Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy
Qiong Liu,1,2 Yafei Chen,1 Bo Wang,1 Yinying Chen,3 Bing Li,4 Shuang Guan,1 Kehe Du,5 Xiaoyang Liu,5 Yanan Yu,1 Jun Liu,1 Zhong Wang1 1Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Postdoctoral Research Station, Chi...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2023-12-01
|
| Series: | Diabetes, Metabolic Syndrome and Obesity |
| Subjects: | |
| Online Access: | https://www.dovepress.com/arginine-biosynthesis-pathway-found-to-play-a-key-role-in-the-neuropro-peer-reviewed-fulltext-article-DMSO |
| _version_ | 1827586394250280960 |
|---|---|
| author | Liu Q Chen Y Wang B Chen Y Li B Guan S Du K Liu X Yu Y Liu J Wang Z |
| author_facet | Liu Q Chen Y Wang B Chen Y Li B Guan S Du K Liu X Yu Y Liu J Wang Z |
| author_sort | Liu Q |
| collection | DOAJ |
| description | Qiong Liu,1,2 Yafei Chen,1 Bo Wang,1 Yinying Chen,3 Bing Li,4 Shuang Guan,1 Kehe Du,5 Xiaoyang Liu,5 Yanan Yu,1 Jun Liu,1 Zhong Wang1 1Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Postdoctoral Research Station, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 5iPhase Pharma Services, Beijing, People’s Republic of ChinaCorrespondence: Zhong Wang, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email zhonw@vip.sina.comAim: Liu-Wei-Luo-Bi (LWLB) granules was a Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study was to investigate the effect of LWLB granules on diabetic mice with peripheral neuropathy and to elucidate the potential mechanism based on an untargeted metabolomics approach.Methods: One hundred forty db/db mice were randomly divided into seven groups: the Control group, DPN group, Mudan (MD) granules group, Epalrestat (Epa) group, and the LWLB low, medium, or high dose (LW-l, LW-m, or LW-h) group. After 12 weeks of treatment, body weight, blood glucose, mechanical pain threshold, motor conduction velocity (MCV), sensory conduction velocity (SCV), and Pathological Organization of the Sciatic and Caudal Nerves in mice were measured. Serum samples were collected for untargeted metabolomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and multivariate statistics. Disease-related pathways were screened out with function enrichment analyses of candidate biomarkers.Results: LWLB granules can improve the peripheral neuropathy of type 2 diabetic mice with peripheral nerve conduction disorders, mainly through significantly improving the nerve conduction velocity (P < 0.05) and lowering the mechanical pain threshold (P < 0.05). A total of 43 metabolites were identified as potential biomarkers related to the therapeutic effect of LWLB granules. Fifty, 4, and 26; 23, 4, and 22; and 24, 1, and 16 biomarkers were discovered in the LW-l, LW-m, and LW-h groups at the 4th, 6th, and 12th weeks, respectively. Five, three, seven, five, and four metabolic pathways were found in MD, Epa, LW-l, LW-m, and LW-h groups, respectively. The arginine biosynthesis pathway is the overlapping pathway in LW-l, LW-m, and LW-h groups.Conclusion: LWLB granules have an obvious neuroprotective effect on diabetic peripheral neuropathy, and the metabolism mechanism of LWLB is mainly related to the arginine biosynthesis pathway on diabetic db/db mice with peripheral neuropathy.Keywords: diabetic peripheral neuropathy, Traditional Chinese Medicine, Liu-Wei-Luo-Bi granules, untargeted metabolomics, arginine biosynthesis |
| first_indexed | 2024-03-09T00:01:28Z |
| format | Article |
| id | doaj.art-f46fc428d12d427793c8c8ed8d686038 |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-03-09T00:01:28Z |
| publishDate | 2023-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-f46fc428d12d427793c8c8ed8d6860382023-12-12T18:00:05ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072023-12-01Volume 164065408088924Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics StrategyLiu QChen YWang BChen YLi BGuan SDu KLiu XYu YLiu JWang ZQiong Liu,1,2 Yafei Chen,1 Bo Wang,1 Yinying Chen,3 Bing Li,4 Shuang Guan,1 Kehe Du,5 Xiaoyang Liu,5 Yanan Yu,1 Jun Liu,1 Zhong Wang1 1Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Postdoctoral Research Station, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 5iPhase Pharma Services, Beijing, People’s Republic of ChinaCorrespondence: Zhong Wang, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email zhonw@vip.sina.comAim: Liu-Wei-Luo-Bi (LWLB) granules was a Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study was to investigate the effect of LWLB granules on diabetic mice with peripheral neuropathy and to elucidate the potential mechanism based on an untargeted metabolomics approach.Methods: One hundred forty db/db mice were randomly divided into seven groups: the Control group, DPN group, Mudan (MD) granules group, Epalrestat (Epa) group, and the LWLB low, medium, or high dose (LW-l, LW-m, or LW-h) group. After 12 weeks of treatment, body weight, blood glucose, mechanical pain threshold, motor conduction velocity (MCV), sensory conduction velocity (SCV), and Pathological Organization of the Sciatic and Caudal Nerves in mice were measured. Serum samples were collected for untargeted metabolomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and multivariate statistics. Disease-related pathways were screened out with function enrichment analyses of candidate biomarkers.Results: LWLB granules can improve the peripheral neuropathy of type 2 diabetic mice with peripheral nerve conduction disorders, mainly through significantly improving the nerve conduction velocity (P < 0.05) and lowering the mechanical pain threshold (P < 0.05). A total of 43 metabolites were identified as potential biomarkers related to the therapeutic effect of LWLB granules. Fifty, 4, and 26; 23, 4, and 22; and 24, 1, and 16 biomarkers were discovered in the LW-l, LW-m, and LW-h groups at the 4th, 6th, and 12th weeks, respectively. Five, three, seven, five, and four metabolic pathways were found in MD, Epa, LW-l, LW-m, and LW-h groups, respectively. The arginine biosynthesis pathway is the overlapping pathway in LW-l, LW-m, and LW-h groups.Conclusion: LWLB granules have an obvious neuroprotective effect on diabetic peripheral neuropathy, and the metabolism mechanism of LWLB is mainly related to the arginine biosynthesis pathway on diabetic db/db mice with peripheral neuropathy.Keywords: diabetic peripheral neuropathy, Traditional Chinese Medicine, Liu-Wei-Luo-Bi granules, untargeted metabolomics, arginine biosynthesishttps://www.dovepress.com/arginine-biosynthesis-pathway-found-to-play-a-key-role-in-the-neuropro-peer-reviewed-fulltext-article-DMSOdiabetic peripheral neuropathytraditional chinese medicineliu-wei-luo-bi granulesuntargeted metabolomicsarginine biosynthesis. |
| spellingShingle | Liu Q Chen Y Wang B Chen Y Li B Guan S Du K Liu X Yu Y Liu J Wang Z Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy Diabetes, Metabolic Syndrome and Obesity diabetic peripheral neuropathy traditional chinese medicine liu-wei-luo-bi granules untargeted metabolomics arginine biosynthesis. |
| title | Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy |
| title_full | Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy |
| title_fullStr | Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy |
| title_full_unstemmed | Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy |
| title_short | Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy |
| title_sort | arginine biosynthesis pathway found to play a key role in the neuroprotective effect of liu wei luo bi lwlb granules in diabetic db db mice with peripheral neuropathy using an untargeted metabolomics strategy |
| topic | diabetic peripheral neuropathy traditional chinese medicine liu-wei-luo-bi granules untargeted metabolomics arginine biosynthesis. |
| url | https://www.dovepress.com/arginine-biosynthesis-pathway-found-to-play-a-key-role-in-the-neuropro-peer-reviewed-fulltext-article-DMSO |
| work_keys_str_mv | AT liuq argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT cheny argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT wangb argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT cheny argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT lib argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT guans argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT duk argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT liux argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT yuy argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT liuj argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy AT wangz argininebiosynthesispathwayfoundtoplayakeyroleintheneuroprotectiveeffectofliuweiluobilwlbgranulesindiabeticdbdbmicewithperipheralneuropathyusinganuntargetedmetabolomicsstrategy |