PMID- 37095163 OWN - NLM STAT- MEDLINE DCOM- 20230426 LR - 20230724 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 13 IP - 1 DP - 2023 Apr 24 TI - Standardized Centella asiatica (ECa 233) extract decreased pain hypersensitivity development in a male mouse model of chronic inflammatory temporomandibular disorder. PG - 6642 LID - 10.1038/s41598-023-33769-w [doi] LID - 6642 AB - Chronic inflammatory temporomandibular disorder (TMD) pain has a high prevalence, and available nonspecific treatments have adverse side effects. ECa 233, a standardized Centella asiatica extract, is highly anti-inflammatory and safe. We investigated its therapeutic effects by injecting complete Freund's adjuvant (CFA) into right temporomandibular joint of mice and administering either ibuprofen or ECa 233 (30, 100, and 300 mg/kg) for 28 days. Inflammatory and nociceptive markers, bone density, and pain hypersensitivity were examined. CFA decreased ipsilateral bone density, suggesting inflammation localization, which ipsilaterally caused immediate calcitonin gene-related peptide elevation in the trigeminal ganglia (TG) and trigeminal subnucleus caudalis (TNC), followed by late increase of NaV1.7 in TG and of p-CREB and activation of microglia in TNC. Contralaterally, only p-CREB and activated microglia in TNC showed delayed increase. Pain hypersensitivity, which developed early ipsilaterally, but late contralaterally, was reduced by ibuprofen and ECa 233 (30 or 100 mg/kg). However, ibuprofen and only 100-mg/kg ECa 233 effectively mitigated marker elevation. This suggests 30-mg/kg ECa 233 was antinociceptive, whereas 100-mg/kg ECa 233 was both anti-inflammatory and antinociceptive. ECa 233 may be alternatively and safely used for treating chronic inflammatory TMD pain, showing an inverted U-shaped dose-response relationship with maximal effect at 100 mg/kg. CI - (c) 2023. The Author(s). FAU - Rotpenpian, Nattapon AU - Rotpenpian N AD - Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Srisavarindhira Bldg., 13Th Floor, Wanglang Road, Siriraj Subdistrict, Bangkoknoi District, Bangkok, 10700, Thailand. AD - Department of Oral Biology and Occlusion, Faculty of Dentistry, Prince of Songkla University, Songkhla, Thailand. FAU - Wanasuntronwong, Aree AU - Wanasuntronwong A AD - Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand. FAU - Tapechum, Sompol AU - Tapechum S AD - Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Srisavarindhira Bldg., 13Th Floor, Wanglang Road, Siriraj Subdistrict, Bangkoknoi District, Bangkok, 10700, Thailand. FAU - Vattarakorn, Anchalee AU - Vattarakorn A AD - Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Srisavarindhira Bldg., 13Th Floor, Wanglang Road, Siriraj Subdistrict, Bangkoknoi District, Bangkok, 10700, Thailand. FAU - Care, Chit AU - Care C AD - Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Srisavarindhira Bldg., 13Th Floor, Wanglang Road, Siriraj Subdistrict, Bangkoknoi District, Bangkok, 10700, Thailand. FAU - Chindasri, Wongsathit AU - Chindasri W AD - Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Srisavarindhira Bldg., 13Th Floor, Wanglang Road, Siriraj Subdistrict, Bangkoknoi District, Bangkok, 10700, Thailand. FAU - Tilokskulchai, Kanokwan AU - Tilokskulchai K AD - Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Srisavarindhira Bldg., 13Th Floor, Wanglang Road, Siriraj Subdistrict, Bangkoknoi District, Bangkok, 10700, Thailand. FAU - Tantisira, Mayuree H AU - Tantisira MH AD - Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand. FAU - Pakaprot, Narawut AU - Pakaprot N AD - Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Srisavarindhira Bldg., 13Th Floor, Wanglang Road, Siriraj Subdistrict, Bangkoknoi District, Bangkok, 10700, Thailand. narawut.pak@mahidol.ac.th. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230424 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (ECa 233 extract) RN - 0 (Centella asiatica extract) RN - WK2XYI10QM (Ibuprofen) RN - 9007-81-2 (Freund's Adjuvant) RN - 0 (Analgesics) SB - IM EIN - Sci Rep. 2023 Jul 21;13(1):11794. PMID: 37479881 MH - Animals MH - Male MH - *Centella MH - Ibuprofen MH - Pain MH - *Temporomandibular Joint Disorders MH - Freund's Adjuvant MH - Disease Models, Animal MH - *Hypersensitivity MH - Analgesics PMC - PMC10126003 COIS- N.P. is currently an instructor at Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. He has received a research grant (R016331041) from Siriraj Research Fund (SRF) type 1, Faculty of Medicine Siriraj Hospital, Mahidol University. Other authors declare no financial relationships or activities with any organizations that might have an influence on the submitted work. EDAT- 2023/04/25 00:41 MHDA- 2023/04/26 06:41 PMCR- 2023/04/24 CRDT- 2023/04/24 11:20 PHST- 2022/06/22 00:00 [received] PHST- 2023/04/18 00:00 [accepted] PHST- 2023/04/26 06:41 [medline] PHST- 2023/04/25 00:41 [pubmed] PHST- 2023/04/24 11:20 [entrez] PHST- 2023/04/24 00:00 [pmc-release] AID - 10.1038/s41598-023-33769-w [pii] AID - 33769 [pii] AID - 10.1038/s41598-023-33769-w [doi] PST - epublish SO - Sci Rep. 2023 Apr 24;13(1):6642. doi: 10.1038/s41598-023-33769-w.