Effect of arctigenin on neurological diseases: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Arctium lappa L. is a common specie of Asteraceae. Its main active ingredient, Arctigenin (AG), in mature seeds exerts pharmacological effects on the Central Nervous System (CNS). AIM OF THE STUDY: To review studies on the specific effects of the AG mechanism on various CNS diseases and elucidate signal transduction mechanisms and their pharmacological actions. MATERIALS AND METHODS: This investigation reviewed the essential role of AG in treating neurological disorders. Basic information on Arctium lappa L. was retrieved from the Pharmacopoeia of the People's Republic of China. The related articles from 1981 to 2022 on the network database (including CNKI, PubMed, and Wan Fang and so on) were reviewed using AG and CNS diseases-related terms such as Arctigenin and Epilepsy. RESULTS: It was confirmed that AG has a therapeutic effect on Alzheimer's disease, Glioma, infectious CNS diseases (such as Toxoplasma and Japanese Encephalitis Virus), Parkinson's disease, Epilepsy, etc. In these diseases, related experiments such as a Western blot analysis revealed that AG could alter the content of some key factors (such as the reduction of Aß in Alzheimer's disease). However, in-vivo AG's metabolic process and possible metabolites are still undetermined. CONCLUSION: Based on this review, the existing pharmacological research has indeed made objective progress to elucidate how AG prevents and treats CNS diseases, especially senile degenerative disease such as Alzheimer's diseases. It was revealed that AG could be used as a potential nervous system drug as it has a wide range of effects in theory with markedly high application value, especially in the elder group. However, the existing studies are limited to in-vitro experiments; therefore, little is known about how AG metabolizes and functions in-vivo, limiting its clinical application and requiring further research.

Neferine Protects against Hypoxic-Ischemic Brain Damage in Neonatal Rats by Suppressing NLRP3-Mediated Inflammasome Activation.

Hypoxic-ischemic encephalopathy (HIE) is recognized as the main cause of neonatal death, and efficient treatment strategies remain limited. Given the prevalence of HIE and the associated fatality, further studies on its pathogenesis are warranted. Oxidative stress and neuroinflammatory injury are two important factors leading to brain tissue injury and nerve cell loss in HIE. Neferine, an alkaloid extracted from lotus seed embryo, exerts considerable effects against several diseases such as cancers and myocardial injury. In this study, we demonstrated the neuroprotective effect of neferine on HIE and hypothesized that it involves the inhibition of neuronal pyroptosis, thereby ameliorating neurological inflammation and oxidative stress. We demonstrated that the mRNA levels of proteins associated with pyroptosis including caspase-1, the caspase adaptor ASC, gasdermin D, interleukin- (IL-) 18, IL-1ß, and some inflammatory factors were significantly increased in neonatal HIBD model rats compared to those in the control group. The increase in these factors was significantly suppressed by treatment with neferine. We stimulated PC12 cells with CoCl2 to induce neuronal HIBD in vitro and investigated the relationship between neferine and pyroptosis by altering the expression of the NLRP3 inflammasome. The overexpression of NLRP3 partially reversed the neuroprotective effect of neferine on HIBD, whereas NLRP3 knockdown further inhibited caspase-1 activation and IL-1ß and IL18 expression. In addition, simultaneous alteration of NLRP3 expression induced changes in intracellular oxidative stress levels after HIBD. These findings indicate that neferine ameliorates neuroinflammation and oxidative stress injury by inhibiting pyroptosis after HIBD. Our study provides valuable information for future studies on neferine with respect to neuroinflammation and pyroptosis.

The Effects of Early Oropharyngeal Administration of Microdosed Colostrum on Feeding Status in Ventilated Extremely Low-Birth-Weight Infants.

Background: For extremely low-birth-weight infants (ELBWIs), mechanical ventilation and total parenteral nutrition are generally required in the early stages and lose the protective effect of early gastrointestinal nutrition of colostrum. We conducted a prospective randomized controlled trial to explore the effectiveness of early colostrum oropharyngeal administration on the feeding status of ELBWIs on mechanical ventilation. Materials and Methods: We randomly divided mechanically ventilated ELBWIs into an intervention group and a control group. In the intervention group, we provided oropharyngeal administration of colostrum during mechanical ventilation. The first colostrum oropharyngeal administration ended within 24 hours of birth. In the control group, we gave colostrum only for gastrointestinal nutrition, and other interventions were the same as for the intervention group. We collected the 1st and 6th day of life airway secretions and urine specimens from both groups. We recorded feeding status, including corrected gestational age at onset of enteral nutrition, corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, corrected gestational age of sucking began, and corrected gestational age of per oral feeding. We also recorded growth of body mass, the incidence of feeding intolerance, and necrotizing enterocolitis (NEC). Results: On the 6th day of life, concentrations of secretory immunoglobulin A, and lactoferrin in airway secretions and urine of the intervention group were significantly higher than those of the control group (p < 0.05). The intervention group showed younger corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, the corrected gestational age of sucking began and per oral feeding than those in the control group (p < 0.05). The day of recovery to birth weight was earlier than those in the control group (p < 0.05). The rate of feeding intolerance and NEC incidence in the intervention group was significantly lower than in the control group (p < 0.05). Conclusions: Early oropharyngeal administration of colostrum improves immune function of the gastrointestinal tract and the systemic anti-infective capability in ELBWI on mechanical ventilation, promoting the maturity of gastrointestinal function, improving feeding condition, and reducing the risk of feeding intolerance and NEC.

PDE1 or PDE5 inhibition augments NO-dependent hypoxic constriction of porcine coronary artery via elevating inosine 3',5'-cyclic monophosphate level.

Hypoxic coronary vasospasm may lead to myocardial ischaemia and cardiac dysfunction. Inosine 3',5'-cyclic monophosphate (cIMP) is a putative second messenger to mediate this pathological process. Nevertheless, it remains unclear as to whether levels of cIMP can be regulated in living tissue such as coronary artery and if so, what is the consequence of this regulation on hypoxia-induced vasoconstriction. In the present study, we found that cIMP was a key determinant of hypoxia-induced constriction but not that of the subsequent relaxation response in porcine coronary arteries. Subsequently, coronary arteries were treated with various phosphodiesterase (PDE) inhibitors to identify PDE types that are capable of regulating cIMP levels. We found that inhibition of PDE1 and PDE5 substantially elevated cIMP content in endothelium-denuded coronary artery supplemented with exogenous purified cIMP. However, cGMP levels were far lower than their levels in intact coronary arteries and lower than cIMP levels measured in endothelium-denuded coronary arteries supplemented with exogenous cIMP. The increased cIMP levels induced by PDE1 or PDE5 inhibition further led to augmented hypoxic constriction without apparently affecting the relaxation response. In intact coronary artery, PDE1 or PDE5 inhibition up-regulated cIMP levels under hypoxic condition. Concomitantly, cGMP level increased to a comparable level. Nevertheless, the hypoxia-mediated constriction was enhanced in this situation that was largely compromised by an even stronger inhibition of PDEs. Taken together, these data suggest that cIMP levels in coronary arteries are regulated by PDE1 and PDE5, whose inhibition at a certain level leads to increased cIMP content and enhanced hypoxic constriction.

Electro-Acupuncture on ST36 and SP6 Acupoints Ameliorates Lung Injury via Sciatic Nerve in a Rat Model of Limb Ischemia-Reperfusion.

INTRODUCTION: Electro-acupuncture (EA) can significantly improve inflammatory response, but the specific mechanism is not clear. Limb ischemia-reperfusion (I/R) first produces inflammatory reactions in the lungs. In this study, EA on Zusanli (ST36) and Sanyinjiao (SP6) were used to explore the mechanism of improving tissue inflammation by sciatic nerve disconnection. MATERIAL AND METHODS: A total of 56 male Sprague-Dawley rats were randomly divided into sham group, model group, EA group, SEA group, SNC+EA group, TNC+EA group and PNC+EA group. The sham groups were not given any treatment. Rats in the model group were treated with limb I/R without acupuncture intervention. In the EA group, ST36 and SP6 were given EA treatment for 30min before modeling. No electric current was given in the SEA group, and other operations were the same as those in the EA group. The SNC+EA group, TNC+EA group and PNC+EA group were respectively given sciatic nerve, tibial nerve or peroneal nerve amputation 72h before modeling, and the others were the same as the model group. RESULTS: Compared with the sham group, PaO2 and a/A ratios decreased significantly in the model group (P <0.05), while PA-aO2, RI, the ratio of wet to dry, lung injury value and inflammatory factor TNF-α, IL-1, IL-6, and MPO increased significantly (P <0.05). Compared with the model group, PaO2, a/A ratios increased significantly in the EA group (P <0.05), while PA-aO2, RI, the ratio of wet to dry lung, lung injury value, and TNF-α, IL-1, IL-6, and MPO decreased significantly (P <0.05). After transection of the sciatic nerve, the protective effect of EA disappeared. However, when the peroneal or tibial nerve was severed, EA continued to maintain the protective effect. CONCLUSION: EA on ST36 and SP6 can alleviate lung injury caused by limb I/R through the sciatic nerve.

Risk Factors for Recurrent Intussusception in Children: A Systematic Review and Meta-Analysis.

Background: Intussusception is a common abdominal emergency in infancy and childhood, and the recurrence rate is reported to be up to 20%. Numerous potential risk factors for recurrence have been reported, although some of them are still controversial. Objective: The present study was conducted to identify the risk factors or predictive symptoms for recurrent intussusception in children who successfully recovered via enema reduction. Methods: The databases of PUBMED, EMBASE, and Cochrane were searched up to August 2018. The primary outcome was the odds ratio involving the following potential risk factors: sex, the presence of blood in stool, fever, abdominal pain, right abdominal mass, pathological lead point, and vomiting. Results: A total of 12,008 participants from 10 studies included in the abovementioned databases were enrolled in this meta-analysis. The correlation strength with each risk factor was as follows: Sex (OR = 0.87 [0.69, 1.09], P = 0.22); fever (OR = 1.85 [1.29, 2.65], P = 0.0008); blood in stool (OR = 0.93 [0.52, 1.67], P = 0.25); abdominal pain (OR = 0.82 [0.49, 1.37], P = 0.46); vomiting (OR = 0.55 [0.37, 0.80], P = 0.002); pathological lead point (PLP) (OR = 7.71 [1.96,30.29], P = 0.003); location of the mass (OR = 0.51 [0.03, 8.28], P = 0.64). Besides, children who were relatively older (over 1-2 years of age) were seen to have a higher risk of recurrence. Conclusion: The main conclusion of this meta-analysis was that children with the presence of fever and PLP may have a higher risk of recurrence following enema reduction for intussusception. The prevalence of vomiting was found to be lower in RI (Recurrent Intussusception) patients than in the non-RI patients (control group).

A newborn with seizures born to a mother diagnosed with primary carnitine deficiency.

BACKGROUND: Maternofetal carnitine transport through the placenta is the main route of fetal carnitine uptake. Decreased free carnitine levels discovered by newborn screening has identified many asymptomatic adult women with systemic primary carnitine deficiency (PCD). Here, we presented amplitude integrated electroencephalogram (aEEG) and magnetic resonance imaging (MRI) findings from a neonate with epilepsy whose mother was carnitine deficient. CASE PRESENTATION: A one-day-old female newborn was admitted after experiencing seizures for half a day; status epilepticus was found on the continuous normal voltage background pattern with immature sleep-wake cycling during aEEG monitoring. On T1-weighted, T2-weighted, FLAIR, and DWI head MRI, there were various degrees of hyperintense signals and diffusion restrictions in the deep white matter of the right hemisphere. Tandem mass spectrometry discovered carnitine deficiency on the second day, which elevated to normal by the 9th day before L-carnitine supplementation was started. The patient was treated with phenobarbital after admission. No further seizures were noted by day 5. It was confirmed that the patient's mother had a low level of serum-free carnitine. Gene analyses revealed that the newborn had heterozygote mutations on c.1400C > G of the SLC22A5 gene, and her mother had homozygous mutations on c.1400C > G. The patient had a good outcome at the 8-month follow up. CONCLUSIONS: Maternal carnitine deficiency that occurs during the perinatal period may manifest as secondary epilepsy with cerebral injury in neonates. The short-term neurodevelopmental outcomes were good. Early diagnosis of asymptomatic PCD in female patients can provide guidance for future pregnancies.

[Clinical analysis and follow-up of neonatal purulent meningitis caused by group B streptococcus].

OBJECTIVE: To study the clinical characteristics, antibiotics sensitivity and outcome of group B streptococcus (GBS) meningitis in neonates in order to provide the guide for early diagnosis and appropriate treatment. METHOD: A retrospective review was performed and a total of 13 cases of neonatal purulent meningitis caused by GBS were identified in the Neonatal Intensive Care Unit of Yuying Children's Hospital of Wenzhou Medical University from January 1, 2005 to May 31, 2013. The clinical characteristics, antibiotics sensitivity test results and outcome were analyzed. RESULT: Fever, poor feeding, seizure and lethargy were common clinical signs of neonatal purulent meningitis caused by GBS. Three cases of early onset GBS meningitis received prepartum antibiotics. All 13 cases had abnormal C-reactive protein (CRP) level, and 11 cases had increased CRP within hours after admission. Of the 13 patients, 7 were cured, 4 discharged with improvement, 2 patients died during hospitalization after being given up because of serious complication. The average length of stay for recovered patients was (47 ± 21)d. Acute complications mainly included hyponatremia (5 cases), intracranial hemorrhage (3 cases) , ventriculomegaly (3 cases) , subdural collection (2 cases) , hydrocephalus (2 cases), septic shock (2 cases), cerebral hernia (1 case), encephalomalacia (1 case). One preterm patient with early onset GBS meningitis died 1 month after hospital discharge. Among 7 survivors with 10-24 months follow-up, 3 were early onset GBS meningitis, 2 with normal results of neurologic examination, 1 with delayed motor development, 4 were late onset GBS meningitis, 1 with normal results of neurologic examination, 3 were neurologically impaired with manifestations including delayed motor development (2 cases) and seizures (1 case). All the GBS strains were sensitive to penicillin and linezolid (13/13, 10/10), the susceptibility to levofloxacin, ampicillin and vancomycin were 11/12, 9/10, 8/13 respectively. CONCLUSION: The clinical manifestations of neonatal purulent meningitis caused by GBS are usually non-specific. It is associated with long hospitalization, neurological impairments and sequelae. Monitoring of serum CRP level is valuable for early diagnosis. Antepartum prophylaxis, early diagnosis and therapy are vital. Large dose penicillin is the priority choice to treat the neonatal purulent meningitis caused by GBS, linezolid should be used in intractable cases.

Randomized-controlled study of treating attention deficit hyperactivity disorder of preschool children with combined electro-acupuncture and behavior therapy.

OBJECTIVE: To study the effectiveness of electro-acupuncture with behavior therapy on preschool children with attention deficit hyperactivity disorder (ADHD). METHODS: 180 preschool children with ADHD diagnosed by DSM-IV were classified into three subtypes: predominantly inattentive subtype (PI subtype, 60 cases), predominantly hyperactive-impulsive subtype (HI subtype, 60 cases) and combined subtype (CT subtype, 60 cases). In each subtype, the patients were recruited randomly into experimental group, which received electro-acupuncture and behavior therapy; and control group, which received sham electro-acupuncture and behavior therapy. The treatment efficacy was evaluated by measuring the change in core symptoms of ADHD according to the standard enacted by the national traditional Chinese medicine committee after 12 courses of treatment (lasted 12 weeks) and relapse rate was evaluated after a half-year follow up. RESULTS: (1) In PI subtype, 11 cases showed effectiveness with treatment and 12 cases showed improvement with treatment among experimental group, while five cases showed effectiveness and 12 cases showed improvement among control group; in HI subtype, 10 cases showed effectiveness and 17 cases showed improvement among experimental group, while four cases showed effectiveness and 14 cases showed improvement among control group; in CI subtype, 12 cases showed effectiveness and 12 cases showed improvement among experimental group, while five cases showed effectiveness and 12 cases showed improvement among control group; The overall comparison manifested that the efficacy of experimental group was better than that of control group (p<0.05). (2) The core symptoms of experimental group were significantly decreased than that of control group at half-year follow up (p<0.05). CONCLUSION: The treatment of ADHD in preschool children with electro-acupuncture combining behavior therapy has positive effect in reducing symptoms of ADHD. Adverse events are mild to patients. It is recommendable for this combined therapy, while multi-center RCT needs to be further studied.