Determination of the Combined Effects of Asian Herbal Medicine with Calcium and/or Vitamin D Supplements on Bone Mineral Density in Primary Osteoporosis: A Systematic Review and Meta-Analysis.

Our review of 52 RCTs from 5 databases suggests a tendency for notable improvement in BMD when combining herbal medicine with supplements (calcium and vitamin D variants) compared to supplement monotherapy in primary osteoporosis. However, caution is needed in interpreting results due to substantial heterogeneity among included studies. PURPOSE: To conduct a systematic review and meta-analysis to determine whether herbal medicine (HM) plus supplements such as calcium (Ca) or vitamin D (Vit.D) improves bone mineral density (BMD) compared to supplements alone in primary osteoporosis (OP) patients. METHODS: We searched 5 databases for randomized controlled trials (RCTs) using HMs with supplements (Ca or Vit.D variants) as interventions for primary OP patients published until August 31, 2022. Meta-analysis using BMD score as the primary outcome was performed using RevMan 5.4 version. Risk of bias in the included studies was assessed useing RoB 2.0 tool. RESULTS: In total, 52 RCTs involving 4,889 participants (1,408 men, 3,481 women) were included, with average BMD scores of 0.690 ± 0.095 g/cm2 (lumbar) and 0.625 ± 0.090 g/cm2 (femoral neck). As a result of performing meta-analysis using BMD scores for all 52 RCTs included in this review, combination of HMs with Ca and Vit.D variants improved the BMD score by 0.08 g/cm2 (lumbar, 38 RCTs, 95% CI: 0.06-0.10, p < 0.001, I2 = 97%) and 0.06 g/cm2 (femoral neck, 19 RCTs, 95% CI: 0.04-0.08, p < 0.001, I2 = 92%)compared to controls. However, statistical significance of the lumbar BMD improvement disappeared after adjusting for potential publication bias. CONCLUSION: Our data suggest that combining of HM and supplements tends to be more effective in improving BMD in primary OP than supplements alone. However, caution is needed in interpretation due to the reporting bias and high heterogeneity among studies, and well-designed RCTs are required in the future.

The additive effect of herbal medicines on lifestyle modification in the treatment of non-alcoholic fatty liver disease: a systematic review and meta-analysis.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is difficult to manage because of its complex pathophysiological mechanism. There is still no effective treatment other than lifestyle modification (LM) such as dietary modifications, regular physical activity, and gradual weight loss. Herbal medicines from traditional Chinese Medicine and Korean Medicine have been shown to be effective in the treatment of NAFLD based on many randomized controlled trials. This systematic review and meta-analysis aims to evaluate the additive effects of herbal medicines on LM in the treatment of NAFLD. Methods: Two databases (PubMed and Cochrane library) were searched using keywords related to NAFLD and herbal medicines. Then the randomized controlled trials (RCTs) evaluating the therapeutic effects of herbal medicines combined with LM were selected. The pooled results were analyzed as mean difference (MD) with 95% confidence interval (CI) for continuous data, and risk ratio (RR) with 95% CI for dichotomous data. Results and Discussion: Eight RCTs with a total of 603 participants were included for this review study. Participants were administered with multi-herbal formulas (Yiqi Sanju Formula, Tiaogan Lipi Recipe, and Lingguizhugan Decoction) or single-herbal extracts (Glycyrrhiza glabra L., Magnoliae offcinalis, Trigonella Foenum-graecum L. semen, Portulaca oleracea L., and Rhus Coriaria L. fructus) along with LM for 12 weeks. The meta-analysis showed a significant improvement in ultrasoundbased liver steatosis measured by odds ratio (OR) in the herbal medicine group than those with LM alone (OR = 7.9, 95% CI 0.7 to 95.2, p < 0.1). In addition, herbal medicines decreased the levels of aspartate transferase (MD -7.5, 95% CI -13.4 to -1.7, p = 0.01) and total cholesterol (MD -16.0, 95% CI -32.7 to 0.7, p = 0.06) more than LM alone. The meta-analysis partially showed clinical evidence supporting the additive benefits of herbal medicines for NAFLD in combination with LM. Whereas, it is necessary to provide a solid basis through higher-quality studies using a specific herbal medicine.

Efficacy of Moxibustion for Cancer-Related Fatigue in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Breast cancer is the most commonly diagnosed cancer worldwide, and most patients experience fatigue. However, there are no effective treatments for cancer-related fatigue (CRF). Several randomized controlled trials (RCTs) have suggested that moxibustion improves CRF. We conducted a systematic review and meta-analysis to compare the differences in fatigue scale scores, quality of life, and clinical efficacy in patients with breast cancer who developed CRF and did versus did not receive moxibustion. METHODS: RCTs were searched in 7 databases using a standardized search method from database inception to March 2023, and RCTs that met the inclusion criteria were selected. RESULTS: Among 1337 initially identified RCTs, 10 RCTs involving 744 participants were selected for this study. The meta-analysis involved assessment of the revised Piper Fatigue Scale scores, Cancer Fatigue Scale scores, Karnofsky Performance Scale scores, Athens Insomnia Scale scores, clinical efficacy, and Qi deficiency syndrome scale scores. Compared with the control, moxibustion was associated with significantly better Piper Fatigue Scale scores (P < 0.0001), quality of life [Karnofsky Performance Scale scores (P < 0.0001)], clinical efficacy (P = 0.0007), and Qi deficiency syndrome scale scores (P = 0.02). CONCLUSIONS: Moxibustion improves CRF in patients with breast cancer. The efficacy of moxibustion should be further examined by high-quality studies in various countries with patients subdivided by their breast cancer treatment status. REGISTRATION: PROSPERO ID: CRD42023451292.

Lactobacillus Casei-fermented Amomum Xanthioides Mitigates non-alcoholic fatty liver disease in a high-fat diet mice model.

Non-alcoholic fatty liver disease (NAFLD) is a substantial global health issue owing to its high prevalence and the lack of effective therapies. Fermentation of medicinal herbs has always been considered a feasible strategy for enhancing efficacy in treating various ailments. This study aimed to investigate the potential benefits of the Lactobacillus casei-fermented Amomum xanthioides (LAX) on NAFLD in a high-fat diet model. HFD-fed C57BL6/j mice were administered with 200 mg/kg of LAX or unfermented Amomum xanthioides (AX) or 100 mg/kg of metformin for 6 weeks from the 4th week. The 10-week HFD-induced alterations of hepatic lipid accumulation and hepatic inflammation were significantly attenuated by LAX dominantly (more than AX or metformin), which evidenced by pathohistological findings, lipid contents, inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 6 and IL-1ß, oxidative parameters such as reactive oxygen species (ROS) and malondialdehyde (MDA), and molecular changes reversely between lipogenic proteins such as glycerol-3-phosphate acyltransferase (GPAM) and sterol regulatory element-binding protein (SREBP)- 1, and lipolytic proteins including peroxisome proliferator-activated receptor (PPAR-α) and AMP-activated kinase (AMPK)-α in the liver tissues. In addition, the abnormal serum lipid parameters (triglyceride, total cholesterol and LDL-cholesterol) notably ameliorated by LAX. In conclusion, these findings support the potential of LAX as a promising plant-derived remedy for NAFLD.

A Capsicum annuum L. seed extract exerts anti-neuroexcitotoxicity in HT22 hippocampal neurons.

The hippocampal memory deficit stands out as a primary symptom in neurodegenerative diseases, including Alzheimer's disease. While numerous therapeutic candidates have been proposed, they primarily serve to delay disease progression. Given the irreversible brain atrophy or injury associated with these conditions, current research efforts are concentrated on preventive medicine strategies. Herein, we investigated whether the extracts of Capsicum annuum L. seeds (CSE) and Capsicum annuum L. pulp (CPE) have preventive properties against glutamate-induced neuroexcitotoxicity (one of the main causes of Alzheimer's disease) in HT22 hippocampal neuronal cells. Pretreatment with CSE demonstrated significant anti-neuroexcitotoxic activity, whereas CPE did not exhibit such effects. Specifically, CSE pretreatment dose-dependently inhibited the elevation of excitotoxic elements (intracellular calcium influx and reactive oxygen species; ROS) and apoptotic elements (p53 and cleaved caspase-3). In addition, the glutamate-induced alterations of neuronal activity indicators (brain-derived neurotrophic factor; BDNF and cAMP response element-binding protein phosphorylation; CREB) were significantly attenuated by CSE treatment. We also found that luteolin is the main bioactive compound corresponding to the anti-neuroexcitotoxic effects of CSE. Our results strongly suggest that Capsicum annuum L. seeds (but not its pulp) could be candidates for neuro-protective resources especially under conditions of neuroexcitotoxicity. Its underlying mechanisms may involve the amelioration of ROS-mediated cell death and BDNF-related neuronal inactivity and luteolin would be an active compound.

A Review of Herbal Resources Inducing Anti-Liver Metastasis Effects in Gastrointestinal Tumors via Modulation of Tumor Microenvironments in Animal Models.

Liver metastases remain a major obstacle for the management of all types of tumors arising from digestive organs, and the tumor microenvironment has been regarded as an important factor in metastasis. To discover herbal candidates inhibiting the liver metastasis of tumors originating from the digestive system via the modulation of the tumor microenvironment and liver environment, we searched three representative public databases and conducted a systematic review. A total of 21 studies that employed experimental models for pancreatic (9), colon (8), and stomach cancers (4) were selected. The herbal agents included single-herb extracts (5), single compounds (12), and multiherbal decoctions (4). Curcuma longa Linn was most frequently studied for its anti-colon-liver metastatic effects, and its possible mechanisms involved the modulation of tumor microenvironment components such as vascular endothelial cells and immunity in both tumor tissues and circulating cells. The list of herbal agents and their mechanisms produced in this study is helpful for the development of anti-liver metastasis drugs in the future.

A Mixture of Cervus elaphus sibiricus and Glycine max (L.) Merrill Inhibits Ovariectomy-Induced Bone Loss Via Regulation of Osteogenic Molecules in a Mouse Model.

Osteoporosis is a metabolic skeletal disease characterized by lowered bone mineral density and quality, which lead to an increased risk of fracture. The aim of this study was to evaluate the anti-osteoporosis effects of a mixture (called BPX) of Cervus elaphus sibiricus and Glycine max (L.) Merrill and its underlying mechanisms using an ovariectomized (OVX) mouse model. BALB/c female mice (7 weeks old) were ovariectomized. From 12 weeks of ovariectomy, mice were administered BPX (600 mg/kg) mixed in a chow diet for 20 weeks. Changes in bone mineral density (BMD) and bone volume (BV), histological findings, osteogenic markers in serum, and bone formation-related molecules were analyzed. Ovariectomy notably decreased the BMD and BV scores, while these were significantly attenuated by BPX treatment in the whole body, femur, and tibia. These anti-osteoporosis effects of BPX were supported by the histological findings for bone microstructure from H&E staining, increased activity of alkaline phosphatase (ALP), but a lowered activity of tartrate-resistant acid phosphatase (TRAP) in the femur, along with other parameters in the serum, including TRAP, calcium (Ca), osteocalcin (OC), and ALP. These pharmacological actions of BPX were explained by the regulation of key molecules in the bone morphogenetic protein (BMP) and mitogen-activated protein kinase (MAPK) pathways. The present results provide experimental evidence for the clinical relevance and pharmaceutical potential of BPX as a candidate for anti-osteoporosis treatment, especially under postmenopausal conditions.

Adjuvant effect of herbal medicine on transarterial chemoembolization in patients with hepatocellular carcinoma: A systematic review and meta-analysis.

Objectives: Primary hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, especially in Asian countries. As a practical treatment option, transarterial chemoembolization (TACE) has been well applied; however, its limited efficacy remains challenging. This study analyzed the adjuvant effects of herbal medicine on TACE to determine whether it improves clinical outcomes in patients with HCC. Methods: A systematic review and meta-analysis was performed to compare the adjuvant effects of herbal medicine on TACE versus TACE therapy alone. We searched the literature from eight databases since January 2011. Results: Twenty-five studies involving 2,623 participants were selected. The adjuvant therapy of herbal medicine on TACE improved the overall survival at 0.5 years (OR = 1.70; 95% CI 1.21-2.38), 1 year (OR = 2.01; 95% CI 1.65-2.46), 2 years (OR = 1.83; 95% CI 1.20-2.80), and 3 years (OR = 1.90; 95% CI 1.25-2.91). The combination therapy also increased the tumor response rate (OR = 1.84; 95% CI 1.40-2.42). Conclusions: Despite the unsatisfactory quality of the included studies, the adjuvant therapy of herbal medicine on TACE may provide survival benefits to patients with HCC. Systematic reviews registration: http://www.crd.york.ac.uk/PROSPERO, identifier (376691).

Ginseng Sprouts Attenuate Mortality and Systemic Inflammation by Modulating TLR4/NF-κB Signaling in an LPS-Induced Mouse Model of Sepsis.

Sepsis leads to multi-organ failure due to aggressive systemic inflammation, which is one of the main causes of death clinically. This study aimed to evaluate whether ginseng sprout extracts (GSE) can rescue sepsis and explore its underlying mechanisms. C57BL/6J male mice (n = 15/group) were pre-administered with GSE (25, 50, and 100 mg/kg, p.o) for 5 days, and a single injection of lipopolysaccharide (LPS, 30 mg/kg, i.p) was administered to construct a sepsis model. Additionally, RAW264.7 cells were treated with LPS with/without GSE/its main components (Rd and Re) to explain the mechanisms corresponding to the animal-derived effects. LPS injection led to the death of all mice within 38 h, while GSE pretreatment delayed the time to death. GSE pretreatment also notably ameliorated LPS-induced systemic inflammation such as histological destruction in both the lung and liver, along with reductions in inflammatory cytokines, such as TNF-α, IL-6, and IL-1ß, in both tissues and serum. Additionally, GSE markedly diminished the drastic secretion of nitric oxide (NO) by suppressing the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) in both tissues. Similar changes in TNF-α, IL-1ß, NO, iNOS, and COX2 were observed in LPS-stimulated RAW264.7 cells, and protein expression data and nuclear translocation assays suggested GSE could modulate LPS-binding protein (LBP), Toll-like receptor 4 (TLR4), and NF-κB. Ginsenoside Rd could be a major active component in GSE that produces the anti-sepsis effects. Our data support that ginseng sprouts could be used as an herbal resource to reduce the risk of sepsis. The corresponding mechanisms may involve TLR4/NF-κB signaling and a potentially active component.

CGX, a standardized herbal syrup, inhibits colon-liver metastasis by regulating the hepatic microenvironments in a splenic injection mouse model.

Background: Colon-liver metastasis is observed in approximately 50% of patients with colorectal cancer and is a critical risk factor for a low survival rate. Several clinical studies have reported that colon-liver metastasis is accelerated by pathological hepatic microenvironments such as hepatic steatosis or fibrosis. Chunggan syrup (CGX), a standardized 13-herbal mixture, has been prescribed to patients with chronic liver diseases, including fatty liver, inflammation and fibrotic change, based on preclinical and clinical evidence. Aim of the study: In the present study, we investigated anti-liver metastatic the effects of CGX in a murine colon carcinoma (MC38)-splenic injection mouse model. Materials and methods: C57BL/6N mice were administered with CGX (100, 200 or 400 mg/kg) for 14 days before or after MC38-splenic injection under normal and high-fat diet (HFD) fed conditions. Also, above experiment was repeated without MC38-splenic injection to explore underlying mechanism. Results: The number of tumor nodules and liver weight with tumors were sup-pressed by preadministration of CGX in both normal and HFD fed mice. Regarding its mechanisms, we found that CGX administration significantly activated epithelial-cadherin (E-cadherin), but decreased vascular endothelial-cadherin (VE-cadherin) in hepatic tissues under MC38-free conditions. In addition, CGX administration significantly reduced hepatic steatosis, via modulation of lipolytic and lipogenic molecules, including activated adenosine monophosphate activated protein kinase (AMPK) and peroxisome proliferator activated receptor-alpha (PPARα). Conclusion: The present data indicate that CGX exerts an anti-colon-liver metastatic property via modulation of hepatic lipid related microenvironments.

Succinum extracts inhibit microglial-derived neuroinflammation and depressive-like behaviors.

Microglia are emerging as important targets for the treatment of neuropsychiatric disorders. The phagocytic microglial phenotype and the resulting neuroinflammation lead to synaptic loss and neuronal cell death. To explore potential candidates that inhibit microglial hyperactivation, we first investigated ten candidate extracts of traditional Chinese medicine (TCM) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Among the candidates, Pinus spp. succinum extract (PSE) was superior; thus, we further investigated its pharmacological activity and underlying mechanisms both in vitro and in vivo. Pretreatment with PSE (10, 20, and 40 µg/ml) attenuated the increases in inflammatory factors (nitric oxide and tumor necrosis factor-α), translocation of nuclear factor-kappa B (NF-κB), and phenotypic transformations (phagocytic and migratory) in a dose-dependent manner. These inhibitory effects of PSE on microglia were supported by its regulatory effects on the CX3C chemokine receptor 1 (CX3CR1)/nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. In particular, intragastric administration of PSE (100 mg/kg) considerably improved sickness, anxiety, and depressive-like behaviors in mice subjected to chronic restraint stress (CRS). Our results suggest that PSE has strong antineuroinflammatory and antidepressant properties, and the underlying mechanisms may involve not only the regulation of NF-κB translocation but also the normalization of the CX3CR1/Nrf2 pathway.

Experimental Evidence for the Anti-Metastatic Action of Ginsenoside Rg3: A Systematic Review.

Cancer metastasis is the leading cause of death in cancer patients. Due to the limitations of conventional cancer treatment, such as chemotherapy, there is a need for novel therapeutics to prevent metastasis. Ginsenoside Rg3, a major active component of Panax ginseng C.A. Meyer, inhibits tumor growth and has the potential to prevent tumor metastasis. Herein, we systematically reviewed the anti-metastatic effects of Rg3 from experimental studies. We searched for articles in three research databases, MEDLINE (PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 2022. In total, 14 studies (eight animal and six in vitro) provide data on the anti-metastatic effects of Rg3 and the relevant mechanisms. The major anti-metastatic mechanisms of Rg3 involve cancer stemness, epithelial mesenchymal transition (EMT) behavior, and angiogenesis. Taken together, Rg3 would be one of the herbal resources in anti-metastatic drug developments through further well-designed investigations and clinical studies. Our review provides valuable reference data for Rg3-derived studies targeting tumor metastasis.

Incidence Rate of Bee Venom Acupuncture Related Anaphylaxis: A Systematic Review.

BACKGROUND: Bee venom acupuncture (BVA) is an effective treatment method for various diseases. Bee venom, however, can cause adverse effects, even rarely including life-threatening anaphylaxis, so safety-related evidence is required. In this study, we systematically estimated the incidence rate of anaphylaxis in response to BVA. METHODS: We searched eight databases (MEDLINE (Pubmed), EMBASE, Cochrane Central Register of Controlled, KISS, KMBASE, Koreamed, OASIS, and NDSL) and systematically reviewed the articles that met the inclusion/exclusion criteria. RESULTS: Among 225 potentially relevant articles, 49 were selected for this study. The overall incidence rate of anaphylaxis in response to BVA was 0.045% (95% CI 0.028-0.062). Women (0.083%, 95% CI 0.010-0.157) showed a higher incidence rate than men (0.019%, 95% CI -0.018 to 0.055), while the incidence for patients who had a skin test conducted (0.041%, 95% CI 0.011-0.072) was not significantly different compared to that obtained for patients for which there was no information about a skin test (0.047%, 95% CI 0.026-0.067). The publication year affected the incidence rate: it was highest before 1999 (1.099%, 95% CI -1.043 to 3.241), lower between 2000 and 2009 (0.049%, 95% CI 0.025-0.073), and lowest between 2010 and 2021 (0.037% 95% CI 0.014-0.060). CONCLUSIONS: In this study, we provide reference data about risk size and factors of BVA-related anaphylaxis, which is essentially required for BVA application in clinics.

Systematic Review for the Medical Applications of Meditation in Randomized Controlled Trials.

BACKGROUND: Meditation has been increasingly adapted for healthy populations and participants with diseases. Its beneficial effects are still challenging to determine due to the heterogeneity and methodological obstacles regarding medical applications. This study aimed to integrate the features of therapeutic meditation in randomized controlled trials (RCTs). METHODS: We conducted a systematic review of RCTs with meditation for populations with diseases using the PubMed database through June 2021. We analyzed the characteristics of the diseases/disorders, participants, measurements, and their overall benefits. RESULTS: Among a total of 4855 references, 104 RCTs were determined and mainly applied mindfulness-based (51 RCTs), yoga-based (32 RCTs), and transcendental meditation (14 RCTs) to 10,139 patient-participants. These RCTs were conducted for participants with a total of 45 kinds of disorders; the most frequent being cancer, followed by musculoskeletal and connective tissue diseases and affective mood disorder. Seven symptoms or signs were frequently assessed: depressive mood, feeling anxious, quality of life, stress, sleep, pain, and fatigue. The RCTs showed a higher ratio of positive outcomes for sleep (73.9%) and fatigue (68.4%). CONCLUSIONS: This systematic review produced the comprehensive features of RCTs for therapeutic meditation. These results will help physicians and researchers further study clinical adaptations in the future as reference data.

Yeokwisan, a Standardized Herbal Formula, Enhances Gastric Emptying via Modulation of the Ghrelin Pathway in a Loperamide-induced Functional Dyspepsia Mouse Model.

Background: Yeokwisan, a standardized herbal formula, has exhibited clinical benefit for patients suffering from refractory functional dyspepsia (FD) in Korea since 2016. However, data about the mechanism of action of this formula are yet not available. Aim of the study: To evaluate and explore the effects of Yeokwisan on gastric emptying, a major symptom of functional dyspepsia, and its underlying mechanisms of action using a mouse model. Materials and methods: BALB/C mice were pretreated with Yeokwisan (100, 200, and 400 mg/kg, po) or mosapride (3 mg/kg, po) for 5 days and then treated with loperamide (10 mg/kg, ip) after 20 h of fasting. A solution of 0.05% phenol red (500 µL) or diet of 5% charcoal (200 µL) was orally administered, followed by assessment of gastric emptying or intestinal transit. Plasma acyl-ghrelin (ELISA), C-kit (immunofluorescence and western blotting), nNOS (western blotting) and gastric contraction- and ghrelin-related gene/protein expression levels were examined in stomach and small intestine tissues. Results: Loperamide injection substantially delayed gastric emptying, while Yeokwisan pretreatment (especially 200 and 400 mg/kg Yeokwisan) significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of phenol red retained in the stomach (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The levels of plasma acyl-ghrelin and expression of gastric ghrelin-related genes, such as growth hormone secretagogue receptor (GHSR), ghrelin-O-acyltransferase (GOAT), adrenergic receptor ß1 (ADRB1) and somatostatin receptor (SSTR), were significantly normalized (p < 0.05 or 0.01) by Yeokwisan (400 mg/kg). Yeokwisan (400 mg/kg) significantly tempered the loperamide-induced alterations in the c-kit and nNOS levels (p < 0.01) as well as the expression of contraction- and ghrelin-related genes, such as 5-HT4 receptor (5-HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK), in the stomach, but not in the small intestine. Conclusion: The present results showed the clinical relevance of Yeokwisan, in treating FD, especially in promoting gastric emptying but not small intestinal transit. The main mechanisms corresponding to these effects may involve the modulation of the ghrelin pathway and activation of interstitial cells of Cajal in stomach tissue.

Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor ß (TGF-ß) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-ß expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.

Efficacy of a Traditional Herbal Formula, Banha-Sasim-Tang in Functional Dyspepsia Classified as Excess Pattern.

This study evaluated the efficacy and safety of Banha-sasim-tang (BST) in patients with functional dyspepsia (FD). BST (Banxia-xiexin-tang in traditional Chinese medicine and Hange-shashin-to in Kampo medicine) is traditionally prescribed for the treatment of dyspepsia with epigastric stiffness and gastric fullness in China, Japan, and Korea. Patients with FD were randomly administered an oral dose (10 g) of BST syrup or placebo, twice a day for 4 weeks. The primary outcome was the symptom checklist part of the Nepean dyspepsia index (NDI). The secondary outcomes were the quality of life (QoL) part of the NDI, functional dyspepsia-related QoL (FD-QoL), and visual analog scale (VAS). A total of 60 patients with FD were screened, and 50 were randomized into BST group (n = 25) and placebo group (n = 25). Two patients in the placebo group withdrew before the start of the treatment. Administration of BST syrup resulted in improvement in the symptom-related NDI score in the BST group compared with that in the control group; however, the difference was not significant. BST syrup significantly improved "fullness after eating" index of NDI at follow-up time point (2.88 ± 2.65 vs 4.78 ± 2.69, p = 0.0081). In the total score of the QoL section of the NDI and FD-QoL scales, there was no significant improvement in the BST group compared to that in the placebo group. With regard to improvement in overall FD symptoms, the VAS scale showed improvement in both groups, but the difference was not significant. Interestingly, follow-up investigation showed a significantly beneficial effect of BST on FD symptoms, when compared to placebo. Significant improvement observed in VAS score (39.60 ± 22.29 vs 52.17 ± 20.55, p = 0.048). This indicated that the effect of BST lasted even after the completion of the medication regimen. Overall, our data suggest that while BST showed no significant improvement in the symptom-related NDI score and the QoL related scores in NDI and FD-QoL after 4 weeks of treatment, it effectively improved the VAS score and fullness after eating-related symptoms in the follow-up visit. Clinical Trial Registration:https://cris.nih.go.kr; Identifier KCT 0002013.

Korean Red Ginseng Ameliorates Fatigue via Modulation of 5-HT and Corticosterone in a Sleep-Deprived Mouse Model.

Central fatigue, which is neuromuscular dysfunction associated with neurochemical alterations, is an important clinical issue related to pathologic fatigue. This study aimed to investigate the anti-central fatigue effect of Korean red ginseng (KRG) and its underlying mechanism. Male BALB/c mice (8 weeks old) were subjected to periodic sleep deprivation (SD) for 6 cycles (forced wakefulness for 2 days + 1 normal day per cycle). Simultaneously, the mice were administered KRG (0, 100, 200, or 400 mg/kg) or ascorbic acid (100 mg/kg). After all cycles, the rotarod and grip strength tests were performed, and then the changes regarding stress- and neurotransmitter-related parameters in serum and brain tissue were evaluated. Six cycles of SD notably deteriorated exercise performance in both the rotarod and grip strength tests, while KRG administration significantly ameliorated these alterations. KRG also significantly attenuated the SD-induced depletion of serum corticosterone. The levels of main neurotransmitters related to the sleep/wake cycle were markedly altered (serotonin was overproduced while dopamine levels were decreased) by SD, and KRG significantly attenuated these alterations through relevant molecules including brain-derived neurotropic factor and serotonin transporter. This study demonstrated the anti-fatigue effects of KRG in an SD mouse model, indicating the clinical relevance of KRG.

Interstitial Cells of Cajal: Potential Targets for Functional Dyspepsia Treatment Using Medicinal Natural Products.

INTRODUCTION: The pathophysiology of functional dyspepsia (FD) remains uncertain, but the interstitial cells of Cajal (ICCs), pacemakers that regulate gastrointestinal motility, are garnering attention as key modulators and therapeutic targets in FD. This review comprehensively discusses the involvement of ICCs in the pharmacologic actions of FD and as therapeutic targets for herbal products for FD. METHODS: A search of the literature was performed using PubMed by pairing "interstitial cells of Cajal" with "medicinal plant, herbal medicine, phytotherapy, flavonoids, or traditional Chinese medicine (TCM)." RESULTS: From the 55 articles screened in the initial survey, 34 articles met our study criteria. The search results showed that herbal products can directly depolarize ICCs to generate pacemaker potentials and increase the expression of c-kit and stem cell factors, helping to repair ICCs. Under certain pathological conditions, medicinal plants also protect ICCs from oxidative stress and/or inflammation-induced impairment. Two representative herbal decoctions (Banhasasim-tang, , and Yukgunja-tang, ) have been shown to modulate ICC functions by both clinical and preclinical data. CONCLUSION: This review strongly indicates the potential of herbal products to target ICCs and suggests that further ICC-based studies would be promising for the development of FD treatment agents.