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.

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.

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.

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.

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.

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.

Treatment of nausea and vomiting associated with cerebellar infarction using the traditional herbal medicines banhabaekchulcheonma-tang and oryeong-san: Two case reports (CARE-complaint).

RATIONALE: Metoclopramide is commonly used to treat nausea and vomiting. However, long-term administration of metoclopramide is associated with various adverse effects, and its therapeutic effects are short-lasting. Hence, traditional East Asian medicine has received increasing attention as a short-term strategy for treating these symptoms. PATIENT CONCERNS: The present report discusses the cases of a 71-year-old man and an 80-year-old woman diagnosed with cerebellar infarction. Both patients reported nausea and vomiting, which appeared during hospitalization following cerebellar infarction. DIAGNOSES: One patient was diagnosed with a left cerebellar infarction and hemorrhagic transformation, while the other was diagnosed with a bilateral cerebellar infarction. INTERVENTIONS: Both patients took Banhabaekchulcheonma-tang (BT) and Oryeong-san (OS) extracts. OUTCOMES: The patient in Case 1 experienced a rapid decrease in nausea from day 5 of BT and OS administration, and metoclopramide was discontinued on day 7. The patient in Case 2 experienced a clear decrease in the number of vomiting episodes from day 6 of BT and OS administration and did not take metoclopramide thereafter. LESSONS: Other than drugs used to mitigate symptoms, there are no suitable treatments available for nausea and vomiting caused by cerebellar infarction. In the present cases, nausea and vomiting remained unresolved even after 3 weeks of treatment with conventional therapies; however, these symptoms significantly improved after administration of the traditional East Asian herbal medicines BT and OS, and there were no recurrences. These cases demonstrate that traditional herbal medicine can reduce the side effects associated with long-term administration of metoclopramide and help patients resume their daily lifestyle. In addition, BT and OS treatment can facilitate administration of other drugs, highlighting its potential to aid in the treatment of stroke. Further research including relevant clinical trials is required to obtain more conclusive evidence.

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).

Effectiveness and safety of herbal medicine Ukgansan for clinical symptoms in Parkinson's disease: A pilot, randomized, assessor-blinded clinical trial.

Objectives: Parkinson's disease (PD) is a neurodegenerative disease in which patients are suffering various symptoms. Previous experimental studies suggested that herbal medicine Ukgansan (UGS) could be beneficial for PD. The aim of this pilot clinical trial was to evaluate the efficacy of UGS for improving clinical symptoms in patients with PD. Methods: Sixty patients with idiopathic PD were randomly assigned to receive either UGS plus acupuncture or acupuncture alone for 6 weeks. During the trial, all anti-parkinsonian medications were maintained. Subjects were evaluated for various clinical assessments of PD, including the Movement Disorder Society-Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS) and the 39-item Parkinson's Disease Questionnaire (PDQ-39), until 12 weeks. Results: In MDS-UPDRS between the groups, no significant time x group interaction was found. In the subgroup analysis of participants with anxiety, a significant time x group interaction was found in the PDQ-39 domain of mobility (P = 0.007), activities of daily living (P = 0.042), and the PDQ-39 summary index (P = 0.048). In addition, post-hoc analysis in participants with anxiety showed a significant decrease in the domains of mobility (P = 0.001) and activities of daily living (P = 0.013) at week 7. There were no adverse events associated with UGS. Conclusion: The additional administration of UGS has the potential to significantly improve the quality of life of PD patients with anxiety. In order to create more definitive evidence, clinical trials with more rigorous methodologies should be conducted in future. Clinical trial registration: http://cris.nih.go.kr, identifier: KCT0003444.

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, >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.

A Study on the Perceptions of Korean Older Adult Patients and Caregivers about Polypharmacy and Deprescribing.

Polypharmacy is continuously increasing among older adults. The resultant potentially inappropriate medications (PIMs) can be harmful to patient health. Deprescribing refers to stopping or reducing PIMs. In this study, the current status of polypharmacy and willingness of older adults to deprescribe were investigated among patients and caregivers who are not associated with one another. The survey used the Korean translated version of the revised Patients' Attitude Towards Deprescribing (rPATD) Scale. Data were collected through an online survey of 500 participants (250 patients and caregivers each) in this study. The following results were found for patients and caregivers, respectively: 74.8% and 63.6% felt their number of medications was high, 64.4% and 55.6% desired to reduce their medications, 70.4% and 60.8% were concerned about medication discontinuation, 63.2% and 61.2% had a good understanding of their medications, 77.6% and 76.4% were willing to be well informed, and 79.6% and 72% wanted to reduce the number of medications if medically feasible. Patients and caregivers commonly agreed to the burden of the number of medications they were taking, and were willing to reduce the number of medications if the doctor said it was possible. Doctors should consider this information during the deprescribing process, and promote deprescription while involving patients and caregivers in the decision-making process.

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.

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.

Traditional East Asian Herbal Medicine for Amyotrophic Lateral Sclerosis: A Scoping Review.

This study aimed to analyze and summarize the existing evidence regarding herbal medicine treatments for amyotrophic lateral sclerosis (ALS). Studies on herbal medicine treatment in patients with ALS were searched within English, Chinese, Japanese, and Korean databases up to July 31, 2021. In the selected studies, we collected the following information: the first author, year of publication, country, language, study methodology, sample size, demographic characteristics of the study participants, disease duration, diagnostic criteria, treatment method, treatment periods, evaluation tools, results, and side effects. The organized data were classified and analyzed narratively. This study included 59 studies. The first clinical study on the effect of herbal medicine was published in 1995; moreover, most studies were conducted in China. Among the 59 selected studies, 47.5% were observational studies, including case reports and case series. Moreover, there was one meta-analysis. The El Escorial criteria were the most commonly used diagnostic criterion for ALS; moreover, the ALS functional rating scale was the most common evaluation tool. Buzhongyiqitang, Sijunzitangjiawei, and Jianpiyifeitang were the most commonly used herbal medicines, with anti-inflammatory, protein aggregation, and anti-oxidant effects. There remain evidence of gaps in the effectiveness of herbal medicine for ALS. To allow effective treatment of patients with ALS using herbal medicine, large-scale and rigorously designed high-quality clinical studies should be performed.

An Analysis of Characteristics of Post-Stroke Fatigue in Patients without Depression: A Retrospective Chart Review.

Post-stroke fatigue (PSF) is among the most common stroke sequelae and affects rehabilitation, resulting in poor recovery. A main influencing factor may be depression, which has been investigated with fatigue in several clinical trials. We aimed to evaluate the characteristics of fatigue in post-stroke patients without depression through a retrospective chart review. The medical records of stroke patients hospitalized in the Stroke and Brain Disease Center, Kyung Hee University Korean Medicine Hospital were reviewed. Stroke patients without depression were divided into a PSF group and control group (without fatigue). The demographic characteristics, type of stroke, medical history, laboratory examinations, clinical features, and pattern identification of each patient were recorded and compared between the study groups. The medical records of 216 patients were reviewed; 85 and 131 patients were assigned to the PSF and control group, respectively. Apolipoprotein A1 levels were significantly lower in the PSF than in the control group (105.6 ± 16.5 vs. 116.2 ± 21.8). We found a significantly higher occurrence of reversal cold of the extremities and a lower probability of fire-heat pattern in the PSF group than in the control group. This study suggests that apolipoprotein A1 levels are lower and cold manifestations are more common in PSF patients without depression than in those without fatigue.

A Systematic Review and Meta-Analysis of the Effects of Herbal Medicine Buyang Huanwu Tang in Patients with Poststroke Fatigue.

Poststroke fatigue (PSF) is reported to occur in 30%-72% of all patients with stroke. PSF not only is a symptom of stroke but has also been reported to adversely affect the prognosis of patients with stroke. However, no treatment has had a significant effect on PSF. In East Asian countries, several herbal medicines have been used to treat stroke, with Buyang Huanwu Tang (BHT) being the most common. This review aimed to evaluate the efficacy and safety of BHT for PSF. A literature search was conducted on MEDLINE, CENTRAL, Scopus, CiNii, CNKI, OASIS, NDSL, and KTKP databases for randomized controlled trials that evaluated the effects and safety of BHT on PSF. Six studies (n = 427) were included. The overall methodological quality of these studies was relatively low. In the adjunctive BHT group, the meta-analysis indicated statistically significant improvements in the Fatigue Severity Scale score (mean difference -1.49, 95% CI [-2.25, -0.73]) and total clinical efficacy rate (risk ratio 0.11, 95% CI [0.03, 0.41]) compared to those in the nonherbal group. Adverse events were only reported in one study, and no serious adverse events occurred. BHT administration might be effective in the treatment of PSF. We were unable to draw definitive conclusions owing to the limitations of the included studies. The trial is registered with CRD42019130178 in PROSPERO.

Current Utilization and Research Status of Traditional East Asian Herbal Medicine Treatment for Multiple Sclerosis: A Scoping Review.

Background: Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease of the central nervous system that is gradually increasing in prevalence. The etiology of MS remains unknown; however, it is assumed to be caused by a deterioration of autoimmune regulation. Although immunomodulatory agents are a standard treatment option in patients with MS, there is insufficient evidence about their clinical efficacy in symptomatic treatment, and many MS patients resort to complementary and alternative medicine. For this reason, we conducted a scoping review to investigate the current status of the clinical evidence related to traditional East Asian herbal medicine treatment for MS and to inform future research and treatment strategies. Method: A scoping review is an emerging methodology for knowledge synthesis that adopts the Arksey and O'Malley framework. The research question was, "What has been studied about the herbal medicine treatments administered to patients with MS?" Articles published until 2019 were identified in six databases (PubMed, Embase, Cochrane, KoreaMed, NDSL, and OASIS) in March of 2020. Data from the included studies were charted and descriptively analyzed in relation to the study's research questions. Results: Of the 1,445 articles identified, 14 studies were included in this review. Single and serial case reports constituted the majority (42.86%), with 57.14% of studies conducted in China. A total of 20 prescriptions containing 95 herbs were used in the intervention and observational studies. Herbal medicines were effective at improving clinical symptoms of MS and reducing recurrence frequency. The main cause of MS was presumed to be oxidative stress, which enhances inflammation and, consequently, causes neuronal death. Conclusion: Herbal medicines were determined to improve the symptoms of MS and to reduce the frequency of recurrences. This study suggests that herbal medicines are promising and worth pursuing further studies but the state of current evidence is poor. Thus, further, high-quality studies included larger randomized trial are required.

Analysis of Factors Affecting Post-Stroke Fatigue: An Observational, Cross-Sectional, Retrospective Chart Review Study.

Post-stroke fatigue (PSF) is one of the most common emotional and mood disorders in stroke survivors. Several studies have suggested associations between PSF and various factors. However, they describe conflicting results. Therefore, this study aimed to evaluate the factors affecting PSF. We retrospectively reviewed the medical records of 178 hospitalized stroke patients. The collected data were compared between the PSF and control groups. To evaluate the association between factors and PSF, regression analysis was conducted. A total of 96 patients (53.9%) were assigned to the PSF group, and 82 patients were assigned to the control group. Age, neurological deficits, cognitive dysfunction, degree of depression, hs-CRP, and ESR differed significantly between the two groups. For both types of stroke, multiple linear regression analyses showed that degree of depression and degree of inflammation were significantly associated with PSF. Through subgroup analysis, multiple linear regression analyses showed that the degree of depression in ischemic and hemorrhagic stroke and the platelet-to-lymphocyte ratio in hemorrhagic stroke had a significant association with PSF. In conclusion, post-stroke depression and degree of inflammation could be clinically significant predictors of PSF in all types of stroke patients. However, larger, prospective studies are required to obtain more concrete results.