EC Pharmacology and Toxicology

Background: Chronic and unpredictable psychosocial stressors produce endocrine, immune and structural organ changes that have broad consequences for health. Moringa oleifera (MO) leaf preparations are widely consumed for nutritional and medicinal purposes and are reported to possess antioxidant, hepatoprotective and anti-inflammatory properties; however, their effects when consumed during periods of chronic stress are incompletely characterized.

Objective: To evaluate the phytochemical constituents of methanolic M. oleifera leaf extract (MoLE) and to determine the histological effects of MoLE administration on the uterus, ovaries, heart and liver in female Wistar rats exposed to chronic unpredictable stress (CUS).

Methods: Methanolic MoLE GC-MS profiling has been previously published by our group. In brief, twenty mature virgin female Albino-Wistar rats were randomized into four groups (n = 5): (I) Control (no stress); (II) CUS only; (III) CUS + MoLE 200 mg·kg^-1·day^-1; (IV) CUS + MoLE 300 mg·kg^-1·day^-1. CUS was applied unpredictably for 14 days using validated stressors. MoLE was administered by oral gavage daily after stress exposure. At study end, reproductive organs, heart and liver were harvested for routine histology; lesions were described and semi-quantitatively graded.

Results: GC-MS identified 41 compounds in MoLE; the major constituents included hexadecanoic acid, methyl ester (26.18% TIC), methyl stearate (12.11% TIC), and dodecanoic acid methyl ester (6.01% TIC). Histological assessment showed that CUS alone induced marked degenerative changes across organs (uterine cystic degeneration and hemorrhage; ovarian fibrocystic change; myocardial inflammation/hemorrhage; severe hepatic fatty change and fibrosis). Administration of MoLE during CUS did not prevent these changes and, at the doses tested, was associated with persistent or, in some tissues, dose-related alterations (e.g. cystic uterine changes, ongoing hepatic steatosis and inflammatory aggregates). The presence of steroidal and fatty-acid methyl esters with potential estrogenic activity (as per our GC-MS and docking data) may contribute to organ-specific interactions observed.

Conclusion: Under the present experimental conditions, MoLE consumption during short-term CUS did not protect against and may have exacerbate stress-related histopathology in female rats. These findings underscore the need for careful evaluation of botanical supplements during periods of physiological stress and for mechanistic follow-up (endocrine profiling, receptor assays, oxidative stress markers).

 Keywords: Moringa oleifera; Chronic Unpredictable Stress; GC-MS; Histology; Uterus; Ovary; Liver; Heart

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