Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide-Induced Sickness-Like Behaviour in Mice
Sickness behaviour, a set of behavioural changes associated with neuroinflammation, is expressed as decreased mobility and depressed behaviour. Activation of AMP-activated protein kinase (AMPK) is reported to regulate inflammation in conditions such as Alzheimer and traumatic brain injury. Metformin...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Advances in Pharmacological and Pharmaceutical Sciences |
| Online Access: | http://dx.doi.org/10.1155/2024/8599268 |
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| author | Triveni Kodi Sharanya Praveen Sravan Kumar Paka Runali Sankhe Adarsh Gopinathan Nandakumar Krishnadas Anoop Kishore |
| author_facet | Triveni Kodi Sharanya Praveen Sravan Kumar Paka Runali Sankhe Adarsh Gopinathan Nandakumar Krishnadas Anoop Kishore |
| author_sort | Triveni Kodi |
| collection | DOAJ |
| description | Sickness behaviour, a set of behavioural changes associated with neuroinflammation, is expressed as decreased mobility and depressed behaviour. Activation of AMP-activated protein kinase (AMPK) is reported to regulate inflammation in conditions such as Alzheimer and traumatic brain injury. Metformin, an antidiabetic agent acting via AMPK activation, possesses anti-inflammatory properties. Similarly, the reported anti-inflammatory activities of berberine could be partially attributed to its ability to activate AMPK. In this study, we investigated the effects of metformin and berberine against lipopolysaccharide (LPS)-induced sickness-like behaviour, associated with neuroinflammation, impaired cognition, and oxidative stress. Swiss albino mice were divided into four groups, normal control, LPS control, metformin treatment, and berberine treatment. The control groups received saline for 7 days. Groups 3 and 4 received metformin (200 mg/kg) and berberine (100 mg/kg), respectively, orally once daily for 7 days. On day 7, 1 h after the treatments, animals received LPS (1.5 mg/kg i.p.) to induce sickness-like behaviour. Open field test (OFT) and forced swim test (FST), were performed within 2 h of LPS administration. Then, proinflammatory cytokines (IL-1β and TNF-α), acetylcholinesterase activity (AChE), and oxidative stress markers were estimated in the brain homogenate. In the LPS control group, immobility state, proinflammatory cytokines, AChE, and lipid peroxidation were significantly increased, whereas the glutathione levels were decreased. Pretreatment with metformin significantly improved immobility in the FST, with reduced IL-1β, oxidative stress markers, and AChE activity. However, no significant changes were observed in OFT. Berberine pretreatment exhibited only an apparent, statistically insignificant, improvement in sickness-like behaviour assessed using FST and OFT, cytokine levels, oxidative markers, and AChE. Several factors affect treatment efficacy, such as treatment duration and administered dose. Considering these, berberine warrants elaborate preclinical evaluation for neuroinflammation. Nevertheless, based on the effects observed, AMPK activators could regulate neuroinflammation, cognition, and oxidative stress linked with sickness-like behaviour. |
| format | Article |
| id | doaj-art-8041acebe6354b46932ccdcfac574bce |
| institution | Kabale University |
| issn | 2633-4690 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Pharmacological and Pharmaceutical Sciences |
| spelling | doaj-art-8041acebe6354b46932ccdcfac574bce2025-02-02T23:14:13ZengWileyAdvances in Pharmacological and Pharmaceutical Sciences2633-46902024-01-01202410.1155/2024/8599268Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide-Induced Sickness-Like Behaviour in MiceTriveni Kodi0Sharanya Praveen1Sravan Kumar Paka2Runali Sankhe3Adarsh Gopinathan4Nandakumar Krishnadas5Anoop Kishore6Department of PharmacologyDepartment of PharmacologyDepartment of PharmacologyDepartment of PharmacologyDepartment of PharmacologyDepartment of PharmacologyDepartment of PharmacologySickness behaviour, a set of behavioural changes associated with neuroinflammation, is expressed as decreased mobility and depressed behaviour. Activation of AMP-activated protein kinase (AMPK) is reported to regulate inflammation in conditions such as Alzheimer and traumatic brain injury. Metformin, an antidiabetic agent acting via AMPK activation, possesses anti-inflammatory properties. Similarly, the reported anti-inflammatory activities of berberine could be partially attributed to its ability to activate AMPK. In this study, we investigated the effects of metformin and berberine against lipopolysaccharide (LPS)-induced sickness-like behaviour, associated with neuroinflammation, impaired cognition, and oxidative stress. Swiss albino mice were divided into four groups, normal control, LPS control, metformin treatment, and berberine treatment. The control groups received saline for 7 days. Groups 3 and 4 received metformin (200 mg/kg) and berberine (100 mg/kg), respectively, orally once daily for 7 days. On day 7, 1 h after the treatments, animals received LPS (1.5 mg/kg i.p.) to induce sickness-like behaviour. Open field test (OFT) and forced swim test (FST), were performed within 2 h of LPS administration. Then, proinflammatory cytokines (IL-1β and TNF-α), acetylcholinesterase activity (AChE), and oxidative stress markers were estimated in the brain homogenate. In the LPS control group, immobility state, proinflammatory cytokines, AChE, and lipid peroxidation were significantly increased, whereas the glutathione levels were decreased. Pretreatment with metformin significantly improved immobility in the FST, with reduced IL-1β, oxidative stress markers, and AChE activity. However, no significant changes were observed in OFT. Berberine pretreatment exhibited only an apparent, statistically insignificant, improvement in sickness-like behaviour assessed using FST and OFT, cytokine levels, oxidative markers, and AChE. Several factors affect treatment efficacy, such as treatment duration and administered dose. Considering these, berberine warrants elaborate preclinical evaluation for neuroinflammation. Nevertheless, based on the effects observed, AMPK activators could regulate neuroinflammation, cognition, and oxidative stress linked with sickness-like behaviour.http://dx.doi.org/10.1155/2024/8599268 |
| spellingShingle | Triveni Kodi Sharanya Praveen Sravan Kumar Paka Runali Sankhe Adarsh Gopinathan Nandakumar Krishnadas Anoop Kishore Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide-Induced Sickness-Like Behaviour in Mice Advances in Pharmacological and Pharmaceutical Sciences |
| title | Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide-Induced Sickness-Like Behaviour in Mice |
| title_full | Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide-Induced Sickness-Like Behaviour in Mice |
| title_fullStr | Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide-Induced Sickness-Like Behaviour in Mice |
| title_full_unstemmed | Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide-Induced Sickness-Like Behaviour in Mice |
| title_short | Neuroprotective Effects of Metformin and Berberine in Lipopolysaccharide-Induced Sickness-Like Behaviour in Mice |
| title_sort | neuroprotective effects of metformin and berberine in lipopolysaccharide induced sickness like behaviour in mice |
| url | http://dx.doi.org/10.1155/2024/8599268 |
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