Hovenia dulcis Thunb. Fruit Extract Attenuates Psoriatic Skin Inflammation in Tumor Necrosis Factor-α-Stimulated Human Keratinocyte HaCaT Cells In Vitro.

Hovenia dulcis Thunb. fruit (HDF) is traditionally used for treating liver diseases and alcohol poisoning. The purpose of this study was to explore the effects of HDF on hyperproliferation, levels of inflammatory cytokines, and signaling mechanisms in human psoriatic keratinocyte HaCaT cells. HDF showed a preventive effect on tumor necrosis factor-α (TNF-α)-induced abnormal proliferation of psoriatic keratinocytes. Furthermore, real-time reverse transcription-PCR analysis showed that HDF suppressed the expressions of inflammatory cytokines; interleukin (IL)-1α and IL-1ß and chemokines; CCL-20 and CXCL-8 in TNF-α-induced HaCaT cells. Western blotting revealed that HDF suppressed the levels of phosphorylated IκB and STAT3 together with a decline in the levels of phosphorylated mitogen-activated protein kinases (MAPKs). These outcomes indicate that HDF prevents the abnormal proliferation of keratinocytes and modulates inflammatory responses by suppressing nuclear factor-κB (NF-κB) and STAT3 activation through downregulation of the MAPK signaling pathway in TNF-α-induced psoriatic keratinocytes. Our study demonstrates that HDF is prospective and beneficial for psoriatic skin inflammation.

Characterization of Alternaria porri causing onion purple blotch and its antifungal compound magnolol identified from Caryodaphnopsis baviensis.

Alternaria porri (Ellis) Clf. causes purple blotch disease on Allium plants which results in the reduction of crop yields and quality. In this study, to efficiently find natural antifungal compounds against A. porri, we optimized the culture condition for the spore production of A. porri and the disease development condition for an in vivo antifungal assay. From tested plant materials, the methanol extracts derived from ten plant species belonging to the families Cupressaceae, Fabaceae, Dipterocarpaceae, Apocynaceae, Lauraceae, and Melastomataceae were selected as potent antifungal agents against A. porri. In particular, the methanol extract of Caryodaphnopsis baviensis (Lec.) A.-Shaw completely inhibited the growth of A. porri at a concentration of 111 µg/ml. Based on chromatographic and spectroscopic analyses, a neolignan compound magnolol was identified as the antifungal compound of the C. baviensis methanol extract. Magnolol showed a significant inhibitory activity against the spore germination and mycelial growth of A. porri with IC50 values of 4.5 and 5.4 µg/ml, respectively. Furthermore, when magnolol was sprayed onto onion plants at a concentration of 500 µg/ml, it showed more than an 80% disease control efficacy for the purple blotch diseases. In terms of the antifungal mechanism of magnolol, we explored the in vitro inhibitory activity on individual oxidative phosphorylation complexes I-V, and the results showed that magnolol acts as multiple inhibitors of complexes I-V. Taken together, our results provide new insight into the potential of magnolol as an active ingredient with antifungal inhibitory action to control purple blotch on onions.

Effectiveness and safety of motion style acupuncture treatment of the pelvic joint for herniated lumbar disc with radiating pain: A prospective, observational pilot study.

CONTEXT: Conservative treatment is effective for treating and managing herniated lumbar disc with radiating leg pain. OBJECTIVES: To investigate the effects of motion style acupuncture treatment (MSAT) on the pelvic joint for this condition. DESIGN: This prospective observational study was a pilot study for a future randomized, controlled trial (RCT). SETTING: [masked for review]. PATIENTS/INTERVENTIONS: We enroled 40 patients and allocated them to two groups (both n = 20). Groups 1 and 2 received integrative Korean medicine treatment (KMT) and integrative KMT with MSAT for pelvic joint, respectively. Primary outcome was the Numeric Rating Scale (NRS) score for low back pain. Secondary outcomes were the Oswestry Disability Index (ODI), Visual analogue Scale (VAS), and EuroQol 5-Dimension-5-level (EQ-5D-5 L) scores. Efficacy was assessed by comparing the baseline and Day 4 results. Safety was assessed based on the frequency and severity of all adverse events. RESULTS: On Day 14, except for ODI in Group 1, the NRS, VAS, and EQ-5D-5 L scores showed significant improvements in both groups. On Day 90, both groups showed significant improvements in the NRS, ODI, and EQ-5D-5 L scores. There was a significant between-group difference in the NRS score on Day 7. On Day 14, Group 2 had a significantly lower VAS score for radiating leg pain than Group 1. Twelve patients reported adverse events associated with integrative KMT; however, there was no association with pelvic joint MSAT. CONCLUSION: Adding MSAT for pelvic joint to conventional integrative KMT may ameliorate radiating leg pain and improve the quality of life.

Chuna Manual Therapy vs Usual Care for Patients With Nonspecific Chronic Neck Pain: A Randomized Clinical Trial.

Importance: The incidence rate of neck pain is increasing worldwide, and the disease is associated with a high social burden. Manual therapy has been widely applied in the treatment of neck pain, but a high-quality, pragmatic randomized clinical trial for this treatment has not been conducted to date. Objective: This study aimed to compare the effectiveness of Chuna manual therapy with that of usual care for patients with chronic neck pain. Design, Setting, and Participants: A multicenter, assessor-blinded, pragmatic, randomized clinical trial was conducted between October 18, 2017, and June 28, 2019. This intention-to-treat analysis included 108 patients with chronic neck pain persisting for at least 3 months; patients were recruited from 5 hospitals in Korea. Interventions: Ten sessions (2 sessions per week for 5 weeks) of Chuna manual therapy or usual care (electrotherapy and oral medication) were conducted. Main Outcomes and Measures: The main outcome was the difference in visual analog scale (VAS) score for chronic neck pain between baseline and 5 weeks after randomization. Results: This randomized clinical trial recruited 108 patients (mean [SD] age, 38.4 [9.3] years; 73 women [67.6%]). Fifty-four patients were allocated to the Chuna therapy group, and 54 received usual care. At 5 weeks after randomization, manual therapy showed statistically superior results compared with usual care in terms of pain (difference in chronic neck pain VAS, 16.8 mm; 95% CI, 10.1-23.5 mm), function (difference in Neck Disability Index, 8.6%; 95% CI, 4.2%-13.1%), and quality of life (difference in the European Quality of Life-5 Dimension 5 Levels (EQ-5D-5L) scores, -0.07 points; 95% CI, -0.11 to -0.02 points). Regarding the 1-year cumulative values measured using area under the curve analyses, superior outcomes were attained in the manual therapy group in terms of the numerical rating scale for chronic neck pain (1.3 points; 95% CI, 0.5-2.0 points), Neck Disability Index (6.7%; 95% CI, 2.5%-10.9%), Neck Pain Questionnaire (7.4%; 95% CI, 2.3%-12.6%), and EQ-5D-5L scores (-0.03 points; -0.07 to 0.00 points). Conclusions and Relevance: In this randomized clinical trial, for patients with chronic neck pain, Chuna manual therapy was more effective than usual care in terms of pain and functional recovery at 5 weeks and 1 year after randomization. These results support the need to consider recommending manual therapies as primary care treatments for chronic neck pain. Trial Registration: ClinicalTrials.gov identifier: NCT03294785.

Genotoxicity of Water Extract from Bark-Removed Rhus verniciflua Stokes.

Rhus verniciflua Stokes (RVS) has been traditionally used as an herbal remedy to support the digestive functions in traditional Korean medicine. Additionally, the pharmacological effects of RVS, including antioxidative, antimicrobial and anticancer activities, have been well-reported. The genotoxicity of RVS, however, is elusive; thus, we evaluated the genotoxicity of RVS without bark (RVX) for safe application as a resource of functional food or a medical drug. To evaluate the genotoxicity of RVX, we used a bacterial reverse mutation test, chromosomal aberration test and comet assay, according to the "Organization for Economic Co-operation and Development" (OECD) guidelines. Briefly, for the reverse mutation test, samples (5000, 1667, 556, 185, 62 and 0 µg/plate of RVX or the positive control) were treated with a precultured strain (TA98, TA100, TA1535, TA1537 or WP2µvrA) with or without the S9 mix, in which RVX partially induced a reverse mutation in four bacterial strains. From the chromosomal aberration test and comet assay, the RVX samples (556, 185, 62, 20 and 0 µg/mL of RVX or the positive control) were treated in a Chinese hamster ovary cell line (CHO-K1 cells) in the conditions of the S9 mix absent or S9 mix present and in Chang liver cells and C2C12 myoblasts, respectively. No chromosomal aberrations in CHO-K1 or DNA damage in Chang liver cells and C2C12 myoblasts was observed. In conclusion, our results suggest the non-genotoxicity of RVX, which would be helpful as a reference for the safe application of bark-removed Rhus verniciflua Stokes as functional raw materials in the food, cosmetics or pharmaceutical fields.

Observational study on effectiveness and safety of integrative Korean medicine treatment for inpatients with sciatica due to lumbar intervertebral disc herniation.

We developed a protocol for a prospective registry to prove the effectiveness and safety of integrative Korean medicine treatment for inpatients with sciatica due to lumbar intervertebral disc herniation. We plan on recruiting 1000 inpatients receiving integrative Korean medicine treatment for lumbar intervertebral disc herniation at four spine specialized Korean medical hospitals. Patients enrolled in the registry will be evaluated at the time of hospitalization, 2 weeks after hospitalization, at discharge, and 6 months after hospitalization on predefined outcome variables such as intensity of back and leg pain, Oswestry Disability Index, quality of life, Patient Global Impression of Change, and adverse effects. The protocol of this study was registered in CRIS (KCT0003709) and Clinical trial gov (NCT03750591). This study is significant in that it cannot only be a basis for safety-related evidence of complementary alternative medicine, which has been lacking, but it also gives clear evidence on the effectiveness and validity of treatment effects such as accompaniment of stenosis, sex, age, and type of disc herniation.

Phenolic compounds and antioxidant activity in sweet potato after heat treatment.

BACKGROUND: The ability of heat treatment with a soaking solvent to increase soluble phenolic compounds due to the liberation or breakdown of the cell matrix has been investigated in various plants. This study investigated the changes in phenolic compounds and antioxidant activities of 12 sweet potato cultivars after heat treatment with distilled water or prethanol A. RESULTS: The highest total polyphenol content (134.67 mg gallic acid equivalents/g extract residue) and flavonoid content (65.43 mg catechin equivalents/g extract residue) was observed in the 'Jami' (JM) cultivar after heat treatment with prethanol A. Higher polyphenol and flavonoid content was generally observed in the purple sweet potato cultivars. Salicylic acid was the major phenolic acid, followed by protocatechuic acid or chlorogenic acid in almost all untreated sweet potato cultivars. The salicylic acid, vanillic acid, gallic acid, and caffeic acid content of the sweet potatoes increased after the heat treatment, whereas the protocatechuic acid and chlorogenic acid content decreased. The highest 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis(3-ethyl benzothiazoline)-6-sulfonic acid (ABTS) radical scavenging activity levels were observed in the JM cultivar subjected to heat treatment with prethanol A (48.15 and 80.00 mg TE/g extract residue, respectively). CONCLUSION: These results suggest that heat treatment with a soaking solvent is an efficient method to enhance the antioxidant characteristics of Korean sweet potato cultivars. © 2019 Society of Chemical Industry.

Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney.

The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months. Renal expressions of RAS components, as well as pro- and antioxidant enzymes, were measured and mouse kidneys were isolated for histopathology. Resveratrol-treated mice demonstrated better renal function and reduced albuminuria, with improved renal histologic findings. Resveratrol suppressed the Ang II/AT1R axis and enhanced the AT2R/Ang 1-7/MasR axis. Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2'-deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin was decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 was increased by resveratrol treatment. These findings demonstrate that resveratrol exerts protective effects on aging kidneys by reducing oxidative stress, inflammation, and fibrosis, through Ang II suppression and MasR activation.

Influence of organic acids and heat treatment on ginsenoside conversion.

BACKGROUND: Heat treatments are applied to ginseng products in order to improve physiological activities through the conversion of ginsenosides, which are key bioactive components. During heat treatment, organic acids can affect ginsenoside conversion. Therefore, the influence of organic acids during heat treatment should be considered. METHODS: Raw ginseng, crude saponin, and ginsenoside Rb1 standard with different organic acids were treated at 130°C, and the chemical components, including ginsenosides and organic acids, were analyzed. RESULTS: The organic acid content in raw ginseng was 5.55%. Organic acids were not detected in crude saponin that was not subjected to heat treatment, whereas organic acids were found in crude saponin subjected to heat treatment. Major ginsenosides (Rb1, Re, and Rg1) in ginseng and crude saponin were converted to minor ginsenosides at 130°C; the ginsenoside Rb1 standard was very stable in the absence of organic acids and was converted into minor ginsenosides in the presence of organic acids at high temperatures. CONCLUSION: The major factor affecting ginsenoside conversion was organic acids in ginseng. Therefore, the organic acid content as well as ginsenoside content and processing conditions should be considered important factors affecting the quality of ginseng products.

Antiangiogenic Herbal Composition Ob-X Reduces Abdominal Visceral Fat in Humans: A Randomized, Double-Blind, Placebo-Controlled Study.

Adipose tissue growth is angiogenesis-dependent, and angiogenesis inhibitors can regulate adipose tissue mass by cutting off the blood supply. We examined whether antiangiogenic herbal composition Ob-X can reduce fast-growing abdominal fat, especially visceral fat in humans by inhibiting angiogenesis. Eighty abdominally obese subjects (body mass index: 25-29.9 kg/m2, waist circumference: exceeding 90 cm for males and 85 cm for females) participated in a 12-week randomized, double-blind, placebo-controlled human study to evaluate the efficacy and safety of Ob-X. 690 mg of Ob-X was administered orally twice a day. The Ob-X group showed a noticeable reduction in visceral fat of 20.5% after the 12-week treatment as compared to baseline measured by computed tomography. The change in visceral fat in the Ob-X group was statistically significant as compared to the placebo group (p = 0.0495) and 1.9 times higher than in the placebo group. Therefore, angiogenesis inhibitor Ob-X has the potential to improve obesity-related metabolic syndrome by reducing dangerous visceral fat.

Mori Folium water extract alleviates articular cartilage damages and inflammatory responses in monosodium iodoacetate­induced osteoarthritis rats.

Mori folium, the leaf of Morus alba L. (Moraceae), has been widely used in traditional medicine for the treatment of various diseases. It has been recently reported that Mori folium possesses potential chondroprotective effects in interleukin (IL)­1ß­stimulated human chondrocytes; however, its protective and therapeutic potential against osteoarthritis (OA) in an animal model remains unclear. In this study, as part of an ongoing screening program to evaluate the anti­osteoarthritic potential of Mori folium, the protective effects of a water extract of Mori folium (MF) on cartilage degradation and inflammatory responses in a monosodium iodoacetate (MIA)­induced OA rat model were evaluated. The results demonstrated that administration of MF had a tendency to attenuate the damage to articular cartilage induced by MIA, as determined by knee joint swelling and the histological grade of OA. The elevated levels of matrix metalloproteinases­13 and two bio­markers for the diagnosis and progression of OA, such as the cartilage oligomeric matrix protein and C­telopeptide of type II collagen, were markedly ameliorated by MF administration in MIA­induced OA rats. In addition, MF significantly suppressed the production of pro­inflammatory cytokines, including IL­1ß, IL­6 and tumor necrosis factor­α. MF also effectively inhibited the expression of inducible nitric oxide (NO) synthase and cyclooxygenase­2, thus inhibiting the release of NO and prostaglandin E2. Although further work is required to fully understand the critical role and clinical usefulness, these findings indicate that MF may be a potential therapeutic option for the treatment of OA.

Diagnostic and prognostic relevance of CP2c and YY1 expression in hepatocellular carcinoma.

Recent studies have demonstrated an oncogenic role of the transcription factor (TF) CP2c in hepatocellular carcinoma (HCC) based on a strong correlation between CP2c expression, tumor grade, and aggressiveness. We recently found that CP2c directly interacts with another TF, YY1, which is also overexpressed in multiple cancers, including HCC. To evaluate if these proteins are co-regulated in carcinogenesis, we analyzed the expression of CP2c and YY1 in HCC (n = 136) tissues and examined the correlation between their expression and clinicopathological characteristics of HCC. Receiver operating characteristic analysis exhibited the validity of CP2c and nuclear YY1 expression as a diagnostic factor in HCC tissues. High expression of CP2c was significantly correlated with patient age, and higher histological grade, American Joint Committee on Cancer (AJCC) stage, and small and large vessel invasion in HCC tissues, whereas high expression of nuclear YY1 was significantly associated with higher AJCC stage and small vessel invasion. In univariate and multivariate analyses, high expression of CP2c was significantly correlated with disease free survival (DFS), indicating that CP2c expression is an independent prognostic factor for DFS in HCC patients. Patients with high expression of both CP2c and nuclear YY1 usually had a shorter median survival time and worse DFS prognosis than other patients, suggesting that combined detection of CP2c and nuclear YY1 is a useful prognostic marker in HCC patients.

Changes of phenolic-acids and vitamin E profiles on germinated rough rice (Oryza sativa L.) treated by high hydrostatic pressure.

This study was performed to investigate changes in the phenolic acid and vitamin E profiles of germinated rough rice following high hydrostatic pressure treatment (HPT). Rough rice was germinated at 37°C for two days and subjected to 0.1, 10, 30, 50, and 100MPa pressures for 24h. The total phenolic acid content increased from 85.37µg/g at 0.1MPa to 183.52µg/g at 100MPa. The highest gallic acid (4.29µg/g), catechin (9.55µg/g), p-coumaric acid (8.36µg/g), ferulic acid (14.99µg/g), salicylic acid (14.88µg/g), naringin (6.18µg/g), trans-cinnamic acid (45.23µg/g), and kaempferol (40.95µg/g) contents occurred in the sample treated at 100MPa after germination. The maximum vitamin E content of about 2.56 (BG) and 4.34mg/100g (AG) were achieved at 30MPa. These result suggest that a combination of HPT and germination are efficient method for enhancement of functionality in rough rice, and clarify the influence of HPT conditions on the vitamin E and phenolic acid in germination rough rice.

Efficacy of horse chestnut leaf extract ALH-L1005 as a matrix metalloproteinase inhibitor in ligature-induced periodontitis in canine model.

Matrix metalloproteinases (MMPs) are the main proteinases associated with periodontal tissue destruction and remodeling. Therefore, inhibition of host-derived MMPs has a key role in the prevention and reduction of periodontitis progression. Horse chestnut (Aesculus hippocastanum L.) extracts have been used as treatments for inflammatory disease, traditionally. This study assessed the clinical effect as a MMP inhibitor of horse chestnut leaf extract ALH-L1005 on periodontitis. ALH-L1005 was obtained from horse chestnut leaf and its MMP inhibitory activities estimated. Periodontitis was induced in beagles assigned to 4 groups and medicated for 6 weeks: low dose test (LT; ALH-L1005, 100 mg/kg/day), high dose test (HT; ALH-L1005, 200 mg/kg/day), positive control (PC; doxycycline, 10 mg/kg/day), or negative control (NC; placebo). Before and after administration, clinical indices of the teeth and MMP quantity in gingival tissues using zymography were measured. Clinical conditions of the LT, HT, and PC groups were significantly improved after 6 weeks. In zymographic evaluations, gelatinolytic and caseinolytic activities were suppressed in LT, HT, and PC groups but not in the NC group. The results suggest that ALH-L1005 could be an effective agent for clinical prevention and treatment of periodontitis by inhibiting the gelatinase and collagenase activities, which can detach periodontal ligaments from alveolar bone.

Palliative 5-fluorouracil and cisplatin chemotherapy in recurrent metastatic sebaceous carcinoma: Case report and literature review.

Sebaceous carcinoma is a rare malignant tumor of the skin. Although this tumor is not completely understood due to its rarity and the paucity of published reports, it is known to be an aggressive tumor with a high incidence in Asia. Sebaceous carcinomas occur preferentially in the periocular region and require attention not to miss the associated Muir-Torre syndrome. In the case of localized disease, a wide local excision with clear margin followed by adjuvant radiation therapy is usually considered the standard treatment strategy but there is no agreed treatment strategy or standard chemotherapeutic regimen for recurrent metastatic sebaceous carcinoma. We report here two cases of recurrent metastatic sebaceous carcinoma patients who responded to 5-fluorouracil and cisplatin combination chemotherapy, and review the literature. We suggest that 5-fluorouracil-cisplatin can be considered a feasible and effective treatment modality for recurrent sebaceous carcinoma.

Estimating functional connectivity using 2D tangential components in MEG sensor space.

BACKGROUND: Connectivity analysis in magnetoencephalography (MEG) sensor space is commonly used for the preliminary estimation of the functional relationship between cortical areas, but the results are difficult to interpret due to the field spread effect. To improve the interpretability of sensor-level connectivity analysis, we introduce and test a new connectivity measure based on imaginary coherence in this study. NEW METHOD: MEG signals from axial gradiometers are subjected to a wavelet transform at a frequency of interest, and are used to reconstruct 2D tangential magnetometer signals. The Euclidean norm of imaginary coherence values obtained from four available pairs between 2D tangential components at two locations is then used to estimate functional connectivity between sensor locations. The use of this new connectivity measure can be extended to 2D planar gradiometer signals or 3D source signals, where the functional relationship between multi-dimensional signals at different locations needs to be quantified as scalar variables. RESULTS: The proposed method was applied to measured and simulated auditory evoked MEG data. The Euclidean norm of imaginary coherence reliably eliminated the field spread effect and showed increased inter-hemispheric coherence between sensors above the left and the right auditory cortex. The significance of the results was tested by introducing variability in spontaneous brain activities in multi-trial evoked data simulations. COMPARISON WITH EXISTING METHOD: The distribution of imaginary coherence among axial gradiometer signals shows peaks not at the sensors directly above the neuronal current sources, but at sensors with field extreme.

The anti-angiogenic herbal extract from Melissa officinalis inhibits adipogenesis in 3T3-L1 adipocytes and suppresses adipocyte hypertrophy in high fat diet-induced obese C57BL/6J mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from M. officinalis L. (Labiatae; lemon balm) has an anti-angiogenic activity, we hypothesized that ALS-L1023 could inhibit adipogenesis and adipocyte hypertrophy. MATERIALS AND METHODS: ALS-L1023 was prepared by a two-step organic solvent fractionation from M. officinalis. The effects of ALS-L1023 on adipogenesis in 3T3-L1 adipocytes and adipocyte hypertrophy in high fat diet (HFD)-fed obese mice were measured using in vivo and in vitro approaches. RESULTS: ALS-L1023 inhibited angiogenesis in a dose-dependent manner in the HUVEC tube formation assay in vitro. Treatment of cells with ALS-L1023 inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or MDI differentiation mix. ALS-L1023 reduced mRNA expression of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9) in differentiated cells. In contrast, mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) increased. Protease activity, as measured by zymography, showed that activity of MMP-2 and MMP-9 decreased in ALS-L1023-treated cells. ALS-L1023 also inhibited MMP-2 and MMP-9 reporter gene expression in the presence of the MMP inducer phorbol 12-myristate 13-acetate. An in vivo study showed that ALS-L1023 not only decreased adipose tissue mass and adipocyte size, but also reduced mRNA levels of adipose tissue angiogenic factors and MMPs in HFD-fed obese mice. CONCLUSIONS: These results suggest that the anti-angiogenic herbal extract ALS-L1023 suppresses adipogenesis and adipocyte hypertrophy, and this effect may be mediated by inhibiting angiogenesis and MMP activities. Thus, by curbing adipogenesis, anti-angiogenic ALS-L1023 yields a possible therapeutic choice for the prevention and treatment of human obesity and its associated conditions.

Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.

Anthocyanin-rich Seoritae extract ameliorates renal lipotoxicity via activation of AMP-activated protein kinase in diabetic mice.

BACKGROUND: Anthocyanins are major constituents of food colours and have been reported to possess anti-diabetic activities for potential medicinal use. The precise role of anthocyanins in diabetic nephropathy is poorly understood. We investigated whether anthocyanin-rich Seoritae extract (SE) can potentially prevent oxidative stress and lipotoxicity, which are the main causes of renal damage in diabetic nephropathy, via activation of AMP-activated protein kinase (AMPK) and the consequent effects on its target molecules. METHODS: Four groups of male C57BLKS/J db/m and db/db mice were used. Diabetic and non-diabetic mice were orally administered 10 mg/kg body weight SE daily for 12 weeks, starting at 8 weeks of age. RESULTS: db/db mice treated with anthocyanins showed decreased albuminuria. Anthocyanins ameliorated intra-renal lipid concentrations in db/db mice with improvement of glomerular matrix expansion and inflammation, which was related to increased phosphorylation of AMPK and activation of peroxisome proliferator-activated receptor (PPAR) α and PPARγ, and inhibited the activity of acetyl-CoA carboxylase and sterol regulatory element-binding protein 1. Anthocyanins reversed diabetes-induced increases in renal apoptosis and oxidative stress. In cultured human glomerular endothelial cells, anthocyanins prevented high glucose-induced oxidative stress and apoptosis through activation of AMPK in the same manner. CONCLUSIONS: The results revealed that anthocyanins ameliorated diabetic nephropathy in db/db mice via phosphorylation of AMPK, the major energy-sensing enzyme, and the consequent effects on its target molecules, which appeared to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.