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The purpose of this study was to evaluate the efficacy and safety of steamed ginger extract (GGE03) in subjects with mild knee osteoarthritis (OA). In total, 100 subjects were randomly assigned (1 : 1) to the GGE03 (0.48 g day-1 as GGE03) or placebo (0 g day-1 as GGE03) group and administered 1.6 g of the product for 12 weeks. Biomarkers were measured before and after intervention. At the efficacy endpoint, pain visual analog scale (VAS) Korean-Western Ontario and McMaster University Osteoarthritis Index (K-WOMAC; total scores, sub-scores) and patient global assessment (PGA) were found to be decreased in a statistically significantly manner in the GGE03 group compared to the placebo group. No significant changes were observed in any safety endpoint. These results suggest that GGE03 intake is useful as a functional food because it has beneficial effects in terms of improving joint pain as well as managing or preventing knee OA without side effects.
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Elaeocarpus sylvestris var. ellipticus (ES), which our research group had confirmed inhibits influenza A and SARS-CoV-2 viruses, was investigated to identify new potent and selective inhibitors of herpes simplex virus-1 (HSV-1) replication. To clarify the optimal condition for ES extract (ESE), ES was extracted at different concentrations of 0, 30, 50, 70, and 100%, to screen for its anti-HSV-1 effect. Among these ESE samples, ESE50 (50% concentration) exhibited the strongest inhibition of HSV-1 replication (EC50 23.2 µg/mL) while showing low cytotoxicity on host cells (IC50 342.8 µg/mL). The treatment of ESE50 clearly demonstrated a decrease in the expression of ICP0 in the lungs of HSV-1-infected BALB/c nude mice, compared to the MOCK group. Geraniin, which was isolated from ESE50 and analyzed using ESI-MS and 1D-(1H- and 13C-) and 2D-NMR, showed greater potency in inhibiting HSV-1 replication, as determined by the plaque reduction assay (EC50 8.3 µg/mL) and luciferase inhibition (EC50 36.9 µg/mL). The results demonstrate that ESE50 and geraniin show great potential as candidates for new drug discovery in the treatment of HSV-1 and related diseases.
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Cnidium monnieri fructus is widely used in traditional Oriental medicine for treating female genital disorders, male impotence, frigidity, and skin-related conditions in East Asia. However, the role of C. monnieri fructus extract (CMFE) in melanin synthesis is not well elucidated. This study aimed to investigate the anti-melanogenesis effect and mechanism of action of CMFE in α-MSH-stimulated B16F10 cells. Intracellular melanin content and tyrosinase activity were measured in α-MSH-stimulated B16F10 cells treated with various concentrations of CMFE (0.5-5 µg/mL). mRNA and protein levels of tyrosinase and MITF were evaluated using qRT-PCR and ting. CMFE's effect on the proteasomal degradation of tyrosinase was confirmed using a proteasomal degradation inhibitor, MG132. CMFE treatment activated p38, a protein associated with proteasomal degradation. Treatment with CMFE at up to 5 µg/mL showed no significant cytotoxicity. CMFE significantly reduced α-MSH-stimulated melanin production (43.29 ± 3.55% decrease, p < 0.05) and cellular tyrosinase activity (31.14 ± 3.15% decrease, p < 0.05). Although mRNA levels of MITF and tyrosinase increased, CMFE suppressed tyrosinase protein levels. The suppressive effect of CMFE on tyrosinase protein was blocked by MG132. CMFE inhibited melanogenesis by promoting the proteasome degradation of tyrosinase through p38 activation. These findings suggest that CMFE has the potential to be a natural whitening agent for inhibiting melanogenesis.
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The prevalence of metabolic syndrome is increasing globally due to behavioral and environmental changes. There are many therapeutic agents available for the treatment of chronic metabolic diseases, such as obesity and diabetes, but the data on their efficacy and safety are lacking. Through a pilot study by our group, Zingiber officinale rhizomes used as a spice and functional food were selected as an anti-obesity candidate. In this study, steam-processed ginger extract (GGE) was used and we compared its efficacy at alleviating metabolic syndrome-related symptoms with that of conventional ginger extract (GE). Compared with GE, GGE (25-100 µg/mL) had an increased antioxidant capacity and α-glucosidase inhibitory activity in vitro. GGE was better at suppressing the differentiation of 3T3-L1 adipocytes and lipid accumulation in HepG2 cells and promoting glucose utilization in C2C12 cells than GE. In 16-week high-fat-diet (HFD)-fed mice, GGE (100 and 200 mg/kg) improved biochemical profiles, including lipid status and liver function, to a greater extent than GE (200 mg/kg). The supplementation of HFD-fed mice with GGE (200 mg/kg) resulted in the downregulation of SREBP-1c and FAS gene expression in the liver. Collectively, our results indicate that GGE is a promising therapeutic for the treatment of obesity and metabolic syndrome.
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Fármacos Antiobesidade , Síndrome Metabólica , Zingiber officinale , Camundongos , Animais , Vapor , Síndrome Metabólica/tratamento farmacológico , Projetos Piloto , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Dieta Hiperlipídica , Fármacos Antiobesidade/farmacologia , Lipídeos/farmacologia , Camundongos Endogâmicos C57BL , Células 3T3-L1 , AdipogeniaRESUMO
This study aimed to identify substances including Lactobacillus rhamnosus vitaP1 (KACC 92054P) that alleviate hangover-induced emotional anxiety and liver damage. The association between emotional anxiety caused by hangover and the genes P2X4, P2X7, SLC6A4 was investigated. In vitro and in vivo analyses were conducted to assess the influence of free-panica on alcohol-induced upregulated gene expression. Additionally, the concentration of AST, ALT, alcohol, and acetaldehyde in blood was measured. Free-panica, consisting of five natural products (Phyllanthus amarus, Phoenix dactylifera, Vitis vinifera, Zingiber officinale, and Lactobacillus rhamnosus), were evaluated for their regulatory effects on genes involved in alcohol-induced emotional anxiety and liver damage. The combination of these natural products in free-panica successfully restored emotional anxiety, and the concentration of AST, ALT, alcohol, and acetaldehyde in blood to those of the normal control group. These findings support the potential development of free-panica as a health functional food or medicinal intervention for relieving hangover symptoms and protecting liver from alcohol consumption.
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BACKGROUND: Lung cancer is the predominant cause of cancer-related fatalities. This prompted our exploration into the anti-lung cancer efficacy of Labisia pumila, a species meticulously selected from the preliminary screening of 600 plants. METHODS: Through the strategic implementation of activity-guided fractionation, ardisiacrispin A (1) was isolated utilizing sequential column chromatography. Structural characterization was achieved employing various spectroscopic methods, including nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR). RESULTS: L. pumila 70% EtOH extract showed significant toxicity in A549 lung cancer cells, with an IC50 value of 57.04 ± 10.28 µg/mL, as well as decreased expression of oncogenes and induced apoptosis. Compound 1, ardisiacrispin A, induced a 50% cell death response in A549 cells at a concentration of 11.94 ± 1.14 µg/mL. CONCLUSIONS: The present study successfully investigated ardisiacrispin A extracted from L. pumila leaves, employing a comprehensive spectroscopic approach encompassing NMR, IR, and MS analyses. The anti-lung cancer efficacy of ardisiacrispin A and L. pumila extract was successfully demonstrated for the first time, to the best of our knowledge.
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Antibiotic-resistant bacteria and antibiotic resistance genes (ARGs) are pollutants of worldwide concern that seriously threaten public health and ecosystems. Machine learning (ML) prediction models have been applied to predict ARGs in beach waters. However, the existing studies were conducted at a single location and had low prediction performance. Moreover, ML models are "black boxes" that do not reveal their predictions' internal nuances and mechanisms. This lack of transparency and trust can result in serious consequences when using these models in high-stakes decisions. In this study, we developed a gradient boosted regression tree based (GBRT) ML model and then described its behavior using six explainable artificial intelligence (XAI) model-agnostic explanation methods. We used hydro-meteorological and qPCR data from the beaches in South Korea and Pakistan and developed ML prediction models for aac (6'-lb-cr), sul1, and tetX with 10-fold time-blocked cross-validation performances of 4.9, 2.06 and 4.4 root mean squared logarithmic error, respectively. We then analyzed the local and global behavior of the developed ML model using four interpretation methods. The developed ML models showed that water temperature, precipitation and tide are the most important predictors for prediction of ARGs at recreational beaches. We show that the model-agnostic interpretation methods not only explain the behavior of the ML model but also provide insights into the behavior of the ML model under new unseen conditions. Moreover, these post-processing techniques can be a debugging tool for ML-based modeling.
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Inteligência Artificial , Ecossistema , Bactérias/genética , Aprendizado de Máquina , Resistência Microbiana a Medicamentos/genéticaRESUMO
Monkeypox (MPX) was first reported in 1970 in humans and outbreaks were restricted and highly localised to endemic regions of western and central Africa. However, after the first reported case in the UK in early May, 2022, the pattern of epidemic spreading in the geographical regions was much larger compared to past, posing a risk MPX might become entrenched beyond endemic areas. This virus is less transmissible than SARS-CoV-2, as it transmitted mainly through personal, close, often skin-to-skin contact with infectious MPX rash, body fluids, or scabs from an individual with MPX. Infections usually present with chills, fever, fatigue, muscle aches, headache, sore throat, skin lesions, and lymphadenopathy. Currently, there are no antivirals approved for MPX. However, an antiviral drug called "tecovirimat," approved for the treatment of smallpox, has been made accessible to treat MPX. Moreover, to prevent MPX, there are two vaccines available which are approved by FDA: Bavarian Nordic JYNNEOS, and ACAM2000 vaccine. Contact tracing is absent in case of MPX outbreak and there is lack of information from the data systems in rapid manner. Additionally, test capacity needs to be increased. Like SARS-CoV-2, global MPX outbreak demand for vaccines far exceeds availability.
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The skin tissue of the scalp is unique from other skin tissues because it coexists with hair, and many differences in microbial composition have been confirmed. In scalp tissues, hair loss occurs due to a combination of internal and external factors, and several studies are being conducted to counteract this. However, not many studies have addressed hair loss from the perspective of the microbiome. In this study, subjects with hair loss and those with normal scalps were set as experimental and control groups, respectively. In the experimental group, hair loss had progressed, and there was a large difference in microbiome composition compared to the group with normal scalps. In particular, differences in Accumulibacter, Staphylococcus, and Corynebacterium were found. From Staphylococcus epidermidis Cicaria, two active components were isolated as a result of repeated column chromatography. Spectroscopic data led to the determination of chemical structures for adenosine and biotin. Fractions were obtained, and ex vivo tests were conducted using hair follicles derived from human scalp tissue. When the microbiome adenosine-treated group was compared to the control group, hair follicle length was increased, and hair root diameter was maintained during the experimental periods. In addition, the Cicaria culture medium and the microbial adenosine- and biotin-treated groups maintained the anagen phase, reducing progression to the catagen phase in the hair growth cycle. In conclusion, it was confirmed that the Cicaria culture medium and the microbial adenosine and biotin derived from the culture were effective in inhibiting hair loss.
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Microbiota , Staphylococcus epidermidis , Adenosina , Alopecia , Biotina , Folículo Piloso , HumanosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum piperitum has been used as a traditional Asian medicine to treat hypertension, stroke, bruise and muscle pain. It has been known to induce detoxification; affect anti-bacterial, anti-oxidant, and tyrosinase activity; inhibit osteosarcoma proliferation; anti-osteoarthritis inflammation. In this study, we aim to identify the therapeutic effect of Z. piperitum 90% EtOH extract (ZPE-LR) on rheumatoid arthritis. MATERIAL AND METHODS: We investigated the anti-rheumatoid arthritis and -immunomodulatory activities of the ZPE-LR in collagen-induced arthritic (CIA) mice, a rheumatoid arthritis animal model. In order to assess the analgesic effects of ZPE-LR in vivo, acetic acid injection, formaldehyde injection, hot plate model was used. The mechanism for anti-inflammatory activity of ZPE-LR was identified with LPS-stimulated Raw 264.7 cells. RESULTS: Pharmacologically, oral administration of ZPE-LR into CIA mice resulted in a significant and dose-dependent decrease in clinical arthritis score and paw swelling compared to untreated negative control. Pathologic examination showed that ZPE-LR prevented morphological change in cartilage and destruction of phalanges in CIA mice. This protective effect was associated with reduced pain, inflammatory mediators such as NO, TNF-α, IL-1ß, and IL-6, as well as COX-2 and iNOS expression. Furthermore, reduction of phosphor-ERK and BDNF indicates a novel rheumatoid arthritis-regulating mechanism by ZPE-LR treatment. CONCLUSIONS: These data suggest that the administration of ZPE-LR remarkably inhibited CIA progression and might be helpful in suppressing inflammation and pain in rheumatoid arthritis.
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Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Colágeno Tipo II , Relação Dose-Resposta a Droga , Inflamação/patologia , Mediadores da Inflamação/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos DBA , Mialgia/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Células RAW 264.7 , ZanthoxylumRESUMO
PURPOSE: Herpes zoster (HZ), or shingles, is a clinical syndrome resulting from the reactivation of latent varicella zoster virus (VZV) within the sensory ganglia. We evaluated the safety and tolerability of ES16001 (ethanol extract of Elaeocarpus sylvestris var. ellipticus), a novel inhibitor of varicella zoster virus reactivation in healthy adults. METHOD: Single-center, randomized, double-blind, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) studies were conducted in 20- to 45-year-old healthy adults without chronic disease. In the SAD study (n = 32), subjects randomly received a single oral dose of 240, 480, 960, or 1440 mg ES16001 or a placebo. In the MAD study (n = 16), subjects randomly received once daily doses of 480 or 960 mg ES16001 or a placebo for 5 days. The safety and tolerability of the drug were evaluated by monitoring participants' treatment emergent adverse events (TEAEs) and vital signs, electrocardiograms (ECGs), physical examinations, and clinical laboratory tests. RESULTS: In the SAD study, 11 adverse reactions were seen in 5 subjects, and in the MAD study, 8 adverse reactions were seen in 6 subjects. All adverse reactions were mild, and no serious adverse reactions occurred. The most common adverse reaction was an increase in alanine aminotransferase (ALT), but all test values were in the clinically non-significant range, and their clinical significance was judged to be small considering the fact that most of the test values returned to normal immediately after the end of drug administration. CONCLUSION: ES16001 has good safety and tolerability when administered both once and repeatedly to healthy subjects. Further research is needed to identify any possible drug-induced hepatotoxicity, which appears infrequently. Our findings provide a rationale for further clinical investigations of ES16001 for the prevention of HZ. TRIAL REGISTRATION: CRIS, KCT0006066. Registered 7 April 2021-Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/19071 ).
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Antivirais/efeitos adversos , Elaeocarpaceae/química , Herpes Zoster/tratamento farmacológico , Extratos Vegetais/efeitos adversos , Adulto , Alanina Transaminase/sangue , Antivirais/administração & dosagem , Antivirais/farmacologia , Antivirais/uso terapêutico , Tolerância a Medicamentos , Feminino , Herpes Zoster/prevenção & controle , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ativação Viral/efeitos dos fármacosRESUMO
In the present study, we investigated the effects of Galla Rhois (GR) on obesity and gene expression. We prepared a GR extract and various solvent fractions and evaluated the degree to which they inhibited adipocyte differentiation and adipogenesis in vitro. Among them, the GR ethyl acetate fraction (GE) had the lowest EC50 for adipocyte differentiation and adipogenesis and thus was selected for in vivo experiments. We induced obesity in C57BL/6 mice by providing them a high-fat diet (HFD). Then, GE (10-40 mg/kg) or orlistat (positive control, 4 mg/kg) was orally administered daily for six weeks. Mean body weights and weight gain were significantly lower in the GE40 group (40 mg/kg of GE) compared with the HFD group (p < 0.05). The most significant changes in serum glucose, total cholesterol, and triglyceride levels were confirmed in the GE40 group (p < 0.05). Epididymal fat was weighed and stained for body fat measurement, and significant differences were recorded from GE10 to GE40 (p < 0.05). Finally, 3T3-L1 pre-adipocytes were treated with GE, and cDNA from these cells was used for microarray analysis and qRT-PCR. Microarray analysis revealed 13 genes up-regulated and 21 genes down-regulated by GE. From the qRT-PCR analysis, we found that GE altered the mRNA expression of eosinophil peroxidase, glucose-dependent insulinotropic polypeptide receptor, and apolipoprotein B. Based on this study, we suggest that GR could be developed as an anti-obesity therapeutic agent.
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Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Produtos Biológicos/farmacologia , Obesidade/tratamento farmacológico , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipogenia/genética , Animais , Peso Corporal/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Dieta Hiperlipídica , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Aumento de Peso/efeitos dos fármacosRESUMO
N-acetyl-p-aminophenol (acetaminophen, APAP) is a well-known component of analgesic and antipyretic monotherapy products. However, exceeding the recommended dose can lead to serious injury to the liver. We conducted this study to determine the potential of Centella asiatica as a natural substance to protect against APAP-induced liver injury. When acute hepatotoxicity was induced in mice by APAP overdose, their liver weight decreased significantly (p < 0.05). However, mice treated with C. asiatica 50% ethanol extract (CA-HE50, 200 mg/kg) for a week before induction of hepatotoxicity by APAP had similar liver weights to those of mice in which hepatotoxicity was not induced. In particular, levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, which are biomarkers of liver injury, were significantly increased by APAP and dose-dependently decreased by CA-HE50 (p < 0.05). Glutathione and malondialdehyde, indicators of oxidative stress, were significantly changed by APAP and CA-HE50 (p < 0.05). In addition, hepatic necrosis and expression of genes encoding pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1ß, and IL-4) induced by APAP were inhibited by CA-HE50, and these results were dose-dependent. Through our in vivo studies, we found that CA-HE50 can help prevent APAP-induced hepatic tissue injury in BALB/c mice. Furthermore, CA-HE50 was effective at protecting RAW 264.7 cells from lipopolysaccharide-induced cytotoxicity and inhibiting the release of nitric oxide from these cells; in particular, asiaticoside was found to be a key component of CA-HE50 responsible for these effects. Therefore, we suggest that CA-HE50 has potential applications in functional health foods and drugs.
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Agrimonia pilosa (AP) and Rhus gall (RG) are traditional medicinal plants. The bioflavonoid composition standardized by HPLC analysis was named APRG64. Despite many studies reported to beneficial bioactivities of AP and RG, very limited range of toxicity tests have documented. So, we did experiment diversely on the toxicity tests of the substance APRG64. Genotoxicity (mammalian chromosomal aberration test, micronoucleus test) against APRG64, acute and sub-chronic toxicity test from rodent/non-rodent, and systemic safety pharmacology test were conducted. As a result of the test, genotoxicity against APRG64 was not observed. The NOAEL of rodents was confirmed as 2000 mg/kg/day and non-rodents was confirmed as 500 mg/kg/day. In addition, systemic safety pharmacological toxicity (effects on respiratory system, central nervous system, cardiovascular system) following administration of APRG64 was not observed. Finally, we accomplished ten potential toxicity tests and evaluated extensive safety of APRG64. Consequently, APRG64 may be a promising material for nutraceuticals and natural medicines.
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ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza is a traditional oriental medicine widely used for preventing and treating disorders of the liver, menstrual, and blood circulation systems. Osteoporosis, loss of bone with age and/or estrogen deficiency, is an important causal factor of fracture. S. miltiorrhiza extract has been used to alleviate dysmenorrhea and painful osteoarthritis. AIM OF THE STUDY: This study was performed to investigate the anti-osteoporosis activity of the Salvia miltiorrhiza ethanol extract (SME) in osteoporosis-prone conditions: ovariectomized (OVX) and naturally menopaused (NM) ICR mice. MATERIALS AND METHODS: Anti-osteoporotic potentials of SME (50-200 mg/kg) were evaluated based on bone mineral density using microCT analysis, biochemical parameters, and changes in the gene expressions involved in bone resorption. RESULTS: SME ameliorated the loss of trabecular bone both in OVX and NM mice. SME was effective in correcting aberrant levels of RANKL, osteocalcin, and BALP, which are critically involved in bone resorption. In addition, SME suppressed the expression of TRAF6 and NFATc1, which play a role in osteoclast differentiation. CONCLUSIONS: SME suppressed the loss of trabecular bone via suppressing bone resorption and osteoclast differentiation both in OVX and NM mice. SME is likely to be developed as a therapeutic agent for osteoporosis.
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Densidade Óssea/efeitos dos fármacos , Osteoporose Pós-Menopausa/prevenção & controle , Extratos Vegetais/farmacologia , Salvia miltiorrhiza/química , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/química , Feminino , Humanos , Menopausa , Camundongos , Camundongos Endogâmicos ICR , Osteoclastos/efeitos dos fármacos , Ovariectomia , Extratos Vegetais/administração & dosagemRESUMO
This trial aimed to determine the effect of a standardized Cynanchum wilfordii Radix extract (CWE) on the lipid profiles of individuals with elevated total cholesterol (T-Chol) using a double-blind randomized placebo-controlled design. Ninety-six Korean individuals with elevated T-Chol level (200-240 mg/dL) were recruited and randomly allocated to groups that received VasH300 (300 mg CWE/day, n = 32), VasH600 (600 mg CWE/day, n = 32), or a placebo (n = 32) groups. Primary outcomes included T-Chol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, and safety (adverse events, biochemical parameters, and hematological parameters). Data were compared using a one-way analysis of variance followed by Duncan's post-hoc tests (among groups) and paired t tests (within groups). Values for T-Chol and LDL-cholesterol were significantly reduced in the VasH300 and groups (VasH300: 4.0 and 6.4%, respectively; VasH600; 3.8 and 5.8% respectively; both p < .05) compared with the placebo group and were not dose-dependent. VasH300 significantly improved the lipid profiles of individuals with elevated T-Chol without any serious side effects. Daily supplementation with VasH might be an alternative strategy with which to modify cholesterol-related parameters, especially in individuals with elevated T-Chol levels.
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Cynanchum/química , Suplementos Nutricionais/análise , Hipercolesterolemia/tratamento farmacológico , Extratos Vegetais/química , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
Although the dried root of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae) is a popular medicinal plant in East Asia, there has been no systemic toxicological evaluation of a water extract of Saposhnikoviae Radix (SRE). In this experiment, an oral acute and 13-week subchronic toxicological evaluations of SRE (500-5,000 mg/ kg body weight) were performed in both sexes of Crl:CD(SD) rats. Based on the results from mortality, clinical signs, effects on body weight and organ weight, clinical biochemistry, hematology, urinalysis, and histopathology, significant acute, 4-week repeated dose range finding (DRF) and 13-week subchronic toxicity of SRE was not observed in either sex of rats; thus, the no observed adverse effect level (NOAEL) was 5,000 mg (kg/day). To identify anti-hyperuricemia potential of SRE, the suppressive effect of SRE was determined in mice challenged with potassium oxonate (PO; 250 mg/kg) via intraperitoneal injection for 8 days (each group; n = 7). SRE supplementation suppressed the uric acid level in urine through significant xanthine oxidase (XO) inhibitory activity. Kidney dysfunctions were observed in PO-challenged mice as evidenced by an increase in serum creatinine level. Whereas, SRE supplementation suppressed it in a dose-dependent manner. Collectively, SRE was safe up to 5,000 mg (kg/day) based on NOAEL found from acute and 13-week subchronic toxicological evaluations. SRE had anti-hyperuricemia effect and lowered the excessive level of uric acid, a potential factor for gout and kidney failure.
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Hepatitis C virus (HCV) infection is a significant health problem, with a worldwide prevalence of about 170 million. Recently, the development of direct acting antiviral (DAA) as a therapeutic agent for HCV has been rapidly increasing. However, DAA has a side effect and is costly. Therefore, it is still necessary to develop a therapeutic agent to treat HCV infection using products. Agrimonia pilosa (AP) and Galla rhois (RG) are traditional medicines and are known to display therapeutic activity on various diseases. Notably, they have been reported to have an anti-viral effect on HBV and influenza virus infections. It is expected that anti-viral activity will increase when two extracts are mixed. To investigate their anti-viral activity, the expression level of HCV Core 1b and NS5A was measured. Remarkably, AP, RG, and their mixed compound (APRG64) strongly inhibited the expression of viral proteins, which led us to identify their metabolites. A total of 14 metabolites were identified using liquid chromatography mass spectrometry (LC-MS). These metabolites were evaluated for their anti-HCV activity to identify active ingredients. In conclusion, our results unveiled that anti-HCV activity of Agrimonia pilosa and Galla rhois extract mixture could lead to the development of a novel therapy for HCV infection.
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Agrimonia/química , Antivirais/farmacologia , Produtos Biológicos/química , Hepacivirus/efeitos dos fármacos , Extratos Vegetais/farmacologia , Linhagem Celular , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Espectrometria de Massas/métodos , Testes de Sensibilidade MicrobianaRESUMO
Water hyacinth (Eichhornia crassipes) was used as a feedstock for ethanol production. The optimal hyper-thermal (HT) acid hydrolysis conditions were 8% (w/v) slurry content, 200 mM H2SO4, at 160 °C for 20 min and enzymatic saccharification for 48 h using an enzyme mixture of 20 units/mL Viscozyme L and Cellic C Tec2. After pretreatment, 48.2 g/L monosaccharides were obtained. Fermentation was conducted with wild and adapted Saccharomyces cerevisiae, Pichia stipitis and Candida lusitaniae. Wild-type S. cerevisiae, P. stipitis, and C. lusitaniae produced 15.3, 19.5 and 22.7 g/L of ethanol, respectively. Adaptive evolution was carried out on 6% (w/v) xylose. S. cerevisiae, P. sipitis and C. lusitaniae adapted to xylose produced 15.3, 21.4 and 23.9 g/L of ethanol with YEtOH of 0.32, 0.44 and 0.49, respectively. These results indicate that water hyacinth has potential as a feed stock for ethanol.
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Candida/crescimento & desenvolvimento , Eichhornia/química , Etanol/metabolismo , Temperatura Alta , Pichia/crescimento & desenvolvimento , Saccharomyces cerevisiae/crescimento & desenvolvimento , Xilose/química , HidróliseRESUMO
In this study, Ascophyllum nodosum was studied as a biomass for ethanol production. A. nodosum was degraded to monosaccharide by hyper-thermal (HT) acid hydrolysis and enzymatic saccharification and analyzed using response surface methodology (RSM) and the Michaelis-Menten equation. Maximum monosaccharide concentrations of 20.3 g/L glucose and 7.0 g/L mannitol were obtained from HT acid hydrolysis and enzymatic saccharification from 8%(w/v) of A. nodosum. Fermentation was conducted using Pichia stipitis and P. angophorae adapted to high mannitol concentrations. Neither non-adapted P. stipitis and P. angophorae nor adapted P. stipitis could ferment all mannitol in the A. nodosum hydrolysate. Adapted P. angophorae produced the highest ethanol concentration among various yeasts, with ethanol production reaching 13.6 g/L with an ethanol yield (YEtOH) of 0.50. Optimization of HT acid hydrolysis and enzymatic saccharification, in combination with the use of adapted yeast, could enhance overall A. nodosum ethanol fermentation yields.