Cassia senna (Senna alexandrina) Leaves as a Prospective Source of Anti-Ulcer Therapeutics in Nigeria: An Ethnopharmacological, Phytochemical, and Drug Discovery Perspective

1. Introduction

Peptic ulcer disease (PUD), encompassing gastric and duodenal ulcers, arises from an imbalance between aggressive factors—gastric acid, pepsin, Helicobacter pylori infection, NSAIDs, stress, smoking, and dietary irritants—and defensive mechanisms of the gastroduodenal mucosa, including mucus-bicarbonate barrier, mucosal blood flow, prostaglandins, nitric oxide, and endogenous antioxidant systems (Lanas & Chan, 2017). Despite decades of therapeutic progress, PUD remains a leading cause of gastrointestinal morbidity worldwide, contributing to complications such as bleeding, perforation, obstruction, and, in chronic cases, increased risk of gastric malignancy.

Globally, the lifetime prevalence of PUD has been estimated at 5–10%, with incidence rates of 0.1–0.3% per year in high-income settings where H. pylori eradication programs and widespread PPI use have driven declines (Abdu et al., 2025). In stark contrast, many low- and middle-income countries, particularly across sub-Saharan Africa, continue to bear a disproportionate burden. A recent comprehensive meta-analysis of 58 African studies reported a pooled PUD prevalence of 15.2% (95% CI: 13.2–17.2%), with West Africa exhibiting the highest regional estimate at 19% (Abdu et al., 2025). In Nigeria specifically, H. pylori seroprevalence among dyspeptic and ulcer patients frequently exceeds 80% in multiple regional studies, reaching 82.5% in recent Owerri data and up to 87.7% nationally in aggregated reports (Smith et al., 2022; Yahya, 2023).

Compounding factors include high NSAID consumption for pain and fever (often without gastroprotection), prevalent self-medication practices, limited endoscopic diagnostic capacity outside urban tertiary centers, erratic electricity and cold-chain infrastructure affecting drug storage, and the escalating problem of antibiotic resistance that undermines standard triple or quadruple eradication therapies.

These realities create both a clinical imperative and an economic opportunity for the discovery and development of locally sourced, affordable, multi-mechanistic anti-ulcer agents. Natural products have historically supplied a significant proportion of the modern pharmacopeia; Fabricant and Farnsworth (2001) estimated that approximately 25% of prescription drugs contain plant-derived active principles or their derivatives. In the African context, where up to 80% of the population in some rural areas relies on traditional medicine for primary healthcare (WHO, 2019), medicinal plants represent not only cultural heritage but also a strategic reservoir for pharmaceutical innovation that aligns with principles of local production, reduced import dependence, and sustainable utilization of biodiversity.

Cassia senna L. (syn. Senna alexandrina Mill., Cassia angustifolia Vahl), commonly known as Alexandrian senna or Indian senna, is a perennial shrub belonging to the Fabaceae (Leguminosae) family. Native to the arid and semi-arid zones of northeastern Africa (Egypt, Sudan, Somalia) and the Arabian Peninsula, it has been introduced and cultivated widely across tropical and subtropical regions, including parts of West Africa. While its primary global recognition stems from the stimulant laxative activity of its leaves and pods—driven by sennosides A and B—traditional healers across Africa have employed preparations of Senna species for a wider array of gastrointestinal complaints, including stomach pain, indigestion, and ulcer-like symptoms (Gill, 1992; Akah et al., 1998).

Modern phytochemical and pharmacological investigations have begun to elucidate that the plant's bioactivity extends well beyond laxation. Leaves contain, in addition to anthraquinones, appreciable quantities of flavonoids (kaempferol, quercetin derivatives), phenolic acids, tannins, and saponins. Preliminary reports on aqueous extracts of S. alexandrina indicate dose-dependent reduction of ethanol-induced gastric lesions in mice, accompanied by increased mucus secretion and antioxidant markers (Belkheit, 2025). Parallel work on the related species Senna multiglandulosa demonstrated robust anti-ulcer activity in rats (92% protection at 500 mg/kg) mediated by enhanced non-protein sulfhydryl groups and mucus output (Palomino-Pacheco et al., 2022).

Against this backdrop, the present paper offers a critical, integrative assessment of the anti-ulcer drug discovery potential of Cassia senna leaves from a distinctly Nigerian perspective. We synthesize ethnobotanical records, phytochemical inventories, mechanistic pharmacology, and toxicological data; highlight research gaps; and articulate a pragmatic, phased drug discovery roadmap designed to leverage Nigeria's biodiversity, traditional knowledge systems, and emerging pharmaceutical research infrastructure.

2. Literature Review and Background

2.1 Ethnobotanical Significance and Traditional Uses

The genus Senna (formerly part of Cassia s.l.) enjoys a venerable place in African traditional medicine. Ethnobotanical surveys conducted across Nigeria and neighboring countries document the use of various Senna species for gastrointestinal, dermatological, and infectious conditions. Gill (1992), in his comprehensive compilation of ethnomedicinal uses of Nigerian plants, recorded applications of Cassia/Senna species for stomach pain, indigestion, constipation, and related complaints. Akah et al. (1998) specifically evaluated Nigerian traditional medicines for effects on peptic ulcer models, providing early scientific validation of folk claims for certain Cassia-related taxa.

In broader African contexts, leaves and pods of S. alexandrina and close relatives have been employed as carminatives, antidysenterics, and remedies for "dull stomach pain," liver complaints, and abdominal troubles (various regional monographs cited in EMA, 2018). While the dominant use remains purgative—particularly for occasional constipation and pre-procedural bowel evacuation—traditional practitioners in some communities prepare milder decoctions or combine Senna with demulcent herbs (e.g., Ocimum, Aloe, or honey) for "stomach ulcers" or chronic dyspepsia. Such polyherbal formulations may inadvertently achieve a degree of fractionation, attenuating the harsher laxative action while preserving other bioactivities.

The persistence of these practices despite the availability of modern laxatives and anti-ulcer drugs speaks to cultural resonance, accessibility, affordability, and perceived holistic efficacy. Rigorous documentation of contemporary traditional use patterns could guide targeted phytochemical and pharmacological prioritization—a gap this research framework addresses directly.

2.2 Botanical Description, Taxonomy, and Nigerian Distribution

Senna alexandrina Mill. (Fabaceae, subfamily Caesalpinioideae) is an erect, branched shrub or small tree reaching 0.5–2 m in height. Leaves are paripinnate with 3–7 pairs of lanceolate to ovate-lanceolate leaflets (2–6 cm long); stipules are linear and caducous. Flowers are yellow, arranged in axillary racemes; pods are flat, oblong, dehiscent, containing 6–10 seeds. The plant thrives in sandy, well-drained soils under full sun and is notably drought-tolerant, making it well-suited to the Sahel and Sudan savanna zones of northern Nigeria as well as drier pockets in the middle belt.

Taxonomic confusion historically surrounded "senna" materials; the current consensus recognizes S. alexandrina as the correct name for the medicinal Alexandrian/Indian senna of commerce, distinct from but closely related to S. angustifolia and others previously lumped under Cassia. Accurate authentication via morphology, DNA barcoding (ITS, matK, rbcL), and chemotaxonomic profiling is therefore essential for any Nigerian research program to ensure reproducibility and regulatory compliance.

2.3 Phytochemical Composition

The phytochemistry of S. alexandrina leaves is dominated by two major classes: anthraquinone derivatives and flavonoid/phenolic compounds. Sennosides A and B (dianthrone glycosides) constitute the principal laxative principles, typically present at 1–5% or higher in dried leaf material depending on provenance, season, and post-harvest handling. Free anthraquinones and their glycosides—including aloe-emodin, chrysophanol, rhein, emodin, and physcion—occur in smaller quantities but are of significant pharmacological interest.

Flavonoids, particularly kaempferol and its glycosides (e.g., kaempferol-3-O-rutinoside), along with quercetin derivatives, apigenin, and luteolin, have been identified in leaf extracts. These compounds are well-documented in the broader literature for potent antioxidant and anti-inflammatory activities. Phenolic acids (caffeic, ferulic, gallic), tannins (condensed and hydrolyzable), and saponins further enrich the profile and likely contribute to astringent, antimicrobial, and membrane-stabilizing effects relevant to mucosal protection.

2.4 Pharmacological Evidence for Gastroprotective Potential

Oxidative stress is a central pathogenic mechanism in both NSAID- and H. pylori-associated ulceration. Reactive oxygen species (ROS) generated by activated neutrophils, xanthine oxidase, and mitochondrial leakage damage epithelial lipids, proteins, and DNA, while simultaneously impairing mucus synthesis and mucosal blood flow. Flavonoid- and phenolic-rich extracts of Senna species consistently demonstrate robust free-radical scavenging (DPPH, ABTS, FRAP assays) and the ability to upregulate or preserve endogenous antioxidant enzymes—SOD, CAT, GPx—in gastric tissue (Ripanda et al., 2023).

Inflammation amplifies and perpetuates mucosal injury. Kaempferol and structurally related flavonoids inhibit NF-κB nuclear translocation, thereby suppressing transcription of TNF-α, IL-1β, IL-6, COX-2, and iNOS. The aqueous extract of S. alexandrina itself produced statistically significant, dose-dependent gastroprotection in mice (100–500 mg/kg), with histological corroboration of preserved mucosal architecture (Belkheit, 2025). In the Senna multiglandulosa ethanol-ulcer study, extract treatment reduced lesion area dramatically (92% protection at 500 mg/kg) while also elevating non-protein sulfhydryl groups and increasing mucus production by 61% at the effective dose—a finding of direct translational relevance (Palomino-Pacheco et al., 2022).

Direct antimicrobial activity against H. pylori remains incompletely characterized for S. alexandrina. However, several anthraquinones (rhein, aloe-emodin) and flavonoid aglycones exhibit MIC values in the low-to-mid μg/mL range against Gram-negative bacteria in published screens. Given the high H. pylori burden in Nigerian PUD patients, even modest direct or synergistic inhibitory activity would be clinically meaningful and could help mitigate resistance selection pressure.

2.5 Toxicological and Safety Considerations

No discussion of senna-derived therapeutics is complete without addressing the well-documented safety profile of anthraquinone laxatives. The European Medicines Agency (EMA) herbal monograph for Senna alexandrina restricts use to short-term (≤1–2 weeks) occasional constipation in adults and adolescents; contraindicates use in pregnancy, lactation, children under 12, intestinal obstruction, inflammatory bowel disease, and undiagnosed abdominal pain (EMA, 2018). Chronic or excessive use is associated with abdominal cramps, diarrhea, electrolyte imbalance (particularly hypokalemia), dehydration, and pseudomelanosis coli. Rare cases of hepatotoxicity have been reported with prolonged abuse (Beuers et al., 1991; Vanderperren et al., 2005).

Genotoxicity and carcinogenicity concerns center on certain free anthraquinones (emodin, aloe-emodin) that have shown mutagenic activity in bacterial assays and promotional effects on colonic carcinogenesis at very high doses in some rodent studies. Nevertheless, these signals justify a conservative approach: any anti-ulcer development program must prioritize fractions with minimized anthraquinone content or demonstrate, through rigorous toxicological packages, an acceptable safety margin for the intended shorter- or medium-term use in ulcer healing.

Importantly, the compounds responsible for gastroprotection (flavonoids, selected phenolics) may be separable from the bulk sennosides by chromatographic or solvent-partition methods. Bioassay-guided fractionation that simultaneously tracks gastroprotective efficacy and laxative/toxic liability offers a rational path forward.

3. Proposed Drug Discovery and Development Framework

Given the promising but incomplete evidence base, we advocate a structured, phased drug discovery program explicitly designed for feasibility within Nigerian research ecosystems while meeting international standards for rigor and reproducibility. The pipeline integrates ethnopharmacological intelligence, modern phytochemistry, and translational pharmacology, with built-in decision gates to terminate or redirect efforts based on efficacy, safety, and developability criteria.

3.1 Phase 1: Ethnobotanical Survey, Plant Collection, and Authentication

Multi-site ethnobotanical surveys across Nigeria's six geopolitical zones, targeting traditional healers, herb sellers, and community elders with documented use of Senna or "Cassia" for stomach complaints. Semi-structured interviews and voucher collection will generate a geo-referenced database of use patterns, preparation methods, and perceived efficacy/safety. Plant material (leaves) will be collected from multiple accessions representing different agro-ecological zones (Sahel, Sudan savanna, Guinea savanna, derived savanna) during peak vegetative or early flowering stages.

Authentication will combine classical taxonomy with DNA barcoding (ITS, matK, rbcL) and HPLC chemoprofiling against authenticated reference standards. Voucher specimens will be deposited at recognized Nigerian herbaria (e.g., University of Lagos, Forestry Research Institute of Nigeria) and duplicate samples retained for future genomic/metabolomic studies.

3.2 Phase 2: Extraction Optimization and Phytochemical Characterization

Dried, milled leaves will be subjected to sequential or parallel extraction using solvents of increasing polarity (n-hexane, ethyl acetate, methanol, 70% ethanol, water) via maceration, reflux, or ultrasound-assisted methods. Green extraction alternatives (supercritical CO₂, deep eutectic solvents) will be explored for sustainability and regulatory appeal. Crude extracts will be profiled by HPLC-DAD, LC-MS/MS, and GC-MS for known markers (sennosides, rhein, aloe-emodin, kaempferol) and dereplication of unknowns.

Bioassay-guided fractionation (normal- and reversed-phase column chromatography, preparative HPLC, flash chromatography) will be coupled with rapid in vitro screens to prioritize sub-fractions for further purification and structural elucidation (NMR, HR-MS). The goal is to generate enriched fractions or isolated compounds with high gastroprotective index (efficacy : laxative/toxicity ratio).

3.3 Phase 3: In Vitro and Mechanistic Pharmacology

Prioritized extracts/fractions/compounds will undergo a battery of mechanistic assays: (i) comprehensive antioxidant profiling (DPPH, ABTS, FRAP, superoxide anion, hydroxyl radical; cellular antioxidant activity in Caco-2 or AGS cells); (ii) anti-inflammatory activity (LPS- or H. pylori-stimulated RAW 264.7 or primary macrophages: NO, PGE₂, TNF-α, IL-1β, IL-6, NF-κB luciferase reporter); (iii) direct anti-H. pylori (broth microdilution MIC/MBC against local Nigerian clinical isolates, including resistant strains; urease inhibition assay); (iv) in vitro gastroprotection (cell viability, LDH release, mucus production, tight-junction integrity); (v) molecular docking and in vitro enzyme inhibition on validated ulcer targets (H⁺/K⁺-ATPase, COX-2, 5-LOX). Synergy studies with standard agents (omeprazole, clarithromycin, amoxicillin) will be performed where appropriate.

3.4 Phase 4: In Vivo Anti-Ulcer Validation

Lead candidates advancing from in vitro work will be evaluated in at least three complementary rodent ulcer models: (1) Ethanol-induced acute gastric ulcer (rapid oxidative/necrotic insult; assesses cytoprotection and mucus); (2) Indomethacin/NSAID-induced ulcer (prostaglandin depletion, inflammation); (3) Pylorus-ligation or stress (cold-restraint) models for acid-secretory and mucosal defense components. Sprague-Dawley or Wistar rats (n=6–8 per group, power-calculated) will receive oral gavage of test materials at 3–4 dose levels plus vehicle and positive controls (omeprazole 20 mg/kg or misoprostol).

Endpoints include: ulcer index (macroscopic scoring + planimetry), gastric juice volume/pH/acidity, mucus content (Alcian blue binding), biochemical markers in tissue homogenates (MDA, GSH, SOD, CAT, GPx, PGE₂, NO, TNF-α, IL-1β), histopathology (H&E, PAS for mucus), and immunohistochemistry for key proteins (COX-2, iNOS, Nrf2, tight-junction proteins). All studies will be conducted under ethical approval from an accredited Nigerian institutional animal care and use committee, following ARRIVE 2.0 guidelines.

3.5 Phase 5: Toxicological and Safety Pharmacology Assessment

Parallel to efficacy work, a tiered safety package will be executed: (i) Acute oral toxicity (OECD 423 or 425) in rats to establish LD₅₀ or limit dose; (ii) 28-day repeated-dose oral toxicity (OECD 407) with hematology, clinical chemistry, urinalysis, organ weights, and histopathology; (iii) Genotoxicity battery (Ames bacterial reverse mutation, in vitro micronucleus or chromosomal aberration in mammalian cells); (iv) Safety pharmacology (CNS, cardiovascular, respiratory core battery if warranted by early signals). Special attention will be paid to gastrointestinal effects (motility, diarrhea scoring) and any hepatobiliary findings.

3.6 Phase 6: Preclinical Development, Standardization, and Translational Steps

Successful leads will undergo formulation development (standardized dry extract, capsule, or liquid; stability testing under ICH conditions), analytical method validation (HPLC/UPLC with appropriate markers or fingerprint), batch-to-batch reproducibility studies, and pilot-scale cultivation/agronomic optimization to ensure sustainable supply. Intellectual property considerations, including potential plant variety protection or process patents, will be addressed early in collaboration with Nigerian technology transfer offices.

Engagement with the National Agency for Food and Drug Administration and Control (NAFDAC) will clarify the most appropriate regulatory pathway—herbal medicinal product, standardized extract, or eventual new chemical entity if a novel isolated compound emerges. Early dialogue with the Nigeria Natural Medicine Development Agency (NNMDA) and traditional medicine practitioners will ensure benefit-sharing and community involvement consistent with the Nagoya Protocol and Nigerian ABS regulations.

4. Discussion

The evidence assembled in this review supports the hypothesis that leaves of Senna alexandrina constitute a viable, if currently underexploited, starting point for anti-ulcer drug discovery relevant to Nigerian and broader African health needs. The coexistence within a single species of compounds with complementary mechanisms—antioxidant flavonoids capable of bolstering mucosal defense, anti-inflammatory phenolics that dampen the cytokine storm of ulcerogenesis, and antimicrobial anthraquinones with potential activity against H. pylori—offers the attractive prospect of a multi-target phytocomplex or rationally designed fraction that could address several pathogenic pillars simultaneously. Such multi-mechanistic action contrasts favorably with the single-target paradigm of most conventional anti-ulcer drugs and may translate to lower recurrence rates and reduced reliance on prolonged acid suppression.

Nevertheless, enthusiasm must be tempered by recognition of significant knowledge gaps and development hurdles. Direct gastroprotective data for S. alexandrina remain limited to a handful of preliminary extract studies in related species or single rodent models; rigorous, head-to-head comparisons with standard agents, dose-response characterization, and chronic efficacy/safety studies are lacking. Chemotypic and seasonal variability, if not tightly controlled through good agricultural and collection practices (GACP) and robust analytical specifications, could undermine reproducibility and regulatory acceptance. The toxicological baggage of anthraquinones, while manageable through fractionation, adds complexity and cost to the development pathway.

From a Nigerian perspective, the opportunity is strategic. Successful development of a locally sourced anti-ulcer agent could reduce the national drug import bill, create agricultural and manufacturing jobs in the value chain (cultivation, extraction, formulation), generate foreign exchange through potential regional exports, and demonstrate proof-of-concept for the broader Nigerian phytomedicine sector. It would also align with national policies promoting traditional medicine integration, the African Union's Pharmaceutical Manufacturing Plan for Africa, and the African Continental Free Trade Area's potential to expand markets for quality-assured African health products.

Methodologically, the proposed framework deliberately balances scientific rigor with pragmatism. By front-loading bioassay-guided fractionation and mechanistic work in vitro, expensive and ethically sensitive animal studies can be reserved for well-characterized, high-potential candidates. Collaboration across Nigerian universities, research institutes (NIPRD, NNMDA), and potentially international phytochemistry centers will be essential to access specialized instrumentation (LC-MS, NMR) and expertise. Funding diversification—combining TETFund, PTDF, national research grants, private-sector partnerships, and diaspora or impact-investment capital—will be necessary to sustain a multi-year program.

5. Conclusion and Recommendations

Cassia senna (Senna alexandrina) leaves represent a promising but insufficiently investigated resource for the development of novel anti-ulcer therapeutics tailored to the Nigerian epidemiological and healthcare context. The plant's rich phytochemical diversity, traditional use patterns, and emerging experimental evidence of gastroprotective, antioxidant, and anti-inflammatory activities provide a strong scientific rationale for dedicated research investment. By pursuing a disciplined, bioassay-guided drug discovery program that explicitly addresses the separation of beneficial gastroprotective principles from laxative and potentially toxic anthraquinones, Nigerian researchers and institutions can position themselves at the forefront of African phytopharmaceutical innovation.

We recommend the following priority actions:

1. Immediate initiation of multi-regional ethnobotanical documentation and geo-referenced plant collection with community consent and benefit-sharing agreements.
2. Establishment or strengthening of dedicated phytochemistry and pharmacology laboratories with capacity for LC-MS-based dereplication and bioassay-guided fractionation.
3. Design and execution of a coordinated in vitro-to-in vivo screening program focused on enriched flavonoid/phenolic fractions.
4. Parallel toxicological de-risking with emphasis on genotoxicity and hepatobiliary endpoints.
5. Early and ongoing engagement with NAFDAC and NNMDA to align development with regulatory expectations.
6. Investment in sustainable cultivation research and pilot-scale extraction infrastructure.
7. Active pursuit of collaborative grants and public-private partnerships that prioritize Nigerian leadership and capacity building.

If these steps are pursued with scientific integrity, cultural sensitivity, and strategic vision, the prospect of a Nigerian-developed, evidence-based anti-ulcer product derived from Senna alexandrina—or from the broader portfolio of indigenous medicinal plants—could move from aspiration to reality within the coming decade. Such an achievement would deliver tangible health benefits to Nigerian patients, catalyze the growth of a competitive local pharmaceutical sector, and contribute meaningfully to the global scientific literature on ethnopharmacology and natural product drug discovery.

Acknowledgments

The author acknowledges the traditional healers and communities across Nigeria whose knowledge of medicinal plants, including various Senna species, forms the foundation of this work. Appreciation is extended to colleagues in Nigerian universities and research institutes engaged in natural product research for ongoing dialogue and collaboration. No specific funding was received for the preparation of this review; the perspectives expressed are those of the author and do not necessarily represent the views of any affiliated institution.

Author Contributions and Declarations: Mabrig Korie conceived the study, conducted the literature synthesis, and prepared the manuscript. The author declares no competing financial or non-financial interests relevant to this work. This manuscript has not been published previously and is not under consideration for publication elsewhere. All sources of information have been appropriately acknowledged through citation.

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