{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:27:09Z","timestamp":1785421629735,"version":"3.56.0"},"reference-count":63,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dr. Rath health Foundation"},{"id":[{"id":"https:\/\/ror.org\/02bzj4420","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Obesity is a multifactorial metabolic disorder characterized by excessive adiposity, chronic low-grade inflammation, and dysregulated incretin and energy-sensing pathways, including glucagon-like peptide-1 (GLP-1) and AMP-activated protein kinase (AMPK). Methods: This in vitro and in vivo study evaluated the potential of select phytochemical candidates and botanical formulations to stimulate GLP-1 secretion and activate AMPK signaling. Results: Fourteen phytochemicals and six combinations were screened in human NCI-H716 enteroendocrine cells at 10\u201320 \u00b5g\/mL to assess cytotoxicity and GLP-1 secretion. In human adipocytes, selected combinations reduced lipid accumulation and monocyte chemoattractant protein-1 (MCP-1) secretion. Among the tested formulations, combination #4, consisting of ginseng root extract, curcumin, white kidney bean extract, fenugreek extract, capsaicin, and bitter melon extract, significantly increased phosphorylated AMPK levels in vitro. In high-fat diet-induced obese mice, oral administration of combination 4 reduced body weight gain and white adipose tissue mass, improved metabolic biochemical parameters, restored leptin and MCP-1 levels toward normal values, increased GLP-1 level, and normalized GLP-1 receptor expression in subcutaneous adipose tissue. Conclusions: These preclinical findings demonstrate that this multi-component botanical formulation modulates GLP-1 secretion, AMPK phosphorylation, lipid accumulation, and inflammatory markers in cellular and murine models. These data provide a foundational rationale for its further evaluation as a non-toxic candidate for metabolic management.<\/jats:p>","DOI":"10.3390\/nu18132111","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:16:44Z","timestamp":1782699404000},"page":"2111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Activation of GLP-1 and AMPK Pathways by a Multi-Botanical Formulation Improves Obesity and Metabolic Dysfunction in Experimental Models"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-2941","authenticated-orcid":false,"given":"Anna","family":"Goc","sequence":"first","affiliation":[{"name":"Dr. Rath Research Institute BV, 5941 Optical Ct., San Jose, CA 95138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Sumera","sequence":"additional","affiliation":[{"name":"Dr. Rath Research Institute BV, 5941 Optical Ct., San Jose, CA 95138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Niedzwiecki","sequence":"additional","affiliation":[{"name":"Dr. Rath Research Institute BV, 5941 Optical Ct., San Jose, CA 95138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100375","DOI":"10.1016\/j.metop.2025.100375","article-title":"Obesity: Prevalence, causes, consequences, management, preventive strategies and future research directions","volume":"27","author":"Ahmed","year":"2025","journal-title":"Metabol. 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