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Arthritis is mainly a geriatric disease that causes joint pain and lowers the quality of life. This clinical trial was performed to evaluate the efficacy of Lilium lancifolium Thunb. (HY-LL) in alleviating joint pain. Six candidate anti-inflammatory components including regaloside A were identified in HY-LL using HPLC analysis. All participants were assigned to the HY-LL or the placebo group and took tablets twice a day for 12 weeks. As a result, pain VAS and K-WOMAC total scores significantly decreased after 12 weeks compared to the baseline in the HY-LL group, with a statistically significant difference between the two groups (p = 0.043, 0.043). The K-WOMAC sub-scores for pain and function showed a statistically significant improvement in the HY-LL group compared to the placebo group (p = 0.023, 0.047). Furthermore, the participants’ overall quality of life improved after 12 weeks of HY-LL consumption (p = 0.024). However, no significant differences were observed in the blood biomarkers. Therefore, this study demonstrated the positive effect of 12 weeks of HY-LL consumption on joint pain and quality of life.

Allium hookeri (AH) has been used as a nutritional and medicinal food in Asia for many years. Our previous studies have described its anti-diabetic, anti-obesity, and anti-inflammatory activities in animal models and prediabetes. This study investigated whether AH could improve glycemia by modulating insulin secretion in prediabetic subjects through an in-depth study. Eighty prediabetic subjects (100 ≤ fasting plasma glucose < 140 mg/dL) were randomly assigned to a placebo (n = 40) group or an ethanol AH extract (500 mg/day, n = 40) group for 12 weeks. Dietary intake and physical activity, blood glucose (an oral glucose tolerance test for 120 min), insulin (insulin response to oral glucose for 120 min), area under the curve (AUC) of glucose or insulin after oral glucose intake, insulin sensitivity markers, C-peptide, adiponectin, glycated hemoglobin A1c (HbA1c) levels, hematological tests (WBC, RBC, hemoglobin, hematocrit, and platelet count), blood biochemical parameters (ALP, AST, total bilirubin, total protein, albumin, gamma-GT, BUN, creatinine, LD, CK, and hs-CRP), and urine parameters (specific gravity and pH) were examined at both baseline and 12 weeks after supplementation with placebo or AH capsules. Fifty-eight participants (placebo group: 20 men and 10 women; AH group: 13 men and 15 women) completed the study. AH supplementation moderately reduced postprandial blood glucose at 60 min (−6.14 mg/dL, p = 0.061), postprandial insulin levels at 90 min (−16.69 µU/mL, p = 0.017), the glucose AUC at 90 min (−412.52 mg*min/dL, p = 0.021), as well as the insulin AUC at 90 min (−978.77 µU*min/mL, p = 0.021) and 120 min (−1426.41 µU*min/mL, p = 0.015) when compared with the placebo group. However, there were no effects of AH on dietary intake and physical activity; HOMA index; HbAlc; C-peptide; or adiponectin, hematological-, blood biochemical-, and urinary markers. To confirm the effects of AH extract on blood glucose insulin sensitivity, C57BL/6J or C57BL/KsJ-db/db mice were used (n = 8/group). Body weight, fasting plasma glucose level, lipid profiles, liver and renal function, pancreatic histology, and insulin immunoreactivity were assessed. In the diabetic db/db mice, hyperglycemia, which was accompanied by an increase in insulin secretion in diabetic mice, was significantly reduced by AH treatment, resulting in the alleviation of β-cell overcompensation and insulin resistance. We confirmed that AH supplementation can effectively control blood glucose and insulin levels by improving insulin sensitivity and may be a potential agent for glycemic control in subjects with prediabetes and type 2 diabetes mellitus.

Objectives: This study was designed to evaluate the efficacy and the safety of constitutional herbal tea for treating chronic fatigue with no diagnosed cause, which is called Mibyeong in Korea. Methods: Males and females with ages between 40 and 59 years who had complained of fatigue for 1 month consistently or for 6 months intermittently without a definite cause were recruited. At the same time, a Chalder fatigue scale (CFS) score of 19 was essential for participation in this study. Sixty five subjects completed the entire process, including blood tests and tests with medical devices. Five assessments of health status were accomplished over 8 weeks by using the CFS and the visual analogue scale (VAS). To ensure that the constitutional herbal tea was being safely used, we conducted and analyzed renal function and liver function tests. For the diagnosis of the Sasang constitution, the Sasang Constitutional Analysis Tool (SCAT) was used, and a specialist in Sasang constitutional medicine made the final diagnosis based on the SCAT result. Constitutional herbal tea was served four weeks after the first visit. The subjects took the constitutional herbal tea twice a day for one month. Results: The results are as follows: The CFS and the VAS scores were significantly improved for the subjects in the constitutional herbal tea. No abnormalities were found on the blood tests to evaluate safety after taking the constitutional herbal tea. The improvements in the CFS and the VAS scores due to the constitutional herbal tea had no significant differences according to the Sasang constitution. Conclusion: Constitutional herbal tea may be used to reduce fatigue and improve health and has no adverse effect on either the kidney or the liver.

Houttuynia cordata Thunb ( H cordata ), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata , suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells. FOXO3 transcription factors regulate target genes involved in apoptosis. H cordata significantly increased the mRNA and protein expression of HIF-1A and FOXO3 and stimulated MEF2A expression in addition to increased apoptosis in HepG2 cells within 24 hours. Therefore, we determined the potential role of FOXO3 on apoptosis and on H cordata –induced MEF2A in HepG2 cells. HIF-1A silencing by siRNA attenuated MEF2A and H cordata –mediated FOXO3 upregulation in HepG2 cells. Furthermore, H cordata –mediated MEF2A expression enhanced caspase-3 and caspase-7, which were abolished on silencing FOXO3 with siRNA. In addition, H cordata inhibited growth of human hepatocellular carcinoma xenografts in nude mice. Taken together, our results demonstrate that H cordata enhances HIF-1A/FOXO3 signaling, leading to MEF2A upregulation in HepG2 cells, and in parallel, it disturbs the expression of Bcl-2 family proteins (Bax, Bcl-2, and Bcl-xL), which results in apoptosis. Taken together, these findings demonstrate that H cordata promotes the activation of HIF-1A–FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular carcinoma cells and is, therefore, a promising candidate for antitumor drug development.

Objectives: Yamen is the fifteenth acupoint of the Governor Vessel Meridian (GV15). It is anatomically close to the medulla oblongata, so finding the safety depth of the acupoint is very important. However, few studies on the safety depth of GV15 have been done. Methods: This study tried to measure the safety depth of GV15 by using magnetic resonance imaging (MRI) scans and to analyze the factors affecting the safety depth through multiple regression analyses. This study was carried out for patients who had a brain MRI scan while visiting Jeonju Wonkwang Hospital, Korea. The shortest distance between the glabella and the occipital protuberance (DGO), the horizontal distance between the glabella and the back of the head (DGB) and the dangerous depth (DD) were measured from the sagittal views of the MRI images. The DD is the horizontal distance from the skin’s surface at GV15 to the spinal dura mater. Results: The model suggested that the safety depth (SD) was significantly associated with gender (β = 0.474, P < 0.0001), DGO (β = 0.272, P = 0.027), and BMI (β = 0.249, P = 0.005) and the combination of three variables can explain the SD, with R2 = 0.571 (Table 3) A longer SD was associated with males and with greater BMI and DGO. Conclusion: This study suggests that gender, BMI and DGO may be important factors when the SD of GV15 is considered clinically through a multiple regression analysis of GV15.

Objectives: To report the effect of cultivated wild ginseng pharmacopuncture on the lung cancer patient. Methods: Treatment of cultivated wild ginseng pharmacopuncture was conducted on the patient during 7 months. Pharmacopuncture therapy was done twice a week with a dosage of 2ml per each treatment. Computed Topography(CT) was performed to evaluate the therapeutic efficacy. Results: After the treatment of 7 months, chest CT revealed the mass size was decreased. Conclusions: This case provides us a possibility that cultivated wild ginseng pharmacopuncture offers potential benefits for lung cancer patient.

The purpose of this study is to evaluate the clinical effect of Hwangryunhaedok-tang Herbal-Acupuncture. Hwangryunhaedok-tang is used in all heating diseases. Chest Heating Sensation is a unique concept in Oriental Medicine. So we applied Hwangryunhaedok-tang Herbal-Acupuncture to treat the Chest Heating Sensation. We used DITI(Digital Infrared Thermographic Imaging) to estimate the temperatures of chest surface for the outcome assessment. We came to know that the chest surface temperatures were all reduced in both cases after Herbal-Acupuncture treatment. The reduced average temperature was 1.5℃ in case 1 and 0.9℃ in case 2. The above result indicates that Hwangryunhaedok-tang Herbal-Acupuncture treatment has an effect on Chest Heating Sensation, thus continuous Hwangryunhaedok-tang Herbal-Acupuncture study will be needed for more clinical applications.

The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed ‘CKDB-315’. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George’s Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is one of the major causes of death among females in worldwide. Cisplatin is a primary anti-cancer drug against ovarian cancer, but the recurrent tumors after treatment frequently show acquired chemoresistance. Extract of Scutellaria baicalensis (SbE) has been reported to have functional compounds including baicalin, which has anti-cancer effects. However, the anti-cancer effects of SbE in ovarian cancer and its underlying mechanisms are elusive. Methods: We investigated that the effects of SbE and/or cisplatin on cell death in the cisplatin sensitive ovarian cancer cell line A2780 (CSC) and the counterpart cell line that has cisplatin resistance (CRC). Molecular mechanisms of the effects, focusing on apoptosis and autophagy, were examined. Results: Treatment of cisplatin or SbE reduced cell viability significantly in CSC and too much lesser extent in CRC. Cisplatin-induced cell death in CSC was mediated by p53-induced apoptosis acompanied by expresson of damage- regulated autophagy modulator (DRAM). In CRC, decreased DRAM expression (p < 0.01) hindered p21-mediated cell death and contributed to cisplatin resistance. Treatment of SbE also induced cell death in CSC by p53-dependent apoptosis, not in CRC. Autophagy was not induced by neither cisplatin nor SbE. Intriguingly, the combinational treatment of SbE and cisplatin significantly decreased cell viability in CRC. The cell death was mediated by autophagy with increased expression of Atg5 and Atgl2 (p < 0.05), rather than p53-dependent pathway with repressed expression of p2l (p < 0.001) through HDAC1 activation. Conclusions: The combined treatment of SbE with cisplatin was effective in CRC, leading to cell death via Beclin1- independent autophagy, suggesting that SbE treatment in combination with cisplatin has a potential as a chemotherapeutic agent in cisplatin-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: The Paeonia lactiflora extract (PLE) has been reported to have neuroprotective effect against neurodegeneration that are induced by cellular stress such as oxidative stress. Its underlying mechanisms, however, remain unclear. In latest decades, emerging evidence has suggested that epigenetic mechanisms play a key role in gene regulation in response to the cellular stress. We investigated whether epigenetic modulation was involved in neuronal cell death by the neurotoxicant, 1-Methyl-4-phenylpyridinium (MPP+), and the neuroprotective effect of PLE. Methods: Differentiated SH-SY5Y, which is a well-established dopaminergic cell line model, was treated with 0~200 µg/ml PLE for 4 h prior to MPP+ treatment. The effect of PLE on cell viability was determined by MTT assays. Gene expression levels of oxidative stress responsive genes, such as Heme oxygenase 1 (HMOX1), and histone modifiers, such as histone acetyltransferases (HATs) and deacetylases (HDACs) were measured by quantitative RT PCR. In order to investigate the changes in epigenetic modifications, the acetylated lysine 9 (H3K9ac) and lysine 27 (H3K27ac) of Histone H3 were measured by western blot using histones extracted from the cells. Results: MPP+-induced cell death in SH-SY5Y cells was significantly reduced by PLE pretreatment in a dose-dependent manner, indicating the potent neuroprotective effects of PLE. It was accompanied by induced expression of H MOX1 MPP+ treatment increased the expression of HATs and consistently increased H3K9ac and H3K27ac of Histone H3. PLE pretreatment impeded the changes in H3K9ac and H3K27ac, coincided with increased expression of HDAC5 without changes in HAT expression. Conclusions: The results suggested that MPP+-induced cell death in the dopaminergic SH-SY5Y cells was related with transcriptional induction of HATs and increased histone H3 acetylation and that PLE might prevent the cells from MPP+-induced cell death via tempering histone H3 acetylation. [ABSTRACT FROM AUTHOR]

Multidrug resistance 1 (MDR1) is a gene that expresses P-glycoprotein (P-gp), a drug transporter protein. Genetic polymorphisms of MDR1 can be associated with Sasang constitutions because Sasang constitutional medicine (SCM) prescribes different drugs according to different constitutions. A Questionnaire for Sasang Constitution Classification II (QSCC II) was used to diagnose Sasang constitutions. Two hundred and seven healthy people whose Sasang constitutions had been identified were tested. Genotype analyses, restriction fragment length polymorphism (RFLP) and pyrosequencing were used in MDR1 C1236T, and in MDR1 G2677T/A and C3435T, respectively. Significant differences in MDR1 C1236T genotypes were found between So-yangin and So-eumin. MDR1 G2677T/A genotype also showed significant differences in allele distribution between So-yangin and Tae-eumin. So-yangin and So-eumin showed significant differences in the distribution of both 1236C-2677G-3435C and 1236T-2677G-3435T, haplotypes of MDR1. The genetic polymorphism of the MDR1 gene was thus shown to be an indicator that could distinguish So-yangin from other constitutions. [ABSTRACT FROM PUBLISHER]

Abstract Background This trial aimed to evaluate the anti-obesity effects and safety of Neoagaro-oligosaccharides (NAOs) in humans in a 16 week, randomized, double-blind, placebo-controlled clinical trial. Methods One hundred overweight or obese subjects with a body mass index of 23 to 34.9 kg/m2 and a percent body fat of > 25% for males or > 30% for females were enrolled. NAOs or placebo products were administered at 3 g (twice a day, four capsules once) each for 16 weeks. Efficacy and safety biomarkers were measured before and after intervention. Results After 16 weeks of intervention, the group administered with NAOs had statistically significant decreases in visceral fat area and visceral-subcutaneous fat area ratio compared to the placebo group. The NAOs group suppressed the increase in weight and BMI compared to the placebo group, which was significant between groups. High-density lipoprotein- cholesterol was increased in the group administered with NAOs, which showed a significant trend compared to the placebo group. Clinical changes were not observed for any safety biomarkers. Conclusions These results suggest that NAOs have a beneficial effect on obesity. Thus, NAOs could be used as an anti-obesity supplement without side effects. Trial registration cris.nih.go.kr: (KCT0006640, 07/10/2021).

This trial aimed to evaluate the effectiveness and safety of SGL 121(ginsenoside F2-enhanced mixture) in ameliorating human liver dysfunction. A total of 120 participants (46 ≤ alanine aminotransferase (ALT) ≤ 135 IU/L) were randomly distributed into two groups, the SGL 121 and placebo (crystalline cellulose) groups, which received 500 mg and 0 mg SGL 121 per day, respectively. After 12 weeks of intervention, gamma-glutamyl transferase (GGT) levels in the SGL 121 group were significantly decreased compared to the placebo group (p = 0.022). Similarly, ALT levels showed a tendency to decrease (p = 0.080). Regarding fatigue, the subscale scores (interference in daily living activities) and the total multidimensional fatigue scale (MFS) scores were lower in the SGL 121 group than in the placebo group (p = 0.009 and p = 0.046, respectively). No significant differences in adverse events were apparent between the two groups. The results of this study suggest that SGL 121 exerted beneficial effects on liver dysfunction by improving liver enzyme levels and fatigue.

Background: Cervical cancer is the fourth most common malignant tumor among women worldwide. This study aimed to evaluate the efficacy of Astragalus-containing Chinese herbal medicine (CHM) combined with chemotherapy (CT) for the treatment of cervical cancer.Methods: Ten electronic databases including PubMed, Cochrane Library, Embase, Korean databases, and Chinese medical databases, were systematically searched up to July 2020. All randomized controlled trials using Astragalus-containing CHM combined with CT to treat cervical cancer were included.Results: A total of 19 trials were included in the analysis. Compared with the control group, the Astragalus-containing CHM combined with CT group showed a significantly increased tumor response (complete and partial response (CR and PR)) (risk ratio [RR] = 1.25, 95% confidence interval [CI]: 1.17–1.33, p < 0.00001) and Karnofsky performance score (KPS) (standardized mean difference [SMD] = 1.81, 95% CI: 1.46–2.17, p < 0.00001). This group also displayed remarkably reduced CT toxicity.Conclusion: Our study suggests that Astragalus-containing CHM might be a potential option for cervical cancer to enhance the curative efficacy and reduce CT toxicity.

Cellular FLICE inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that associates with the signaling complex downstream of NF-κB, negatively interfering with apoptotic signaling. The role of c-FLIP downregulation by negative regulation of NF-κB signaling during apoptosis is poorly understood. Here, we demonstrate that NF-κB-mediated c-FLIPL negatively regulates the JNK signaling pathway, and that cordycepin treatment of human renal cancer cells leads to apoptosis induction through c-FLIPL inhibition. TNF-α-induced inflammatory microenvironments stimulated NF-κB signaling and the c-FLIP long form (c-FLIPL) in TK-10 cells. Specifically, cordycepin inhibited TNF-α-mediated NF-κB activation, which induced renal cancer cell apoptosis. Cordycepin downregulated GADD45B and c-FLIPL, but upregulated MKK7 and phospho-JNK, by preventing nuclear mobilization of NF-κB. Furthermore, siRNA-mediated knockdown of GADD45B in cordycepin-treated TK-10 cells considerably increased MKK7 compared to cordycepin alone. siRNA-mediated knockdown of c-FLIPL prevented TNF-α-induced JNK inactivation, whereas c-FLIPL overexpression inhibited cordycepin-mediated JNK activation. The JNK inhibitor SP600125 strongly inhibited Bax expression. In nude mice, cordycepin significantly decreased tumor volume. Taken together, the results indicate that cordycepin inhibits TNF-α-mediated NF-κB/GADD45B signaling, which activates the MKK7-JNK signaling pathway through inhibition of c-FLIPL expression, thus inducing TK-10 cell apoptosis.