{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T16:04:29Z","timestamp":1784736269083,"version":"3.55.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Plant-derived nanovesicles (NVs) have emerged as promising natural nanotherapeutics for metabolic and inflammatory diseases due to their inherent biocompatibility, multi-target potential, and ability to mediate cross-kingdom communication. Postmenopausal osteoporosis (PMOP), a prevalent skeletal disorder driven by estrogen deficiency, is characterized by gut-bone axis dysregulation, chronic inflammation, and excessive oxidative stress\u2014pathological features that demand synergistic multi-target interventions. This study aimed to characterize\n                      <jats:italic>Panax quinquefolius<\/jats:italic>\n                      -derived nanovesicles (PQs) and systematically validate their anti-osteoporotic efficacy, bone-targeting property, and underlying molecular mechanisms in preclinical models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PQs were isolated via modified differential centrifugation and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and high-performance liquid chromatography (HPLC). Their bone-targeting capacity was evaluated via\n                      <jats:italic>in vivo<\/jats:italic>\n                      biodistribution and cellular uptake assays. Anti-osteoporotic efficacy was assessed in ovariectomized (OVX) mice using dual-energy X-ray absorptiometry (DXA), micro-computed tomography (\u03bcCT), and histomorphometric analysis. Gut microbiota modulation was analyzed via 16S rRNA gene sequencing. Network pharmacology, molecular docking, and loss-of-function experiments (pharmacological inhibition and siRNA-mediated Nrf2 silencing) were employed to elucidate the core mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PQs exhibited a typical cup-shaped morphology (mean diameter ~89\u202fnm), negative zeta potential (\u221242.21\u202f\u00b1\u202f0.12\u202fmV), and stable batch-to-batch naringin content (0.65\u202f\u00b1\u202f0.03\u202f\u03bcg\/mL).\n                      <jats:italic>In vivo<\/jats:italic>\n                      studies confirmed intrinsic bone-targeting of PQs, with &amp;gt;35% uptake by mouse bone marrow mesenchymal stem cells (mBMSCs) at 48\u202fh post-injection. In OVX mice, PQs dose-dependently improved bone mineral density (BMD), trabecular microarchitecture (increased BV\/TV, Tb. N, Tb. Th; decreased Tb. Sp), and serum osteogenic markers (ALP, OCN, Ca), while reducing osteoclastic markers (TRAP5b, CTX-I) and systemic inflammation (IL-6, KC, LPS). PQs treatment was associated with normalization Firmicutes\/Bacteroidetes ratio, enriching probiotics (Bifidobacterium, Lactobacillus), and suppressing pathogenic bacteria (Desulfovibrio, Enterococcus). Mechanistically, PQs exerted therapeutic effects by synergistically suppressing MYC-mediated inflammatory signaling and activating the Nrf2\/HO-1 antioxidant pathway. Pharmacological inhibition (ML385 for Nrf2, HY-11798 for HO-1) or genetic silencing of Nrf2 completely abolished the osteoprotective, anti-inflammatory, and antioxidant effects of PQs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Panax quinquefolius<\/jats:italic>\n                      -derived nanovesicles represent a novel synergistic nanotherapy for PMOP. Their therapeutic effects are mediated by concurrent modulation of gut microbiota homeostasis, suppression of MYC-dependent inflammation, and activation of the Nrf2\/HO-1 pathway. Given their natural origin, biocompatibility, and multi-target action, PQs hold significant potential for clinical translation as a safe and effective alternative for PMOP management.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1836521","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:42:31Z","timestamp":1784734951000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Panax quinquefolius-derived nanovesicles: a synergistic nanotherapy for postmenopausal osteoporosis via modulating gut microbiota, MYC-mediated inflammation, and Nrf2\/HO-1 antioxidant pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Qin","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Wuxi Ninth People's Hospital Affiliated to Soochow University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Wuxi Ninth People's Hospital Affiliated to Soochow University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijun","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Wuxi Ninth People's Hospital Affiliated to Soochow University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Wuxi Ninth People's Hospital Affiliated to Soochow University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiubo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Wuxi Ninth People's Hospital Affiliated to Soochow University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Wuxi Ninth People's Hospital Affiliated to Soochow University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Wuxi Ninth People's Hospital Affiliated to Soochow University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Wuxi Ninth People's Hospital Affiliated to Soochow University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.ecl.2021.03.009","article-title":"Postmenopausal Osteoporosis: Latest Guidelines","volume":"50","author":"Arceo-Mendoza","year":"2021","journal-title":"Endocrinol. 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