Cannabidiol (CBD), a nonpsychotropic phytocannabinoid that was once largely disregarded, is currently the subject of significant medicinal study. CBD is found in Cannabis sativa, and has a myriad of neuropharmacological impacts on the central nervous system, including the capacity to reduce neuroinflammation, protein misfolding and oxidative stress. On the other hand, it is well established that CBD generates its biological effects without exerting a large amount of intrinsic activity upon cannabinoid receptors. Because of this, CBD does not produce undesirable psychotropic effects that are typical of marijuana derivatives. Nonetheless, CBD displays the exceptional potential to become a supplementary medicine in various neurological diseases. Currently, many clinical trials are being conducted to investigate this possibility. This review focuses on the therapeutic effects of CBD in managing neurological disorders like Alzheimer's disease, Parkinson's disease and epilepsy. Overall, this review aims to build a stronger understanding of CBD and provide guidance for future fundamental scientific and clinical investigations, opening a new therapeutic window for neuroprotection. Please cite this article as: Tambe SM, Mali S, Amin PD, Oliveira M. Neuroprotective potential of Cannabidiol: Molecular mechanisms and clinical implications. J Integr Med. 2023; 21(3): 236-244.
Humans ; Cannabidiol/therapeutic use* ; Neuroprotection ; Cannabinoids/therapeutic use* ; Epilepsy/drug therapy* ; Cannabis ; Neuroprotective Agents/therapeutic use*

Benzofurans ; therapeutic use ; Humans ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; drug effects

OBJECTIVEFructose-1, 6-diphosphate (FDP), serving as a cellular energy substance, has shown its roles in the treatment of hypoxic-ischemic encephalopathy and myocardial damage. The present study aimed at exploring the potentiality of the protective effect of FDP against ultrastructural damage of the hippocampus caused by febrile seizures (FS) in rats.

METHODSThirty-six 21-day-old male Sprague-Dawley rats were randomly divided into three groups: untreated FS (control), high-dose FDP-treated FS and low-dose FDP-treated FS. FS were induced by hyperthermal bath. Thirty minutes before FS induction, rats in the high-dose and low-dose FDP-treated groups received a peritoneal injection of FDP at a dosage of 50 and 25 mg per 100 g of body weight respectively, whereas the same volume of 0.9% sodium chloride solution were injected to the rats in the control group. Transmission electron microscopy was used to examine the ultrastructural pathologic changes of neurons and organelles as well as the features of synaptic morphological parameters in the hippocampal CA1 area.

RESULTSNeuronal degeneration and necrosis, mitochondria swelling, polyribosomes disaggregation from endoplasmic reticula, and golgiosomes dilation in the hippocampal CA1 area in the two FDP intervention groups were less severe compared with the control group. FDP treatment resulted in significant increases in postsynaptic density thickness (F=12.47, P<0.01), synaptic active zone length (F=14.75, P<0.01) and synaptic interface curvature (F=3.77, P<0.05), as well as a shorter interspace of neural synapses (F=7.29, P<0.01) when compared with the control group. There were no significant differences in the ultrastructural changes between the two FDP treatment groups.

CONCLUSIONSFDP can ameliorate ultrastructural damage in the hippocampus caused by FS in rats. However, further research is warranted for a reasonable and effective dosage of FDP.

Animals ; Fructosediphosphates ; therapeutic use ; Hippocampus ; ultrastructure ; Male ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Seizures, Febrile ; drug therapy ; pathology

BACKGROUNDGranulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against cerebral ischemia injury, but the molecular mechanisms have been unclear. This study aimed to investigate the influences of a short-acting (half-life 3.5 hours) G-CSF and a long-acting (half-life 40 hours) pegylated G-CSF on the JNK signaling pathway after cerebral ischemia reperfusion.

METHODSA total of 52 Sprague-Dawley rats were randomly divided into four groups: a sham group (n = 4), a vehicle with saline (n = 16), a short-acting G-CSF treatment group (n = 16) and a long-acting G-CSF treatment group (n = 16). The cerebral ischemia reperfusion model was established for the sham group and G-CSF treatment groups by middle cerebral artery occlusion (MCAO). Five days post reperfusion, rats were sacrificed and the brains were removed. Changes in neurological function after cerebral ischemia reperfusion was evaluated according to Neurological Severity Score (NSS) and the lesion volume and infarct size were measured by 2,3,5-triphenyltetrazolium chloride staining. The numbers of apoptotic neurons in these ischemic areas: left cerebral cortex, striatum and hippocampus were calculated by TUNEL assay, and expression of JNK/P-JNK, c-jun/P-c-jun in these areas was detected by Western blotting.

RESULTSCompared with the saline vehicle group ((249.68±23.36) mm(3), (19.27±3.37)%), G-CSF-treated rats revealed a significant reduction in lesion volume (long-acting: (10.89±1.90)%, P < 0.01; short-acting G-CSF: (11.69±1.41)%, P < 0.01) and infarct size (long-acting: (170.53±18.47) mm3, P < 0.01; short-acting G-CSF: (180.74±16.93) mm3, P < 0.01) as well as less neuron functional damage (P < 0.01) and a smaller number of apoptotic neurons in ischemic areas (P < 0.01). The activity of P-JNK and P-c-jun in the cerebral ischemia reperfusion-damaged cortex and hippocampus was significantly decreased in all G-CSF-treated rats (P < 0.05). However, between the long-acting and short-acting G-CSF sets, there were no significant differences found in the activity of P-JNK and P-c-jun in the cortex, hippocampus and striate body (P > 0.05).

CONCLUSIONSHypodermic injection of 50 µg/kg G-CSF attenuated the damage caused by cerebral ischemia reperfusion in rats, which might be associated with down-regulated activation of the P-JNK and P-c-jun pathway after cerebral ischemia reperfusion. Long-acting G-CSF may be a novel choice for both clinical and basic research in treating cerebral ischemia.

Animals ; Brain Ischemia ; drug therapy ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley

Acute spinal cord injury(ASCI),mainly caused by traffic accidents and fall injuries,is a catastrophic event that can profoundly affect the trajectory of a patient's life. Debate continues over the medical management of ASCI,in particular the usefulness,dosage,and potential risks of methylprednisolone(MP). Although the results of American National Acute Spinal Cord Injury Study 2 and 3 trials led to the wide adoption of a high-dose MP regimen for ASCI patients,the reliabilities of their study methods and data were still questionable. Based on the currently available literature,we conclude that high-dose MP is no longer a recommended therapy for ASCI;however,due to the lack of effective treatment,it remains a useful option for this condition.
Clinical Trials as Topic ; Humans ; Methylprednisolone ; therapeutic use ; Neuroprotective Agents ; therapeutic use ; Spinal Cord Injuries ; drug therapy ; Treatment Outcome

OBJECTIVETo analyze the mechanism of neuroprotection of insulin and which blood glucose range was benefit for insulin exerting neuroprotective action.

DATA SOURCESThe study is based on the data from PubMed.

STUDY SELECTIONArticles were selected with the search terms "insulin", "blood glucose", "neuroprotection", "brain", "glycogen", "cerebral ischemia", "neuronal necrosis", "glutamate", "γ-aminobutyric acid".

RESULTSInsulin has neuroprotection. The mechanisms include the regulation of neurotransmitter, promoting glycogen synthesis, and inhibition of neuronal necrosis and apoptosis. Insulin could play its role in neuroprotection by avoiding hypoglycemia and hyperglycemia.

CONCLUSIONSIntermittent and long-term infusion insulin may be a benefit for patients with ischemic brain damage at blood glucose 6-9 mmol/L.

Blood Glucose ; drug effects ; Brain Ischemia ; prevention & control ; Humans ; Hyperglycemia ; prevention & control ; Insulin ; therapeutic use ; Neuroprotective Agents ; therapeutic use

Survival rates after cardiac arrest have not changed substantially over the past 5 decades. Postcardiac arrest (CA) syndrome (PCAS) is the primary reason for the high mortality rate after successful restoration of spontaneous circulation (ROSC). Intravenous administration of Shenfu Injection (, SFI) may attenuate post-CA myocardial dysfunction and cerebral injury, inhibit systemic ischemia/reperfusion responses, and treat underlying diseases. In this article, we reviewed the therapeutic effects of SFI in PCAS. SFI might be useful in the treatment of PCAS, incorporating the multi-link and multi-target advantages of Chinese medicine into PCAS management. Further experimental and clinical research to verify the therapeutic effects of SFI in PCAS is required.
Cardiotonic Agents ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Heart Arrest ; drug therapy ; physiopathology ; Humans ; Injections ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Syndrome

Rasayana tantra is one of the eight specialties of Ayurveda. It is a specialized practice in the form of rejuvenative recipes, dietary regimen, special health promoting behaviour and drugs. Properly administered Rasayana can bestow the human being with several benefits like longevity, memory, intelligence, freedom from diseases, youthful age, excellence of luster, complexion and voice, optimum strength of physique and sense organs, respectability and brilliance. Various types of plant based Rasayana recipes are mentioned in Ayurveda. Review of the current literature available on Rasayanas indicates that anti-oxidant and immunomodulation are the most studied activities of the Rasayana drugs. Querying in Pubmed database on Rasayanas reveals that single plants as well as poly herbal formulations have been researched on. This article reviews the basics of Rasayana therapy and the published research on different Rasayana drugs for specific health conditions. It also provides the possible directions for future research.
Animals ; Anti-Ulcer Agents ; pharmacology ; therapeutic use ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Antiparasitic Agents ; pharmacology ; therapeutic use ; Aphrodisiacs ; pharmacology ; therapeutic use ; Free Radical Scavengers ; pharmacology ; therapeutic use ; Giardiasis ; drug therapy ; Herbal Medicine ; classification ; methods ; trends ; Humans ; Immunologic Factors ; pharmacology ; therapeutic use ; Medicine, Ayurvedic ; Models, Biological ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Plant Preparations ; classification ; therapeutic use ; Radiation-Protective Agents ; pharmacology ; therapeutic use

Animals ; Brain Ischemia ; drug therapy ; Calcium Channel Blockers ; therapeutic use ; Humans ; Neuroprotective Agents ; therapeutic use ; Nitric Oxide Synthase ; antagonists & inhibitors ; Sodium Channel Blockers ; therapeutic use

Antioxidants ; therapeutic use ; Diabetic Neuropathies ; drug therapy ; physiopathology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; drug effects ; Phytotherapy