Neuroprotective Effects of Geopung-Chunghyuldan Based on Its Salvianolic Acid B Content Using an In Vivo Stroke Model.

BACKGROUND: Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD's effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of GCD based on salvianolic acid B content. METHODS: The neuroprotective effects of GCD based on the salvianolic acid B content were evaluated by measuring infarct volume 24 h after permanent middle cerebral artery occlusion in an in vivo stroke model. For the experimental group, each GCD was administered immediately before surgery. The control groups were administered distilled water and aspirin (30 mg/kg) in the same way. The salvianolic acid B content in five types of Salviae Miltiorrhizae Radix (two Chinese and three Korean regions) based on different cultivation regions was analyzed by high-performance liquid chromatography. RESULTS: Three samples met the Korean and Chinese Pharmacopeia standards for salvianolic acid B. However, two samples did not. GCDs with high salvianolic acid B showed marked neuroprotective effects compared to the control groups, whereas GCDs with low salvianolic acid B did not. CONCLUSIONS: The salvianolic acid B content of Salviae miltiorrhizae Radix affects the neuroprotection effect of GCD. Stable, raw Salviae miltiorrhizae Radix is essential for GCD homogenization.

Atrial Fibrillation is Strongly Associated With the Neutrophil to Lymphocyte Ratio in Acute Ischemic Stroke Patients: A Retrospective Study.

BACKGROUND: No study has investigated the relationship between hospital-admission neutrophil and lymphocyte ratio (NLR) and various stroke risk factors. We sought to determine which stroke risk factor could be the most appropriate predictor of NLR in acute ischemic stroke. METHODS: We collected data on various stroke risk factors and National Institutes of Health Stroke Scale (NIHSS) score in 1,053 acute ischemic stroke patients. The regression analysis was adjusted for confounding factors such as stroke risk factors. RESULTS: There was a trend of increased NLR with a rise in alcohol consumption, the prevalence of hypertension, cardioembolism (CE) etiology, the NIHSS scores in men and the prevalence of atrial fibrillation, other heart diseases, CE and small vessel occlusion etiology and the NIHSS scores in women. Multiple linear regression analyses, adjusted for confounding factors, showed that the atrial fibrillation and NIHSS scores in men and atrial fibrillation, diabetes mellitus as well as NIHSS scores in women had a significant positive association with NLR. However, a negative association was showed for body mass index (BMI). CONCLUSION: We confirmed that the atrial fibrillation can be a predictor of high NLR in acute stroke patients, and diabetes mellitus as well as low BMI could be a predictor of high NLR in female acute ischemic stroke patients.

Effects of a combination treatment of KD5040 and L-dopa in a mouse model of Parkinson's disease.

BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects of KD5040 and l -dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by l -dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically improved the motor function when low-dose l -dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in patients with PD.

Gastrodia elata Blume alleviates L-DOPA-induced dyskinesia by normalizing FosB and ERK activation in a 6-OHDA-lesioned Parkinson's disease mouse model.

BACKGROUND: Gastrodia elata Blume (GEB), commonly used medicinal herb, has been reported as a promising candidate for neurodegenerative diseases such as Parkinson's disease. The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), is the gold-standard drug for Parkinson's disease, but long-term treatment results in the L-dopa-induced dyskinesia (LID). This study was undertaken to examine the beneficial effects of GEB on L-DOPA induced dyskinesia in 6-hydroxydopamine (6-OHDA)-induced experimental Parkinsonism. METHODS: We tested the effects of GEB on LID in 6-hydroxydopamine hydrochloride-hemiparkinsonian mice. To analyze the dyskinetic anomalies, we measured abnormal involuntary movement (AIM). Immunohistological analyses of pERK and FosB expressions in the striatum are performed to explore the mechanism of GEB on LID. RESULTS: The finding of this study demonstrated that GEB (200, 400 and 800 mg/kg) alleviated L-dopa induced AIMs in a dose-dependent manner. In each integrative AIM subtype analysis, we also found that the GEB (400 and 800 mg/kg) treatment decreased L-DOPA-induced axial, limb, orolingual, and locomotive AIMs compared to the LID group. In addition, GEB normalized the abnormal LID-induced increase of pERK1/2 and FosB, the immediate early genes of LID in the striatum. CONCLUSIONS: In conclusion, our results provide a novel insight into the pharmacological actions of GEB that could have a benefit for PD patients through the reduction of LID.

The effectiveness of Kami Guibi-tang for cognitive impairment patients: A retrospective chart review.

Background: and Purpose: The number of patients with cognitive impairment is increasing worldwide. Therapeutic drugs that slow disease progression are being developed; however, further research is required. This study investigated the effects of Kami Guibi-tang on patients with various types of cognitive decline. Methods: This study was a single-center, retrospective chart review of patients who visited KyungHee University Hospital at Gangdong from January 2015 to March 2022. The study included participants who took Kami Guibi-tang for more than 90 days and were assessed on the Korean version Mini-Mental State Examination (MMSE-K) scores before and after treatment. Participants who received other liquid herbal medicines during the treatment were excluded. The outcome of interest was changed scores in MMSE-K and Short form of Geriatric Depression Scale (S-GDS). Results: A total of 31 participants were included. The total MMSE-K score significantly increased with time and showed a significant increase at 3 and 9 months compared with baseline. Among the MMSE-K subscores, the orientation subscore showed a significant increase at three months compared with baseline, and the attention and calculation subscore showed a significant increase with time. In addition, four participants with vascular dementia showed a significant increase in the total MMSE-K score over time and a significant increase after 9 months compared with baseline. The S-GDS score in 31 participants showed a significant decrease with time and at all time points compared with baseline. Conclusions: Kami Guibi-tang may improve cognitive function in patients with cognitive decline.

A Systematic Review of In Vivo Studies of the Efficacy of Herbal Medicines for Anti-Aging in the Last Five Years.

BACKGROUND: The world's population is rapidly aging, and attention to and research on the increase in life expectancy and age-related diseases are needed. This study aimed to review the in vivo studies on the anti-aging effects of herbal medicines. METHODS: In vivo studies of single or complex herbal medicines for anti-aging that were published in the last five years were included in this review. The following databases were used: PubMed, Scopus, ScienceDirect, Web of Science and EMBASE. RESULTS: A total of 41 studies were considered eligible for the review. The articles were classified into body organs and functions, experimental country, herbal medicine, extraction method, administration route, dosage, duration, animal model, aging-induced method, sex, number of animals per group, and outcomes and mechanisms A single herbal extract was used in a total of 21 studies including Alpinia oxyphylla Miq., Acanthopanax senticosus and Lyceum barbarum, and a multi-compound herbal prescription was used in a total of 20 studies, including Modified Qiongyu paste, Wuzi Yanzong recipe, etc. Each herbal medicine had anti-aging effects on learning and memory, cognition, emotion, internal organs, gastrointestinal tracts, sexual functions, musculoskeletal function and so on. The common mechanisms of action were antioxidant and anti-inflammatory, and various effects and mechanisms for each organ and function were identified. CONCLUSIONS: Herbal medicine exhibited beneficial effects on anti-aging in various parts of the body and its function. Further investigation of the appropriate herbal medicine prescriptions and their components is recommended.

Efficacy of Artemisia annua Linné in improving cognitive impairment in a chronic cerebral hypoperfusion-induced vascular dementia animal model.

BACKGROUND: Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Currently, no FDA-approved drugs are available for the treatment of VaD. Artemisia annua Linné (AA) is known to have antioxidant properties, but its effects and mechanisms of action on cognitive impairment are still unknown. PURPOSE: In this study, the improvement in cognitive impairment by AA in terms of protection against oxidative stress, neuroinflammation, and preservation of the integrity of the neurovascular unit (NVU) was assessed in an animal model of VaD with bilateral common carotid artery occlusion (BCCAO). METHODS: Eight-week-old male Wistar rats were allowed to adapt for four weeks, and BCCAO was induced at 12 weeks of age. The rats were randomly assigned into four groups, with seven rats in each group: sham group without BCCAO, VaD group that received oral administration of distilled water after BCCAO surgery, and two AA groups that received oral administration of 150 mg/kg or 750 mg/kg AA after BCCAO surgery for 8 weeks. Nine weeks after BCCAO surgery, the cognitive function of the rats was evaluated and accumulated oxidative stress was assessed by immunohistochemistry, immunofluorescence, and western blotting. Damage to the components of the NVU was evaluated, and sirtuin (Sirt) 1 and 2 expression and nuclear factor-erythrocyte 2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) activation were investigated to assess the reduction in cell signaling and antioxidant pathways. RESULTS: BCCAO-induced cerebral perfusion decreased memory function and induced neuroinflammation and oxidative stress. But AA treatment mitigated cognitive impairment and reduced neuroinflammation and oxidative stress caused by chronic cerebral hypoperfusion. AA extracts activated the Nrf2/Keap1/activating antioxidant response elements pathway and maintained Sirt 1 and 2, subsequently leading to the maintenance of neurons, improved construct of microvessels, increased platelet-derived growth factor receptor beta, and platelet-endothelial cell adhesion molecule-1 associated with the blood-brain barrier integrity. CONCLUSION: AA is effective in alleviating BCCAO-induced cognitive decline and its administration may be a useful therapeutic approach for VaD.

Effectiveness and Therapeutic Mechanism of Pharmacopuncture for Pain in Parkinson's Disease: A Study Protocol for a Pilot Pragmatic Randomized, Assessor-Blinded, Usual Care-Controlled, Three-Arm Parallel Trial.

Pain in Parkinson's disease (PD) represents a complex phenotype known to decrease quality of life. This pragmatic randomized, controlled clinical trial evaluated the efficacy of pharmacopuncture (PA) for improving pain symptoms and investigated the corresponding therapeutic mechanisms in patients with PD. Ninety patients with PD-related pain were randomly allocated to receive either PA, manual acupuncture, or usual care in a 1:1:1 ratio; sixty healthy controls were included for comparative analysis of brain imaging data. Over 12 weeks, study treatment provided 2 days per week for 8 weeks with a follow-up period of 4 weeks. The primary outcome measure was the King's Parkinson's Disease Pain Scale score for assessing improvement in PD-related pain, including a sub-analysis to investigate the pattern of changes in pain according to a PD-related pain mechanism-based classification. Secondary outcome measures included a numerical rating scale-based assessment of the intensity and location of pain and changes in pain-associated symptoms, such as depression, anxiety, and sleep disorders. Exploratory outcome measures included structural and functional brain patterns on magnetic resonance imaging, blood molecular signature changes, gait analysis, facial expression and movement assessment in response to emotional stimuli, and a traditional Korean medicine syndrome differentiation questionnaire. The trial findings provided important clinical evidence for the effectiveness of PA in the management of PD-related pain and its associated symptoms, and helped elucidate the mechanism of its therapeutic effect on PD-related pain.

Efficacy of Kami Guibi-tang as an Add-On Therapy to Acetylcholinesterase Inhibitor for Cognitive Function in Mild Alzheimer's Disease: A Pilot Study.

Background: Kami Guibi-tang (KGT), a traditional Korean herbal medicine is mainly used to treat insomnia and nervousness. Acetylcholinesterase inhibitors (AChEIs) are the main treatments for mild Alzheimer's disease (AD), a degenerative brain disease. However, currently no drug can fundamentally treat AD or reverse the advanced cognitive decline. This clinical study explored the efficacy and safety of adding KGT to AChEI for cognitive function in mild AD. Methods: This was a pilot study for a larger randomized, double-blind, placebo-controlled trial. Participants between 55-90 years diagnosed with mild AD were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea. They were randomized to receive either KGT or placebo for 24 weeks, in addition to their regular AChEI. The primary outcome was treatment efficacy, as assessed by the relative amount of change over the study period in total scores on the Dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D). Changes in SNSB subscores were assessed as secondary outcomes. Safety parameters, including adverse events and abnormalities in blood tests, electrocardiograms, and brain magnetic resonance imaging were also monitored. Results: Between March 2018 and November 2020, seven participants each in the KGT group and the placebo group completed the 24-week trial. There were no significant changes in SNSB-D total or subindex scores for either group (p = 0.69 and 0.63, respectively), and no significant differences were observed between them (p=0.71). No adverse events related to KGT were reported. We also compared and analyzed the results of a previous pilot study conducted on amnestic mild cognitive impairment (aMCI) using protocol of this study. The aMCI group showed a significant improvement in the total SNSB-D score, especially in the memory domain, compared to the mild AD group (p = 0.04 and 0.02, respectively). The Korean Mini-Mental State Exam and Korean Instrumental Activities of Daily Living scores also significantly improved in the aMCI group (p = 0.01 and 0.02, respectively). Conclusions: Compared to placebo, adding KGT to AChEI did not significantly improve cognitive function in SNSB in patients with mild AD. We suggest that KGT would have a positive effect on patients with early stages of cognitive impairment such as aMCI. The findings could assist design larger, longer-term clinical trials of KGT use in elderly patients with mild AD. This study was registered in the Korean Clinical Trial Registry on December 26, 2017, with the CRIS approval number KCT0002904.

Effect of Kami Guibi-tang (KGT) in elderly subjects with insomnia: a study protocol from a single center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The incidence of insomnia increases with age and is related to cognitive function in older adults; therefore, it is important to manage it actively. In this study, we report a protocol for the evaluation of the efficacy and safety of Kami Guibi-tang (KGT), a herbal prescription that has been widely used in East Asia for insomnia, forgetfulness, and depression, in older adults with insomnia. METHODS: In this single-center, double-blind, randomized controlled trial, 60 older adults with insomnia and subjective cognitive decline will be recruited and randomly assigned to the KGT or placebo group. The KGT group will take KGT granules thrice a day for 12 weeks, whereas the control group will take placebo granules in the same manner. Participants will be assessed for sleep, cognitive function, quality of life, and depression using the Pittsburgh Sleep Quality Index-Korean (PSQI-K), Insomnia Severity Index-Korean (ISI-K), Seoul Neuropsychological Screening Battery-Dement (SNSB-D), 36-item MOS Short Form Survey (SF-36) and Short version of the Geriatric Depression Scale (S-GDS) before and at the end of administration of the investigational product. The PSQI-K, ISI-K, and SF-36 will be further assessed 12 weeks after the end of medication to determine whether the effects on sleep and quality of life are sustained. The PSQI-K total score difference between the two groups at 12 and 24 weeks will be the primary outcome; all other endpoints will be secondary. Safety will be assessed by performing blood tests and electrocardiograms before taking the investigational drug, 6 weeks after taking the drug, and 12 weeks after taking the drug; any adverse events will be observed throughout the study. DISCUSSION: The protocol will provide a detailed process for a clinical trial to evaluate the efficacy and safety of KGT in elderly patients with insomnia. We will also investigate if changes in cognitive function correlated with improvements in insomnia. TRIAL REGISTRATION: This trial was registered at CRIS (Clinical Research Information Service) on April 27, 2023 (KCT0008391, version 2.0).  https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24811&search_page=L .

A Comparative Study on the Neuroprotective Effect of Geopung-Chunghyuldan on In Vitro Oxygen-Glucose Deprivation and In Vivo Permanent Middle Cerebral Artery Occlusion Models.

Geopung-Chunghyuldan (GCD), which is a mixture of Chunghyuldan (CD), Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, is used to treat ischemic stroke in traditional Korean medicine. This study aimed to investigate the effects of GCD and CD on ischemic brain damage using in vitro and in vivo stroke models, as well as to elucidate the synergistic effects of GCD against ischemic insult. To study the effect of GCD in an in vitro ischemia model, SH-SY5Y cells were exposed to oxygen-glucose deprivation (OGD). Cell death after 16 h of OGD exposure was measured using the MTT assay and live/dead cell counting methods. An in vivo ischemia mice model was established through permanent middle cerebral artery occlusion (pMCAO). To determine the neuroprotective effect of GCD, it was orally administered immediately and 2 h after pMCAO. The infarct volume was measured through 2,3,5-triphenyltetrazolium chloride staining at 24 h after pMCAO. Compared with the control group, GCD treatment significantly reduced OGD-induced cell death in SH-SY5Y cells; however, CD treatment did not show a significant protective effect. In the pMCAO model, compared with the control group, treatment with GCD and CD significantly and mildly reduced the infarct volume, respectively. Our findings indicate that compared with CD, GCD may allow a more enhanced neuroprotective effect in acute ischemic stroke, indicating a potential synergistic neuroprotective effect. The possibility of GCD as a novel alternative choice for the prevention and treatment of ischemic stroke is suggested.

Effect of an herbal medicine, Chunghyul-dan, on prevention of recurrence in patients with ischemic stroke: A retrospective cohort study.

Research indicates that Chunghyul-dan (CHD), a herbal medicine, has an inhibitory effect on stroke recurrence in small vessel disease. Recent studies have suggested that CHD might also act on large arteries. This study aimed to verify the preventive effect of CHD on strokes of all the Trial of Org 10172 in Acute Stroke Treatment (TOAST) causative classifications. We retrospectively analyzed 2 years of medical records of patients with ischemic stroke treated with CHD, 600 mg once daily, in combination with antiplatelet or anticoagulant agents. The prevalence of stroke recurrence in 2 years was analyzed. Stroke recurrence was defined as new neurological symptoms with corresponding brain imaging results. Nine of the 202 patients (4.46%) had recurrent ischemic stroke. Four occurred within 180 days, 3 between 180 and 365 days, and 2 between 365 and 730 days. All had only 1 recurrence. The recurrence rates were 1.12%, 5%, and 5.48% for small vessel occlusion, cardioembolism, and large vessel atherosclerosis, respectively. There were no adverse effects. These results suggest that CHD could inhibit ischemic stroke recurrence of all TOAST causative categories. A randomized controlled trial is needed to confirm this hypothesis.

Effects of Hyul-Bu-Chuke-Tang on Erythrocyte Deformability and Cerebrovascular CO(2) Reactivity in Normal Subjects.

Aim. Hyul-bu-chuke-tang (HCEt) is a well-known traditional herbal medicine that is used for the treatment of ischemic cerebrovascular disorders. We investigated the acute effects of HCEt on erythrocyte deformability and cerebrovascular CO(2) reactivity (CVR) in healthy male subjects. Materials and Methods. We examined erythrocyte deformability in an HCEt group (n = 14) and a control group (n = 10). CVR was measured using hyperventilation-induced CO(2) reactivity of the middle cerebral artery and transcranial Doppler (TCD) in the HCEt group (n = 11). A historical control group (n = 10) of CVR measurements was also created from our previous study. All measurements were performed prior to and 1, 2, and 3 hours after HCEt administration. Results. HCEt significantly improved erythrocyte deformability 1 hour after administration compared to the control group (2.9 ± 1.1% versus -0.6 ± 1.0%, P = 0.034). HCEt significantly improved the CVR 2 hours after administration compared to the historical control group (9.1 ± 4.0% versus -8.1 ± 4.1%, P = 0.007). The mean blood pressure and pulse rate did not vary from baseline values in either group. Conclusions. We demonstrated that HCEt improved erythrocyte deformability and CVR. Our findings suggest that an improvement in erythrocyte deformability contributes to HCEt's effect on cerebral microcirculation.

Relationship between Blood Stasis Syndrome Score and Cardioankle Vascular Index in Stroke Patients.

Blood stasis syndrome (BSS) in traditional Asian medicine has been considered to correlate with the extent of atherosclerosis, which can be estimated using the cardioankle vascular index (CAVI). Here, the diagnostic utility of CAVI in predicting BSS was examined. The BSS scores and CAVI were measured in 140 stroke patients and evaluated with respect to stroke risk factors. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy of CAVI for the diagnosis of BSS. The BSS scores correlated significantly with CAVI, age, and systolic blood pressure (SBP). Multiple logistic regression analysis showed that CAVI was a significant associate factor for BSS (OR 1.55, P = 0.032) after adjusting for the age and SBP. The ROC curve showed that CAVI and age provided moderate diagnostic accuracy for BSS (area under the ROC curve (AUC) for CAVI, 0.703, P < 0.001; AUC for age, 0.692, P = 0.001). The AUC of the "CAVI+Age," which was calculated by combining CAVI with age, showed better accuracy (0.759, P < 0.0001) than those of CAVI or age. The present study suggests that the CAVI combined with age can clinically serve as an objective tool to diagnose BSS in stroke patients.

Traditional East Asian Herbal Medicine Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) is a leading progressive neurodegenerative disease worldwide, and its treatment is a challenging clinical problem. This review was conducted to evaluate the efficacy and safety of herbal medicine for AD treatment. The PubMed, CENTRAL, EMBASE, CNKI, OASIS, KTKP, and CiNii databases were searched until June 2020 for randomized controlled trials (RCTs) on herbal medicine for AD, and a meta-analysis of 57 RCTs was conducted. For cognitive function, herbal medicine significantly improved the Mini-Mental State Examination (MMSE) and AD Assessment Scale-Cognitive Subscale (ADAS-cog) scores compared with conventional medicine. The MMSE scores showed no significant difference between the groups treated with herbal medicine and donepezil; however, herbal medicine significantly lowered the ADAS-cog score. Acori Graminei Rhizoma-containing and Cnidii Rhizoma-containing herbal medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine showed a positive, but not statistically significant, tendency toward improving the MMSE score compared with conventional medicine. Herbal medicine with conventional medicine significantly improved the MMSE, ADAS-cog, and Montreal Cognitive Assessment (MoCA) scores compared with conventional medicine, and herbal medicine with donepezil also significantly improved these scores compared with donepezil. Acori Graminei Rhizoma or Cnidii Rhizoma-containing herbal medicine with conventional medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine + conventional medicine significantly improved the MMSE score, but not the ADAS-cog score, compared with conventional medicine. For behavioral and psychological symptoms of dementia, the Neuropsychiatry Inventory (NPI) score was not significantly different between herbal and conventional medicines. Herbal medicine with conventional medicine significantly improved the NPI and Behavioral Pathology in Alzheimer's Disease Rating Scale scores compared with conventional medicine. The NPI score showed no significant difference between the groups treated with herbal medicine and placebo. Furthermore, herbal medicine with conventional medicine significantly lowered plasma amyloid beta levels compared with conventional medicine alone. Herbal medicine, whether used alone or as an adjuvant, may have beneficial effects on AD treatment. However, owing to the methodological limitations and high heterogeneity of the included studies, concrete conclusions cannot be made.

Effects of Kami Guibi-tang in patients with mild cognitive impairment: study protocol for a phase III, randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is often considered a precursor to Alzheimer's disease (AD) and represents a key therapeutic target for early intervention of AD. However, no treatments have been approved for MCI at present. Our previous pilot study has shown that Kami Guibi-tang (KGT), a traditional herbal prescription widely used in Korean medicine for treating amnesia, might be beneficial for improving general cognitive function of aMCI patients. We will conduct a larger-scale clinical trial to validate the findings of our pilot study and further examine the efficacy and safety of KGT in aMCI. METHODS: This trial is designed as a randomized, double-blind, placebo-controlled clinical trial. A total of 84 aMCI patients will be recruited and randomized into the treatment and control groups. Participants will be administered either KGT or placebo granules for 24 weeks, with a follow-up period of 12 weeks after the last treatment. Primary outcomes will include changes in cognitive performance assessed using a neuropsychological test battery, called the Seoul Neuropsychological Screening Battery, between the baseline, post-intervention visit, and follow-up visit (24th and 36th week, respectively). Secondary outcomes will involve the rate of progression to AD, changes in neuroimaging signals assessed using structural magnetic resonance imaging (MRI), resting-state functional MRI (rs-fMRI), and task-based fMRI, and changes in blood biomarkers measured by the ratio of plasma amyloid-ß 42/40 levels (Aß42/Aß40) between the baseline and post-intervention visit (24th week). For safety assessments, blood chemistry tests and electrocardiograms (ECG) will also be performed. DISCUSSION: This study aims to provide confirmatory evidence of the effect of the Korean herbal medicine, KGT, on improving cognitive function in patients with aMCI. We will identify the possible mechanisms underlying the effects of KGT using neuroimaging signals and blood biomarkers. TRIAL REGISTRATION: Korean Clinical Trial Registry ( https://cris.nih.go.kr/cris/search/detailSearch.do/16918; Registration number: KCT0007039; Date of registration: February 24, 2022).

Are herbal medicines alone or in combination for diabetic peripheral neuropathy more effective than methylcobalamin alone? A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: In Asian countries, herbal medicines have been used to treat diabetic peripheral neuropathy (DPN) as an adjunctive therapy. This review aims to assess the effectiveness and safety of herbal medicines for the treatment of DPN. METHODS: A literature search was conducted on PubMed, Embase, CENTRAL, Scopus, CINAHL, CNKI, DBPIA, and OASIS for randomized controlled trials that evaluated the effects of herbal medicines on DPN. The oral methylcobalamin administered group was selected as the control. The primary outcome measure was nerve conduction velocity (NCV), and the secondary outcome measure was the total efficacy rate (TER). The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. A meta-analysis was conducted using Review Manager 5.4.1 software. RESULTS: Seventy-two RCTs with a total of 6260 patients were included. The meta-analysis showed that herbal medicine and co-administration of herbal medicine and methylcobalamin (CHM) treatment for DPN significantly increased the sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of the median and common peroneal nerves than methylcobalamin treatment alone. Herbal medicine and CHM treatment for DPN also significantly improved the TER compared to the control group. Herbal medicine and CHM treatment was found to be relatively safe. CONCLUSION: Our study suggests that herbal medicine and CHM might be more effective than methylcobalamin alone in the management of DPN. Further rigorous studies should be conducted to make more definite conclusions.

Investigation of the Adverse Events Associated with Bee Venom Pharmacopuncture in Patients Hospitalized in a Korean Hospital: A Retrospective Chart Review Study.

In bee venom pharmacopuncture (BVP), bee venom isolated from the venom sac of bees is injected into the acupoint or muscle associated with a disease. However, the histamine component in bee venom can cause adverse events; therefore, attention is required for BVP use. This study investigated the frequency, severity and characteristics of patients developing BVP-associated adverse events. The medical records of patients treated with BVP at Kyung Hee University Korean Medicine Hospital between 1 January 2013 and 1 May 2021 were reviewed. The demographic characteristics, disease-related characteristics, treatment-related characteristics and impressions of each patient were analyzed. In this study, &gt;50% of 4821 inpatients were hospitalized for neurological disorders. The mean age of the overall study population was 54.62 ± 16.38 years and 61% were women. The frequency of adverse events was 2.32%. The mean age in the adverse events group was 58.20 ± 16.10 years and 76% were women. Two patients experienced moderate adverse events, with no commonality between these events. Every patient recovered naturally with no sequelae. The results showed that BVP is a relatively safe therapeutic method. However, further studies are needed to determine the frequency of adverse events and identify the causality between baseline characteristics and adverse events.

Clinical approach to the standardization of oriental medical diagnostic pattern identification in stroke patients.

In Korea, many stroke patients receive oriental medical care, in which pattern-identification plays a major role. Pattern-identification is Oriental Medicine's unique diagnostic system. This study attempted to standardize oriental medical pattern-identification for stroke patients. This was a community-based multicenter study that enrolled stroke patients within 30 days after their ictus. We assessed the patients' general characteristics and symptoms related to pattern-identification. Each patient's pattern was determined when two doctors had the same opinion. To determine which variables affect the pattern-identification, binary logistic regression analysis was used with the backward method. A total of 806 stroke patients were enrolled. Among 480 patients who were identified as having a certain pattern, 100 patients exhibited the Fire Heat Pattern, 210 patients the Phlegm Dampness Pattern, nine patients the Blood Stasis Pattern, 110 patients the Qi Deficiency Pattern, and 51 patients the Yin Deficiency Pattern. After the regression analysis, the predictive logistic equations for the Fire Heat, Phlegm Dampness, Qi Deficiency, and Yin Deficiency patterns were determined. The Blood Stasis Pattern was omitted because the sample size was too small. Predictive logistic equations were suggested for four of the patterns. These criteria would be useful in determining each stroke patient's pattern in clinics. However, further studies with large samples are necessary to validate and confirm these criteria.

Effect of herbal extracts on peripheral nerve regeneration after microsurgery of the sciatic nerve in rats.

BACKGROUND: Recent experimental studies using herbal extracts have shown the possibility of peripheral nerve regeneration. This study aimed to investigate the effects of herbal extracts on peripheral nerve regeneration in a rat sciatic nerve injury model. METHODS: A total of 53 rats were randomly assigned to a control group or one of four experimental groups. In all rats, the sciatic nerve was completely severed and microscopic epineural end-to-end neurorrhaphy was performed. Normal saline (2 mL) was topically applied to the site of nerve repair in the control group, whereas four different herbal extracts - 2 mL each of Astragalus mongholicus Bunge, Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, or Paeonia lactiflora Pall. - were topically applied to the site of nerve repair in each experimental group. Nerve conduction studies were performed at an average of 11.9 weeks after the operation, and conduction velocity and proximal and distal amplitudes were measured. Biopsies were performed at an average of 13.2 weeks after the initial neurorrhaphy. The quality of nerve anastomosis and perineural adhesion to the surrounding soft tissues was macroscopically evaluated. The neuroma size at the site of the neurorrhaphy was microscopically measured, whereas the size of the scar tissue was evaluated relative to the diameter of the repaired nerve. RESULTS: The nerve conduction study results showed the highest nerve conduction velocity in the experimental group that used the Coptis japonica (Thunb.) Makino extract and the highest proximal and distal amplitudes in the experimental group that used the Aconitum carmichaelii Debeaux extract. Macroscopic evaluations after the second operation showed that grade 2 perineural adhesion was found in 70.8% of rats. The mean neuroma size in the Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, and Paeonia lactiflora Pall. groups showed statistically significant decreases relative to the control group. The mean scar tissue formation index in the Paeonia lactiflora Pall. group showed a statistically significant decrease relative to the control group. CONCLUSIONS: The peripheral nerve regeneration effect of the herbal extracts was confirmed through decreased neuroma and scar tissue formation.