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      Berberine enhances L1 expression and axonal remyelination in rats after brachial plexus root avulsion

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          Abstract

          Background and Purpose

          Enhanced remyelination of the regenerated axons results in functional re‐innervation and improved functional motor recovery after brachial plexus root avulsion (BPRA). The neural cell adhesion molecule L1 (L1CAM, L1) regulates myelination and promotes regeneration after acute injury in the nervous system. Berberine (BBR) can exert neuroprotective roles against the lesion. Herein, we investigated whether berberine (BBR) can affect the expression of L1 and enhance the axonal remyelination in rats following BPRA.

          Methods

          The surgical procedures were performed to build the rat brachial plexus avulsion and re‐implantation model, and then, the rats were treated with BBR. After the rehabilitation for 12 weeks, the musculocutaneous nerves were collected for quantitative real‐time PCR, Western blot analysis, and histochemical and immunofluorescence staining.

          Results

          We observed that, BBR treatment ameliorated the abnormal musculocutaneous nerve fibers morphology, up‐regulated the L1 expression, increased the myelination‐related genes, decreased the differentiated‐associated genes, and up‐regulated the phosphorylation of ERK.

          Conclusion

          These results suggest that BBR may enhance L1 expression and promote axonal remyelination after spinal root avulsion.

          Abstract

          Effect of BBR on the L1 changes in musculocutaneous nerve fibers after BPRA after BPRA in rats.

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          Current knowledge and pharmacological profile of berberine: An update.

          Anil Pandey Kumar, Kanwaljit Chopra, Madhurima Mukherjee … (2015)
          Berberine, a benzylisoquinoline alkaloid, occurs as an active constituent in numerous medicinal plants and has an array of pharmacological properties. It has been used in Ayurvedic and Chinese medicine for its antimicrobial, antiprotozoal, antidiarrheal and antitrachoma activity. Moreover, several clinical and preclinical studies demonstrate ameliorative effect of berberine against several disorders including metabolic, neurological and cardiological problems. This review provides a summary regarding the pharmacokinetic and pharmacodynamic features of berberine, with a focus on the different mechanisms underlying its multispectrum activity. Studies regarding the safety profile, drug interactions and important clinical trials of berberine have also been included. Clinical trials with respect to neurological disorders need to be undertaken to exploit the beneficiary effects of berberine against serious disorders such as Alzheimer's and Parkinson's disease. Also, clinical studies to detect rare adverse effects of berberine need to be initiated to draw a complete safety profile of berberine and strengthen its applicability.
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            Tissue Distribution of Berberine and Its Metabolites after Oral Administration in Rats

            Xiang-Shan Tan, Jing-Yi Ma, Ru Feng … (2013)
            Berberine (BBR) has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR’s plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MSn-IT-TOF) as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS) was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg). The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR’s level in most of studied tissues was higher (or much higher) than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR’s metabolites was also investigated paralleled with that of BBR. Thalifendine (M1), berberrubine (M2) and jatrorrhizine (M4), which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t) (area under the concentration-time curve) for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites) was higher than its concentration in the blood after oral administration. It might explain BBR’s pharmacological effects on human diseases in clinic.
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              Mechanisms of Disease: what factors limit the success of peripheral nerve regeneration in humans?

              Ahmet Höke (2006)
              Functional recovery after repair of peripheral nerve injury in humans is often suboptimal. Over the past quarter of a century, there have been significant advances in human nerve repair, but most of the developments have been in the optimization of surgical techniques. Despite extensive research, there are no current therapies directed at the molecular mechanisms of nerve regeneration. Multiple interventions have been shown to improve nerve regeneration in small animal models, but have not yet translated into clinical therapies for human nerve injuries. In many rodent models, regeneration occurs over relatively short distances, so the duration of denervation is short. By contrast, in humans, nerves often have to regrow over long distances, and the distal portion of the nerve progressively loses its ability to support regeneration during this process. This can be largely attributed to atrophy of Schwann cells and loss of a Schwann cell basal lamina tube, which results in an extracellular environment that is inhibitory to nerve regeneration. To develop successful molecular therapies for nerve regeneration, we need to generate animal models that can be used to address the following issues: improving the intrinsic ability of neurons to regenerate to increase the speed of axonal outgrowth; preventing loss of basal lamina and chronic denervation changes in the denervated Schwann cells; and overcoming inhibitory cues in the extracellular matrix.
              Article 0 comments Cited 84 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Heng Wu: 2915176817@qq.com
                Zijian Xiao:
                ORCID: https://orcid.org/0000-0001-5137-9549
                zijian6340@21cn.com
                Journal
                Journal ID (nlm-ta): Brain Behav
                Journal ID (iso-abbrev): Brain Behav
                Journal ID (doi): 10.1002/(ISSN)2157-9032
                Journal ID (publisher-id): BRB3
                Title: Brain and Behavior
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2162-3279
                Publication date (Electronic): 07 August 2020
                Publication date Collection: October 2020
                Volume: 10
                Issue: 10 ( doiID: 10.1002/brb3.v10.10 )
                Electronic Location Identifier: e01792
                Affiliations
                [ 1 ] The First Affiliated Hospital University of South China Hengyang China
                [ 2 ] Leiyang People's Hospital Leiyang China
                Author notes
                [*] [* ] Correspondence

                Heng Wu and Zijian Xiao, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China.

                Emails: 2915176817@ 123456qq.com ; zijian6340@ 12345621cn.com

                Author information
                https://orcid.org/0000-0001-5137-9549
                Article
                Publisher ID: BRB31792
                DOI: 10.1002/brb3.1792
                PMC ID: 7559605
                PubMed ID: 32770668
                SO-VID: 25b40bcc-a3dc-48c5-97b3-8b137ec24ad7
                Copyright © © 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 06 April 2020
                Date revision received : 17 June 2020
                Date accepted : 19 July 2020
                Page count
                Figures: 5, Tables: 1, Pages: 10, Words: 5615
                Funding
                Funded by: Hunan Provincial Natural Science Foundation of China
                Award ID: 2017JJ3273
                Award ID: 2018JJ2358
                Award ID: 2019JJ40267
                Funded by: Scientific Research Fund Project of Hunan Provincial Health Commission
                Award ID: 20200469
                Award ID: 20201911
                Award ID: 20201963
                Award ID: C20180238
                Funded by: Hengyang Science and Technology Project
                Award ID: 2016KJ38
                Categories
                Subject: Original Research
                Subject: Original Research
                Custom metadata
                source-schema-version-number 2.0
                cover-date October 2020
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.2 mode:remove_FC converted:15.10.2020

                ScienceOpen disciplines: Neurosciences
                Keywords: brachial plexus root avulsion,l1cam,motoneuron
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: brachial plexus root avulsion, l1cam, motoneuron

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