Chronic Oral Administration of Phyllanthus niruri Extract Is Well Tolerated in Sheep: Hematological, Biochemical, and Histopathological Evidence

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This preprint studied the organ-level safety of chronic oral Phyllanthus niruri extract in 24 healthy male sheep (6–8 months), using randomized dosing for eight weeks with control vehicle (0.5% CMC-Na) or extract at 5%, 10%, or 20% w/v once daily, with assessments of hematology and serum hepatic (AST, ALT, GGT) and renal (BUN, creatinine) biomarkers plus liver and kidney histopathology. Total leukocyte counts increased significantly in extract-treated groups, but the animals showed no clinical abnormalities and histology revealed no inflammation. All other measured hematological indices and serum hepatic/renal biomarkers stayed within physiological limits, and liver/kidney tissue architecture was preserved without degeneration, necrosis, congestion, or tubular damage. A major caveat is that it is an unpublished preprint without peer review, and it includes limited immunological profiling despite the leukocyte response; relevance to endometriosis: the paper does not explicitly discuss endometriosis or adenomyosis and was included in the corpus via an upstream keyword match.

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Abstract

Abstract Phytogenic additives are increasingly explored as alternatives to synthetic feed additives in ruminant production, yet chronic organ-level safety evidence in sheep remains scarce. Phyllanthus niruri is widely reported to possess antioxidant, anti-inflammatory, and hepatoprotective activities, but its long-term safety in small ruminants has not been established. This study evaluated hematological indices, serum biomarkers of hepatic and renal function, and liver–kidney histopathology following eight weeks of oral supplementation with P. niruri extract in sheep. Twenty-four healthy male sheep (6–8 months) were randomly assigned to four groups (n = 6): control (0.5% CMC-Na) and extract-treated groups (5%, 10%, or 20% w/v), administered once daily at 1 mL/kg body weight. Hematology and serum biochemistry (AST, ALT, GGT, BUN, creatinine) were assessed at baseline and week 8, and tissues were examined histologically at study end. Total leukocyte counts increased significantly in all extract-treated groups; however, animals showed no clinical abnormalities and no histological evidence of inflammation. Other hematological indices and all serum hepatic and renal biomarkers remained within physiological limits with no adverse deviations. Histopathological evaluation revealed preserved hepatic and renal architecture without degeneration, necrosis, congestion, or tubular damage. Overall, chronic oral supplementation with P. niruri extract (5–20%) for eight weeks was well tolerated in sheep, supporting its safety as a candidate phytogenic additive, while further immunological profiling is warranted to clarify the leukocyte response.
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Chronic Oral Administration of Phyllanthus niruri Extract Is Well Tolerated in Sheep: Hematological, Biochemical, and Histopathological Evidence | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Chronic Oral Administration of Phyllanthus niruri Extract Is Well Tolerated in Sheep: Hematological, Biochemical, and Histopathological Evidence Emy Koestanti Sabdoningrum, Sri Hidanah, Nazri Nayan, Ira Sari Yudaniayanti, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8715915/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Phytogenic additives are increasingly explored as alternatives to synthetic feed additives in ruminant production, yet chronic organ-level safety evidence in sheep remains scarce. Phyllanthus niruri is widely reported to possess antioxidant, anti-inflammatory, and hepatoprotective activities, but its long-term safety in small ruminants has not been established. This study evaluated hematological indices, serum biomarkers of hepatic and renal function, and liver–kidney histopathology following eight weeks of oral supplementation with P. niruri extract in sheep. Twenty-four healthy male sheep (6–8 months) were randomly assigned to four groups (n = 6): control (0.5% CMC-Na) and extract-treated groups (5%, 10%, or 20% w/v), administered once daily at 1 mL/kg body weight. Hematology and serum biochemistry (AST, ALT, GGT, BUN, creatinine) were assessed at baseline and week 8, and tissues were examined histologically at study end. Total leukocyte counts increased significantly in all extract-treated groups; however, animals showed no clinical abnormalities and no histological evidence of inflammation. Other hematological indices and all serum hepatic and renal biomarkers remained within physiological limits with no adverse deviations. Histopathological evaluation revealed preserved hepatic and renal architecture without degeneration, necrosis, congestion, or tubular damage. Overall, chronic oral supplementation with P. niruri extract (5–20%) for eight weeks was well tolerated in sheep, supporting its safety as a candidate phytogenic additive, while further immunological profiling is warranted to clarify the leukocyte response. Phyllanthus niruri sheep phytogenic feed additive hematology liver enzymes kidney function Full Text Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 08 Apr, 2026 Reviewers invited by journal 08 Apr, 2026 Editor assigned by journal 20 Mar, 2026 First submitted to journal 17 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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