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pmid:34132355

Gypenoside XVII protects against spinal cord injury in mice by regulating the microRNA‑21‑mediated PTEN/AKT/mTOR pathway.

Tianyu Sun · Liying Duan · Jiaju Li · Hongyu Guo · Mingyue Xiong

International journal of molecular medicine · 2021 doi:10.3892/ijmm.2021.4979

Paper

complete

Experiment

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Data

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Analysis

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title
Gypenoside XVII protects against spinal cord injury in mice by regulating the microRNA‑21‑mediated PTEN/AKT/mTOR pathway.
doi
10.3892/ijmm.2021.4979
pmid
34132355
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Tianyu Sun
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Liying Duan
[2]
Jiaju Li
[3]
Hongyu Guo
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Mingyue Xiong
journal
International journal of molecular medicine
year
2021
abstract
Gypenoside XVII (GP‑17), one of the dominant active components of Gynostemma pentaphyllum, has been studied extensively and found to have a variety of pharmacological effects, including neuroprotective properties. However, the neuroprotective effects of GP‑17 against spinal cord injury (SCI), as well as its underlying mechanisms of action remain unknown. The present study aimed to investigate the effects of GP‑17 on motor recovery and histopathological changes following SCI and to elucidate the mechanisms underlying its neuroprotective effects in a mouse model of SCI. Motor recovery was evaluated using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Spinal cord edema was detected by the wet/dry weight method. H&E staining was performed to examine the effect of GP‑17 on spinal cord damage. Inflammatory response production was assessed by ELISA. Candidate miRNAs were identified following the integrated analysis of the Gene Expression Omnibus (GEO) dataset GSE67515. Western blot analysis was also performed to detect the expression levels of associated proteins. The results revealed that GP‑17 treatment improved functional recovery, and suppressed neuronal apoptosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that miR‑21 expression was downregulated following SCI, whereas it was upregulated following the administration of GP‑17. The inhibition of miR‑21 eliminated the protective effects of GP‑17 on SCI‑induced neuronal apoptosis and the inflammatory response. In addition, phosphatase and tensin homologue (PTEN), a key molecule in the activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, was identified as a target of miR‑21, and PTEN expression was downregulated by GP‑17 through miR‑21. Furthermore, the PTEN/AKT/mTOR pathway was inactivated by SCI, whereas it was re‑activated by GP‑17 through the regulation of miR‑21 in mice with SCI. On the whole, the findings of the present study suggest that GP‑17 plays a protective role in SCI via regulating the miR‑21/PTEN/AKT/mTOR pathway.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34132355", "kind": "science-record", "revision": 7, "content_hash": "sha256:b7dcdf27c99309ee8578026cf1a8a077f4660d064eaf63a8fcdab2b601d72195", "created_at": "2026-11-01T15:41:39Z", "updated_at": "2026-11-01T22:03:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Gypenoside XVII protects against spinal cord injury in mice by regulating the microRNA‑21‑mediated PTEN/AKT/mTOR pathway.", "doi": "10.3892/ijmm.2021.4979", "pmid": "34132355", "authors": ["Tianyu Sun", "Liying Duan", "Jiaju Li", "Hongyu Guo", "Mingyue Xiong"], "journal": "International journal of molecular medicine", "year": 2021, "abstract": "Gypenoside XVII (GP‑17), one of the dominant active components of Gynostemma pentaphyllum, has been studied extensively and found to have a variety of pharmacological effects, including neuroprotective properties. However, the neuroprotective effects of GP‑17 against spinal cord injury (SCI), as well as its underlying mechanisms of action remain unknown. The present study aimed to investigate the effects of GP‑17 on motor recovery and histopathological changes following SCI and to elucidate the mechanisms underlying its neuroprotective effects in a mouse model of SCI. Motor recovery was evaluated using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Spinal cord edema was detected by the wet/dry weight method. H&E staining was performed to examine the effect of GP‑17 on spinal cord damage. Inflammatory response production was assessed by ELISA. Candidate miRNAs were identified following the integrated analysis of the Gene Expression Omnibus (GEO) dataset GSE67515. Western blot analysis was also performed to detect the expression levels of associated proteins. The results revealed that GP‑17 treatment improved functional recovery, and suppressed neuronal apoptosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that miR‑21 expression was downregulated following SCI, whereas it was upregulated following the administration of GP‑17. The inhibition of miR‑21 eliminated the protective effects of GP‑17 on SCI‑induced neuronal apoptosis and the inflammatory response. In addition, phosphatase and tensin homologue (PTEN), a key molecule in the activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, was identified as a target of miR‑21, and PTEN expression was downregulated by GP‑17 through miR‑21. Furthermore, the PTEN/AKT/mTOR pathway was inactivated by SCI, whereas it was re‑activated by GP‑17 through the regulation of miR‑21 in mice with SCI. On the whole, the findings of the present study suggest that GP‑17 plays a protective role in SCI via regulating the miR‑21/PTEN/AKT/mTOR pathway.", "claims": [{"id": "claim-method", "statement": "GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/), an interactive web tool, was applied to compare the samples in two different groups under the same experimental condition.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34132355", "locator": "sections[9] \"Analysis of GEO database\" paragraph 2", "quote": "GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/), an interactive web tool, was applied to compare the samples in two different groups under the same experimental condition."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated and/or analyzed during the present study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34132355", "locator": "sections[26] \"Availability of data and materials\" paragraph 2", "quote": "All data generated and/or analyzed during the present study are included in this published article."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34132355"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE67515"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE67515"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34132355", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3892/ijmm.2021.4979", "sha256": "sha256:d76c6192be2e00296061e081fd90556e30bb4d780338cb043d8d4b8ca4b841ff", "bytes": 53377, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3892/ijmm.2021.4979", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8208621", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE67515", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE67515", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE67515", "version": null, "note": "All data generated and/or analyzed during the present study are included in this published article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated and/or analyzed during the present study are included in this published article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1648464", "GSM1648465", "GSM1648466", "GSM1648467", "GSM1648468", "GSM1648469", "GSM1648470", "GSM1648471", "GSM1648472", "GSM1648473"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "6193;6096", "taxon": "Mus musculus", "title": "Expression data from ICR mouse spinal cords - normal or injured spinal cord", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34132355:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d280b3b26f5516455c66e4492635c1aec449ce33fcb8810f8197aedc6158fe57", "bytes": 1117, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#tI-ijmm-48-02-04979", "version": null, "note": "Sequences of primers used in the present study.", "structure": {"pmcid": "PMC8208621", "section_index": 10, "section_title": "Reverse transcription-quantitative PCR (RT-qPCR)", "row_count": 21, "column_count": 2}, "table": {"label": "Table I", "caption": "Sequences of primers used in the present study.", "rows": [["Gene", "Primer sequences"], ["PTEN", "F: 5′-CAGAAAGACTTGAAGGCGTAT-3′"], ["R: 5′-TGGCGGTGTCATAATGTC-3′"], ["GAPDH", "F: 5′ CTCATGACCACAGTCCATGCCATCACTG-3′"], ["R: 5′-CATGAGGTCCACCACCCTGTTGCTGTA-3′"], ["U6", "F: 5′-CTCGCTTCGGCAGCACA-3′"], ["R: 5′-GTCATACTCCTGCTTGCTGAT-3′"], ["miR-21", "F: 5′-GCAGGGTCCGAGGTATTC-3′"], ["R: 5′-CTACTCACAAAACAGGAGTGGAATC-3′"], ["miR-34a-5p", "F: 5′-AGCCGCTGGCAGTGTCTTA-3′"], ["R: 5′-CAGAGCAGGGTCCGAGGTA-3′"], ["miR-494", "F: 5′-TGGTGATGGGATTTGAAACATACACGGGAAAC-3′"], ["R: 5′-AGATAGACGG-TGTCGCTGTTGAAGTCAG-3′"], ["miR-142", "F: 5′-AACTCCAGCTGGTCCTTAG-3′"], ["R: 5′-TCTTGAACCCTCATCCTGT-3′"], ["let-7", "F: 5′-UGAGGUAGUAGAUUGUAUAGUU-3′"], ["R: 5′-CUAUACAAUCUACCUCAUU-3′"], ["miR-155", "F: 5′-CTCGTGGTAATGCTAATTGTGA-3′"], ["R: 5′-GTGCAGGGTCCGAGGT-3′"], ["miR-543", "F: 5′-GGAAACATTCGCGGTGC-3′"], ["R: 5′-GTGCGTGTCGTGGAGTCG-3′"]], "row_count": 21, "column_count": 2, "numeric_cells": 27, "header_rows": 1, "locator": "section[10]/table-wrap[1]#tI-ijmm-48-02-04979"}}], "gaps": ["asset:data:geo:GSE67515 not downloaded", "asset:data:geo:GSE67515 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-3", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"id": "method-4", "family": null, "specific": null, "label": "GEO2R analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "GEO2R (www.ncbi.nlm.nih.gov/geo/geo2r/), an interactive web tool, was applied to compare the samples in two different groups under the same experimental condition."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.student_t"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Motor recovery was evaluated using t", "optosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that miR‑2", "onal apoptosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that"], "order_basis": "paper_text_order:7", "id": "assay:1"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ammatory response production was assessed by ELISA. Candidate miRNAs were identified following"], "order_basis": "paper_text_order:941", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e Expression Omnibus (GEO) dataset GSE67515. Western blot analysis was also performed to detect the ex", "ression of cleaved caspase 3 was measured by western blot analysis at 28 days following GP-17 treatmen"], "order_basis": "paper_text_order:1070", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["functional recovery, and suppressed neuronal apoptosis and the inflammatory response in the mouse m", "ive effects of GP‑17 on SCI‑induced neuronal apoptosis and the inflammatory response. In addition,", "s recovery following SCI in mice by reducing apoptosis. After the mouse model of SCI was establishe", "eatment. (E and F) The expression of cleaved caspase 3 was measured by western blot analysis at 2"], "order_basis": "paper_text_order:1263", "id": "assay:4"}, {"role": "data_generation", "definition_id": "clinical_trial", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": [". (C) Changes in BBB scores of mice with SCI treated with or without GP-17 at the indicated days. (D) Water conte"], "order_basis": "paper_text_order:3320", "id": "assay:5"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ression of cleaved caspase 3 was measured by Immunohistochemistry at 28 days following GP-17 treatment. Data r", "in, and sectioned at a thickness of 4 µm for immunohistochemistry. Analysis of GEO database A microarray datas"], "order_basis": "paper_text_order:3670", "id": "assay:6"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["nohistochemistry. Analysis of GEO database A microarray dataset was obtained from the GEO database ("], "order_basis": "paper_text_order:6859", "id": "assay:7"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Technologies, Inc.). Cells, cell culture and transfection Immortal BV-2 murine microglial cells were o", "hanghai GenePharma Co., Ltd. BV-2 cells were transfected with 100 nM agomir-21 or antagomir-21 or con", "ions. The cells were harvested at 24 h after transfection for testing. Statistical analysis Statistica"], "order_basis": "paper_text_order:7401", "id": "assay:8"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["Technology Co., Ltd. (cat. no. 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