A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial for Evaluation of the Efficacy and Safety of DKB114 on Reduction of Uric Acid in Serum.

This study sought to investigate the antihyperuricemia efficacy and safety of DKB114 (a mixture of Chrysanthemum indicum Linn flower extract and Cinnamomum cassia extract) to evaluate its potential as a dietary supplement ingredient. This clinical trial was a randomized, 12-week, double-blind, placebo-controlled study. A total of 80 subjects (40 subjects with an intake of DKB114 and 40 subjects with that of placebo) who had asymptomatic hyperuricemia (7.0-9.0 mg/dL with serum uric acid) was randomly assigned. No significant difference between the DKB114 and placebo groups was observed in the amount of uric acid in serum after six weeks of intake. However, after 12 weeks of intake, the uric acid level in serum of subjects in the DKB114 group decreased by 0.58 ± 0.86 mg/dL and was 7.37 ± 0.92 mg/dL, whereas that in the placebo group decreased by 0.02 ± 0.93 mg/dL and was 7.67 ± 0.89 mg/dL, a significant difference (p = 0.0229). In the analysis of C-reactive protein (CRP) change, after 12 weeks of administration, the DKB114 group showed an increase of 0.05 ± 0.27 mg/dL (p = 0.3187), while the placebo group showed an increase of 0.10 ± 0.21 mg/dL (p = 0.0324), a statistically significant difference (p = 0.0443). In the analysis of amount of change in apoprotein B, after 12 weeks of administration, the DKB114 group decreased by 4.75 ± 16.69 mg/dL (p = 0.1175), and the placebo group increased by 3.13 ± 12.64 mg/dL (p = 0.2187), a statistically significant difference between the administration groups (p = 0.0189). In the clinical pathology test, vital signs and weight measurement, and electrocardiogram test conducted for safety evaluation, no clinically significant difference was found between the ingestion groups, confirming the safety of DKB114. Therefore, it may have potential as a treatment for hyperuricemia and gout. We suggest that DKB114 as a beneficial and safe food ingredient for individuals with high serum uric acid. Trial registration (CRIS.NIH. go. Kr): KCT0002840.

Anti-Obesity Effect of DKB-117 through the Inhibition of Pancreatic Lipase and α-Amylase Activity.

This study sought to evaluate the effects of Phaseolus multiflorus var. albus Bailey extract (PM extract) and Pleurotus eryngii var. ferulae extract (PF extract) on the inhibition of digestive enzymes and to confirm the anti-obesity effect of DKB-117 (a mixture of PM extract and PF extract) in digestive enzyme inhibition in a mouse model of obesity induced by a high-fat diet. In in vitro studies, PM extract and PF extract have increased dose-dependent inhibitory activity on α-amylase (Inhibitory concentration (IC50 value: 6.13 mg/mL)) and pancreatic lipase (IC50 value; 1.68 mg/mL), respectively. High-fat diet-induced obese mice were orally administered DKB-117 extracts at concentrations of 100, 200, and 300 mg/kg/day, while a positive control group was given orlistat (pancreatic lipase inhibitor) and Garcinia cambogia (inhibiting the enzymes needed to synthesize carbohydrates into fat) at concentrations of 40 and 200 mg/kg/day, respectively, for eight weeks. As a result, body weight, fat mass (total fat mass, abdominal fat, and subcutaneous fat) detected with microcomputed tomography, fat mass (abdominal fat and inguinal fat) after an autopsy, and liver triglyceride levels were decreased significantly in the DKB-117 (300 mg/kg/day) group compared to those in the HFD control group. Additionally, we obtained results indicating that the presence of carbohydrates was found more in the DKB-117-300 (300 mg/kg/day) group than in the HFD control group. These data clearly show that DKB-117 extracts are expected to have an anti-obesity effect through a complex mechanism that promotes carbohydrate release through the inhibition of carbohydrate-degrading enzymes while blocking lipid absorption through lipase inhibition.

Protective Mechanisms of Avocado Oil Extract Against Ototoxicity.

Despite the excellent antimicrobial activity of aminoglycoside antibiotics, permanent inner ear damage associated with the use of these drugs has resulted in the need to develop strategies to address the ototoxic risk given their widespread use. In a previous study, we showed that avocado oil protects ear hair cells from damage caused by neomycin. However, the detailed mechanism by which this protection occurs is still unclear. Here, we investigated the auditory cell-protective mechanism of enhanced functional avocado oil extract (DKB122). RNA sequencing followed by pathway analysis revealed that DKB122 has the potential to enhance the expression of detoxification and antioxidant genes associated with glutathione metabolism (Hmox4, Gsta4, Mgst1, and Abcc3) in HEI-OC1 cells. Additionally, DKB122 effectively decreased ROS levels, resulting in the inhibition of apoptosis in HEI-OC1 cells. The expression of the inflammatory genes that encode chemokines and interleukins was also downregulated by DKB122 treatment. Consistent with these results, DKB122 significantly inhibited p65 nuclear migration induced by TNF-α or LPS in HEI-OC1 cells and THP-1 cells and the expression of inflammatory chemokine and interleukin genes induced by TNF-α was significantly reduced. Moreover, DKB122 treatment increased LC3-II and decreased p62 in HEI-OC1 cells, suggesting that DKB122 increases autophagic flux. These results suggest that DKB122 has otoprotective effects attributable to its antioxidant activity, induction of antioxidant gene expression, anti-inflammatory activity, and autophagy activation.

Avocado Oil Extract Modulates Auditory Hair Cell Function through the Regulation of Amino Acid Biosynthesis Genes.

Sensorineural hearing loss (SNHL) is one of the most common causes of disability, affecting over 466 million people worldwide. However, prevention or therapy of SNHL has not been widely studied. Avocado oil has shown many health benefits but it has not yet been studied in regards to SNHL. Therefore, we aimed to investigate the efficacy of avocado oil on SNHL in vitro and in vivo and elucidate its mode of action. For the present study, we used enhanced functional avocado oil extract (DKB122). DKB122 led to recovery of otic hair cells in zebrafish after neomycin-induced otic cell damage. Also, DKB122 improved auditory sensory transmission function in a mouse model of noise induced-hearing loss and protected sensory hair cells in the cochlea. In addition, RNA sequencing was performed to elucidate the mechanism involved. KEGG pathway enrichment analysis of differentially expressed genes showed that DKB122 protected House Ear Institute-Organ of Corti 1 (HEI-OC1) cells against neomycin-related alterations in gene expression due to oxidative stress, cytokine production and protein synthesis.

Protective effects of Centella asiatica leaf extract on dimethylnitrosamine­induced liver injury in rats.

Oxidative stress in liver injury is a major pathogenetic factor in the progression of liver damage. Centella asiatica (L.) Urban, known in the United States as Gotu kola, is widely used as a traditional herbal medicine in Chinese or Indian Pennywort. The efficacy of Centella asiatica is comprehensive and is used as an anti­inflammatory agent, for memory improvement, for its antitumor activity and for treatment of gastric ulcers. The present study investigated the protective effects of Centella asiatica on dimethylnitrosamine (DMN)­induced liver injury in rats. The rats in the treatment groups were treated with Centella asiatica at either 100 or 200 mg/kg in distilled water (D.W) or with silymarin (200 mg/kg in D.W) by oral administration for 5 days daily following intraperitoneal injections of 30 mg/kg DMN. Centella asiatica significantly decreased the relative liver weights in the DMN­induced liver injury group, compared with the control. The assessment of liver histology showed that Centella asiatica significantly alleviated mass periportal ± bridging necrosis, intralobular degeneration and focal necrosis, with fibrosis of liver tissues. Additionally, Centella asiatica significantly decreased the level of malondialdehyde, significantly increased the levels of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase and catalase, and may have provided protection against the deleterious effects of reactive oxygen species. In addition, Centella asiatica significantly decreased inflammatory mediators, including interleukin (IL)­1ß, IL­2, IL­6, IL­10, IL­12, tumor necrosis factor­α, interferon­Î³ and granulocyte/macrophage colony­stimulating factor. These results suggested that Centella asiatica had hepatoprotective effects through increasing the levels of antioxidant enzymes and reducing the levels of inflammatory mediators in rats with DMN­induced liver injury. Therefore, Centella asiatica may be useful in preventing liver damage.

Centella asiatica Leaf Extract Protects Against Indomethacin-Induced Gastric Mucosal Injury in Rats.

The present study evaluated the protective effect of Centella asiatica (gotu kola) leaf extract (CAE) against indomethacin (IND)-induced gastric mucosal injury in rats. Gastric mucosal injury was induced by the oral administration of IND to the rats after a 24 h fast. CAE (50 or 250 mg/kg) or lansoprazole (a reference drug) was orally administrated 30 min before the IND administration, and 5 h later, the stomachs were removed to quantify the lesions. Orally administered CAE significantly reduced IND-induced gastric injury. The histopathological observations (hematoxylin-eosin and Periodic acid-Schiff staining) confirmed the protection against gastric mucosal injury. Also, CAE decreased the malondialdehyde content compared to the control group. Moreover, pretreatment with CAE resulted in a significant reduction in the elevated expression of tumor necrosis factor, Cyclooxygenase (COX)-2, and inducible nitric oxide synthase. These results suggested that CAE possesses gastroprotective effects against IND-induced gastric mucosal injury, which could be attributed to its ability to inhibit lipid peroxidation and stimulate gastric mucus secretion in the rat gastric mucosa.

Ameliorating Effects of Ethanol Extract of Fructus mume on Scopolamine-Induced Memory Impairment in Mice.

We previously reported that Fructus mume (F. mume) extract shows protective effects on memory impairments and anti-inflammatory effects induced by chronic cerebral hypoperfusion. Neurodegeneration of basal cholinergic neurons is also observed in the brain with chronic cerebral hypoperfusion. Therefore, the present study was conducted to examine whether F. mume extracts enhance cognitive function via the action of cholinergic neuron using a scopolamine-induced animal model of memory impairments. F. mume (50, 100, or 200 mg/kg) was administered to C57BL/6 mice for 14 days (days 1-14) and memory impairment was induced by scopolamine (1 mg/kg), a muscarinic receptor antagonist for 7 days (days 8-14). Spatial memory was assessed using Morris water maze and hippocampal level of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) was examined by ELISA and immunoblotting. Mice that received scopolamine alone showed impairments in acquisition and retention in Morris water maze task and increased activity of AChE in the hippocampus. Mice that received F. mume and scopolamine showed no scopolamine-induced memory impairment and increased activity of AChE. In addition, treatments of F. mume increased ChAT expression in the hippocampus. These results indicated that F. mume might enhance cognitive function via action of cholinergic neurons.