ABSTRACT
BACKGROUND: Lagerstroemia indica (L. indica) is reported to have diverse biological activities including anti-inflammatory, anti-cancer, neuro-regulatory, antidiabetic, and antioxidant activity. AIMS: The purpose of this study is to examine the potential of hair growth promotion and/or hair loss prevention by L. indica extract. PATIENTS/METHODS: The effects of L. indica on hair growth have been studied in human hair follicle dermal papillary (hHFDP) cells and follicular organ culture ex vivo by cell proliferation assay, PCR, western blot analysis, and reporter gene activity assay. Moreover, a clinical trial was conducted in healthy volunteers. RESULTS: Lagerstroemia indica significantly promoted the proliferation of hHFDP cells, which was associated with increased expression of TCF/LEF, VEGF, and Gli1 mRNA, and inhibition of STAT6 and Smad2 mRNA. Treatment with L. indica also increased the TCF/LEF reporter gene activity but downregulated the SBE- and STAT6-luciferase activities. The expression of total ß-catenin, CDK4, and CDK2 were elevated, while that of STAT6 and SMAD2/3 was suppressed upon treatment with L. indica. In human hair follicles organ culture, L. indica significantly inhibited hair follicular degeneration. The clinical trial showed a statistically significant rise in total hair count in test group (n = 24) after 24 weeks of applying the hair tonic enriched with L. indica (141.46 ± 21.27 number/cm2 , p < 0.05). CONCLUSION: We suggest that L. indica extract prevents hair loss as well as stimulate hair growth by regulating the Wnt-ß-catenin, JAK3-STAT6, and TGF-ß1-Smad signaling pathways, and may be further developed as a novel functional cosmetic for preventing hair loss.
Subject(s)
Lagerstroemia , beta Catenin , Alopecia/metabolism , Cell Proliferation , Cells, Cultured , Hair , Hair Follicle , Humans , Lagerstroemia/genetics , Lagerstroemia/metabolism , Plant Extracts/metabolism , Plant Extracts/pharmacology , RNA, Messenger/metabolism , STAT6 Transcription Factor/metabolism , STAT6 Transcription Factor/pharmacology , Wnt Signaling Pathway , beta Catenin/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum (C. indicum), a perennial plant, has long been used to treat inflammation-related disorders, such as pneumonia, hypertension, gastritis, and gastroenteritis. AIM OF THE STUDY: The inhibitory effect of C. indicum extract (C.I) on inflammasome activation was investigated to validate its potential in treating inflammation related disorders. MATERIALS AND METHODS: LPS-primed bone marrow-derived macrophages (BMDMs) were used to confirm the inhibitory effect of C.I on selective inflammasome activation in vitro. A monosodium urate (MSU)-induced murine peritonitis model was employed to study the effect of C.I in vivo. RESULTS: C.I inhibited activation of NLRP3 and AIM2 inflammasomes, leading to suppression of interleukin-1ß secretion in vitro. Further, C.I regulates the phosphorylation of apoptosis-associated speck-like protein containing a CARD (ASC), which could be the main contribution to attenuate these inflammasomes activation. C.I also suppressed secretion of pro-inflammatory cytokines and neutrophils recruitment in MSU-induced murine peritonitis model. CONCLUSIONS: This study provides scientific evidence substantiating the traditional use of C. indicum in the treatment of inflammatory diseases, including gout, which is induced by physiologically analogous cause to MSU-induced peritonitis.
Subject(s)
Anti-Inflammatory Agents/pharmacology , CARD Signaling Adaptor Proteins/metabolism , Chrysanthemum , DNA-Binding Proteins/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Peritonitis/metabolism , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents/therapeutic use , Female , Gout/drug therapy , Gout/metabolism , Gout Suppressants/pharmacology , Gout Suppressants/therapeutic use , MAP Kinase Kinase 4/metabolism , Mice, Inbred C57BL , Peritonitis/chemically induced , Peritonitis/drug therapy , Phosphorylation/drug effects , Plant Components, Aerial , Plant Extracts/therapeutic use , Uric AcidABSTRACT
Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1ß regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1ß levels, significantly (p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.
Subject(s)
Artemisia/chemistry , DNA-Binding Proteins/metabolism , Inflammasomes/drug effects , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Plant Extracts/therapeutic use , Animals , Cells, Cultured , DNA-Binding Proteins/genetics , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique , Interleukin-1beta/metabolism , Male , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Phosphorylation/drug effects , Plant Extracts/chemistry , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Arctium lappa (A. lappa), Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1ß secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS) generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1ß in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa, which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders.
ABSTRACT
Eucalyptus globulus Labill. (E. globulus, Myrtaceae) is used in Europe as a traditional folk remedy for inflammation-related disorders such as arthritis, diabetes, asthma, and gout. We investigated this study to evaluate the protective effects of E. globulus extract (EG) on inflammatory responses, and provide scientific and mechanistic evidence in in vitro and in vivo experimental models. LPS-stimulated murine bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of EG on inflammasome activation in vitro. Monosodium urate (MSU)-induced peritonitis was used to study the effect of EG in an in vivo murine model. EG suppressed IL-[Formula: see text] secretion via the regulation of apoptosis-associated speck-like proteins containing a CARD (ASC) oligomerization and caspase-1 maturation, leading to the inhibition of inflammasome activation. In the in vivo study, EG suppressed the MSU-induced peritonitis by attenuating interleukin (IL)-1[Formula: see text], providing scientific support for its traditional use in the treatment of inflammation-related disorders.
Subject(s)
Eucalyptus/chemistry , Inflammasomes/metabolism , Inflammation/drug therapy , Macrophages/drug effects , Peritonitis/drug therapy , Peritonitis/etiology , Phytotherapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Uric Acid/adverse effects , Animals , CARD Signaling Adaptor Proteins/metabolism , Caspase 1/metabolism , Cells, Cultured , Disease Models, Animal , Female , Inflammation/genetics , Interleukin-1beta/metabolism , Lipopolysaccharides/adverse effects , Mice, Inbred C57BLABSTRACT
CONTEXT: Allium senescens Linn. (Liliaceae) (ASL) has been traditionally used in Korea and other Asian countries for improving digestive and liver functions. OBJECTIVE: The anti-hepatofibrosis effect of ASL ethanol extract in cellular and experimental fibrosis rat model was investigated. MATERIALS AND METHODS: In vitro cell viability, cell cycle and apoptosis in hepatic stellate cells (HSCs) were studied using MTT assay, flow cytometry and Annexin V-FITC/PI staining. Thioacetamide (TAA; 200 mg/kg, i.p.)-induced liver fibrosis model using Sprague Dawley rats (n = 10) was developed in vivo by injecting TAA twice per week for 13 weeks. ASL (25 and 100 mg/kg) and silymarin (50 mg/kg) were administered through oral gavage 2 times per week from 7th to 13th week. Specific fibrotic-related biomarkers such as aspartate transaminase (AST), alanine transaminase (ALT), glutathione and hydroxyproline levels in serum were analyzed by spectrophotometer using commercial kits. Morphological, histopathological and fibrotic-related gene expression such as TGF-ß, Col1α1 and α-SMA in liver tissues was estimated by hematoxylin and eosin staining, Picrosirius red stain and quantitative real-time polymerase chain reaction, respectively. RESULTS: ASL (0.1 mg/mL) and silymarin (0.05 mg/mL) treatment induced apoptosis (4.06% and 8.67%) in activated HSC-T6 cells, compared with control group (3.7%). The altered morphology in activated primary HSCs was also restored by ASL (0.1 mg/mL) treatment. Further, ASL (100 and 25 mg/kg) ameliorated the TAA-induced altered fibrotic-related biomarkers, histopathological changes and fibrotic-related gene expression significantly (p < 0.05 â¼ p < 0.001). CONCLUSIONS: ASL can potentially be developed as a therapeutic agent in the treatment of hepatic fibrosis.
Subject(s)
Allium , Disease Models, Animal , Hepatic Stellate Cells/drug effects , Liver Cirrhosis/prevention & control , Plant Extracts/therapeutic use , Thioacetamide/toxicity , Animals , Cell Line , Cell Proliferation/drug effects , Cell Proliferation/physiology , Cell Survival/drug effects , Cell Survival/physiology , Cells, Cultured , Hepatic Stellate Cells/metabolism , Humans , Liver Cirrhosis/chemically induced , Liver Cirrhosis/metabolism , Male , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , Treatment OutcomeABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Actinidia arguta (A. arguta) has been widely used in Asian countries as a traditional medicinal herb to treat inflammation-related diseases, such as gastritis, bronchitis, and arthritis. AIM OF THE STUDY: The inhibitory effect of A. arguta leaves' extract (AA) on inflammasome activation was investigated to verify its traditional use in treating inflammation-related diseases. MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) primed by lipopolysaccharide (LPS) were activated by selective inflammasome stimulators, and the effect of AA on inflammasome activation was investigated. A monosodium urate crystal (MSU)-induced peritonitis mouse model was used to study the in vivo efficacy of AA on inflammasome activation. RESULTS: In the in vitro study, AA regulated NLRP3 ubiquitination and apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of NLRP3 inflammasome-mediated interleukin (IL)-1ß secretion. The inhibitory effect of AA on inflammasome activation in vitro was further confirmed in vivo using an MSU-induced peritonitis mouse model. CONCLUSION: AA provided scientific evidence, substantiating the traditional claims for its use in the treatment of inflammation and inflammation-mediated metabolic disorders, including gout.
Subject(s)
Actinidia , Anti-Inflammatory Agents/pharmacology , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents/therapeutic use , Caspase 1/metabolism , Cells, Cultured , Female , Interleukin-1beta/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice, Inbred C57BL , Peritonitis/chemically induced , Peritonitis/drug therapy , Peritonitis/metabolism , Plant Extracts/therapeutic use , Plant Leaves , Ubiquitination , Uric AcidABSTRACT
BACKGROUND: Glutamate (an endogenous excitatory neurotransmitter) at high concentrations contributes to the development of neurodegenerative diseases. Aronia melanocarpa (A. melanocarpa) berries contain anthocyanins and have high antioxidant activities. In this study, we evaluated whether A. melanocarpa berries could protect neuronal cells against glutamate-induced oxidative stress. METHOD: A. melanocarpa berries exerted a protective effect against cytotoxicity in HT22 mouse hippocampal cells by MTT assay. We evaluated oxidative stress parameters including ROS level, intracellular Ca2+ level, glutathione level and antioxidant enzyme activity in HT22 cells to elucidate the mechanism of its neuroprotective effect. RESULTS: A. melanocarpa berries decreased glutamate-induced death of HT22 cells. In addition, A. melanocarpa berries reduced ROS and intracellular Ca2+ levels. Glutathione level, antioxidant enzymes, glutathione reductase and glutathione peroxide activities and mitochondrial membrane potential were also increased in HT22 cells. CONCLUSION: These results suggested that A. melanocarpa berries protected HT22 cells by exerting an antioxidant effect.
Subject(s)
Glutamic Acid/adverse effects , Neurodegenerative Diseases/metabolism , Neurons/drug effects , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Photinia/chemistry , Plant Extracts/pharmacology , Animals , Cell Line, Tumor , Fruit/chemistry , Glutathione/metabolism , Humans , Mice , Neurodegenerative Diseases/drug therapy , Neurons/metabolism , Reactive Oxygen Species/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia (C. cassia, Lauraceae family), commonly used for treating dyspepsia, gastritis, blood circulation, and inflammatory diseases is considered as one of the 50 fundamental herbs in traditional Chinese medicine. AIM OF THE STUDY: The anti-inflammatory action of an ethanol extract of C. cassia (CA), and its underlying mechanisms were explored in both in vitro cellular and in vivo murine models. MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of CA on inflammasome activation. A lipopolysaccharide (LPS)-induced sepsis mouse model and a monosodium urate (MSU)-induced gout model were employed to study the effect of CA on in vivo efficacy. RESULTS: CA improved the survival rate in the LPS-induced septic shock mouse model and inhibited inflammasome activation including NLRP3, NLRC4, and AIM2, leading to suppression of interleukin-1ß secretion. Further, ASC oligomerization and its speck formation in cytosol were attenuated by CA treatment. Furthermore, CA improved both survival rate of LPS-induced septic shock and gout murine model. CONCLUSIONS: CA treatment significantly attenuated danger signals-induced inflammatory responses via regulation of inflammasome activation, substantiating the traditional claims of its use in the treatment of inflammation-related disorders.
Subject(s)
Cinnamomum aromaticum/chemistry , Drugs, Chinese Herbal/pharmacology , Inflammasomes/drug effects , Animals , Drugs, Chinese Herbal/chemistry , Gene Expression Regulation/drug effects , Gout , Lipopolysaccharides/toxicity , Macrophages/drug effects , Male , Mice , Mice, Inbred C57BL , Sepsis/chemically induced , Sepsis/drug therapyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Juniperus rigida Sieb. (J. rigida) is used for medicinal purposes in Asian countries to treat inflammation-related disorders, such as neuralgia, dropsy, and gout. AIM OF THE STUDY: The anti-inflammatory effects of J. rigida extract (JR) and its underlying mechanisms were explored both in in vitro cell lines and in vivo metabolic disease models. MATERIAL AND METHODS: Lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages were used to study the changes in inflammatory responses in vitro. Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of JR on inflammasome activation. The murine model for monosodium urate (MSU)-induced peritonitis and high-fat diet (HFD)-induced type 2 diabetes were employed to study the effect of JR on in vivo efficacy. RESULTS: JR suppressed the MSU-induced in vivo inflammatory response by attenuation of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α). In the in vitro study, JR suppressed IL-1ß secretion via regulation of apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of inflammasome activation. JR also inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide (NO), TNF-α, and IL-6 in RAW264.7 cells. The inhibitory effects of JR were mediated through the regulation of the TRIF-dependent signaling pathway from JAK1/STAT1 phosphorylation. Furthermore, JR showed inhibitory effects on HFD-induced type 2 diabetes in a mouse model through the regulation of blood glucose and serum IL-1ß. CONCLUSIONS: Our results indicate that JR attenuates both LPS-stimulated and danger-signal-induced inflammatory responses in macrophages via regulation of the key inflammatory mechanisms, providing scientific support for its traditional use in the treatment of various inflammation-related metabolic disorders.
Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Anti-Inflammatory Agents/pharmacology , Diabetes Mellitus, Experimental/prevention & control , Diabetes Mellitus, Type 2/prevention & control , Hypoglycemic Agents/pharmacology , Inflammasomes/drug effects , Inflammation/prevention & control , Juniperus/chemistry , Macrophages/drug effects , Peritonitis/prevention & control , Plant Extracts/pharmacology , Signal Transduction/drug effects , Animals , Anti-Inflammatory Agents/isolation & purification , Apoptosis Regulatory Proteins/metabolism , Blood Glucose/drug effects , Blood Glucose/metabolism , CARD Signaling Adaptor Proteins , Chromatography, High Pressure Liquid , Cytokines/metabolism , Diabetes Mellitus, Experimental/immunology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat , Dose-Response Relationship, Drug , Female , Hypoglycemic Agents/isolation & purification , Inflammasomes/immunology , Inflammasomes/metabolism , Inflammation/immunology , Inflammation/metabolism , Inflammation Mediators/metabolism , Janus Kinase 1/metabolism , Lipopolysaccharides/pharmacology , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Peritonitis/chemically induced , Peritonitis/immunology , Peritonitis/metabolism , Phosphorylation , Phytotherapy , Plant Extracts/isolation & purification , Plants, Medicinal , RAW 264.7 Cells , STAT1 Transcription Factor/metabolism , Uric AcidABSTRACT
Aronia melanocarpa (A. melanocarpa) berries are a fruit with a marked antioxidant effect. The objective of this study was to confirm the effect of A. melanocarpa berries extract against scopolamine-induced memory impairment in mice using the Morris water maze and passive avoidance test. Moreover, we determined a possible mechanism of the cognitive-enhancing effect involving AChE activity and BDNF and p-CREB expression in the hippocampus of mice. A. melanocarpa berries extract attenuated the learning and memory impairment induced by scopolamine in the Morris water maze (79.3 ± 0.8 s of 200 mg/kg and 64.4 ± 10.7 s of 400 mg/kg on day 4) and passive avoidance tests (46.0 ± 41.1 s of 200 mg/kg and 25.6 ± 18.7 s of 400 mg/kg). A. melanocarpa berries extract reduced the acetylcholinesterase level in the hippocampus of scopolamine-injected mice and increased BDNF and p-CREB expression in the hippocampus. The major compound, cyanidin-3-O-galactoside, also reversed memory impairment. These results showed that A. melanocarpa berries extract improved memory impairment by inhibiting AChE and increasing BDNF and p-CREB expression, and cyanidin-3-O-galactoside may be responsible for the effect of A. melanocarpa berries extract.
ABSTRACT
This study provides the scientific basis for the inhibitory effect of the aerial parts of Cichorium intybus Linn. (C. intybus) on the activation of the NLRP3 inflammasome in vitro and on high-fat diet (HFD)-induced type-2 diabetes (T2D). Lipopolysaccharide (LPS)-primed bone marrow-derived macrophages were used to study the effects methanolic extract of C. intybus leaf (CI) on inflammasome activation. An insulin resistance model (mice fed a HFD) was used to study the in vivo effect of CI on T2D. CI attenuated interleukin-1ß (IL-1ß) secretion by inhibiting the activation of the NLRP3 inflammasome in mouse bone marrow macrophages. The CI treatment attenuated the intracellular movement of NLRP3 in Triton X-100 insoluble fraction, without affecting the expression of other NLRP3 inflammasome-related proteins. Attenuated IL-1ß secretion may improve glucose metabolism in the HFD-fed insulin resistance mouse model. CI also attenuated the infiltration of M1 macrophages and increased the M2 macrophage population in white adipose tissue. Collectively, our data showed that CI inhibits IL-1ß secretion through attenuation of NLRP3 inflammasome activation, leading to an antidiabetic effect by improving glucose metabolism and inhibiting metainflammation.
Subject(s)
Cichorium intybus/chemistry , Diabetes Mellitus, Type 2/prevention & control , Inflammasomes/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Plant Extracts/administration & dosage , Animals , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/immunology , Down-Regulation/drug effects , Humans , Inflammasomes/genetics , Inflammasomes/immunology , Interleukin-1beta/genetics , Interleukin-1beta/immunology , Macrophages/drug effects , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/immunologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Morus bombycis Koidzumi (M. bombycis, Moraceae) has been used in Asian countries as a traditional medicine for the treatment of hypertension, diabetes, and inflammation-related disorders. AIM OF STUDY: Although its anti-inflammatory actions have been partly documented, scientific evidence involving its molecular mechanisms related to inflammasome activation signaling pathways remains unknown. MATERIALS AND METHODS: Lipopolysaccharide-stimulated RAW 264.7 cells and bone marrow-derived murine macrophages were used to study the in vitro effect of methanolic extract of M. bombycis (MB) on inflammatory responses. A monosodium urate crystal (MSU)-induced peritonitis murine model was used to study the in vivo effects. RESULTS: MB attenuated the production of nitric oxide and interleukin-6, through the regulation of the interferon-ß receptor signaling pathway. MB also inhibited IL-1ß secretion via attenuation of NLRP3 inflammasome activation. Furthermore, MB inhibited MSU-induced peritonitis in the in vivo murine model. CONCLUSIONS: This study provides the key molecular mechanisms involved in the anti-inflammatory effects of M. bombycis, substantiating the traditional claims of its use in the treatment of inflammation-related disorders.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Carrier Proteins/antagonists & inhibitors , Interferon-beta/antagonists & inhibitors , Morus , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents/therapeutic use , Carrier Proteins/metabolism , Cell Line , Cells, Cultured , Female , Inflammasomes , Interferon-beta/metabolism , Interleukin-6/metabolism , Macrophages/drug effects , Macrophages/metabolism , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein , Nitric Oxide/metabolism , Peritonitis/chemically induced , Peritonitis/drug therapy , Peritonitis/metabolism , Phytotherapy , Plant Extracts/therapeutic use , Reactive Oxygen Species/metabolism , Uric AcidABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Impatiens textori Miq. (I. textori, Balsaminaceae) is a traditional medicinal herb used for centuries to treat several inflammatory related skin infections and allergic disorders in Asian countries. AIM OF THE STUDY: In this study, we elucidated the effects of whole plant extracts of I. textori on inflammasome activation using in vitro and in vivo models. MATERIALS AND METHODS: LPS-stimulated murine bone marrow macrophages were used to study the regulatory effect of I. textori extract (IT) on inflammasome activation. ATP, nigericin and MSU were used as danger-associated molecules to activate the NLRP3 inflammasome. An LPS-induced acute lung injury (ALI) mouse model was used to study the in vivo effect of IT on inflammasome activation. RESULTS: IT treated at 25, 50, and 100µg/mL concentrations suppressed interleukin-1ß secretion through the attenuation of NLRP3 inflammasome activation (p<0.001 at 100µg/mL) leading to the decreased amount of ASC oligomerization and caspase-1 maturation. For the in vivo model, IT inhibited the NLRP3 expression and cell recruitment at the lung tissue in the ALI mouse model. CONCLUSION: IT exhibited potent anti-inflammatory effects via the attenuation of NLRP3 inflammasome activation supporting the traditional claims and may provide a valuable therapeutic strategy in treating various inflammation-related disorders.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Impatiens/chemistry , Inflammation/drug therapy , Plant Extracts/pharmacology , Acute Lung Injury/drug therapy , Acute Lung Injury/pathology , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/isolation & purification , Carrier Proteins/metabolism , Cell Line , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Humans , Inflammasomes/metabolism , Inflammation/pathology , Macrophages/drug effects , Macrophages/metabolism , Medicine, Traditional , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein , Plant Extracts/administration & dosageABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Syneilesis palmata (Thunb.) Maxim. (S. palmata, Asteraceae) is a traditional Korean therapeutic herb widely used to treat pain, arthritis, and other symptoms. This study provides the scientific basis for the anti-inflammatory effects of S. palmata extract (SP) in both in vitro and in vivo experimental models. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-stimulated murine macrophages were used to study the regulatory effect of SP on the inflammatory mediators in vitro. Bone marrow-derived macrophages were used to study the effects of SP on inflammasome activation. Escherichia coli-induced sepsis mouse model and LPS-induced endotoxin shock model were employed to study the effect of SP on in vivo efficacy. RESULTS: SP inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide and interleukin (IL)-6 in RAW 264.7 cells. SP treatment also attenuated IL-1ß secretion via the inhibition of NLRP3 inflammasome activation induced by monosodium urate, ATP, and nigericin. Further, SP ameliorated the severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin and E. coli-induced sepsis mouse models. Mechanistic studies revealed that inhibitory effects of SP were mediated through the regulation of TRIF-dependent signaling and inflammasome activation. CONCLUSION: This study was the first to reveal mechanistic-based evidence substantiating the traditional claims of SP in the treatment of inflammation-related disorders, such as pain and arthritis.
Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Anti-Inflammatory Agents/pharmacology , Asteraceae/chemistry , Inflammasomes/metabolism , Inflammation/drug therapy , Plant Extracts/pharmacology , Signal Transduction/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Cell Line , Escherichia coli/pathogenicity , Female , Inflammation/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Nitric Oxide/metabolism , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Sepsis/drug therapy , Sepsis/metabolism , Sepsis/microbiology , Shock, Septic/chemically induced , Shock, Septic/drug therapy , Shock, Septic/metabolismABSTRACT
This study investigated the neuroprotective effects of Hericium erinaceus mycelium enriched with garlic extract (HGE) on rat pheochromocytoma nerve cells (PC12). The survival rates of the PC12 nerve cells and the neurite-bearing cells after the addition of HGE were estimated as 3.5 × 10(3) viable cells/ml and 2.3 × 10(3) viable cells/ml, respectively, which were 50% and 30% higher, respectively, compared with the untreated group. For the in vivo ischemia experiments, after treatment with the HGE extract, the hippocampal CA1 region was more strongly stained (>20%) than the control group, and the HGE extract also promoted higher staining levels than HFB, HM and HGEF, and even the garlic extract. This result indicates that HGE must have neuroprotective effects. Furthermore, HGE greatly decreased p21 gene expression to approximately 70% of the control and decreased p21 gene expression to even lower levels compared with HM, HGEF and the garlic extract. This work suggests that a synergistic effect of the H. erinaceus mycelium and the garlic extract (mainly allicin) exist because the amount of allicin in HGE (5.81 µg/ml) was lower than the garlic extract itself (6.89 µg/ml).
Subject(s)
Basidiomycota/chemistry , Brain Ischemia/drug therapy , Complex Mixtures/pharmacology , Garlic/chemistry , Neurons/drug effects , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Animals , Brain Ischemia/genetics , Brain Ischemia/pathology , CA1 Region, Hippocampal/drug effects , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/pathology , Cell Line, Tumor , Cell Survival/drug effects , Complex Mixtures/isolation & purification , Cyclin-Dependent Kinase Inhibitor p21/antagonists & inhibitors , Cyclin-Dependent Kinase Inhibitor p21/genetics , Disulfides , Drug Synergism , Gene Expression/drug effects , Gerbillinae , Male , Mycelium/chemistry , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/isolation & purification , PC12 Cells , Plant Extracts/isolation & purification , Rats , Sulfinic Acids/pharmacologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Acorus gramineus Solander (Acoraceae, AG), is a widely distributed plant in Asian countries. Rhizome part of this plant has long been used as a traditional medicine for treating various symptoms including central nervous system (CNS) disorders. AIM OF STUDY: The anti-neuroinflammatory effect of AG aqueous extract was investigated using in vitro cellular and in vivo Parkinson's disease (PD) mouse model. MATERIALS AND METHODS: Lipopolysaccharide (LPS) is used to stimulate BV-2 microglial cells in vitro and the changes in neuroinflammatory expressional levels were measured using ELISA, Western blotting, RT-PCR and immunofluorescence techniques. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD was developed followed by immunohistochemical analysis of specific brain tissues. RESULTS: LPS-stimulation to BV-2 cells increased the production of nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß. Pretreatment with AG extract inhibited the increased levels of NO and pro-inflammatory cytokines in LPS-stimulated BV-2 cells. Mechanistic study revealed that AG acts via the regulation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs) and TRIF-dependent signaling pathways. Further, AG protected MPTP-induced neuronal cell death and inhibited neuroinflammation in vivo. CONCLUSION: Our results indicated that AG extract exerted anti-neuroinflammatory effects against activated microglia mediated insults through multiple signaling pathways and prevented in vivo neuronal cell death in mouse model of PD substantiating the traditional claims for its use in CNS disorders.
Subject(s)
Acorus , Anti-Inflammatory Agents/therapeutic use , Neuroprotective Agents/therapeutic use , Parkinson Disease/drug therapy , Plant Extracts/therapeutic use , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Anti-Inflammatory Agents/pharmacology , Cell Line , Cell Survival/drug effects , Cytokines/genetics , Disease Models, Animal , Heme Oxygenase-1/metabolism , Lipopolysaccharides , Male , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , Microglia , Mitogen-Activated Protein Kinases/metabolism , Neuroprotective Agents/pharmacology , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Parkinson Disease/etiology , Parkinson Disease/pathology , Plant Extracts/pharmacology , RhizomeABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Acorus calamus Linn. (Araceae) is a traditional herbal plant used for centuries to treat various allergic symptoms including asthma and bronchitis. AIM OF THE STUDY: The present study was focused to provide a pharmacological basis for the traditional use of Acorus calamus in allergic symptoms using the mast cell-dependent anaphylactic reactions in in vitro and in vivo models. MATERIALS AND METHODS: Cell viabilities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Dinitrophenyl-human serum albumin (DNP-HSA) induced ß-hexosaminidase and interleukin (IL)-4 productions in IgE-sensitized rat basophilic leukaemia (RBL-2H3) cells were measured by enzymatic assay and enzyme-linked immunosorbent assay (ELISA). Passive cutaneous anaphylaxis (PCA) reaction mouse model was implemented for in vivo studies. RESULTS: Hot water (HW), butylene glycol (BG), hexane (HE) and steam distilled (SD) extracts of Acorus calamus showed different cytoxicity levels evaluated in RBL-2H3 cells. Sub-toxic doses of HW extract suppressed the ß-hexosaminidase secretion and IL-4 production significantly and dose dependently in DNP-HSA induced IgE-sensitized RBL-2H3 cells compared to other extracts of Acorus calamus. Further, in vivo studies also revealed that the HW extract significantly inhibited the PCA reaction in mouse compared to the normal control group. CONCLUSION: HW extract of Acorus calamus most effectively inhibited degranulation and IL-4 secretion in DNP-HSA-stimulated RBL-2H3 cells and also reduced the mast cell-mediated PCA reaction in mouse, providing a therapeutic evidence for its traditional use in ameliorating allergic reactions.
Subject(s)
Acorus , Anti-Allergic Agents/pharmacology , Mast Cells/drug effects , Passive Cutaneous Anaphylaxis/drug effects , Plant Extracts/pharmacology , Acorus/chemistry , Animals , Anti-Allergic Agents/isolation & purification , Butylene Glycols/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Chemical Fractionation , Dinitrophenols/immunology , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Haptens , Hexanes/chemistry , Interleukin-4/metabolism , Male , Mast Cells/immunology , Mice , Mice, Inbred BALB C , Phytotherapy , Plant Extracts/isolation & purification , Plants, Medicinal , Rats , Rhizome , Serum Albumin/immunology , Solvents/chemistry , Water/chemistry , beta-N-Acetylhexosaminidases/metabolismABSTRACT
ETHNOPHARMACOLOGICAL EVIDENCE: Agrimonia pilosa Ledeb (Rosaceae, AP) has long been used as a traditional medicine in Korea and other Asian countries to treat various diseases. AIM OF THE STUDY: In the present study, the anti-inflammatory and anti-allergic effects of AP extract in in vitro cell lines and in vivo mouse model of inflammation and the molecular mechanisms involved were reported. MATERIALS AND METHODS: Using Raw 264.7 murine macrophages the effects of methanol extract of AP in lipopolysaccharide (LPS)-induced production of inflammatory mediators were measured. Further IgE-DNP-induced interleukin (IL)-4 production and degranulation in RBL-2H3 rat basophilic cell lines was also estimated. To investigate the anti-asthmatic effect of AP in vivo, airway inflammation in ovalbumin (OVA)-induced mouse model was used. RESULTS: AP attenuated the production of inflammatory mediators such as NO, PGE(2) and pro-inflammatory cytokines in LPS-induced Raw 264.7 cells. Further, AP inhibited IL-4 production and degranulation in IgE-DNP-induced RBL-2H3 cells. Furthermore, AP attenuated the infiltration of immune cells into lung, cytokines production in broncho-alveolar lavage fluid (BALF) and airway-hyperresponsiveness (AHR) on OVA-induced mouse model of inflammation. CONCLUSION: Our results showed that AP attenuated the activation of macrophages, basophils, and inhibited the OVA-induced airway inflammation. The molecular mechanisms leading to AP's potent anti-inflammatory and anti-allergic effects might be through regulation of TRIF-dependent and Syk-PLCγ/AKT signaling pathways, suggesting that AP may provide a valuable therapeutic strategy in treating various inflammatory diseases including asthma.