Oladosu et al., 2018; Wang et al., 2024; Zhang et al., 2021), highlighting the need for safer alternatives.

Pulmonary hypertension (PH) is a complex vascular disorder characterized by remodeling and narrowing of pulmonary arteries, leading to elevated pulmonary arterial pressure, right ventricular failure, and ultimately death (Gao and Raj). Diagnosis is defined by a mean pulmonary artery pressure ≥25 mmHg, though newer guidelines suggest >20 mmHg when combined with other hemodynamic abnormalities (Simonneau et al., 2019; Huetsch et al., 2019).

Smooth muscle cells play a central role in PH pathogenesis through increased proliferation, migration, and enhanced contractile activity, which contribute to vascular stiffening and obstruction. Additionally, the aberrant muscularization of distal arterioles and excessive production of reactive oxygen species (ROS) exacerbate disease progression by promoting inflammation, oxidative stress, and cellular proliferation (Freund-Michel et al., 2013; Fulton et al., 2017; Nozik-Grayck and Stenmark, 2007). Current therapies target vasomotor tone but fail to prevent proliferation and remodeling, underscoring the need for novel interventions.

Allergic respiratory diseases such as asthma and rhinitis involve chronic airway inflammation, oxidative stress, and bronchial hyperreactivity, often leading to structural remodeling and smooth muscle dysfunction (Lambrecht and Hammad, 2015b; Figueiredo et al., 2023).

In experimental models, Arthrospira platensis supplementation has consistently demonstrated antioxidant, anti-inflammatory, and bronchodilatory effects. In asthmatic rats, oral AP (500 mg/kg) reduced airway inflammation, lowering IL-4, IL-5, IL-13, IgE, and tissue damage induced by ovalbumin and cigarette smoke (Riaz et al., 2022). AP also attenuated bronchial smooth muscle hypercontractility. Brito et al. (2022) showed that AP (150–500 mg/kg) decreased tracheal contractile responses to carbachol and increased NO bioavailability, reinforcing its bronchodilatory potential. A key mediator is phycocyanobilin (PhyCB), a biliverdin-derived chromophore abundant in AP, which inhibits NADPH oxidase and decreases oxidative stress, mechanisms that contribute to downregulation of the RhoA/ROCK pathway involved in smooth muscle contraction (McCarty et al., 2021).

In humans, clinical evidence is still limited. A trial in patients with allergic rhinitis found that Spirulina supplementation reduced IL-4 levels (Mao et al., 2005).

Collectively, these data suggest that AP exerts protective effects on airway smooth muscle by reducing hyperresponsiveness and inflammation through antioxidant and NO-mediated pathways. However, these results are restricted to rodent models, and the only available human data derive from an early allergic rhinitis trial with poorly characterized interventions. No randomized controlled trials (RCTs) exist for asthma, and future studies should prioritize standardized preparations, validated biomarkers of airway function, and direct comparisons with bronchodilators or corticosteroids.

Gastrointestinal disorders, including gastritis, ulcers, and reflux, are influenced by multiple factors such as Helicobacter pylori infection, inflammation, and oxidative stress (Wroblewski et al., 2010; Xiao et al., 2021). The gastric smooth muscle contributes to motility and mucosal protection, and its dysfunction is often exacerbated by mucosal injury and reactive oxygen species.

Preclinical evidence indicates that AP exhibits gastroprotective properties mediated by its antioxidant and anti-inflammatory metabolites. In rodent models of gastric ulcer induced by indomethacin or diclofenac, AP supplementation reduced mucosal injury, decreased lipid peroxidation (↓ MDA), and increased antioxidant enzymes (↑ SOD, GSH) (Aleid et al., 2021; Nipa et al., 2020). Similarly, in aspirin-induced gastric injury, AP reduced TNF-α and COX-2 expression while enhancing antioxidant defense (Mahmoud and Abd El-ghffar, 2019). Beyond gastroprotection, a polysaccharide fraction from AP selectively inhibited gastric adenocarcinoma proliferation without affecting normal gastric cells (Uppin et al., 2022).

Taken together, these results support the use of AP as a functional candidate for protecting gastric mucosa and modulating smooth muscle dysfunction. Nonetheless, existing studies are highly heterogeneous in design, extract preparation, and dosing, and none have used pharmacological comparators such as omeprazole or misoprostol. Clinical studies remain absent, and pharmacokinetic assessment of active metabolites is required before translation.

The smooth muscle of the small intestine is essential for peristalsis, nutrient absorption, and intestinal barrier function. Alterations in contractility and redox balance are implicated in inflammatory bowel diseases and obesity-related gastrointestinal dysfunction (Sanders, 2008).

In chemically induced colitis models, AP supplementation reduced disease severity, lowered proinflammatory cytokines (TNF-α, IL-1β, IL-6), and decreased oxidative markers (Fado et al., 2020). In obese rats, AP (25 mg/kg) prevented intestinal contractile dysfunction by modulating voltage-dependent calcium channels and downregulating muscarinic M3 receptors (Diniz et al., 2021). Other studies confirmed that AP modulates the RhoA/ROCK pathway, nitric oxide signaling, prostanoids, and superoxide dismutase activity in intestinal smooth muscle (Diniz et al., 2024). In Wistar rats, AP (150–500 mg/kg) reduced ileal contractile responses to carbachol and KCl while enhancing antioxidant activity (Araújo et al., 2016).

Clinical evidence is scarce but promising. In a randomized trial with patients with irritable bowel syndrome (IBS), AP supplementation improved antioxidant capacity, reduced malondialdehyde (MDA), and improved intestinal permeability and symptom severity (Jafari Nasab et al., 2025).

Thus, evidence from animal models and one clinical trial suggests that AP exerts intestinal protective effects by reducing inflammation, preserving barrier integrity, and preventing contractile dysfunction. However, standardized preparations, dose–response studies, and comparisons with reference drugs are lacking.

Arthrospira platensis has shown promising effects on disorders involving the corpus cavernosum, particularly infertility and erectile dysfunction (ED), often-linked to metabolic conditions such as obesity. Experimental studies in animal models have demonstrated that AP supplementation not only improves erectile function but also promotes overall male reproductive health.

Preclinical studies show that AP supplementation improves erectile function under metabolic stress conditions. In obese rats with diet-induced ED, oral AP (25 mg/kg, 8 weeks) increased erection frequency, reduced latency to first erection, and improved relaxation responses in penile tissue (Diniz et al., 2020; Souza et al., 2022). These effects were absent in healthy animals, suggesting context-specific benefits. Mechanistically, AP enhances NO bioavailability, suppresses contractile prostanoids, and reduces oxidative stress, improving smooth muscle relaxation and vascular function (Souza et al., 2022).

Beyond erectile function, AP demonstrates protective effects on the male reproductive system against environmental toxins. Studies report improvements in sperm count, motility, steroid hormone levels, and reduced testicular oxidative damage following exposure to agents such as arsenic, lead, and cyclophosphamide (Afkhami-Ardakani et al., 2021; Bashandy et al., 2016; El-Hakim et al., 2018). Furthermore, the seaweed improved steroid hormone production and spermatogenesis in rats exposed to the toxin, further reinforcing its role in male reproductive health (El-Desoky et al., 2013; Farag et al., 2016; Ibrahim et al., 2021).

These findings indicate that AP may act as an adjunct therapy for ED and infertility, especially in obesity and toxic exposures. Nevertheless, no clinical trials are available, extract standardization is lacking, and positive pharmacological comparators (e.g., PDE5 inhibitors) have not been used in animal models.

Uterine smooth muscle, primarily located in the myometrium, plays a central role in menstruation, fertility, and parturition. Dysfunctions in its contractility are associated with disorders such as primary dysmenorrhea (PD), adenomyosis, and uterine fibroids (Wray et al., 2019; Stewart et al., 2016).

Arthrospira platensis has demonstrated therapeutic potential in modulating uterine smooth muscle activity, largely due to its antioxidant and anti-inflammatory properties. In experimental models, AP supplementation (50–100 mg/kg) prevented increases in contractile reactivity to KCl and oxytocin in rats undergoing resistance training, while preserving relaxation responses to nifedipine and isoprenaline. These effects were associated with enhanced nitric oxide signaling, inhibition of prostanoid pathways, and reduction in reactive oxygen species (Ferreira et al., 2021; Barros, 2021).

Khatun et al. (2018), K et al. (2019) demonstrated that AP (200 mg/kg) protected uterine and ovarian tissues from arsenic-induced oxidative damage by boosting endogenous antioxidant enzymes (SOD, catalase, peroxidase). In a PD rat model, AP reduced oxytocin-induced writhing and prevented hypercontractility by modulating oxidative stress and prostaglandins (Lacerda-Júnior, 2022; Soares, 2025; Melchiades Júnior, 2024). Additionally, AP extract and its major pigment, C-phycocyanin, exhibited direct spasmolytic effects on pre-contracted guinea pig uterus, likely via L-type calcium channel inhibition (Marangoni et al., 2017; Bannu et al., 2019).

Altogether, these results support AP as a potential therapy for uterine contractility disorders, particularly PD. However, all evidence derives from animal studies with small sample sizes, no comparators with standard uterotonics or spasmolytics, and no clinical validation.

Vascular smooth muscle (VSM) is essential for regulating vascular tone, blood pressure, and vessel remodeling. Dysfunction in VSM contractility and proliferation is implicated in hypertension, atherosclerosis, and endothelial dysfunction. Arthrospira platensis has shown promising vasoprotective effects in both functional and molecular studies.

Brito et al. (2018) demonstrated that AP supplementation (150–500 mg/kg) improved aortic reactivity in Wistar rats, reducing contractile responses to phenylephrine and enhancing acetylcholine-induced relaxation. These effects were associated with increased nitric oxide (NO) bioavailability and reduced lipid peroxidation. The NO synthase inhibitor L-NAME reversed these effects, confirming the involvement of the NO pathway.

In spontaneously hypertensive rats (SHR), aqueous extracts of Spirulina platensis promoted vasorelaxation via enhanced NO production, without affecting superoxide levels. This was accompanied by upregulation of endothelial proteins such as AKT and heme oxygenase-1 (HO-1), which are essential for NO synthesis and oxidative protection (Villalpando et al., 2020; Castro-García et al., 2018).

In preeclampsia models, phycobilins (100 mg/kg/day) lowered systolic blood pressure and increased eNOS expression (Castro-García et al., 2018). C-phycocyanin inhibited vascular smooth muscle cell proliferation in vitro by upregulating cell-cycle inhibitors p21 and p27 (Xianming, 2013). Translational potential is supported by a triple-blind, placebo-controlled clinical trial, where daily consumption of Spirulina-enriched dressing improved vascular function in humans (Ghaem Far et al., 2025).

Overall, these findings provide robust preclinical evidence and some preliminary clinical support for AP’s vasoprotective effects. However, extract standardization is poor, trials remain small, and pharmacological comparators with standard antihypertensives are missing.