TABLE 2.
Comprehensive information about the pharmacological effects and mechanisms of sinomenine in models of intracerebral hemorrhage, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, disorders associated with neuronal hyper-activation, depression, multiple sclerosis, and morphine dependence.
| Pharmacological effect | Object | Drug administration | Possible mechanisms | References |
|---|---|---|---|---|
| Intracerebral hemorrhage | ||||
| Suppress brain edema and neurologic damage | Mice | *20 mg/kg | Shift microglia to an anti-inflammatory phenotype | Shi et al. (2016) |
| *i.p. | ||||
| *once daily, 3 days | ||||
| Prevent neuronal death and apoptosis induced by conditioned medium from microglia treated with erythrocyte lysate | *Neuron; *Microglia | *0.1 or 1 mM, *60 min before erythrocyte lysate simulation | Shift microglia to an anti-inflammatory phenotype | Yang et al. (2014) |
| Traumatic brain injury | ||||
| *Suppress neurological deficits and brain water increase | Mice | *30 or 70 mg/kg | Increase Nrf-2-mediated antioxidant response | Fu et al. (2018) |
| *i.p. | ||||
| *Suppress neuronal apoptosis | *24 h | |||
| *Alleviate cerebral edema and neuronal apoptosis | Mice | *10, 30, or 50 mg/kg | Increase Nrf-2-mediated antioxidant response | Youqing Yang et al. (2016) |
| *i.p. | ||||
| *Improve motor performance | *24 h | |||
| *Attenuate neuroinflammation | Rabbits | *10, 30, or 50 mg/kg | Shift microglia to an anti-inflammatory phenotype | Sharma et al. (2020) |
| *i.p. | ||||
| *30 min after surgery, 1 day | ||||
| Alzheimer’s disease | ||||
| Prevent cell death induced by conditioned medium from oligomeric Aβ-treated astrocytes | *HT22 cells | *100 μM *1.5 h before stimuli |
Prevent pro-inflamamtory mediator production | Shukla and Sharma (2011), Singh et al. (2020) |
| *Cultured hippocampal neurons | ||||
| *C8D1A cells | ||||
| *Cultured human astrocytes | ||||
| *BV-2 microglia | ||||
| Reverse trimethyltin-induced 1) increase in discrimination index in novel object detection, 2) impairment of alternation in the short-term Y maze, 3) decrease in step-through latency in the passive avoidance paradigm, and 4) increase in probe trial error and latency in the Barnes maze task in rats | Rats | *100 mg/kg | *Increase Nrf-2-mediated antioxidant response | Rostami et al. (2022) |
| *p.o. | *Suppress AChE activity | |||
| *1 h after stimuli, once daily, 3 weeks | *Suppress BACE1 activity | |||
| Parkinson’s disease | ||||
| *Suppress MPTP-induced motor impairment, *increase TH-positive neurons | Mice | *20 mg/kg | Enhance autophagy by inhibiting the Akt-mTOR signaling | Bao et al. (2022) |
| *i.p. | ||||
| *5 days before MPTP treatment and another 4 days for a total of 9 days | ||||
| *Prevent LPS- or MPP+-induced impairment of dopamine take up *prevent LPS-induced decrease in TH-positive neurons | Midbrain neuron-enriched cultures | 10−6, 10−5, 10−14, or 10−13 M | Inhibit iNOS expression and TNF-α, PGE2, and NO production | Qian et al. (2007) |
| Disorders associated with neuronal hyper-activation | ||||
| *Prevent kainate-induced status epilepticus, *prevent kainate-induced hippocampal DNA fragmentation and neuronal reduction | Rats | *50 mg/kg | *Enhance antioxidant response | Ramazi et al. (2020) |
| *p.o. | ||||
| *once daily, started 4 days before till day 3 after kainate injection | *Inhibit neuroinflammation | |||
| Suppress pentylenetetrazole-induced decrease in seizure latency and duration | Rats | *20, 40, or 80 mg/kg | *Inhibit NLRP1-inflammasome complex activation and neuroinflammation | Gao et al. (2018) |
| *i.p. | ||||
| *once daily, 29 days | ||||
| *Shorten sleep latency | *Mice | *40 mg/kg | *Promote Cl- flux | Yoo et al. (2017) |
| *p.o. | ||||
| *Prolong total sleep time | *Hypothalamic neurons | *administered 60 min before behavioral tests | *Increase GABAA receptor and GAD65/67 expression | |
| Depression | ||||
| Reverse CUS-induced depression-like behaviors | Mice | *30, 100 or 300 mg/kg | *Reverse NLRP3-inflammasome complex activation | Liu et al. (2018) |
| *p.o. | ||||
| *once daily, 21 days | *Reverse p38 and NF-κB activation | |||
| Reverse CSDS-induced depression-like behaviors | Mice | *20 or 40 mg/kg | Restore the BDNF-CREB signaling | Li et al. (2018) |
| *i.p. | ||||
| * once daily, 14 days | ||||
| Multiple sclerosis | ||||
| Reduce neurological scores associated with clinical symptoms of multiple sclerosis | Mice | *100 mg/kg | Suppress neuroinflammation | Kiasalari et al. (2021) |
| *i.p. | ||||
| *once daily, 18 or 19 days | ||||
| *Prevent weight loss | Mice | *50, 100, or 200 mg/kg | Suppress neuroinflammation | Zeng et al. (2007) |
| *i.p. | ||||
| *Delay disease progression associated with EAE | *once daily, 5 days | |||
| Reduce EAE scores | Mice | *15 mg/kg | Suppress neuroinflammation | Yan et al. (2010) |
| *i.p. | ||||
| *treated from day 1–40 after MOG35-55 immunization | ||||
| Morphine dependence | ||||
| Prevent morphine-induced increase in time spent in the non-preferred white compartment in the conditioned place preference test | Mice | *80 mg/kg | *Reduce TH and NR2B expression | Fang et al. (2017) |
| *i.p. | ||||
| *on days 5–7 after the preconditioning phase and the first and second sessions on day 4 | *Increase MOR expression | |||
| Prevent morphine-induced conditioned place preference | Mice | *60 mg/kg | *Inhibit morphine-induced activation of astrocytes | Ou et al. (2018) |
| *i.p. | ||||
| *45 min before morphine injection, 3 days | ||||
| Reverse morphine-induced 1) increase in Fusobacteria and decrease in Actinobacteria, 2) decrease in tight junction proteins and OPRM1 and OPRD1, and 3) increase in levels of DRD2A, HTR2A, BDNF, and NTRK2 in the zebrafish brain and/or intestine | Zebrafish | 80 mg/kg | Regulate the homeostasis of gut microbiota | Chen et al. (2020) |