A Herbal Prescription of Insamyangyeongtang as a Therapeutic Agent for Frailty in Elderly: A Narrative Review.

Frailty is a major geriatric syndrome with a multifactorial etiology that induces a decline in multiple physiological and psychological functions. In traditional East Asian medicine (TEAM), qi and blood deficiency clinically represent as fatigue, anemia, anorexia, decreased strength after illness, and weakness, commonly interpretated as frailty. An herbal prescription of Insamyangyeongtang (IYT, Ninjin'yoeito in Japanese, Ren-Shen-Yang-Rong-Tang in Chinese) tonifies qi and blood and has the potential to treat multiple targets caused by qi and blood deficiency. As the population ages and frailty increases, there is an increase in the potential effectiveness of IYT in frailty. This study reviewed relevant clinical trials to provide an updated view on the effect of IYT on frailty. IYT has therapeutic effects on frailty associated with chronic respiratory diseases (e.g., chronic obstructive pulmonary disease) and cognitive impairments (e.g., Alzheimer's disease) and improves respiratory symptoms and cognition. IYT also has therapeutic effects on weight gain, muscle mass, and strength, and improves nutritional status in frail elderly individuals who have decreased muscle mass and strength, loss of appetite, and weight loss. The same effect has been shown in frailty in elderly individuals with rehabilitation treatment and chronic diseases. IYT also improves frailty associated with symptoms such as intractable dizziness and genitourinary symptoms. The beneficial effects of IYT in several diseases could be important for medication replacement, reduction, and prevention of polypharmacy. Based on the results of this review, we suggest that IYT has the potential to be a therapeutic agent against frailty.

Safety of herbal decoctions: A scoping review of clinical studies in South Korea focusing on liver and kidney functions.

ETHNOPHARMACOLOGICAL RELEVANCE: Approximately 27% of individuals seeking Korean medicine (KM) services in South Korea are prescribed herbal decoctions. The South Korean government has considered the validity of providing National Health Insurance coverage for herbal decoctions. Therefore, it is important to investigate their safety. AIM OF THE STUDY: To investigate the safety of herbal decoctions commonly prescribed by KM doctors and to assess their effects on liver and kidney function by comprehensively analyzing Korean clinical studies in a scoping review. MATERIALS AND METHODS: The Arksey and O'Malley framework and modified methods were applied in this scoping review. A comprehensive search of seven electronic health databases was conducted, and relevant clinical studies published between 2000 and 2022 were identified. Subsequently, only clinical studies reporting the results of liver and/or renal function tests in patient prescribed herbal decoctions by KM doctors were included. The characteristics of the included clinical studies and the reported proportion of each liver and/or renal function indicator were analyzed. Meta-analyses of the effects of herbal decoction on liver and/or renal function reported in prospective cohort studies were also performed. RESULTS: Fifty-nine clinical studies were included in this review. The proportion of prospective cohort studies markedly decreased in the 2010s compared to the 2000s, while there was no noticeable change in the number of relevant clinical studies. Herbal decoctions were prescribed for less than one month in most included studies. Abnormal changes in liver or renal function indicators were identified in a small number of studies (3.70% and 7.69%, respectively). In a meta-analysis of 15 prospective cohort studies, no statistically significant changes in four liver function indices and two renal function indices were observed before and after the prescription of herbal decoctions. CONCLUSIONS: Qualitative and quantitative analyses demonstrated favorable safety profiles for herbal decoctions. This scoping review includes the gaps noted between clinical application and research regarding the safety profiles of herbal decoctions. These findings could be used as evidence to support the inclusion of herbal decoction prescriptions in the National Health Insurance coverage in South Korea.

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.

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.

Patients with Parkinson Disease in a Traditional Korean Medicine Hospital: A Five-Year Audit.

Parkinson disease (PD) patients' demand for complementary and alternative medicine (CAM) has thus been increasing. We investigated the characteristics of PD patients who visited the Korean Medicine Hospital, the official CAM clinic in Korea. The medical records of PD patients were reviewed retrospectively. The demographic and disease-related characteristics, motivation for visiting, and treatment modalities were collected and analyzed. Medical records from 618 patients were reviewed. Most patients (67.6%) had been already diagnosed with PD at the initial visit. The most frequent complaint was gait disturbance. Previously diagnosed patients visited most frequently for add-on CAM therapies. The most frequently used CAM therapy was acupuncture. The most frequently prescribed herbal medicine was modified Ukgansan. We found the main reason for seeking out CAM was to compensate for the effects of conventional therapies. Further prospective studies will be necessary to collect enough data and evaluate the effectiveness of CAM therapies.

Herbal medicines for the prevention and treatment of cerebral vasospasm after subarachnoid hemorrhage: A protocol for systematic review and meta-analysis.

BACKGROUND: Despite the rapid advances in medical technology, including endovascular interventions and medications, cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is still one of the major threats to the lives of patients with SAH. In East Asian countries, various types of herbal medicines have been used to treat cerebrovascular diseases, including SAH. In this review, we aim to evaluate the efficacy and safety of herbal medicines for the prevention and treatment of CVS after SAH. METHODS AND ANALYSIS: Seven databases will be searched for relevant studies from inception to the present date "June 2020". Only randomized controlled trials (RCTs) that assess the effect and safety of herbal medicines for the prevention and treatment of CVS after SAH will be included. The methodological quality will be evaluated using the Cochrane risk of bias assessment tool. After selecting the appropriate studies, a meta-analysis of the RCTs will be performed. RESULTS: This study will provide a high-quality synthesis of current evidence of herbal medicines for CVS after SAH. CONCLUSION: Our systematic review will provide evidence to judge whether herbal medicines are effective interventions for patients with CVS after SAH. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study is based on a review of published research. This review will be published in a peer-reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION NUMBER: Research registry reviewregistry923.