{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:09:31Z","timestamp":1793236171712,"version":"4.5.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold> This study aimed to evaluate the clinical efficacy and safety of PE extracts developed for the purpose of relieving pain and improving knee joint function on semi-healthy people with mild knee joint pain.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A randomized, double-blind, two-arm, single-center, placebo-controlled clinical trial was conducted. Individuals with knee joint pain and a visual analogue scale (VAS) score &amp;lt; 50\u00a0mm were included in the study, and participants with radiological arthritis were excluded. Participants were administered either PFE or a placebo capsule (700\u00a0mg, twice a day) orally for eight weeks. The comparisons of the changed VAS score and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores between the PFE and placebo groups were primary outcomes, while the five inflammation-related laboratory tests including cartilage oligomeric matrix protein, cyclooxygenase-2, neutrophil and lymphocyte ratio, high sensitive C-reactive protein, and erythrocyte sedimentation rate were secondary outcomes. Also, a safety assessment was done.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Eighty participants (mean age, 38.4 \u00b1 14.0, male: female, 28:52) were enrolled; 75 completed the trial (PFE 36 and placebo 39). After eight weeks, both VAS and WOMAC scores were reduced in the PFE and placebo groups. The changed scores were significantly higher in the PFE group compared to the placebo group: 19.6 \u00b1 10.9 vs. 6.8 \u00b1 10.5; VAS scores (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), and 20.5 \u00b1 14.7 vs. 9.3 \u00b1 16.5; total WOMAC scores (<jats:italic>p<\/jats:italic> &amp;lt; 0.01) including the sub-scores for pain, stiffness, and functions. No significant changes were reported in the five inflammation-related laboratory parameters. All adverse events were considered minor and unlikely to result from the intervention.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Eight weeks of PFE intake was more effective than placebo in reducing knee joint pain and improving knee joint function in sub-healthy people with mild knee joint pain, and there were no major safety concerns.<\/jats:p><jats:p><jats:bold>Clinical Trial Registration:<\/jats:bold><jats:ext-link>https:\/\/cris.nih.go.kr\/cris\/search\/detailSearch.do?search_lang=E&amp;amp;focus=reset_12&amp;amp;search_page=M&amp;amp;pageSize=10&amp;amp;page=undefined&amp;amp;seq=23101&amp;amp;status=5&amp;amp;seq_group=19745<\/jats:ext-link>, identifier CRIS: KCT0007219<\/jats:p>","DOI":"10.3389\/fphar.2023.1114410","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T05:36:21Z","timestamp":1678772181000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy of Perilla frutescens (L.) 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