Treatment Of Epilepsy Research Articles

COST OF ILLNESS ANALYSIS OF EPILEPSY OUTPATIENTS USING VALPROIC ACID, PHENYTOIN AND CARBAMAZEPINE THERAPY IN HOSPITAL IN INDONESIA

Epilepsy is a condition of the onset of attacks in the form of abnormal, irregular brain nerve cell movements, occurring repeatedly and causing temporary motor, sensory or mental function disorders. The treatment of epilepsy has costs that must be known, including direct medical costs, indirect medical costs, and indirect costs; this study aims to determine the cost of illness of epilepsy in one hospital in banyuasin regency with retrospective costing in outpatients. The research method used in this study is a cross-sectional study using patient medical record data and cost data taken from BPJS claims data and hospital rate patterns. This study uses the BPJS perspective and societal perspective, the cost data taken from the BPJS perspective is the result of BPJS claims according to the INACBGs. Package tariff and for the socital perspective the data taken is doctor consultation data, administrative costs, laboratory costs, drug costs and transportation costs and lost productivity costs carried out by interview method for 12 months. The results of this study indicate that the cost of epilepsy outpatients from a societal perspective is Rp.3,141,414 and for BPJS perspective is Rp.2,338,567.

Development of cognitive performance in children before and after surgical treatment of pharmacoresistant temporal lobe epilepsy

Development of cognitive performance in children before and after surgical treatment of pharmacoresistant temporal lobe epilepsy

Design of experiment (DoE) of mucoadhesive valproic acid-loaded nanostructured lipid carriers (NLC) for potential nose-to-brain application

Epilepsy is a highly prevalent neurological disease and valproic acid (VPA) is used as a first-line chronic treatment. However, this drug has poor oral bioavailability, which requires the administration of high doses, resulting in adverse effects. Alternative routes of VPA administration have therefore been investigated, such as the nose-to-brain route, which allows the drug to be transported directly from the nasal cavity to the brain. Here, the use of nanostructured lipid carriers (NLC) to encapsulate drugs administered in the nasal cavity has proved advantageous. The aim of this work was to optimise a mucoadhesive formulation of VPA-loaded NLC for intranasal administration to improve the treatment of epilepsy. The Design of Experiment (DoE) was used to optimise the formulation, starting with component optimisation using Mixture Design (MD), followed by optimisation of the manufacturing process parameters using Central Composite Design (CCD).The optimised VPA-loaded NLC had a particle size of 76.1 ± 2.8 nm, a polydispersity index of 0.190 ± 0.027, a zeta potential of 28.1 ± 2.0 mV and an encapsulation efficiency of 85.4 ± 0.8%. The in vitro release study showed VPA release from the NLC of 50 % after 6 h and 100 % after 24 h. The in vitro biocompatibility experiments in various cell lines have shown that the optimised VPA-loaded NLC formulation is safe up to 75 µg/mL, in neuronal (SH-SY5Y), nasal (RPMI 2650) and hepatic (HepG2) cells. Finally, the interaction of the optimised VPA-loaded NLC formulation with nasal mucus was investigated and mucoadhesive properties were observed. The results of this study suggest that the use of intranasal VPA-loaded NLC may be a promising alternative to promote VPA targeting to the brain, thereby improving bioavailability and minimising adverse effects.

Integrating the 5-SENSE Score for Patient Selection in Vagus Nerve Stimulation for Drug-Resistant Epilepsy.

Addressing the challenge of drug-resistant epilepsy, our study offers a novel perspective by retrospectively applying the 5-SENSE score, initially created for stereoelectroencephalography (SEEG) planning, to evaluate its predictive value in patients undergoing vagus nerve stimulation (VNS) therapy. We conducted a comprehensive preoperative diagnostic work-up, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT), video-electroencephalogram (video-EEG), and clinical semiology. We then stratified 76 patients into three groups - low, moderate, and high focality - based on the focality of the seizure-onset zone. Such stratification was made to check the scoring ability in predictingVNStherapy seizure reduction. Our findings demonstrate an association between the extent of focality at the seizure-onset zone and the effectiveness of VNS, which may help to define the role of the 5-SENSE score in patient selection for VNS. This high dispersion of responses in the group with high focality reinforces the idea that outcome estimation is difficult and argues for an individualized strategy in the treatment of drug-resistant epilepsy. A study at the level of the 5-SENSE score indicates the importance of detailed preoperative assessments that may better optimize selection for VNS therapy and further improve clinical outcomes.

Deep brain stimulation of hippocampus in treatment of refractory temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common cause of focal onset seizures, affecting 40% of adolescents and adults with epilepsy. TLE is also one of the most common drug resistant forms of epilepsy. Surgical resection remains the treatment of choice for TLE, but not all patients with TLE are suitable candidates for resective neurosurgery. For such patients, deep brain stimulation (DBS) of the hippocampus remains a reversible and efficient treatment alternative. We undertook a systematic review of the literature on hippocampal DBS efficacy and safety in the management of patients with TLE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL), was conducted. We found 14 articles related to hippocampal DBS for the treatment of TLE. The responder rate (defined as at least 50% reduction in seizure frequency) for all patients was 83.4%, Of 99 patients treated by hippocampal DBS, 82 were regarded as responders, and 17 as non-responders. Hippocampal DBS appears to be a safe and efficacious treatment alternative for patients who are not candidates for temporal lobectomy or selective amygdalohippocampectomy due to serious postoperative cognitive deficits. In selected patients with TLE, this neuromodulatory therapy may be very safe and efficacious.

Targeting heterozygous dominant negative variant of KCNA2 using Gapmer ASO for the treatment of drug-resistant epilepsy

A missense mutation c.1220C>G of KCN2A gene was recently identified in an infant with epilepsy. KCNA2 encodes Kv1.2 subunits that form voltage-gated potassium channels (VGKC) via tetrameric assembly. The mutation results in amino acid change P407R at the highly conserved PVP motif. Functional characterization revealed that mutant Kv1.2_P407R subunits formed loss-of-function channels and suppressed both Kv1.2 and Kv1.1 channel activities. Hetero-tetrameric assembly of the Kv1.2_P407R subunits with other neuronal voltage-gated potassium channels of Shaker subfamily could lead to general deficit of repolarising potassium current and potentially underlie the enhanced seizure susceptibility. Indeed, expression of human Kv1.2_P407R in early postnatal rat cortical neurons or genetically engineered hESC-derived neurons disclosed broadening of action potential duration and early afterdepolarization (EAD), associating with reduced potassium current. We hypothesize that Gapmer antisense oligonucleotides (ASO) targeted to c.1220C>G mutation will selectively degrade the mutant mRNA while allowing the remaining WT subunits to form functional channels. As a proof of principle, delivery of Gapmer packaged in lipid nanoparticle into cortical neurons selectively suppressed Kv1.2_P407R over the WT protein expression, reversing the broadening of action potential duration, abrogating the EAD and leading to overall increase in potassium current.

The relationship between anti-seizures medications and metabolic acidosis in craniotomy operations: is topiramate or zonisamide the cause of metabolic acidosis?

Background/aimThe most commonly prescribed anti-seizures medications (ASMs) for the treatment of epilepsy are currently topiramate, zonisamide, lacosamide, carbamazepine and levetiracetam. The objective of this study was to examine the correlation between preoperative, intraoperative, and postoperative metabolic acidosis and the use of ASMs prior to craniotomy operations.Materials and methodsThis retrospective cross-sectional study evaluated patients who underwent intracranial surgery with craniotomy under general anaesthesia between May 2020 and April 2023 and used ASMs. The patients were classified into four groups based on the pharmacological mechanisms of action of the ASMs administered before intracranial surgery (Group-I, zonisamide or topiramate; Group-II, lacosamide; Group-III, carbamazepine; Group-IV, levetiracetam). Metabolic acidosis severity was defined based on base excess (BE) levels: mild (-3 to -5), moderate (-5 to -10), and severe (below − 10). The study investigated the correlation between ASMs and the severity of metabolic acidosis in preoperative, intraoperative, and postoperative blood gas measurements.ResultsOut of 35 patients, 24 patients underwent intracranial surgery and 11 patients underwent epilepsy surgery. There were statistically significant differences in the severity of metabolic acidosis between preoperative (p < 0.001), intraoperative (p < 0.001) and postoperative (p = 0.01) groups. The preoperative mean BE of group-I was − 4.7, which was statistically lower than that of group-III (p = 0.01) and group-IV (p < 0.001). Intraoperatively and postoperatively, group-I had a mean BE of -7.5 and − 3.2, respectively, which was statistically lower than that of groups II (p = 0.007; p = 0.04), III (p = 0.002; p = 0.03), and IV (p < 0.001; p = 0.009). There was no statistically significant difference in BE between groups II, III and IV at all three time points. Group I had the lowest BE at all three time points. Intraoperative bicarbonate was administered to all patients in group I, whereas no intraoperative bicarbonate was required in the other groups. In group I, 50% of patients required postoperative intensive care.ConclusionThe use of ASMs in patients undergoing surgery is important in terms of mortality and morbidity. Topirimat and zonisamide are ASMs that can cause preoperative, intraoperative and postoperative metabolic acidosis. Patients receiving topirimat or zonisamide are particularly susceptible to metabolic acidosis. Special care should be taken in the management of anaesthesia in patients receiving these drugs, and monitoring of the perioperative metabolic status is essential.

Acute and Sub-acute Oral Toxicity Studies of an Aqueous Extract of Ocimum gratissimum (Lamiaceae) in the Mouse Mus Musculus

Ocimum gratissimum is a medicinal plant that is widely used in the world, and has multiple uses in traditional medicine, including the treatment of epilepsy in children. The objective of this study was to evaluate the acute and subacute toxicity of decoction of Ocimum gratissimum leaves in Mus musculus mice. For the acute toxicity test, a single dose of 50, 300 and 2000 mg/kg of extract was administered orally to randomly selected to mice; then they were observed for 14 days. In the subacute study, the extract was administered orally daily to mice of both sexes at doses of 250, 500 and 1000 mg/kg body weight during the 28 days of the experiment. finally, Body weight was measured weekly, haematological, biochemical and histological analysis were performed. The aqueous extract of Ocimum gratissimum did not cause any mortality or significant changes in relative animal and organ weights during the acute and subacute tests at all doses. Few significant changes in food and water intake were observed at the dose of 1000 mg/kg. The highest dose of aqueous extract (2000 mg/kg) administered orally in the acute toxicity did not induce mortality. There were no significant changes in haematological parameters in the different batches treated. Therefore, the oral aqueous extract of Ocimum gratissimum did not produce any adverse side effects compared to the control group (distiller water) in the acute and subacute study. We can therefore conclude that Ocimum gratissimum can be considered safe in oral administration at the dose tested since it did not cause lethality or undesirable effects in general behaviour in white mice.

Multi-Source Data ETL (Extract, Transform, Load) for a Genetic Epilepsy Diagnosis and Treatment Dashboard.

The growing number of genes identified in relation to epilepsy represents a major breakthrough in diagnosis and treatment, but experts face the challenge of efficiently accessing and consolidating the vast amount of genetic data available. Therefore, we present the process of transforming data from different sources and formats into an Entity-Attribute-Value (EAV) model database. Combined with the use of standard coding systems, this approach will provide a scalable and adaptable database to present the data in a comprehensive way to experts via a dashboard.

TRPML1 ameliorates seizures-related neuronal injury by regulating autophagy and lysosomal biogenesis via Ca2+/TFEB signaling pathway

Alterations in autophagy have been observed in epilepsy, although their exact etiopathogenesis remains elusive. Transient Receptor Potential Mucolipin Protein 1 (TRPML1) is an ion channel protein that regulates autophagy and lysosome biogenesis. To explore the role of TRPML1 in seizures-induced neuronal injury and the potential mechanisms involved, an hyperexcitable neuronal model induced by Mg2+-free solution was used for the study. Our results revealed that TRPML1 expression was upregulated after seizures, which was accompanied by intracellular ROS accumulation, mitochondrial damage, and neuronal apoptosis. Activation of TRPML1 by ML-SA1 diminished intracellular ROS, restored mitochondrial function, and subsequently alleviated neuronal apoptosis. Conversely, inhibition of TRPML1 had the opposite effect. Further examination revealed that the accumulation of ROS and damaged mitochondria was associated with interrupted mitophagy flux and enlarged defective lysosomes, which were attenuated by TRPML1 activation. Mechanistically, TRPML1 activation allows more Ca2+ to permeate from the lysosome into the cytoplasm, resulting in the dephosphorylation of TFEB and its nuclear translocation. This process further enhances autophagy initiation and lysosomal biogenesis. Additionally, the expression of TRPML1 is positively regulated by WTAP-mediated m6A modification. Our findings highlighted crucial roles of TRPML1 and autophagy in seizures-induced neuronal injury, which provides a new target for epilepsy treatment.

MR-guided laser interstitial thermal therapy in the treatment of brain tumors and epilepsy.

MR-guided Laser Interstitial Thermal Therapy (MRgLITT) is a minimally invasive neurosurgical technique increasingly used for the treatment of drug-resistant epilepsy and brain tumors. Utilizing near-infrared light energy delivery guided by real-time MRI thermometry, MRgLITT enables precise ablation of targeted brain tissues, resulting in limited corridor-related morbidity and expedited postoperative recovery. Since receiving CE marking in 2018, the adoption of MRgLITT has expanded to more than 40 neurosurgical centers across Europe. In epilepsy treatment, MRgLITT can be applied to various types of focal lesional epilepsy, including mesial temporal lobe epilepsy, hypothalamic hamartoma, focal cortical dysplasias, periventricular heterotopias, cavernous malformations, dysembryoplastic neuroepithelial tumors (DNET), low-grade gliomas, tuberous sclerosis, and in disconnective surgeries. In neuro-oncology, MRgLITT is used for treating newly diagnosed and recurrent primary brain tumors, brain metastases, and radiation necrosis. This comprehensive review presents an overview of the current evidence and technical considerations for the use of MRgLITT in treating various pathologies associated with drug-resistant epilepsy and brain tumors.

Exploring the efficacy and safety of cannabidiol in individuals with epilepsy: an umbrella review of meta-analyses and systematic reviews.

Epilepsy ranks among the most prevalent neurological conditions worldwide. Cannabidiol (CBD) has received authorization for epilepsy treatment, yet utilizing CBD is linked to a variety of adverse events (AEs). This umbrella review aims to explore risk and frequency of AEs in epilepsy patients undergoing treatment with CBD. International electronic databases comprising Scopus, PubMed, and Web of Science were extensively searched from the most ancient data accessible until May 2024. In line with fundamental principle of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA), this umbrella review was executed. RStudio software version 2023.03.1 along with R software 4.3.2 was used for our statistical analyses. Thirteen meta-analyses and systematic reviews were included. CBD use in epileptic patients compared to controls can be meaningfully linked with 10.87% becoming seizure-free (RD: 10.87%, 95%CI: 2.39%, 19.34%; I2 = 80%). Compared to controls, a meaningful 73% increase in 50% or greater reduction in seizure frequency was observed (RR: 1.73, 95%CI: 1.47, 2.03; I2 = 0%). In epileptic individuals who using CBD with the dosage of 20mg/kg/d, a higher incidence of treatment withdrawal was detected (RR: 4.39, 95%CI: 2.46, 7.83; I2 = 0%). In this umbrella review of meta-analyses and systematic reviews, CBD use in epileptic patients was linked to an increased risk of ample AEs. Further research, specifically targeting various epilepsy categories, is essential to fully understand the effectiveness and potential side effects of CBD across different epilepsy forms.

The electro-responsive nanoliposome as an on-demand drug delivery platform for epilepsy treatment

Nano-based drug delivery systems are regarded as a promising tool for efficient epilepsy treatment and seizure medication with the least general side effects and socioeconomic challenges. In the current study, we have designed a smart nanoscale drug delivery platform and applied it in the kindling model of epilepsy that is triggered rapidly by epileptic discharges and releases anticonvulsant drugs in situ, such as carbamazepine (CBZ). The CBZ-loaded electroactive ferrocene nanoliposomes had an average diameter of 100.6 nm, a surface charge of −7.08 mV, and high drug encapsulation efficiency (85.4 %). A significant increase in liposome size was observed in response to direct current (50–500 μA) application. This liposome-based drug delivery system can release CBZ at a fast rate in response to both direct current and pulsatile electrical stimulation in vitro. The CBZ-liposome can release the anticonvulsant drug upon epileptiform activity in the kindled rat model and can decline electrographic and behavioral seizure activity in response to electrical stimulation of the hippocampus with an initially subconvulsive current. With satisfactory biosafety results, this “smart” nanocarrier has promising potential as an effective and safe drug delivery system to improve the therapeutic index of antiepileptic drugs.

Virtual stimulation of the interictal EEG network localizes the EZ as a measure of cortical excitability.

Introduction: For patients with drug-resistant epilepsy, successful localization and surgical treatment of the epileptogenic zone (EZ) can bring seizure freedom. However, surgical success rates vary widely because there are currently no clinically validated biomarkers of the EZ. Highly epileptogenic regions often display increased levels of cortical excitability, which can be probed using single-pulse electrical stimulation (SPES), where brief pulses of electrical current are delivered to brain tissue. It has been shown that high-amplitude responses to SPES can localize EZ regions, indicating a decreased threshold of excitability. However, performing extensive SPES in the epilepsy monitoring unit (EMU) is time-consuming. Thus, we built patient-specific in silico dynamical network models from interictal intracranial EEG (iEEG) to test whether virtual stimulation could reveal information about the underlying network to identify highly excitable brain regions similar to physical stimulation of the brain. Methods: We performed virtual stimulation in 69 patients that were evaluated at five centers and assessed for clinical outcome 1year post surgery. We further investigated differences in observed SPES iEEG responses of 14 patients stratified by surgical outcome. Results: Clinically-labeled EZ cortical regions exhibited higher excitability from virtual stimulation than non-EZ regions with most significant differences in successful patients and little difference in failure patients. These trends were also observed in responses to extensive SPES performed in the EMU. Finally, when excitability was used to predict whether a channel is in the EZ or not, the classifier achieved an accuracy of 91%. Discussion: This study demonstrates how excitability determined via virtual stimulation can capture valuable information about the EZ from interictal intracranial EEG.

Thermal-controlled cholesteric liquid crystal wavelength filter lens for photosensitive epilepsy treatment

Thermal-controlled cholesteric liquid crystal wavelength filter lens for photosensitive epilepsy treatment

Review of pharmacogenetics of antiseizure medications: focusing on genetic variants of mechanistic targets.

Antiseizure medications (ASMs) play a central role in seizure management, however, unpredictability in the response to treatment persists, even among patients with similar seizure manifestations and clinical backgrounds. An objective biomarker capable of reliably predicting the response to ASMs would profoundly impact epilepsy treatment. Presently, clinicians rely on a trial-and-error approach when selecting ASMs, a time-consuming process that can result in delays in receiving alternative non-pharmacological therapies such as a ketogenetic diet, epilepsy surgery, and neuromodulation therapies. Pharmacogenetic studies investigating the correlation between ASMs and genetic variants regarding their mechanistic targets offer promise in predicting the response to treatment. Sodium channel subunit genes have been extensively studied along with other ion channels and receptors as targets, however, the results have been conflicting, possibly due to methodological disparities including inconsistent definitions of drug response, variations in ASM combinations, and diversity of genetic variants/genes studied. Nonetheless, these studies underscore the potential effect of genetic variants on the mechanism of ASMs and consequently the prediction of treatment response. Recent advances in sequencing technology have led to the generation of large genetic datasets, which may be able to enhance the predictive accuracy of the response to ASMs.

Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

Epilepsy occurs in 35-95% of patients with malignant cerebral gliomas of low malignancy and in 29-71% of patients with gliomas of high malignancy. Seizures can be both the first manifestation of malignant cerebral glioma and appear in the postoperative period and during chemoradiotherapy. This requires the use of antiepileptic drugs, which should control the seizure syndrome, provide control and secondary prevention of seizures, without reducing the response of anti-tumour therapy and the the patient QoL. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms in which glutamate plays a key role. Hypersecretion of glutamate is accompanied by increased expression and activation of its receptors, which increases convulsive readiness. This is accompanied by increased level of brain neurotrophic growth factor, the number of synapses between peritumoral neurons and glioma cells, and increased expression of a number of growth factors, which contributes to tumourous proliferation. In this regard, special attention when treating epilepsy in patients with malignant cerebral gliomas is given to perampanel, a glutamate receptor blocker, a 3rd generation antiepileptic drug. The findings show that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas, but also suppresses tumourous proliferation. Perampanel is able to dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. The findings have revealed synergistic effect of perampanel in combination with temozolamide. In conditions of chemoradiation therapy perampanel has a protective effect on healthy peritumoral tissues. Undesirable drug reactions during the use of perampanel are infrequent and insignificant. Additional studies are needed to further research the anticonvulsant and antitumour efficacy of perampanel to treat epilepsy in patients with malignant brain tumours.

Ghost cells: Wilder Penfield and the characterization of glia and glial pathology, 1924–1932

ABSTRACT Wilder Penfield is known for his contributions to the structure–function relationship of the brain and for the surgical treatment of focal epilepsy. Less well known are his contributions to the study of glial cells and his investigation of their role in human neuropathology. Penfield learned the gold and silver methods for staining neurons, glial cells, and their projections from Charles Sherrington and Pío del Río-Hortega. He and his colleague William Cone established a laboratory for the study of glial cells and human neuropathology using metallic stains, initially at the Presbyterian Hospital in New York City in 1925, and then at the Montreal Neurological Institute in 1928. Penfield, Cone, and their research fellows, building on the findings of Río-Hortega, confirmed the existence of oligodendrocytes and their relationship with myelin, and investigated the putative mesodermal origin of microglia. They discovered the reaction of oligodendrocytes to pathological stressors, and the phagocytic activity of microglia in human gliomas. In this article, we argue that Penfield’s studies of astrocytes, oligodendrocytes, and microglia, and their responses to craniocerebral trauma, epilepsy, malignant brain tumors, and other pathologies of the central nervous system inaugurated a new era in clinical neurocytology and neuropathology.

Nice to know 2: The impact of NICE guidelines on ketogenic diet services in the UK and Ireland - An update.

Ketogenic diet therapy (KDT) has been recommended as a treatment for drug-resistant epilepsy in children and young people since 2012 in the National Institute for Health and Care Excellence Clinical Guidelines for Epilepsies. The Ketogenic Dietitians Research Network completed a survey in 2017 to assess the impact of these guidelines. An online survey was circulated to ketogenic dietitians across the UK and Ireland. The results were compared with those of the 2017 survey. The number of individuals following KDT was 854, comprising an increase of 13% since 2017. Service sizes ranged widely, with 1-74 (median 16) patients on the diet. Of 36 services, 30 had a waiting list, ranging from 2 to 67 (median 9) patients. The classical diet continued to be the most common KDT used (58% of patients). Ten services reported use of a new flexible medium chain triglyceride protocol. Some 48% of patients (n = 427) had been following the KDT for over 2 years, comprising an 18% increase since 2017. Of these, 68 (15.9%) had attempted to wean off KDT but had to re-start as a result of a deterioration in seizures. The number of individuals following medical KDT remains stable. Referral numbers and waiting lists remain high, highlighting that KDT is still a well-recognised treatment option for drug-resistant epilepsy. The types of KDT used are similar to previous years, although increasingly flexible protocols are being adopted. Longer-term use of KDT is increasing, with a proportion of patients requiring long-term use to maintain seizure control.

Sasa veitchii extract alleviates phenobarbital‐induced cell proliferation inhibition by upregulating transforming growth factor‐beta 1

AbstractAimCleft lip is a common congenital disease, accompanied by a complicated etiology. Medical exposure in women is one of the reasons leading to cleft lip. Phenobarbital is a major drug used for the treatment of epilepsy and has been reported to induce cleft lip, with or without cleft palate. This study aimed to explore the protective effects of Sasa veitchii extract (SE) against phenobarbital‐induced inhibition of human lip fibroblast (JCRB9103) cell proliferation.MethodsWe evaluated the cell viability of JCRB9103 cells after 48 h of phenobarbital treatment. We examined the rescue experiment using SE, sodium copper chlorophyllin, or recombinant transforming growth factor‐beta 1. Western blotting was performed to identify key proteins involved in lip formation in JCRB9103 cells.ResultsPhenobarbital treatment decreased the cell viability of JCRB9103 cells in a dose‐dependent manner. Cotreatment with SE or sodium copper chlorophyllin alleviated phenobarbital‐induced inhibition of cell viability in JCRB9103 cells. SE treatment upregulated the transforming growth factor‐beta 1 level, and transforming growth factor‐beta 1 protected against phenobarbital‐induced inhibition of cell proliferation.ConclusionsThese results suggest that phenobarbital‐induced inhibition of cell proliferation was restored by sodium copper chlorophyllin present in SE via the regulation of transforming growth factor‐beta 1.