Feasibility of Imaging Modalities Combined with a Silicone Gel-Filled Breast Implant in Korean Women.

With the occurrence of breast implant crises in Korea, it has become increasingly important to detect complications earlier in patients receiving a device. We have therefore combined imaging modalities with an implant-based augmentation mammaplasty. In this study, we assessed the short-term treatment outcomes and safety of the Motiva ErgonomixTM Round SilkSurface (Establishment Labs Holdings Inc., Alajuela, Costa Rica) in Korean women. A total of 87 women (n = 87) were included in the current study. We compared preoperative anthropometric measurements between the right side and the left side of the breast. Moreover, we also compared the thickness of the skin, subcutaneous tissue and the pectoralis major measured on a breast ultrasound preoperatively and 3 months postoperatively. Furthermore, we analyzed the incidences of postoperative complications and the cumulative complication-free survival. Preoperatively, there was a significant difference in the distance from the nipple to the midline between the left and right side of the breast (p = 0.000). Both sides of the breast showed significant differences in the thickness of the pectoralis major preoperatively and 3 months postoperatively (p = 0.000). A total of 11 cases (12.6%) of postoperative complications occurred; these included five cases (5.7%) of early seroma, two cases (2.3%) of infection, two cases (2.3%) of rippling, one case (1.1%) of hematoma and one case (1.1%) of capsular contracture. Time-to-events were estimated at 386.68 ± 27.79 days (95% CI 334.11-439.27). Here, we describe our experience with imaging modalities in combination with the Motiva ErgonomixTM Round SilkSurface in Korean women.

A Lignan from Alnus japonica Activates Myogenesis and Alleviates Dexamethasone-induced Myotube Atrophy.

To find inhibitors against skeletal muscle loss, we isolated a lignan compound ((-)-(2R,3R-1,4-O-diferuloylsecoisolarciresinol, DFS) from the stem of Alnus japonica. C2C12 myoblasts were treated with DFS during differentiation. To induce an in vitro atrophic condition, differentiated myotubes were treated with dexamethasone (a synthetic glucocorticoid). DFS (10 nM) increased expression levels of myogenic factors and the number of multi-nucleated myotubes expressing myosin heavy chain (MHC). The myogenic potential of DFS could be attributed to p38 MAPK activation. DFS also protected against dexamethasone-induced damage, showing increased expression of MHC and mammalian target of rapamycin (mTOR), a major anabolic factor. Under atrophic condition, the anti-myopathy effect of DFS was associated with inactivation of NF-κB signaling pathway and the subsequent suppression of muscle degradative E3 ligases and myostatin. DFS treatment also restored fast muscle fiber (type II a, II b, and II x), known to be susceptible to dexamethasone. These results indicate that DFS isolated from A. japonica can stimulate myogenesis via p38 MAPK activation and alleviate muscle atrophy by modulating the expression of genes associated with muscle protein anabolism/catabolism. Thus, we propose that DFS can be used as a pharmacological and nutraceutical agent for increasing muscle strength or protecting muscle loss.

The mixture of Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge. extract produces analgesic and anti-inflammatory effects in a collagen-induced arthritis mouse model.

Pain and inflammation typically manifest in patients with arthritis. It is now widely known that Agrimonia pilosa Ledeb (AP) and Salvia miltiorrhiza Bunge (SM) exert anti-inflammatory and antinociceptive effects. We have previously reported that the mixture extract (ME) from AP and SM produces antinociceptive and anti-inflammatory effects in gout arthritis and monoiodoacetate (MIA)-induced arthritis models. In the present study, we assessed the antinociceptive and anti-inflammatory effects on the collagen-induced arthritis (CIA) model. The antinociceptive effects in mice were measured using the von Frey test. ME administered once or for one week (once per day) once, and one-week reduced the pain in a dose-dependent manner (from 50 to 100 mg/kg) in the CIA-induced osteoarthritis (OA) model. ME treatment also reduced tumor necrosis factor (TNF)-α and C-reactive protein (CRP) levels in plasma and ankle tissues. Furthermore, COX-1, COX-2, NF-κB, TNF-α, and IL-6 expressions were attenuated after ME treatment. In most experiments, the antinociceptive and anti-inflammatory effects induced by ME treatment were almost equal to or slightly better than those induced by Perna canaliculus (PC) treatment, which was used as a positive control. Our results suggest that ME possesses antinociceptive and anti-inflammatory effects, indicating its potential as a therapeutic agent for arthritis treatment.

Luteolin-7-O-Glucuronide Improves Depression-like and Stress Coping Behaviors in Sleep Deprivation Stress Model by Activation of the BDNF Signaling.

Stress exposure is a major risk factor for mental disorders such as depression. Because of the limitations of classical antidepressants such as side effects, low efficacy, and difficulty in long-term use, new natural medicines and bioactive molecules from plants with greater safety and efficacy have recently attracted attention. Luteolin-7-O-glucuronide (L7Gn), a bioactive molecule present in Perilla frutescens, is known to alleviate severe inflammatory responses and oxidative stress in macrophages. However, its antistress and antidepressant effects have not been elucidated. The present study aims to explore the antidepressant the effect of L7Gn on stress-induced behaviors and the underlying mechanism in a mouse sleep deprivation (SD) model. L7Gn treatment improved depression-like and stress coping behaviors induced by SD stress, as confirmed by the tail suspension test and forced swimming test. Furthermore, L7Gn treatment reduced the blood corticosterone and hippocampal proinflammatory cytokine levels which were increased by SD stress, and L7Gn also increased the mRNA and protein levels of hippocampal brain-derived neurotrophic factor (BDNF) which were reduced by SD stress. Additionally, treatment with L7Gn resulted in increases in the phosphorylation of tropomyosin-related kinase B (TrkB), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB), which are downstream molecules of BDNF signaling. These findings suggest that L7Gn have therapeutic potential for SD-induced stress, via activating the BDNF signaling.

Antinociceptive activity of the Caesalpinia eriostachys Benth. ethanolic extract, fractions, and isolated compounds in mice.

Caesalpinia eriostachys Benth. (CE) is native to the Mexico and multiple effects have been observed from several plants belonging to the same family. CE was subjected to extraction with 95% ethanol, and the components were isolated through column chromatography. The structure of the compound was elucidated based on nuclear magnetic resonance (NMR) spectral data, electron ionization-mass (EI-MS) spectroscopy, and liquid chromatography-mass (LC-MS) spectroscopy. In vivo antinociceptive studies were conducted using writhing, 5% formalin, tail-flick, hot-plate, and von Frey filament tests. The ethanolic extract showed a significant effect in the acetic acid-induced pain model and nociceptive behavior in the formalin model (second phase). In hot-plate test and tail-flick test, the results showed no difference compared to the control group. The results suggest that the ethanolic extract may act peripherally to reduce pain. In the streptozotocin (STZ)-induced pain model, the ethanolic extract showed significant effect in the von Frey test model. The n-Hex (Hexane) and MC (Methylene chloride) fractions and isolated compounds, ellagic acid and agathisflavone, showed increased effect. Based on these results, we confirmed that the CE ethanolic extract and their compounds, ellagic acid and agathisflavone, have antinociceptive effect on diabetes mellitus-induced pain. Furthermore, the results of this study might be valuable for identifying compounds with antinociceptive activity from natural products.

Fermented Perilla frutescens Ameliorates Depression-like Behavior in Sleep-Deprivation-Induced Stress Model.

Excessive stress plays a critical role in the pathogenesis of mood disorders such as depression. Fermented natural products have recently attracted attention because of their health benefits. We evaluated the antidepressant-like efficacy of fermented Perilla frutescens (FPF), and its underlying mechanisms, in sleep deprivation (SD)-induced stress mice. SD-stressed mice revealed a remarkable increase in the immobility time in both forced swimming test and tail suspension test; this increase was ameliorated by treatment with FPF at doses of 100 and 150 mg/kg. FPF treatment also reduced the level of stress hormones such as corticosterone and adrenocorticotropic hormone. Additionally, FPF increased the levels of serotonin and dopamine which were significantly decreased in the brain tissues of SD-stressed mice. The increased expression of proinflammatory cytokines, such as TNF-α and IL1ß, and the decreased expression of brain-derived neurotrophic factor (BDNF) in the stressed mice were significantly reversed by FPF treatment. Furthermore, FPF also increased phosphorylation of tropomyosin receptor kinase B (TrkB), extracellular regulated protein kinase (ERK), and cAMP response element binding protein (CREB). Among the six components isolated from FPF, protocatechuic acid and luteolin-7-O-glucuronide exhibited significant antidepressant-like effects, suggesting that they are major active components. These findings suggest that FPF has therapeutic potential for SD-induced stress, by correcting dysfunction of hypothalamic-pituitary-adrenal axis and modulating the BDNF/TrkB/ERK/CREB signaling pathway.

The Anti-Inflammatory and the Antinociceptive Effects of Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge Extract.

Arthritis is a common condition that causes pain and inflammation in a joint. Previously, we reported that the mixture extract (ME) from Agrimonia pilosa Ledeb. (AP) and Salvia miltiorrhiza Bunge (SM) could ameliorate gout arthritis. In the present study, we aimed to investigate the potential anti-inflammatory and antinociceptive effects of ME and characterize the mechanism. We compared the anti-inflammatory and antinociceptive effects of a positive control, Perna canaliculus powder (PC). The results showed that one-off and one-week treatment of ME reduced the pain threshold in a dose-dependent manner (from 10 to 100 mg/kg) in the mono-iodoacetate (MIA)-induced osteoarthritis (OA) model. ME also reduced the plasma TNF-α, IL-6, and CRP levels. In LPS-stimulated RAW 264.7 cells, ME inhibited the release of NO, PGE2, LTB4, and IL-6, increased the phosphorylation of PPAR-γ protein, and downregulated TNF-α and MAPKs proteins expression in a concentration-dependent (from 1 to 100 µg/mL) manner. Furthermore, ME ameliorated the progression of ear edema in mice. In most of the experiments, ME-induced effects were almost equal to, or were higher than, PC-induced effects. Conclusions: The data presented here suggest that ME shows anti-inflammatory and antinociceptive activities, indicating ME may be a potential therapeutic for arthritis treatment.

Effect of Extract and Synthesized Derivatives of Isolated Compound from Symplocos chinensis f. Pilosa Ohwi on Neuropathic Pain in Mice.

Neuropathic pain is described as the "most terrible of all tortures that a nerve wound may inflict." The aim of the present study was to demonstrate the antinociceptive effect of Symplocos chinensis f. pilosa Ohwi water extract (SCW) and synthesized derivatives of the isolated compound. The antinociceptive effect was tested using the acetic acid-induced writhing and 5% formalin tests. Antinociceptive effects on neuropathic pain were evaluated using the von Frey test with chronic constriction injury (CCI) and surgical nerve injury (SNI) models and tail-flick test with a vincristine-induced pain model. An Ames test was also conducted. 5-hydroxymethylfurfural (5-HMF) was isolated and derivatives were synthesized with various acid groups. Among the plant water extracts, SCW showed significantly effective activity. Additionally, SCW presented antinociceptive effects in the neuropathic pain models. The SCW water fraction resulted in fewer writhes than the other fractions, and isolated 5-HMF was identified as an effective compound. Because 5-HMF revealed a positive response in the Ames test, derivatives were synthesized. Among the synthesized derivations, 5-succinoxymethylfurfural (5-SMF) showed the best effect in the neuropathic pain model. Our data suggest that SCW and the synthesized compound, 5-SMF, possess effective antinociceptive activity against neuropathic pain.

Four-Year Interim Results of the Safety of Augmentation Mammaplasty Using the Motiva Ergonomix™ Round SilkSurface: A Multicenter, Retrospective Study.

BACKGROUND: The Motiva Ergonomix™ Round SilkSurface (Establishment Labs Holdings Inc., Alajuela, Costa Rica) is the fifth generation of a silicone gel-filled breast implant that is commercially available in Korea. OBJECTIVES: In this study, we describe 4-year interim results of the safety of augmentation mammaplasty using the Motiva Ergonomix™ Round SilkSurface in Korean women. METHODS: In the current multicenter, retrospective study, we performed a retrospective review of medical records of a total of 1314 patients who received augmentation mammaplasty using the Motiva Ergonomix™ Round SilkSurface at our hospitals between September 1, 2016, and August 31, 2020. For safety assessment, we analyzed incidences of postoperative complications and Kaplan-Meier complication-free survival of the patients. RESULTS: We included a total of 873 patients (1746 breasts, mean age = 32.18 ± 6.88 years) in the current study. There were a total of 111 cases (12.70%) of postoperative complications; these include 24 cases (2.70%) of early seroma, 18 cases (2.10%) of hematoma, 18 cases (2.10%) of capsular contracture, 17 cases (1.95%) of dissatisfaction with shape, 16 cases (1.83%) of dissatisfaction with size, 9 cases (1.03%) of asymmetry, 6 cases (0.70%) of infection and 3 cases (0.34%) of rippling. Moreover, time-to-events were estimated at 918.34 ± 36.22 days (95% CI 845.44-988.52). CONCLUSIONS: Here, we describe 4-year interim results of the safety of augmentation mammaplasty using the Motiva Ergonomix™ Round SilkSurface in Korean women in a non-manufacturer-sponsored study. But further large-scale, prospective, multicenter studies with a long period of follow-up are warranted to establish our results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficient Separation of Phytochemicals from Muehlenbeckia volcanica (Benth.) Endl. by Polarity-Stepwise Elution Counter-Current Chromatography and Their Antioxidant, Antiglycation, and Aldose Reductase Inhibition Potentials.

Muehlenbeckia volcanica (Benth.) Endl. (M. volcanica), native to South America, is a traditional Peruvian medicinal plant that has multi-therapeutic properties; however, no phytochemicals have been identified from it yet. In this study, a five-step polarity-stepwise elution counter-current chromatography (CCC) was developed using methanol/water (1:5, v/v) as the stationary phase and different ratios of n-hexane, ethyl acetate, and n-butanol as mobile phases to separate the compounds from the 70% methanol extract of M. volcanica, by which six compounds with a wide range of polarities were separated in a single run of CCC and were identified as gallic acid, protocatechuic acid, 4,4'-dihydroxy-3,3'-imino-di-benzoic acid, rutin, quercitrin, and quercetin. Then, two compounds from the fractions of stepwise elution CCC were separated using conventional high-speed CCC, pH-zone-refining CCC, and preparative high-performance liquid chromatography, and identified as shikimic acid and miquelianin. These compounds are reported from M. volcanica for the first time. Notably, except for shikimic acid, all other compounds showed anti-diabetic potentials via antioxidant, antiglycation, and aldose reductase inhibition. The results suggest that the polarity-stepwise elution CCC can be used to efficiently separate or fractionate compounds with a wide range of polarities from natural products. Moreover, M. volcanica and its bioactive compounds are potent anti-diabetic agents.

Affinity measurement of ligands in Perilla frutescens extract towards α-glucosidase using affinity-based ultrafiltration-high-performance liquid chromatography.

It is a time-consuming and challenging task for affinity measurement of drug lead compounds from a plant extract because of its chemical complexity. In this research, a strategy of ultrafiltration-high-performance liquid chromatography (HPLC) was developed to directly measure dissociation constant (Kd) of compounds from natural product extract to target protein, and the Kd measurement of α-glucosidase ligands from the ethyl acetate fraction of Perilla frutescens (L.) Britt. (PFEA) was performed. The recovery value, binding degree, and signal-to-noise ratio of α-glucosidase ligands from PFEA were first determined according to the ultrafiltration-HPLC results; the Kd values were then calculated using proposed equilibrium. Finally, oleanolic acid (4) and apigenin (8) from PFEA were determined as the high affinity ligands for α-glucosidase, and their Kds were calculated as 44.9 µM and 88.5 µM, respectively, which agreed with the isothermal titration calorimetry analysis, kinetic analysis, and computer simulation of molecular docking. These results suggested that the proposed strategy is a simple and convenient method for the direct Kd determination of compounds from natural product extract without using any internal calibrants or internal standards.

Aldose Reductase, Protein Glycation Inhibitory and Antioxidant of Peruvian Medicinal Plants: the Case of Tanacetum parthenium L. and Its Constituents.

Diabetes complications, including peripheral neuropathy, cataracts, impaired wound healing, vascular damage, arterial wall stiffening and retinopathy diseases, are among the most predominant health problems facing the world's population today. The 22 Peruvian plant extracts were screened for their potential inhibitory activity against rat lens aldose reductase (RLAR) and DPPH radical scavenging. Among them, we have found that Tanacetum parthenium L. (TP) has the RLAR, AGEs and DPPH radical scavenging activities. We used for screening of active components in TP against RLAR and DPPH for the first time by ultrafiltration (UF) and DPPH. Compounds in TP were isolated by Sephadex column chromatography and their structures were established by MS and NMR spectroscopic analyses. Among the isolated compounds, ferulic acid, apigenin, luteolin-7-O-glucoside, luteolin, chrysosplenol, and kaempferol showed potent inhibition with IC50 values of 1.11-3.20 and 6.44-16.23 µM for RLAR and DPPH radical scavenging. Furthermore, these compounds suppressed sorbitol accumulation in rat lenses and ferulic acid, luteolin-7-O-glucoside, and luteolin have AGEs inhibitory activities with IC50 values of 3.43-6.73 µM. In summary, our study provides interesting plants for further study with respect to the treatment and prevention of diabetic complication of Peruvian plant and can provide the scientific base of the traditional uses.

Novel aldose reductase inhibitory and antioxidant chlorogenic acid derivatives obtained by heat treatment of chlorogenic acid and amino acids.

A heating model system (HMS) of chlorogenic acid (CGA) and 20 amino acids was produced by heating at 120 °C for 4 h and evaluated for in vitro antioxidant and aldose reductase (AR). The CGA-glutamic acid (GT) HMS showed high in vitro antiradical activity indicated by ABTS+ (82.37%) and DPPH radical scavenging (83.21%) as well as AR (83.21%) inhibition. The structure of the new compound was established by NMR spectroscopy, as methyl-3-(((E)-3-(3,4-dihydroxyphenyl)acryloyl)oxy)-4,5-dihydroxycyclohexanecarboxylate (1) and 4-O-caffeoylquinic acid (2) from the CGA-GT HMS. The IC50 values of compound 1 for ABTS+, DPPH and AR were 8.21, 56.97 and 3.68 µM, respectively. These activities were similar to or higher than those of known positive controls (5.49, 63.58 and 13.60 µM). We suggest that heat treatment generates novel CGA-GT HMS with increased antioxidant and AR inhibitory effects and contributes to the development of novel functional materials from CGA food products.

Anti-glycation, Carbonyl Trapping and Anti-inflammatory Activities of Chrysin Derivatives.

The aim of this study was searching anti-glycation, carbonyl trapping and anti-inflammatory activities of chrysin derivatives. The inhibitory effect of chrysin on advanced glycation end-products (AGEs) was investigated by trapping methylglyoxal (MGO), and MGO-conjugated adducts of chrysin were analyzed using LC-MS/MS. The mono- or di-MGO-conjugated adducts of chrysin were present at 63.86 and 29.69% upon 48 h of incubation at a chrysin:MGO ratio of 1:10. The MGO adducted positions on chrysin were at carbon 6 or 6 & 8 in the A ring by classic aldol condensation. To provide applicable knowledge for developing chrysin derivatives as AGE inhibitors, we synthesized several O-alkyl or ester derivatives of chrysin and compared their AGE formation inhibitory, anti-inflammatory, and water solubility characteristics. The results showed that 5,7-di-O-acetylchrysin possessed higher AGE inhibitory and water solubility qualities than original chrysin, and retained the anti-inflammation activity. These results suggested that 5,7-di-O-acetylchrysin could be a potent functional food ingredient as an AGE inhibitor and anti-inflammatory agent, and promotes the development of the use of chrysin in functional foods.

Evaluation of Aldose Reductase, Protein Glycation, and Antioxidant Inhibitory Activities of Bioactive Flavonoids in Matricaria recutita L. and Their Structure-Activity Relationship.

The inhibitory activities of Matricaria recutita L. 70% methanol extract were evaluated by isolating and testing 10 of its compounds on rat lens aldose reductase (RLAR), advanced glycation end products (AGEs), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging. Among these compounds, apigenin-7-O-ß-D-glucoside, luteolin-7-O-ß-D-glucoside, apigenin-7-O-ß-D-glucuronide, luteolin-7-O-ß-D-glucuronide, 3,5-O-di-caffeoylquinic acid, apigenin, and luteolin showed potent inhibition, and their IC50 values in RLAR were 4.25, 1.12, 1.16, 0.85, 0.72, 1.72, and 1.42 µM, respectively. Furthermore, these compounds suppressed sorbitol accumulation in rat lens under high-glucose conditions, demonstrating their potential to prevent sorbitol accumulation ex vivo. Notably, luteolin-7-O-ß-D-glucuronide and luteolin showed antioxidative as well as AGE-inhibitory activities (IC50 values of these compounds in AGEs were 3.39 and 6.01 µM). These results suggest that the M. recutita extract and its constituents may be promising agents for use in the prevention or treatment of diabetic complications.

Anti-Nociceptive Effect and Standardization from Mixture of Agrimonia pilosa Ledeb and Salvia miltiorrhiza Bunge Extracts.

Agrimonia pilosa Ledeb has been previously reported to produce an anti-nociceptive effect in ICR mice in both tail-flick and hot-plate tests. Studies have shown that Salvia miltiorrhiza Bunge, also renowned in traditional Chinese medicine, is an effective anti-inflammatory treatment. Among the extraction solvents investigated, a 50% ethanol (EtOH) extract of A. pilosa produced the highest anti-nociceptive effect in monosodium uric acid-induced gout pain models and the greatest yield. The 80% EtOH extract of S. miltiorrhiza moderately inhibited lipopolysaccharide-induced nitric oxide release from RAW 264.7 murine macrophages and exhibited outstanding yield. The mixture of optimized A. pilosa and S. miltiorrhiza extracts were evaluated for enhanced anti-nociceptive effects in gout arthritis treatment. To control extract quality, four marker compounds were determined using an HPLC-DAD method. A 1:1 mixture of A. pilosa 50 and S. miltiorrhiza 80% EtOH extracts of produced better results than when the extracts were administered individually.

Antioxidant activity and inhibitory effects of 2-hydroxy-3-methylcyclopent-2-enone isolated from ribose-histidine Maillard reaction products on aldose reductase and tyrosinase.

This study aimed to better understand the functional properties of ribose and 20 amino acid Maillard reaction products (MRPs). The ABTS+ radical scavenging ability of the ribose-20 amino acid MRPs was evaluated. Among the MRPs, ribose-histidine MRPs (RH-MRPs) showed the highest inhibitory activities on the ABTS+ radical scavenging ability, aldose reductase (AR), and tyrosinase compared to other MRPs. Functional compounds with antioxidant and AR inhibitory activities have been recognized as an important strategy in the prevention and treatment of diabetic complications, and the search for tyrosinase inhibitors is important for the treatment of hyperpigmentation, development of skin-whitening agents, and use as preservatives in the food industry. On this basis, we sought to isolate and identify compounds with inhibitory activities against AR and tyrosinase. RH-MRPs were heated at 120 °C for 2 h and fractionated using four solvents: methylene chloride (MC), ethyl acetate, n-butanol, and water. The highest inhibitions were found in the MC fraction. The two compounds from this fraction were purified by silica gel column and preparative thin layer chromatography, and identified as 2-hydroxy-3-methylcyclopent-2-enone and furan-3-carboxylic acid. AR inhibition, tyrosinase inhibition, and ABTS+ scavenging (IC50) of 2-hydroxy-3-methylcyclopent-2-enone were 4.47, 721.91 and 9.81 µg mL-1, respectively. In this study, inhibitory effects of 2-hydroxy-3-methylcyclopent-2-enone isolated from RH-MRP were demonstrated on AR, tyrosinase, and its antioxidant activity for the first time. RH-MRP and its constituents can be developed as beneficial functional food sources and cosmetic materials and should be investigated further as potential functional food sources.

Antiobesity Effect of Astilbe chinensis Franch. et Savet. Extract through Regulation of Adipogenesis and AMP-Activated Protein Kinase Pathways in 3T3-L1 Adipocyte and High-Fat Diet-Induced C57BL/6N Obese Mice.

Astilbe chinensis Franch. et Savat. (AC) has been used in traditional medicine for the treatment of chronic bronchitis, arthralgia, and gastralgia. In this study, we investigated the antiobesity effect of AC extract on 3T3-L1 preadipocytes and high-fat-diet-fed C57BL/6N obese mice. We found that AC extracts dramatically decreased the lipid content of 3T3-L1 cells in a concentration-dependent manner without cytotoxicity. The action mechanism of AC extract was demonstrated to be the inhibition of lipid accumulation and dose-dependent decrease in the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPAR-γ), and sterol regulatory element-binding protein 1 (SREBP1). Furthermore, AC extract increased the mitochondrial phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), mitochondrial biogenesis, and lipolysis-related factors. In amice model of high-fat-diet-induced obesity, the mice administered AC extract experienced significant decrease of 64% in weight gain, 55% in insulin resistance index, 22% in plasma triglycerides (TG), 56% in total cholesterol (TC), and 21% in nonesterified fatty acid (NEFA) levels compared with those in the high-fat diet-fed control mice. Collectively, these results indicated that AC extract exerted antiobesogenic activity through the modulation of the AMPK signaling pathway, inhibition of adipogenesis, decreased lipid content, and reduced adipocyte size.

An in vitro affinity-based method for studying herb-drug interactions for direct identification of cytochrome P450 1A2, 3A4, and 2C9 specific ligands from herbal extracts using ultrafiltration-high performance liquid chromatography.

A novel in vitro strategy for affinity-based ultrafiltration-high performance liquid chromatography (HPLC) was developed for the direct identification of cytochrome P450 (CYP) 1A2, 3A4, and 2C9 specific ligands from Danshen extracts, in which human liver microsome (HLM) was used as the source of CYP enzymes. The Danshen extract was incubated without HLM, with HLM, or with HLM where the active site of the target enzyme was blocked with a specific competitive probe before ultrafiltration to isolate ligand-enzyme complexes from unbound compounds. Subsequently, HPLC analysis was performed on the released ligands from the complexes. α-Naphthoflavone, ketoconazole, and sulfaphenazole were used as specific competitive probes for CYP1A2, 3A4, and 2C9, respectively. The signal-to-noise ratio (S/N) and specific-signal-to-noise ratio (S-S/N) of each compound were calculated using the obtained peak areas. Finally, two criteria were applied to select putative ligands for each specific target: (1) S/N > 1; (2) S-S/N > 0. Finally, dihydrotanshinone was identified as a specific ligand for CYP1A2 and tanshinone I, cryptotanshinone, and tanshinone IIA were identified as specific ligands for CYP1A2, 2C9, and 3A4. It was demonstrated that the newly developed method can be used to rapidly and directly detect specific ligands from natural product extracts in multi-target systems.

Screening In Vitro Targets Related to Diabetes in Herbal Extracts from Peru: Identification of Active Compounds in Hypericum laricifolium Juss. by Offline High-Performance Liquid Chromatography.

This study investigates in vitro targets related to diabetes in 30 herbal extracts from Peru, for the first time, using α-glucosidase, aldose reductase (AR) inhibitory assays and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging assays. Among the 30 herbal extracts, Hypericum laricifolium Juss. (HL) was the herb which showed more than 50% inhibition in all assays, presenting 97.2 ± 2.0%, 56.9 ± 5.6%, 81.9 ± 2.5%, and 58.8 ± 4.6% inhibition for the α-glucosidase, AR, DPPH, and ABTS assays, respectively. Finally, six bioactive compounds, namely, protocatechuic acid, chlorogenic acid, caffeic acid, kaempferol 3-O-glucuronide, quercetin, and kaempferol were identified in HL by offline high-performance liquid chromatography (HPLC). Quercetin exhibited the strongest inhibition in all enzyme assays and the strongest antioxidant activity. The results suggest that HL shows great potential for the complementary treatment of diabetes and its complications.