{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:12:05Z","timestamp":1767204725696,"version":"build-2238731810"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T00:00:00Z","timestamp":1620950400000},"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. Pharmacol."],"abstract":"\n Tang Luo Ning (TLN), a traditional Chinese compound prescription, has been used clinically to treat diabetic peripheral neuropathy (DPN) in China. However, the exact mechanisms remain unclear. The objective of this study is to unravel the effects of TLN on mitochondrial dynamics of DPN in streptozotocin-induced rat models and Schwann cells cultured in 150\u00a0mM glucose. Mitochondrial function was determined by Ca\n 2+<\/jats:sup>\n and ATP levels of streptozotocin (STZ)-induced DPN rats and mitochondria structure, mitochondrial membrane potential (MMP), and mtDNA of high glucose incubated SCs. Mitochondrial dynamics protein including mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), optic atrophy 1 (Opa1), and dynamin-related protein 1 (Drp1) were investigated using Western blot or immunofluorescence. Myelin basic protein (MBP), myelin protein zero (MPZ), and sex-determining region Y (SRY)-box 10 (Sox10) were measured to represent schwannopathy. Our results showed that TLN increased ATP levels (0.38 of model, 0.69 of HTLN, 0.61 of LTLN,\n P<\/jats:italic>\n \uff1c0.01; 0.52 of 150\u00a0mM glucose, 1.00 of 10% TLN,\n P<\/jats:italic>\n \uff1c0.01, 0.94 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.05), MMP (0.56 of 150\u00a0mM glucose,\n P<\/jats:italic>\n \uff1c0.01, 0.75 of 10% TLN,\n P<\/jats:italic>\n \uff1c0.05, 0.83 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.01), and mtDNA (0.32 of 150\u00a0mM glucose, 0.43 of 10% TLN,\n P<\/jats:italic>\n \uff1c0.01) while decreased Ca\n 2+<\/jats:sup>\n (1.54 of model, 1.06 of HTLN, 0.96 of LTLN,\n P<\/jats:italic>\n \uff1c0.01) to improve mitochondrial function\n in vivo<\/jats:italic>\n and\n in vitro<\/jats:italic>\n . TLN helps maintain balance of mitochondrial dynamics: it reduces the mitochondria number (1.60 of 150\u00a0mM glucose, 1.10 of 10% TLN,\n P<\/jats:italic>\n \uff1c0.01) and increases the mitochondria coverage (0.51 of 150\u00a0mM glucose, 0.80 of 10% TLN, 0.87 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.01), mitochondrial network size (0.51 of 150\u00a0mM glucose, 0.95 of 10% TLN, 0.94 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.01), and branch length (0.63 of 150\u00a0mM glucose,\n P<\/jats:italic>\n \uff1c0.01, 0.73 of 10% TLN,\n P<\/jats:italic>\n \uff1c0.05, 0.78 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.01). Further, mitochondrial dynamics\u2013related Mfn1 (0.47 of model, 0.82 of HTLN, 0.77 of LTLN,\n P<\/jats:italic>\n \uff1c0.01; 0.42 of 150\u00a0mM glucose, 0.56 of 10% TLN, 0.57 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.01), Mfn2 (0.40 of model, 0.84 of HTLN, 0.63 of LTLN,\n P<\/jats:italic>\n \uff1c0.01; 0.46 of 150\u00a0mM glucose, 1.40 of 10% TLN, 1.40 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.01), and Opa1 (0.58 of model, 0.71 of HTLN, 0.90 of LTLN,\n P<\/jats:italic>\n \uff1c0.01; 0.69 of 150\u00a0mM glucose, 0.96 of 10% TLN, 0.98 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.05) were increased, while Drp1 (1.39 of model, 0.96 of HTLN, 1.18 of LTLN,\n P<\/jats:italic>\n \uff1c0.01; 1.70 of 150\u00a0mM glucose, 1.20 of 10% TLN, 1.10 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.05), phosphorylated Drp1 (2.61 of model, 1.44 of HTLN,\n P<\/jats:italic>\n \uff1c0.05; 2.80 of 150\u00a0mM glucose, 1.50 of 10% TLN, 1.30 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.01), and Drp1 located in mitochondria (1.80 of 150\u00a0mM glucose, 1.00 of 10% TLN,\n P<\/jats:italic>\n \uff1c0.05) were decreased after treatment with TLN. Additionally, TLN improved schwannopathy by increasing MBP (0.50 of model, 1.05 of HTLN, 0.94 of HTLN,\n P<\/jats:italic>\n \uff1c0.01; 0.60 of 150\u00a0mM glucose, 0.78 of 10% TLN,\n P<\/jats:italic>\n \uff1c0.01, 0.72 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.05), Sox101 (0.41 of model, 0.99 of LTLN,\n P<\/jats:italic>\n \uff1c0.01; 0.48 of 150\u00a0mM glucose, 0.65 of 10% TLN,\n P<\/jats:italic>\n \uff1c0.05, 0.69 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.01), and MPZ (0.48 of model, 0.66 of HTLN, 0.55 of HTLN,\n P<\/jats:italic>\n \uff1c0.01; 0.60 of 150\u00a0mM glucose, 0.78 of 10% TLN,\n P<\/jats:italic>\n \uff1c0.01, 0.75 of 1% TLN,\n P<\/jats:italic>\n \uff1c0.05) expressions. In conclusion, our study indicated that TLN\u2019s function on DPN may link to the improvement of the mitochondrial dynamics, which provides scientific evidence for the clinical application.\n <\/jats:p>","DOI":"10.3389\/fphar.2021.650448","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T04:07:21Z","timestamp":1620965241000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Tang Luo Ning, a Traditional Chinese Compound Prescription, Ameliorates Schwannopathy of Diabetic Peripheral Neuropathy Rats by Regulating Mitochondrial Dynamics In Vivo and In Vitro"],"prefix":"10.3389","volume":"12","author":[{"given":"Jiayue","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinwei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanbo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/j.neuron.2020.06.037","article-title":"SUMOylation of Enzymes and Ion Channels in Sensory Neurons Protects against Metabolic Dysfunction, Neuropathy, and Sensory Loss in Diabetes","volume":"107","author":"Agarwal","year":"2020","journal-title":"Neuron"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.bbadis.2016.11.010","article-title":"Mitochondrial Dysfunction and Oxidative Stress in Metabolic Disorders \u2014 A Step towards Mitochondria Based Therapeutic Strategies","volume":"1863","author":"Bhatti","year":"2016","journal-title":"Biochim. 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