ABSTRACT
Laminarin is a polysaccharide isolated from brown marine algae and has a wide range of bioactivities, including immunoregulatory and anti-inflammatory properties. However, the effects of laminarin on atopic dermatitis have not been demonstrated. This study investigated the potential effects of topical administration of laminarin using a Balb/c mouse model of oxazolone-induced atopic dermatitis-like skin lesions. Our results showed that topical administration of laminarin to the ear of the mice improved the severity of the dermatitis, including swelling. Histological analysis revealed that topical laminarin significantly decreased the thickening of the epidermis and dermis and the infiltration of mast cells in the skin lesion. Serum immunoglobulin E levels were also significantly decreased by topical laminarin. Additionally, topical laminarin significantly suppressed protein levels of oxazolone-induced proinflammatory cytokines, such as interleukin-1ß, tumor necrosis factor-α, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α in the skin lesion. These results indicate that topical administration of laminarin can alleviate oxazolone-induced atopic dermatitis by inhibiting hyperproduction of IgE, mast cell infiltration, and expressions of proinflammatory cytokines. Based on these findings, we propose that laminarin can be a useful candidate for the treatment of atopic dermatitis.
Subject(s)
Dermatitis, Atopic , Mice , Animals , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/metabolism , Oxazolone/toxicity , Oxazolone/metabolism , Dinitrochlorobenzene/metabolism , Dinitrochlorobenzene/pharmacology , Dinitrochlorobenzene/therapeutic use , Immunoglobulin E , Plant Extracts/pharmacology , Administration, Topical , Cytokines/metabolism , Mice, Inbred BALB C , SkinABSTRACT
The hippocampus has a different vulnerability to ischemia according to the subfields CA1 to CA3 (initials of cornu ammonis). It has been reported that body temperature changes during ischemia affect the degree of neuronal death following transient ischemia. Hypoxiainducible factor 1α (HIF1α) plays a key role in regulating cellular adaptation to low oxygen conditions. In the present study, we investigated the pattern of neuronal death (loss) in CA1 and CA2/3 following 5 min transient forebrain ischemia (TFI) under hyperthermia (39.5±0.2ËC) and the relationship between neuronal death and changes in HIF1α expression using western blot analysis and immunohistochemistry in gerbils. Normothermia or hyperthermia was induced for 30 min before and during the TFI, and neuronal death and HIF1α expression were observed at 0, 3, 6 and 12 h, 1, 2 and 5 days after TFI. Under normothermia, TFIinduced neuronal death of CA1 pyramidal neurons occurred on day 5 after TFI, but CA2/3 pyramidal neurons did not die. In contrast, under hyperthermia, the death of CA1 and CA2/3 pyramidal neurons was observed on day 2 after TFI. Under normothermia, HIF1α expression was significantly elevated in both CA1 and CA2/3 pyramidal neurons at 12 h and 1 day after TFI, and the increased HIF1α immunoreactivity in CA1 was dramatically reduced from 2 days after TFI, but not in CA2/3 pyramidal neurons. Under hyperthermia, the basal expression of HIF1α in the sham group was significantly higher in both CA1 and CA2/3 pyramidal neurons at 0 h after TFI than in the normothermia group. HIF1 expression was continuously higher, peaked at 12 h after TFI, and then significantly decreased from 1 day after TFI. Overall, the present results indicate that resistance to ischemia in CA2/3 pyramidal neurons is closely associated with the persistence of increased expression of HIF1α after ischemic insults and that hyperthermiainduced exacerbation of death of pyramidal neurons is closely related to decreased HIF1α expression after ischemic insults.
Subject(s)
Hippocampus , Hyperthermia, Induced , Animals , Gerbillinae/metabolism , Hippocampus/metabolism , Ischemia/metabolism , Pyramidal Cells/metabolismABSTRACT
We evaluated the efficacy and safety of MS-10® for the treatment of menopausal symptoms. A double-blind randomized placebo-controlled clinical trial was performed in 71 premenopausal women for 4 and 12 weeks. A total of 12 individual menopausal symptom scores were assessed using the Kupperman index. MS-10 treatment effectively improved the symptoms by â¼48%. In addition, the quality of life of the women improved by 36% from four perspectives: vasomotor, psychosocial, physical, and sexual symptoms as evaluated using the menopause-specific quality of life (MenQoL) questionnaire. Our results show that MS-10 improves insulin-like growth factor-1 (IGF-1) and estrogen utilization through receptor activation, which are thought to have causative therapeutic effects on menopause and aging inhibition in women. Improvement of Enthotheline-1 (ET-1) in the blood after MS-10 intake led to an improvement in menopausal vascular symptoms. Improvements in bone formation and absorption markers such as osteocalcin, bone-specific alkaline phosphatase (BSALP), C-telopeptides of type I collagen (CTx), deoxypyridinoline (deoxyPYD), and N-telopeptides of type I collagen (NTx) in blood or urine indicate that MS-10 fundamentally improves bone health in women. By confirming the improvement of the psychological well-being index based on the improvement of stress hormone cortisol, MS-10 can solve causative psychological and physical stress-related symptoms. Moreover, various safety tests, such as those for female hormones, were confirmed. Therefore, it can be confirmed that MS-10 is a natural pharmaconutraceutical that causatively and safely improves health of women and aids in antiaging processes.
Subject(s)
Cirsium , Healthy Aging , Menopause , Plant Extracts , Thymus Plant , Cirsium/chemistry , Female , Hot Flashes/drug therapy , Humans , Plant Extracts/therapeutic use , Quality of Life , Thymus Plant/chemistryABSTRACT
The extract of Clematis mandshurica Rupr. (CMR) inhibits the production of proinflammatory mediators from lipopolysaccharide-stimulated peritoneal macrophages and concanavalin A-stimulated splenocytes. Erigeron annuus Pers. (EAP) extract suppresses the production of reactive oxygen species (ROS) from preadipocytes. Furthermore, the mixture of the leaf extracts of CMR and EAP, YES-10®, protected against nerve injuries induced by ischemia/reperfusion, suggesting a ROS-scavenging action. These observations show the anti-inflammatory action of YES-10. Inflammatory cytokines can cause alterations in mental function, including depression, by influencing the neurotransmitter system. Thus, it was hypothesized that YES-10 could improve mental health, such as depression, anxiety, and sense of well-being. Seventy-two subjects were recruited and randomly divided into YES-10 or placebo groups (n = 36 per group). Each group was daily administered two capsules orally, containing 200 mg of YES-10 or placebo, for 4 weeks in a double-blinded manner and tested for levels of depression, anxiety, well-being, and mental fitness using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Psychosocial Well-being Index (PWI), and Mental Fitness Scale (MFS). In addition, the levels of cortisol (a stress hormone), interleukin-6 (IL-6) (an inflammatory cytokine), and 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative stress) in the serum were measured. The BDI, BAI, PWI, and MFS scores decreased significantly, and the serum levels of cortisol, IL-6, and 8-OHdG were lowered significantly (P < .05), suggesting that YES-10 has the ability to improve mental health by relieving stress and by decreasing inflammation and oxidative stress.
Subject(s)
Hydrocortisone , Interleukin-6 , Anxiety , Cytokines , Depression/drug therapy , Fatigue , HumansABSTRACT
Korean maritime pine bark (Pinus thunbergii) has been used as an alternative medicine due to its beneficial properties, including antiinflammatory effects. To date, the antiinflammatory and hair growthpromoting effects of Pinus densiflora bark extract have remained elusive. Therefore, in the present study, Pinus thunbergii bark was extracted with pure water (100ËC) and the extract was examined to determine its polyphenol and flavonoid content. C57BL/6 mice were used to assess the effects of the extract to promote hair growth. The extract (1, 2 and 4%) was topically applied onto shaved dorsal skin and hair growth was observed for 17 days. A significant increase in hair growth was observed with 2 and 4% extract. Based on this finding, the optimal dose of the extract for effective hair growth promotion was determined to be 2%. The mechanisms of hair growth promotion were investigated via immunohistochemical analysis of changes in inflammatory cytokines and growth factors in the hair follicles following treatment with 2% extract. The treatment reduced the levels of TNFα and IL1ß, which are proinflammatory cytokines, while it enhanced the levels of IL4 and IL13, which are antiinflammatory cytokines, in the hair follicles. In addition, elevated insulinlike growth factor I and vascular epidermal growth factor were detected in hair follicles following treatment. Based on these findings, it was suggested that the extract of Pinus thunbergii bark may be utilized for hair loss prevention and/or hair growth promotion.
Subject(s)
Pinus , Animals , Cytokines/analysis , Flavonoids/analysis , Flavonoids/pharmacology , Hair Follicle , Mice , Mice, Inbred C57BL , Pinus/chemistry , Plant Bark/chemistry , Plant Extracts/chemistryABSTRACT
Korean red pine (Pinus densiflora) belongs to the Genus Pinus, and its bark contains a great amount of naturally occurring phenolic compounds. Until now, few studies have been conducted to assess the neuroprotective effects of Pinus densiflora bark extract against brain ischemic injury. The aim of this study was to investigate the neuroprotective effects of pre-treatment with the extract in the hippocampus following 5-min transient forebrain ischemia in gerbils. Furthermore, this study examined the anti-inflammatory effect as a neuroprotective mechanism of the extract. Pinus densiflora bark was extracted by pure water (100 °C), and this extract was quantitatively analyzed and contained abundant polyphenols, flavonoids, and proanthocyanidins. The extract (25, 50, and 100 mg/kg) was orally administered once a day for seven days before the ischemia. In the gerbil hippocampus, death of the pyramidal neurons was found in the subfield cornu ammonis 1 (CA1) five days after the ischemia. This death was significantly attenuated by pre-treatment with 100 mg/kg, not 25 or 50 mg/kg, of the extract. The treatment with 100 mg/kg of the extract markedly inhibited the activation of microglia (microgliosis) and significantly decreased the expression of pro-inflammatory cytokines (interleukin 1ß and tumor necrosis factor α). In addition, the treatment significantly increased anti-inflammatory cytokines (interleukin 4 and interleukin 13). Taken together, this study clearly indicates that pre-treatment with 100 mg/kg of Pinus densiflora bark extract in gerbils can exert neuroprotection against brain ischemic injury by the attenuation of neuroinflammatory responses.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Brain Ischemia/drug therapy , Hippocampus/drug effects , Neuroprotective Agents/pharmacology , Pinus/chemistry , Prosencephalon/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Brain Ischemia/genetics , Brain Ischemia/metabolism , Brain Ischemia/pathology , Flavonoids/chemistry , Flavonoids/pharmacology , Gene Expression/drug effects , Gerbillinae , Hippocampus/metabolism , Hippocampus/pathology , Inflammation , Interleukin-13/agonists , Interleukin-13/genetics , Interleukin-13/metabolism , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-4/agonists , Interleukin-4/genetics , Interleukin-4/metabolism , Male , Microglia/drug effects , Microglia/metabolism , Microglia/pathology , Neuroprotective Agents/chemistry , Plant Bark/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Polyphenols/chemistry , Polyphenols/pharmacology , Proanthocyanidins/chemistry , Proanthocyanidins/pharmacology , Prosencephalon/metabolism , Prosencephalon/pathology , Pyramidal Cells/drug effects , Pyramidal Cells/metabolism , Pyramidal Cells/pathology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Angelica gigas Nakai root contains decursin which exerts beneficial properties such as anti-amnesic and anti-inflammatory activities. Until now, however, the neuroprotective effects of decursin against transient ischemic injury in the forebrain have been insufficiently investigated. Here, we revealed that post-treatment with decursin and the root extract saved pyramidal neurons in the hippocampus following transient ischemia for 5 min in gerbil forebrain. Through high-performance liquid chromatography, we defined that decursin was contained in the extract as 7.3 ± 0.2%. Based on this, we post-treated with 350 mg/kg of extract, which is the corresponding dosage of 25 mg/kg of decursin that exerted neuroprotection in gerbil hippocampus against the ischemia. In addition, behavioral tests were conducted to evaluate ischemia-induced dysfunctions via tests of spatial memory (by the 8-arm radial maze test) and learning memory (by the passive avoidance test), and post-treatment with the extract and decursin attenuated ischemia-induced memory impairments. Furthermore, we carried out histochemistry, immunohistochemistry, and double immunohistofluorescence. Pyramidal neurons located in the subfield cornu ammonis 1 (CA1) among the hippocampal subfields were dead at 5 days after the ischemia; however, treatment with the extract and decursin saved the pyramidal neurons after ischemia. Immunoglobulin G (IgG, an indicator of extravasation), which is not found in the parenchyma in normal brain tissue, was apparently shown in CA1 parenchyma from 2 days after the ischemia, but IgG leakage was dramatically attenuated in the CA1 parenchyma treated with the extract and decursin. Furthermore, astrocyte endfeet, which are a component of the blood-brain barrier (BBB), were severely damaged at 5 days after the ischemia; however, post-treatment with the extract and decursin dramatically attenuated the damage of the endfeet. In brief, therapeutic treatment of the extract of Angelica gigas Nakai root and decursin after 5 min transient forebrain ischemia protected hippocampal neurons from the ischemia, showing that ischemia-induced BBB leakage and damage of astrocyte endfeet was significantly attenuated by the extract and decursin. Based on these findings, we suggest that Angelica gigas Nakai root containing decursin can be employed as a pharmaceutical composition to develop a therapeutic strategy for brain ischemic injury.
Subject(s)
Angelica/chemistry , Astrocytes/pathology , Benzopyrans/therapeutic use , Blood-Brain Barrier/pathology , Butyrates/therapeutic use , Ischemic Attack, Transient/pathology , Plant Extracts/therapeutic use , Animals , Astrocytes/drug effects , Astrocytes/metabolism , Benzopyrans/chemistry , Benzopyrans/pharmacology , Blood-Brain Barrier/drug effects , Butyrates/chemistry , Butyrates/pharmacology , Gerbillinae , Glial Fibrillary Acidic Protein/metabolism , Glucose Transporter Type 1/metabolism , Immunoglobulin G/metabolism , Male , Neuraminidase/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Plant Extracts/pharmacology , Reference Standards , Spatial Memory/drug effectsABSTRACT
Altered expression levels of NmethylDaspartate receptor (NMDAR), a ligandgated ion channel, have a harmful effect on cellular survival. Hyperthermia is a proven risk factor of transient forebrain ischemia (tFI) and can cause extensive and severe brain damage associated with mortality. The objective of the present study was to investigate whether hyperthermic preconditioning affected NMDAR1 immunoreactivity associated with deterioration of neuronal function in the gerbil hippocampal CA1 region following tFI via histological and western blot analyses. Hyperthermic preconditioning was performed for 1 h before tFI, which was developed by ligating common carotid arteries for 5 min. tFIinduced cognitive impairment under hyperthermia was worse compared with that under normothermia. Loss (death) of pyramidal neurons in the CA1 region occurred fast and was more severe under hyperthermia compared with that under normothermia. NMDAR1 immunoreactivity was not observed in the somata of pyramidal neurons of sham gerbils with normothermia. However, its immunoreactivity was strong in the somata and processes at 12 h posttFI. Thereafter, NMDAR1 immunoreactivity decreased with time after tFI. On the other hand, NMDAR1 immunoreactivity under hyperthermia was significantly increased in the somata and processes at 6 h posttFI. The change pattern of NMDAR1 immunoreactivity under hyperthermia was different from that under normothermia. Overall, accelerated tFIinduced neuronal death under hyperthermia may be closely associated with altered NMDAR1 expression compared with that under normothermia.
Subject(s)
Brain Ischemia/metabolism , Gene Expression Regulation , Hippocampus/metabolism , Hyperthermia, Induced , Memory Disorders/metabolism , Prosencephalon/metabolism , Receptors, N-Methyl-D-Aspartate/biosynthesis , Animals , Brain Ischemia/pathology , Cell Death , Gerbillinae , Hippocampus/pathology , Male , Memory Disorders/etiology , Memory Disorders/pathology , Neurons , Prosencephalon/pathologyABSTRACT
Aronia melanocarpa, a black chokeberry, contains high levels of phenolic acids and polyphenolic flavonoids and displays antioxidative and anti-inflammatory effects. Through high-performance liquid chromatography for extracts from Aronia melanocarpa, we discovered that the extract contained chlorogenic acid and rutin as major ingredients. In this study, we examined the protective effects of the extract against ultraviolet B- (UVB)-induced photodamage in the dorsal skin of institute of cancer research (ICR) mice. Their dorsal skin was exposed to UVB, thereafter; the extract was topically applied once a day for seven days. Photoprotective properties of the extract in the dorsal skin were investigated by clinical skin severity score for skin injury, hematoxylin and eosin staining for histopathology, Masson's trichrome staining for collagens. In addition, we examined change in collagen type I and III, and matrix metalloproteinase (MMP)-1 and MMP-3 by immunohistochemistry. In the UVB-exposed mice treated with the extract, UVB-induced epidermal damage was significantly ameliorated, showing that epidermal thickness was moderated. In these mice, immunoreactivities of collagen type I and III were significantly increased, whereas immunoreactivities of MMP-1 and 3 were significantly decreased compared with those in the UVB-exposed mice. These results indicate that treatment with Aronia melanocarpa extract attenuates UV-induced photodamage by attenuating UVB-induced collagen disruption: these findings might be a result of the chlorogenic acid and rutin contained in the extract. Based on the current results, we suggest that Aronia melanocarpa can be a useful material for developing photoprotective adjuvant.
Subject(s)
Chlorogenic Acid/chemistry , Collagen/metabolism , Photinia/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rutin/chemistry , Ultraviolet Rays/adverse effects , Administration, Topical , Animals , Male , Matrix Metalloproteinases/metabolism , Mice , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Skin Aging/drug effects , Skin Aging/radiation effectsABSTRACT
This current study investigates the facilitative effects and mechanisms of decursin, a major component of Angelica gigas Nakai (AGN), and AGN root extract on hair growth in mice. We perform high-performance liquid chromatography on AGN extract to show it contains 7.3% decursin. Hairs in mouse dorsal skin are shaved distilled in water, 0.15% decursin, and 2% AGN root extract (0.15% decursin in the diluted extract) and topically applied twice a day for 17 days. Hematoxylin and eosin staining are done to examine the morphological changes in the hair follicles. To compare the effects of decursin and AGN extract on inflammatory cytokines in the dorsal skin, Western blot analysis and immunohistochemistry for tumor necrosis factor α (TNF-α) and interleukin (IL)-1ß as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines are conducted. The results show that the application of decursin and AGN extract confer effects on hair growth. Hair growth is significantly facilitated from seven days after the treatments compared to that in the control group, and completely grown hair was found 17 days after the treatments. The protein levels and immunoreactivity of TNF-α and IL-1ß in this case are significantly decreased, whereas the IL-4 and IL-13 levels and immunoreactivity are significantly increased compared to those in the control group. Additionally, high-mobility group box 1, an inflammatory mediator, is elevated by the topical application of decursin and AGN extract. Taken together, the treatment of mouse dorsal skin with AGE root extract containing decursin promotes hair growth by regulating pro- and/or anti-inflammatory cytokines. We, therefore, suggest that AGN root extract as well as decursin can be utilized as materials for developing hair growth-facilitating treatments.
Subject(s)
Angelica/chemistry , Benzopyrans/pharmacology , Butyrates/pharmacology , Cytokines/metabolism , Hair/drug effects , Plant Extracts/pharmacology , Plant Roots/chemistry , Skin/drug effects , Animals , Apoptosis/drug effects , HMGB1 Protein/metabolism , Hair/growth & development , Inflammation/metabolism , Male , Mice , Mice, Inbred C57BL , Skin/cytology , Skin/metabolismABSTRACT
Pycnogenol® (an extract of the bark of French maritime pine tree) is used for dietary supplement and known to have excellent antioxidative efficacy. However, there are few reports on neuroprotective effect of Pycnogenol® supplementation and its mechanisms against ischemic injury following transient forebrain ischemia (TFI) in gerbils. Now, we examined neuroprotective effect and its mechanisms of Pycnogenol® in the gerbils with 5-min TFI, which evokes a significant death (loss) of pyramidal cells located in the cornu ammonis (CA1) region of gerbil hippocampus from 4-5 days post-TFI. Gerbils were pretreated with 30, 40, and 50 mg/kg of Pycnogenol® once a day for 7 days before TFI surgery. Treatment with 50 mg/kg, not 30 or 40 mg/kg, of Pycnogenol® potently protected learning and memory, as well as CA1 pyramidal cells, from ischemic injury. Treatment with 50 mg/kg Pycnogenol® significantly enhanced immunoreactivity of antioxidant enzymes (superoxide dismutases and catalase) in the pyramidal cells before and after TFI induction. Furthermore, the treatment significantly reduced the generation of superoxide anion, ribonucleic acid oxidation and lipid peroxidation in the pyramidal cells. Moreover, interestingly, its neuroprotective effect was abolished by administration of sodium azide (a potent inhibitor of SODs and catalase activities). Taken together, current results clearly indicate that Pycnogenol® supplementation can prevent neurons from ischemic stroke through its potent antioxidative role.
Subject(s)
Antioxidants , CA1 Region, Hippocampal/cytology , Dietary Supplements , Flavonoids/administration & dosage , Flavonoids/pharmacology , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/pathology , Memory Disorders/etiology , Memory Disorders/prevention & control , Neuroprotective Agents , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Pyramidal Cells/drug effects , Pyramidal Cells/pathology , Animals , Catalase/metabolism , Disease Models, Animal , Gerbillinae , Lipid Peroxidation/drug effects , Male , Pyramidal Cells/enzymology , Superoxide Dismutase/metabolismABSTRACT
Atopic dermatitis (AD) is one of the most common skin diseases with inflammation, chronic relapses, and intense pruritus. Its pathogenesis includes genetic susceptibility, an abnormal epidermal lipid barrier, and an increased production of IgE due to immune dysregulation. Recently, AD has been reported to be associated with intestinal inflammation and dysbiosis in human and murine models. Various probiotics are being used to control intestinal dysbiosis and inflammatory reactions. However, it is difficult to predict or determine the therapeutic effects of the probiotics, since it is rare for clinicians to use the probiotics alone to treat AD. It is also difficult to check whether the intestinal inflammation in patients with AD has improved since probiotic treatment. The aim of the present study was to determine whether mice with induced atopic dermatitis had any changes in fecal calprotectin, an indicator of intestinal inflammation, after probiotic administration. Our results showed that the fecal calprotectin levels in mice with induced dermatitis decreased significantly after the administration of probiotics. In addition, epidermal skin lesions were attenuated and inflammatory-related cytokines were downregulated after the administration of probiotics in mice with induced dermatitis. These results suggest that changes in fecal calprotectin levels could be used to assess the effectiveness of a probiotic strain as an adjuvant treatment for AD.
Subject(s)
Dermatitis, Atopic/therapy , Inflammation/metabolism , Leukocyte L1 Antigen Complex/metabolism , Probiotics/pharmacology , Administration, Oral , Animals , Cytokines/metabolism , Dermatitis, Atopic/microbiology , Disease Models, Animal , Feces/chemistry , Female , Gastrointestinal Microbiome , Mice , Polymerase Chain Reaction , Pruritus/metabolism , Recurrence , Skin/metabolismABSTRACT
Since ancient times, various herbs have been used in Asia, including Korea, China, and Japan, for wound healing and antiaging of the skin. In this study, we manufactured and chemically analyzed a novel distillate obtained from a fermented mixture of nine anti-inflammatory herbs (Angelica gigas, Lonicera japonica, Dictamnus dasycarpus Turcz., D. opposita Thunb., Ulmus davidiana var. japonica, Hordeum vulgare var. hexastichon Aschers., Xanthium strumarium L., Cnidium officinale, and Houttuynia cordata Thunb.). The fermentation of natural plants possesses beneficial effects in living systems. These activities are attributed to the chemical conversion of the parent plants to functional constituents which show more potent biological activities. In our current study, the distillate has been manufactured after fermenting the nine oriental medical plants with Lactobacillus fermentum, followed by distilling. We analyzed the chemical ingredients involved in the distillate and evaluated the effects of topical application of the distillate on ultraviolet B (UVB)-induced skin damage in Institute of Cancer Research (ICR) mice. Topical application of the distillate significantly ameliorated the macroscopic and microscopic morphology of the dorsal skin against photodamage induced by UVB radiation. Additionally, our current results showed that topical application of the distillate alleviated collagen disruption and reduced levels of proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 ß expressions) in the dorsal skin against UVB radiation. Taken together, our current findings suggest that the distillate has a potential to be used as a material to develop a photoprotective adjuvant.
Subject(s)
Anti-Inflammatory Agents/chemistry , Plants, Medicinal/chemistry , Skin/drug effects , Skin/radiation effects , Sunscreening Agents/chemistry , Ultraviolet Rays/adverse effects , Animals , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Collagen/analysis , Distillation , Fermentation , Limosilactobacillus fermentum/metabolism , Mice , Mice, Inbred ICR , Plants, Medicinal/metabolism , Skin/pathology , Sunscreening Agents/metabolism , Sunscreening Agents/pharmacologyABSTRACT
To examine the effects of Populus tomentiglandulosa (PT) extract on the expressions of antioxidant enzymes and neurotrophic factors in the cornu ammonis 1 (CA1) region of the hippocampus at 5 min after inducing transient global cerebral ischemia (TGCI) in gerbils, TGCI was induced by occlusion of common carotid arteries for 5 min. Before ischemic surgery, 200 mg·kg-1 PT extract was orally administrated once daily for 7 d. We performed neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B staining. Furthermore, we determined in situ production of superoxide anion radical, expression levels of SOD1 and SOD2 as antioxidant enzymes and brain-derived neurotrophic factor (BDNF) and insulin-like growth factor I (IGF-I) as neurotrophic factors. Pretreatment with 200 mg·kg-1 PT extract prevented neuronal death (loss). Furthermore, pretreatment with 200 mg·kg-1 PT extract significantly inhibited the production of superoxide anion radical, increased expressions of SODs and maintained expressions of BDNF and IGF-I. Such increased expressions of SODs were maintained in the neurons after IRI. In summary, pretreated PT extract can significantly increase levels of SODs and protect the neurons against TGCI, suggesting that PT can be a useful natural agent to protect against TGCI.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , CA1 Region, Hippocampal/drug effects , Insulin-Like Growth Factor I/metabolism , Plant Extracts/administration & dosage , Populus/chemistry , Pyramidal Cells/drug effects , Reperfusion Injury/drug therapy , Superoxide Dismutase/metabolism , Animals , Brain-Derived Neurotrophic Factor/genetics , CA1 Region, Hippocampal/metabolism , Gerbillinae , Humans , Insulin-Like Growth Factor I/genetics , Male , Neuroprotective Agents/administration & dosage , Pyramidal Cells/metabolism , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Superoxide Dismutase/genetics , Up-Regulation/drug effectsABSTRACT
In recent years, the use of botanical agents to prevent skin damage from solar ultraviolet (UV) irradiation has received considerable attention. Oenanthe javanica is known to exert anti-inflammatory and antioxidant activities. This study investigated photoprotective properties of an Oenanthe javanica extract (OJE) against UVB-induced skin damage in ICR mice. The extent of skin damage was evaluated in three groups: control mice with no UVB, UVB-exposed mice treated with vehicle (saline), and UVB-exposed mice treated with 1% extract. Photoprotective properties were assessed in the dorsal skin using hematoxylin and eosin staining, Masson trichrome staining, immunohistochemical staining, quantitative real-time polymerase chain reaction, and western blotting to analyze the epidermal thickness, collagen expression, and mRNA and protein levels of type I collagen, type III collagen, and interstitial collagenases, including matrix metalloproteinase (MMP)-1 and MMP-3. In addition, tumor necrosis factor (TNF)-α and cyclooxygenase (COX)-2 protein levels were also assessed. In the UVB-exposed mice treated with extract, UV-induced epidermal damage was significantly ameliorated. In this group, productions of collagen types I and III were increased, and expressions of MMP-1 and MMP-3 were decreased. In addition, TNF-α and COX-2 expressions were reduced. Based on these findings, we conclude that OJE displays photoprotective effects against UVB-induced collagen disruption and inflammation and suggest that Oenanthe javanica can be used as a natural product for the treatment of photodamaged skin.
Subject(s)
Collagen/metabolism , Oenanthe/chemistry , Plant Extracts/pharmacology , Protective Agents/pharmacology , Skin/drug effects , Skin/metabolism , Skin/radiation effects , Ultraviolet Rays/adverse effects , Animals , Biomarkers , Biopsy , Dermatitis/drug therapy , Dermatitis/etiology , Dermatitis/metabolism , Disease Models, Animal , Gene Expression , Immunohistochemistry/methods , Mice , Plant Extracts/chemistry , Protective Agents/chemistryABSTRACT
BACKGROUND: Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice. METHODS: A total of 39 male ICR mice (12 weeks old) were randomly assigned to vehicle-treated and 100 and 200 mg/kg G. littoralis extract-treated groups (n = 13 in each group). Vehicle and G. littoralis extract were orally administrated for 28 days. To examine neurogenic effects of G. littoralis extract, we performed immunohistochemistry for 5-bromo-2-deoxyuridine (BrdU, an indicator for cell proliferation) and doublecortin (DCX, an immature neuronal marker) and double immunofluorescence staining for BrdU and neuronal nuclear antigen (NeuN, a mature neuronal marker). In addition, we examined expressional changes of brain-derived neurotrophic factor (BDNF) and its major receptor tropomyosin-related kinase B (TrkB) using Western blotting analysis. RESULTS: Treatment with 200 mg/kg, not 100 mg/kg, significantly increased number of BrdU-immunoreactive (+) and DCX+ cells (48.0 ± 3.1 and 72.0 ± 3.8 cells/section, respectively) in the subgranular zone (SGZ) of the dentate gyrus (DG) and BrdU+/NeuN+ cells (17.0 ± 1.5 cells/section) in the granule cell layer as well as in the SGZ. In addition, protein levels of BDNF and TrkB (about 232% and 244% of the vehicle-treated group, respectively) were significantly increased in the DG of the mice treated with 200 mg/kg of G. littoralis extract. CONCLUSION: G. littoralis extract promots cell proliferation, neuroblast differentiation, and neuronal maturation in the hippocampal DG, and neurogenic effects might be closely related to increases of BDNF and TrkB proteins by G. littoralis extract treatment.
Subject(s)
Apiaceae/chemistry , Brain-Derived Neurotrophic Factor/metabolism , Dentate Gyrus/cytology , Plant Extracts/pharmacology , Receptor, trkB/metabolism , Animals , Blotting, Western , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Dentate Gyrus/drug effects , Doublecortin Domain Proteins , Doublecortin Protein , Hippocampus/cytology , Hippocampus/drug effects , Immunohistochemistry , Male , Mice , Microtubule-Associated Proteins/metabolism , Neurogenesis/drug effects , Neuropeptides/metabolismABSTRACT
BACKGROUND: Glehnia littoralis, as a traditional herbal medicine to heal various health ailments in East Asia, displays various therapeutic properties including antioxidant effects. However, neuroprotective effects of G. littoralis against cerebral ischemic insults have not yet been addressed. Therefore, in this study, we first examined its neuroprotective effects in the hippocampus using a gerbil model of transient global cerebral ischemia (TGCI). METHODS: Gerbils were subjected to TGCI for 5 min. G. littoralis extract (GLE; 100 and 200 mg/kg) was administrated orally once daily for 7 days before ischemic surgery. Neuroprotection was examined by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. Gliosis was observed by immunohistochemistry for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1. For neuroprotective mechanisms, immunohistochemistry for superoxide dismutase (SOD) 1 and brain-derived neurotrophic factor (BDNF) was done. RESULTS: Pretreatment with 200 mg/kg of GLE protected pyramidal neurons in the cornu ammonis 1 (CA1) area from ischemic insult area (F = 29.770, P < 0.05) and significantly inhibited activations of astrocytes (F = 22.959, P < 0.05) and microglia (F = 44.135, P < 0.05) in the ischemic CA1 area. In addition, pretreatment with GLE significantly increased expressions of SOD1 (F = 28.561, P < 0.05) and BDNF (F = 55.298, P < 0.05) in CA1 pyramidal neurons of the sham- and ischemia-operated groups. CONCLUSIONS: Our findings indicate that pretreatment with GLE can protect neurons from ischemic insults, and we suggest that its neuroprotective mechanism may be closely associated with increases of SOD1 and BDNF expressions as well as attenuation of glial activation.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , CA1 Region, Hippocampal/drug effects , CA1 Region, Hippocampal/metabolism , Plant Extracts/pharmacology , Superoxide Dismutase/metabolism , Animals , Brain-Derived Neurotrophic Factor/genetics , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Gerbillinae , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Gliosis/metabolism , Immunohistochemistry , Superoxide Dismutase/geneticsABSTRACT
Chrysanthemum indicum Linné extract (CIL) is used in herbal medicine in East Asia. In the present study, gerbils were orally pretreated with CIL, and changes of antioxidant enzymes including superoxide dismutase (SOD) 1 and SOD2, catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal CA1 region following 5 min of transient cerebral ischemia were investigated and the neuroprotective effect of CIL in the ischemic CA1 region was examined. SOD1, SOD2, CAT and GPX immunoreactivities were observed in the pyramidal cells of the CA1 region and their immunoreactivities were gradually decreased following ischemiareperfusion and barely detectable at 5 days postischemia. CIL pretreatment significantly increased immunoreactivities of SOD1, CAT and GPX, but not SOD2, in the CA1 pyramidal cells of the shamoperated animals. In addition, SOD1, SOD2, CAT and GPX immunoreactivities in the CA1 pyramidal cells were significantly higher compared with the ischemiaoperated animals. Furthermore, it was identified that pretreatment with CIL protected the CA1 pyramidal cells in the CA1 region using neuronal nuclei immunohistochemistry and FluoroJade B histofluorescence staining; the protected CA1 pyramidal cells were 67.5% compared with the shamoperated animals. In conclusion, oral CIL pretreatment increased endogenous antioxidant enzymes in CA1 pyramidal cells in the gerbil hippocampus and protected the cells from transient cerebral ischemic insult. This finding suggested that CIL is promising for the prevention of ischemiainduced neuronal damage.
Subject(s)
Antioxidants/metabolism , CA1 Region, Hippocampal/metabolism , Chrysanthemum/chemistry , Ischemic Attack, Transient/metabolism , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Pyramidal Cells/drug effects , Pyramidal Cells/metabolism , Animals , Biomarkers , Catalase/metabolism , Disease Models, Animal , Gerbillinae , Glutathione Peroxidase/metabolism , Immunohistochemistry , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/pathology , Male , Superoxide Dismutase-1/metabolismABSTRACT
Endothelial arginase constrains the activity of endothelial nitric oxide synthase by reducing nitric oxide bioavailability, which contributes to vascular diseases. During screening, we identified a novel compound from the rhizome of Polygonum multiflorum (Polygonaceae), 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (THSG), which inhibited arginase activity. THSG exhibited noncompetitive inhibition of arginase II and inhibited both arginases I and II in a dose-dependent manner. THSG-dependent arginase inhibition reciprocally increased nitric oxide production and decreased reactive oxygen species generation in aortic endothelia. These effects were associated with increased dimerization of endothelial nitric oxide synthase without changes in the protein expression levels of arginase I, arginase II, or endothelial nitric oxide synthase. In vascular tension assays, when aortic vessels from wild-type mice are incubated with THSG, responses to the nitric oxide-dependent vasorelaxant acetylcholine were augmented, but responses to an nitric oxide donor, sodium nitroprusside, were not affected. On the other hand, phenylephrine-dependent vasoconstriction was significantly retarded in THSG-treated vessels. In a high-cholesterol diet-fed atherogenic model mice (ApoE-/-), THSG improved endothelial function by enhancement of the nitric oxide-cGMP pathway. Taken together, these results suggest that THSG may exert vasoprotective effects through augmentation of nitric oxide signaling by inhibiting arginase. Therefore, THSG may be useful in the treatment of vascular diseases that are derived from endothelial dysfunction, such as atherosclerosis.
Subject(s)
Arginase/antagonists & inhibitors , Endothelium, Vascular/drug effects , Glucosides/pharmacology , Nitric Oxide Synthase Type III/metabolism , Stilbenes/pharmacology , Acetylcholine/pharmacology , Animals , Aorta/drug effects , Aorta/enzymology , Aorta/metabolism , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Arginase/metabolism , Dose-Response Relationship, Drug , Endothelium, Vascular/enzymology , Endothelium, Vascular/metabolism , Enzyme Inhibitors/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Male , Mice , Mice, Inbred C57BL , Nitric Oxide/metabolism , Nitroprusside/pharmacology , Phenylephrine/pharmacology , Reactive Oxygen Species/metabolism , Superoxides/metabolism , Vasoconstriction/drug effectsABSTRACT
The genus Populus (poplar) belonging to the Salicaceae family has been used in traditional medicine, and its several species show various pharmacological properties including antioxidant and anti-inflammatory effects. No study regarding protective effects of Populus species against cerebral ischemia has been reported. Therefore, in the present study, we examined neuroprotective effects of ethanol extract from Populus tomentiglandulosa (Korea poplar) in the hippocampal cornu ammonis (CA1) area of gerbils subjected to 5 minutes of transient global cerebral ischemia. Pretreatment with 200 mg/kg of P. tomentiglandulosa extract effectively protected CA1 pyramidal neurons from transient global cerebral ischemia. In addition, glial fibrillary acidic protein immunoreactive astrocytes and ionized calcium binding adapter molecule 1 immunoreactive microglia were significantly diminished in the ischemic CA1 area by pretreatment with 200 mg/kg of P. tomentiglandulosa extract. Briefly, our results indicate that pretreatment with P. tomentiglandulosa extract protects neurons from transient cerebral ischemic injury and diminish cerebral ischemia-induced reactive gliosis in ischemic CA1 area. Based on these results, we suggest that P. tomentiglandulosa can be used as a potential candidate for prevention of ischemic injury.