Showing papers in "Immunopharmacology and Immunotoxicology in 2004"
TL;DR: This is the first study of it's kind regarding the effect of alcoholic extract of Tinospora cordifolia on the activation of tumor associated macrophages and showing the antitumor effect on the spontaneous T‐cell lymphoma (DL), thus may have clinical implications.
Abstract: The present investigations were under taken to study whether the tumor-associated macrophages (TAM) of Dalton's lymphoma (DL), a spontaneous transplantable T cell lymphoma, can be activated by the alcoholic extract of medicinal plant Tinospora cordifolia (ALTC). Intraperitoneal administration of ALTC in DL-bearing mice not only augments the basic function of macrophages such as Phagocytosis as well as their antigen presenting ability and secretion of IL-1, TNF and RNI. The results of the present investigation also indicate that the intraperitoneal administration of ALTC slow down the tumor growth and increases the life span of tumor bearing host, thus showing its anti tumor effect through destabilizing the membrane integrity of DL cells directly or indirectly. This is the first study of it's kind regarding the effect of alcoholic extract of Tinospora cordifolia on the activation of tumor associated macrophages and showing the antitumor effect on the spontaneous T-cell lymphoma (DL), thus may have clinical implications.
60 citations
TL;DR: The difference in disease development and cytokine production strongly suggests that the genetic background of the immune response to CAWS contributes to the occurrence of coronary arteritis.
Abstract: The intraperitoneal administration of CAWS (water‐soluble extracellular polysaccharide fraction obtained from the culture supernatant of Candida albicans) to mice induces coronaritis similar to Kawasaki disease. We analyzed differences in the production of cytokines involved in the occurrence of coronary arteritis among mouse strains, C3H/HeN, C57BL/6, DBA/2 and CBA/J that were injected with CAWS at 4 mg/mouse for 5 consecutive days in the first week and the fifth week of administration. The incidence of arteritis was 100% in C57BL/6, C3H/HeN and DBA/2 mice, but only 10% in CBA/J mice. The coronary arteritis observed in DBA/2 mice was the most serious, with several mice expiring during the observation period. The CAWS‐sensitive strains revealed increased levels of IL‐6 and IFN‐γ during the course of a specific response to CAWS by spleen cells. In contrast, IL‐10 levels were observed to increase markedly in CAWS‐resistant CBA/J mice, but not the CAWS‐sensitive strains. However, TNF‐α levels were more eleva...
52 citations
TL;DR: It is demonstrated that dehydrocostus lactone (DL), the major sesquiterpene lactone isolated from the roots of Saussurea lappa, inhibits NF‐κB activation by preventing TNF‐α‐induced degradation and phosphorylation of its inhibitory protein I-κBα in human leukemia HL‐60 cells and that DL renders HL‐ 60 cells susceptible to TNF-α‐ induced apoptosis by enhancing caspase‐8 and casp
Abstract: Sesquiterpene lactones have raised considerable interest because of their ability to block the activation of nuclear transcription factor-kappaB (NF-kappaB). NF-kappaB plays an important role in the resistance of cancer cells to the induction of apoptosis by anticancer drugs and tumor necrosis factor-alpha (TNF-alpha). Pharmacological inhibition of NF-kappaB offers the promise of enhancing the efficacy of anticancer therapies. Here, we demonstrate that dehydrocostus lactone (DL), the major sesquiterpene lactone isolated from the roots of Saussurea lappa, inhibits NF-kappaB activation by preventing TNF-alpha-induced degradation and phosphorylation of its inhibitory protein I-kappaB alpha in human leukemia HL-60 cells and that DL renders HL-60 cells susceptible to TNF-alpha-induced apoptosis by enhancing caspase-8 and caspase-3 activities.
41 citations
TL;DR: The results strongly suggest that SMEs are effective in preventing the development of bone loss induced by OVX in rats.
Abstract: The preventive effect of Salvia miltiorrhiza extracts (SMEs) on the progress of bone loss induced by ovariectomy (OVX) was studied in rats. We measured body weight and bone histomorphometry in sham, OVX or SMEs-administered OVX rats. From light microscopic analyses, a porous or erosive appearances were observed on the surface of trabecular bone of tibia in OVX rats, whereas those of the same bone in sham rats and in SMEs-administered rats were composed of fine particles. The trabecular bone area and trabecular thickness in OVX rats decreased by 50% from those in sham rats, these decreases were completely inhibited by administration of SMEs for 7 weeks. In this study, the mechanical strength in femur neck was significantly enhanced by the treatment of SMEs for 7 weeks. In OVX rats, free T3 was normal in all cases, whereas free T4 was significantly increased. Although there was no difference between OVX and SMEs-administered rats in T3 level, we have found significant difference between them in T4 level. These results strongly suggest that SMEs are effective in preventing the development of bone loss induced by OVX in rats.
41 citations
TL;DR: Erythrocytes from the rainbow trout Salmo gairdneri Richardson were classified into immature and mature populations, respectively, by measuring longitudinal diameters and MIF activity could play a role in the accumulation of MØ in the context of functional rosettes, while the factor enhancing M Ø phagocytosis could promote clearance of CA in a more efficacious way.
Abstract: Erythrocytes from the rainbow trout Salmo gairdneri Richardson (Salmo g.R.) were classified into immature and mature populations, respectively, by measuring longitudinal diameters. More elongated fish erythrocytes (FE), classified as mature cells, were those interacting with Candida albicans (CA) in a higher frequency in terms of either binding to the fungus or its intracellular engulfment. At the same time, in the rosetting phenomenon more elongated mature FE surrounded macrophages (Mo) phagocytosing CA. Finally, FE activated by CA released in the supernatants cytokine-like factors able to modulate Mo functions. In particular, these active supernatants were analyzed for their capacity to inhibit Mo migration Macrophage Inhibition Factor (MIF) activity and enhance Mo phagocytosis. Both activities were detected in supernatants from CA stimulated FE but not in control supernatants. MIF activity could play a role in the accumulation of Mo in the context of functional rosettes, while the factor enhancing Mo phagocytosis could promote clearance of CA in a more efficacious way.
34 citations
TL;DR: It is suggested that morphine protects the primary rat neonatal astrocytes from glutamate toxicity via modulation of intracellular redox status and significantly prevents the depletion of GSH by glutamate and thereby inhibits the generation of H2O2 in a dose‐dependent manner.
Abstract: This study is designed to investigate the effect of morphine on glutamate-induced toxicity of primary rat neonatal astrocytes. Glutamate decreases the intracellular GSH level, and thereby induces cytolysis of astrocytes and C6 glial cells accompanied by apoptotic features. Glutamate-induced cytotoxicity is protected by morphine and antioxidants such as GSH and NAC, whereas MK-801, an antagonist of glutamate receptor NMDA does not protect astrocytes against glutamate toxicity. Also, morphine antagonist, naloxone, as well as selective ligands for opioid receptor subtypes, including DAMGO, DPDPE, and U69593, do not inhibit the protective effect of morphine on glutamate-induced cytotoxicity. Morphine significantly prevents the depletion of GSH by glutamate and thereby inhibits the generation of H2O2 in a dose-dependent manner. Furthermore, morphine prevents the change of mitochondrial permeability transition by glutamate. Taken together, we suggest that morphine protects the primary rat neonatal astrocytes from glutamate toxicity via modulation of intracellular redox status.
33 citations
TL;DR: A clinical case of CD occurred in a young woman 8 years after a diagnosis of lupus nephritis according to clinical, laboratory and histological criteria and confirms and extends the concept that in patients with CD a more accurate detection of autoimmune associated disorders is required.
Abstract: Association between Crohn's disease (CD) and lupus nephritis is very rare and, to the best of our knowledge, it has been described only once. We report here a clinical case of CD occurred in a young woman 8 years after a diagnosis of lupus nephritis according to clinical, laboratory and histological criteria. CD was unresponsive to steroids and immunosuppressants and, therefore, the patient was treated with anti-tumour necrosis factor alpha monoclonal antibody (Infliximab). This therapy led to the remission of both CD (50% of Crohn's Disease Activity Index--CDAI--decrease) and lupus nephritis (disappearance of pyuria in absence of infection, significant increase of serum albumin and improvement of renal function tests). The immunological background of both diseases has to be taken into account to explain either the association of the two disorders or the therapeutic response. Moreover, this clinical case confirms and extends the concept that in patients with CD a more accurate detection of autoimmune associated disorders is required.
30 citations
TL;DR: In this article, the authors examined the aromatase-inhibiting potency of intracellular aromatases and showed that they can inhibit the peripheral production of estrogen and eliminate the external supply of estrogen to the tumor cell.
Abstract: It is now well documented that a large proportion of breast tumors express their own aromatase. This intratumoral aromatase produces estrogen in situ and therefore may contribute significantly to the amount of estrogen to which the cell is exposed. Thus it is not only important that aromatase inhibitors potently inhibit the peripheral production of estrogen and eliminate the external supply of estrogen to the tumor cell, but that they in addition potently inhibit intratumoral aromatase and prevent the tumor cell from making its own estrogen within the cell. To study the inhibition of intracellular aromatase, we have examined the aromatase-inhibiting potency of the
30 citations
TL;DR: Results suggest that SB reduced the HCG‐promoted proliferation of myometrial and leiomyomal cells, suggesting that human chorionic gonadotrophin (HCG) may influences cell proliferation in uterine leiomers.
Abstract: Scutellaria barbata D. Don (Lamiaceae)(SB) is a perennial herb which is natively distributed throughout Korea and southern China. This herb is known in traditional Chinese Medicine as Ban-Zhi-Lian and traditional Korean medicine as Banjiryun, respectively. SB has been used as an anti-inflammatory and antitumor agent. We aimed to determine the expressin of cell cycle-related signal molecules for growth inhibition after HCG treatment by the herb SB in two different human myometrial smooth muscle cells (SMCs) and leiomyomal SMCs. Water-soluble ingredients of SB, myometrial SMCs and the leiomyomal cell lines were used in vitro. Uterine myomas often enlarge rapidly during pregnancy, implying that human chorionic gonadotrophin (HCG) may influences cell proliferation in uterine leiomyomata. We investigated the effects of SB on the cell proliferation and the expression of cell cycle-related proteins in these cells. Although HCG/LH receptor was present in both cultured myometrial and leiomyomal cells, as assayed by reverse transcription polymerase chain reaction analysis, treatment with HCG significantly increased cell proliferation in both myometrial and leiomyomal cells. However, SB reduced the proliferative effect of HCG in leiomyoma and myometrial cells, respectively. In HCG-treated leiomyomal cells, the expression of proliferating cell nuclear antigen, cyclin E and cdc2 was significantly reduced by SB treatment. These results suggest that SB reduced the HCG-promoted proliferation of myometrial and leiomyomal cells.
28 citations
TL;DR: WSC has potential regulatory effects on allergic inflammatory diseases by down‐modulating Ca2 +‐induced mast cell activation, and is suggested to be a viable treatment for these diseases.
Abstract: Mast cells are known to play an active role as effector cells in allergic inflammation and in diverse immunological and pathological processes. Activated mast cell‐derived pro‐inflammatory cytokine...
28 citations
TL;DR: This is the first study to examine the immunotoxicological effects of PYR and demonstrate that this compound selectively suppresses humoral antibody responses.
Abstract: Pyridostigmine bromide (PYR) is an anticholinesterase drug indicated for the treatment of myasthenia gravis and neuromuscular blockade reversal. It acts as a reversible cholinesterase inhibitor and was used as a pretreatment for soldiers during Operation Desert Storm to protect against possible nerve gas attacks. Since that time, PYR has been implicated as a possible causative agent contributing to Gulf War Illness. PYR's mechanism of action has been well-delineated with regards to its effects on the nervous system, yet little is known regarding potential effects on immunological function. To evaluate the effects of PYR on immunological function, adult female B6C3F1 mice were gavaged daily for 14 days with PYR (0, 1, 5, 10, or 20 mg/kg/day). Immune parameters assessed were lymphoproliferation, natural killer cell activity, the SRBC-specific antibody plaque-forming cell (PFC) response, thymus and spleen weight and cellularity, and thymic and splenic CD4/CD8 lymphocyte subpopulations. Exposure to PYR did not alter splenic and thymus weight or splenic cellularity. However, 20 mg PYR/kg/day decreased thymic cellularity with decreases in both CD4+/CD8+ (20 mg/kg/day) and CD4-/CD8- (10 and 20 mg/kg/day) cell types. Functional immune assays indicated that lymphocyte proliferative responses and natural killer cell activity were normal; whereas exposure to PYR significantly decreased primary IgM antibody responses to a T-cell dependent antigen at the 1, 5, 10 and 20 mg/kg treatment levels for 14 days. This is the first study to examine the immunotoxicological effects of PYR and demonstrate that this compound selectively suppresses humoral antibody responses.
TL;DR: It is demonstrated that BCE has an anti‐allergic potential and it may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.
Abstract: Black cohosh (Cimicifuga racemosa) has been used as therapeutics for pain and inflammation in Korean folk medicine. The potential effects of black cohosh extract (BCE) on mast cell-dependent allergy reaction, however, have not been well elucidated yet. In the present study, we investigated the effect of BCE on the allergy reaction using mast cell-dependent in vivo and in vitro models. BCE showed no potential of skin sensitization in local lymph node assay (LLNA). The oral administration of BCE significantly inhibited the anti-IgE-induced passive cutaneous anaphylaxis (PCA) reaction. BCE also showed inhibitory potential on the compound 48/80-induced histamine release from rat peritoneal mast cells. In addition, BCE inhibited the IL-4, IL-5 and TNF-alpha mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. These results demonstrated that BCE has an anti-allergic potential and it may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.
TL;DR: It is speculated that the physiological alterations induced by the EAT growth can be used to assess the ability of compounds to modulate the hematopoietic response.
Abstract: In previous works, we have demonstrated that the myeloprotective properties of several natural and synthetic compounds are partly responsible for their antitumor activity in the Ehrlich ascites tumor (EAT) model. In this work, we present information that may be useful to the study of pharmacological and toxicological properties of compounds that affect the hematological compartment. Clonogenic studies in EAT-inoculated mice demonstrated a rapid decrease in bone marrow CFU-GM, whereas a progressive increase in splenic CFU-GM and cellularity was observed, followed by splenomegaly. Bone marrow cellularity declined on the third day after tumor challenge, returning to normal values thereafter. Serum from EAT-bearing mice produced detectable colony-stimulating activity in vitro. Similar results were observed with the conditioned medium from Ehrlich tumor cell cultures, but not with the cell-free Ehrlich tumor ascitic fluid. Tumor inoculation also resulted in a more striking depletion in the number of non-adherent cells in long-term bone marrow cell cultures (LTBMCs) with no bone marrow stroma formation. We speculate that the physiological alterations induced by the EAT growth can be used to assess the ability of compounds to modulate the hematopoietic response.
TL;DR: The effects of a Korean traditional prescription, Geiji‐Bokryung‐Hwan (GBH), consisting of five herbs of Cinnamomi Ramulus, on tumor growth‐inhibitory activity and cancer chemopreventive activity in assays representing three major stages of carcinogenesis are investigated.
Abstract: We investigated the effects of a Korean traditional prescription, Geiji-Bokryung-Hwan (GBH) consisting of five herbs of Cinnamomi Ramulus (Korean name Geiji), Poria cocos (Bokryung), Moutan Cortex Radicis (Modanpi). Paeoniae Radix (Jakyak) and Persicae Semen (Doin) on tumor growth-inhibitory activity and cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Effects of the GBH extracts on carrageenan-induced edema inflammation using female (C57BL/6XC3H) F1 (B6C3F1) mice and tumorigenesis were examined. Finally, cyclooxygenase metabolites were determined after extracts treatment. These data suggest that GBH extracts merits investigation as a potential cancer chemopreventive agent in humans.
TL;DR: It is suggested that salicylate exerts its anti‐inflammatory action in part through inhibition of the ERK, IKK, IκB, NF‐κB and resultant COX‐2 expression pathway.
Abstract: The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation and can be inhibited with sodium salicylate. TNF-alpha plus IFN-gamma can induce extracellular signal-regulated kinase (ERK), IKK, IkappaB degradation and NF-kappaB activation. The inhibition of the ERK pathway with selective inhibitor, PD098059, blocked cytokine-induced COX-2 expression and PGE2 release. Salicylate treatment inhibited COX-2 expression induced by TNF-alpha/IFN-gamma and regulated the activation of ERK, IKK and IkappaB degradation and subsequent NF-kappaB activation in MC3T3E1 osteoblasts. As well, antioxidant-catalase, N-acetyl-cysteine or reduced glutathione-attenuated COX-2 expression in combined cytokines-treated cells. These antioxidants also inhibited the activation of ERK, IKK and NF-kappaB in MC3T3E1 osteoblasts. In addition, TNF-alpha/IFN-gamma stimulated ROS release in the osteoblasts. However salicylate had no obvious effect on ROS release in DCFDA assay. The results showed that salicylate inhibited the activation of ERK and IKK, IkappaB degradation and NF-kappaB activation independent of ROS release and suggested that salicylate exerts its anti-inflammatory action in part through inhibition of the ERK, IKK, IkappaB, NF-kappaB and resultant COX-2 expression pathway.
TL;DR: The results suggest that the antiasthmatic effect of DCT is mainly due to its bronchodilatation effect and its ability to inhibit the eosinophil into the airway and there is prophylactic effect ofDCT on allergen‐induced airway inflammation.
Abstract: Ding-Chuan-Tang (DCT), a traditional Chinese medicine, has been used in treatment of the bronchial asthma for several centuries. However, the therapeutic mechanism of these Chinese medicine are still far from clear. To understand the mechanism of antiasthmatic property of DCT. A guinea pig model of allergic asthma was used to investigate the effects of DCT on ovalbumin-induced early and late asthmatic responses and airway inflammation, particularly the extent of eosinophil infiltration, and examine it direct beta2-adrenoceptor agonist activity in guinea-pig isolated trachea. We had used three different protocals in ovalbumin sensitized guinea pigs by administrating 10 g/kg of DCT extracts to sensitized guinea pigs 30 min before antigen challenge (group I), 5 hr after antigen challenge (group II) and 2.5 g/kg once daily from the day of sensitization to the day of challenge. Our result showed that administration of DCT singificantly inhibited the antigen induced immediate asthmatic responses (IAR) in group I and inhibited both IRA and late asthmatic responses (LAR) in actively sensitized guinea pig in group III. DCT caused concentration-dependent relaxations in strips of guinea pig trachea contracted with carbachol, however ICI-118551, a selective beta2-adrenoceptor antagonist, didn't significantly competitively inhibit the relaxations caused by DCT. Furthermore, examination of bronchoalveolar lavage fluid (BALF) revealed that DCT significantly inhibited the increase in percent of eosinophils in the airway after antigen challenge in three group. Histopathologic examination showed DCT suppressed the eosinophil infiltration into lung tissue. These results suggest that the antiasthmatic effect of DCT is mainly due to its bronchodilatation effect and its ability to inhibit the eosinophil into the airway and there is prophylactic effect of DCT on allergen-induced airway inflammation.
TL;DR: The results showed that 14‐day treatment with 0.8 ml daily dosage of CKBM could inhibit 54.1% of tumor growth, and the plasma activities of enzymes specific for heart and liver, remained at normal levels, indicated that CKBM did not produce toxicity to the host.
Abstract: Hepatocellular carcinoma is a major health problem worldwide. Different treatment strategies have been developed to cope with this problem. Herbal medicine is now widely studied in both Eastern and Western countries. In this study, we used both in vitro and in vivo model to illustrate the anti-tumor effect of a product, CKBM, consisting of herbal medicine and specially processed Saccharomyces cerevisiae. Dose-dependent anti-proliferation effect was observed on in vitro growth of human hepatoma HepG2 cells after 48 hours incubation with CKBM. At the 50% inhibitory concentration (IC50) no significant toxic effect was observed on normal human fibroblasts Hs68 and human liver WRL-68 cells. The results of morphological changes, detection of DNA fragmentation, flow cytometric analysis and Western blot analysis indicated that this anti-tumor effect of CKBM was mediated via the process of apoptosis. In addition, HepG2 cells- bearing nude mice model was used for in vivo anti-tumor study. Our results showed that 14-day treatment with 0.8 ml daily dosage of CKBM could inhibit 54.1% of tumor growth. The plasma activities of enzymes specific for heart and liver, namely creatine kinase, lactate dehydrogenase, aspartate transaminase and alanine transaminase, remained at normal levels, indicated that CKBM did not produce toxicity to the host.
TL;DR: This is the first report on the genetic diversity in geographical origin among Astragali radix populations using RAPD analysis, and broader application of this approach to authenticate other morphologically similar medicinal materials is rationalized.
Abstract: The randomly amplified polymorphic DNA (RAPD) analysis has been applied for estimating genetic diversity in plant populations or cultivars. To discriminate geographical origin among Astragali radix populations, RAPD analysis was carried out using 20 mer-random primers. The similarity coefficient between the DNA of Astragali radix plants analyzed was 0.527. Although the coefficients of similarity were high, primer 7, 8 and 10 gave distinguishable bands between Korean and Chinese Astragali radix. We obtained the specific RAPD markers to discriminate between Korean and Chinese Astragali radix at a DNA level. These results suggest that this method is able to discriminate the concerned Astragali radix geographical origin species. Also, this is the first report on the genetic diversity in geographical origin among Astragali radix populations using RAPD analysis. Broader application of this approach to authenticate other morphologically similar medicinal materials is rationalized.
TL;DR: Investigation of the effect of aqueous extract of Stachys riederi var.
Abstract: The effect of aqueous extract of Stachys riederi var. japonica Miq. (Labiatae) (SRAE) on the mast cell‐mediated allergic and inflammatory reactions were investigated. SRAE inhibited systemic allerg...
TL;DR: The data suggest that M‐2000 therapy can ameliorate proteinuria, and suppress the progression of glomerular lesions in experimental model of nephrosis.
Abstract: The therapeutic effect of M-2000 (C6H10O7) molecule was tested in Adriamycin-induced nephropathy. To induce experimental nephrosis, Adriamycin was given once by a single intravenous injection (7.5 mg/kg) through the tail vein. Six days after injection of Adriamycin, therapeutic protocol was developed by intraperitoneally (i.p) administration of 30 mg/kg M-2000 solution. Total of i.p. injections were 14, in which five injections were made every day and nine injections were carried out at regular 48-h intervals. Therapeutic protocol was terminated on day 28 and animals were killed on day 43. The treated patient rats showed a significant reduction in proteinuria, BUN, serum creatinine and serum cholesterol, as well as, administration of M-2000 could significantly diminish the serum level of interleukin-6 (IL-6) in treated animals compared to non-treated controls. Moreover, treatment with M-2000 significantly reduced number of glomerular leukocytes, Hypercellularity and hydropic change in capillary network within the renal cortex and decreased tubular casts. These data suggest that M-2000 therapy can ameliorate proteinuria, and suppress the progression of glomerular lesions in experimental model of nephrosis.
TL;DR: This vaccine, when inoculated into mice, inhibits angiogenesis in response to FGF‐2 in a hepatic sponge model as well as tumor progression in two models of pulmonary metastatic disease and reproductive studies, and characterize the immunological and physiological responses to this vaccine.
Abstract: Angiogenesis, the process of new capillary formation from pre‐existing vessels, has been established as an important mechanism involved in pathologic processes, such as cancer, as well as in normal physiology (Ribatti, D.; Vacca, A.; Roncali, L.; Dammacco, F. Angiogenesis under normal and pathological conditions. Haematologica 1991, 76 (4), 311–320). Basic fibroblast growth factor (FGF‐2) is a critical mediator of angiogenesis that is important for normal reproduction and wound healing. FGF‐2 mediates its pro‐angiogenic effects by binding to heparin sulfate proteoglycan in addition to a tyrosine kinase receptor (Baird, A.; Schubert, D.; Ling, N.; Guillemin, R. Receptor and heparin‐binding domain of basic fibroblast growth factor. Proc. Natl. Acad. Sci. U. S. A. 1998, 5 (7), 2324–2328; Richard, C.; Roghani, M.; Moscatelli, D. Fibroblast growth factor (FGF)‐2 mediates cell attachment through interactions with two FGF receptor‐1 isoforms and extracellular matrix or cell‐associated heparin sulfate proteoglyca...
TL;DR: The results suggest that protein tyrosine kinase participates in fMLP‐mediated superoxide generation by HOT‐treated human neutrophils, and indicates that HOT exerts anti‐inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E2 production, which could be due to a decreased expression of iNOS and COX‐2.
Abstract: Hwaotang, a traditional Korean medicinal formulation, is a dried decoctum of a mixture of 7 herbal medicines, consisting of Angelica gigantis Radix, Rehmanniae radix, Paeoniae radix, Ciniamomi cortex, Cnidii rhizoma, Persicae semen and Carthami flos. We have investigated that Hwaotang water extract (HOT) has various effects on stimulus‐induced superoxide generation in human neutrophils. The effects of HOT on superoxide generation in human neutrophils were investigated. HOT significantly inhibited N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐induced superoxide generation in a concentration‐dependent manner, but not that induced by arachidonic acid (AA). On the other hand, HOT enhanced superoxide generation induced by phorbol 12‐myristate 13‐acetate (PMA) in a concentration‐dependent manner. The superoxide generation induced by PMA with HOT was suppressed by staurosporine, an inhibitor of protein kinase C, but was not suppressed by genistein, an inhibitor of protein tyrosine kinase. Tyrosyl phosphorylatio...
TL;DR: The results suggest that Ninjin‐youei‐to as well as Hochu‐ekki‐to suppress porcine serum‐induced liver fibrosis more effectively than Sho‐saiko‐to.
Abstract: In this study, we estimated the effects of traditional Japanese medicines on liver fibrosis in Wistar rats injected with porcine serum twice a week for 8 weeks. The rats were orally administered Hochu-ekki-to, Ninjin-youei-to (100 and 300 mg/kg/day) or Sho-saiko-to (300 mg/kg/day) 5 days per week. Serum and liver samples were obtained 2 days after the last porcine serum injection. Hochu-ekki-to and Ninjin-youei-to showed significant suppressive effects on the increase in hepatic hydroxyproline, namely total collagen. Further, Ninjin-youei-to significantly suppressed the increases of type IV collagen localized in the basement membrane and prolyl 4-hydroxylase, a collagen synthesis enzyme, in serum or liver. Hochu-ekki-to showed a similar trend. Although Sho-saiko-to did not significantly suppress the increase in hepatic hydroxyproline, it intensely suppressed serum type IV collagen. Further, Hochu-ekki-to, Ninjin-youei-to, and Sho-saiko-to inhibited the production of fibrogenic cytokines, namely TGF-beta1 and IL-13, in the serum and liver. Additionally, we showed that IL-13 levels were positively correlated with hydroxyproline contents in the liver. These results suggest that Ninjin-youei-to as well as Hochu-ekki-to suppress porcine serum-induced liver fibrosis more effectively than Sho-saiko-to. The effects of these three medicines probably depend on the inhibition of fibrogenic cytokine production, resulting in the suppression of collagen synthesis and deposition in the liver, though different mechanisms underlie their anti-fibrogenic effects.
TL;DR: A 42‐years‐old non‐atopic man who developed a severe eczematous reaction in the genital area some hours after the use of a condom (Settebello‐Hatù® Durex) containing a retarding cream is described.
Abstract: We describe the case of a 42-years-old non-atopic man who developed a severe eczematous reaction in the genital area some hours after the use of a condom (Settebello-Hatu Durex) containing a retarding cream. Patch test revealed a strong allergic reaction to the retarding cream and to benzocaine and paraben mix contained in the cream itself. Condoms with retarding cream should be avoided in man sensitized to local anestethetics.
TL;DR: The possible role played by polyamines in the pathogenesis of periodontal disease by dysregulating apoptosis of gingival PMN is discussed.
Abstract: Apoptosis provides a mechanism for clearance of unwanted cells in a variety of situations in which programmed or physiological cell death occurs; but the premature death of defensive cells could promote infection, inflammation and concomitant diseases. Polymorphonuclear cells (PMN) of gingival sulcus play an important role in host defense against periodontal tissue-invading bacteria, but their phagocytic activity is conditioned by several virulence factors released by oral pathogens. Polyamines derived from oral bacteria frequently occur at concentrations approaching 1 mM in gingival fluid at diseased periodontal sites. Brief exposure of PMN to polyamines shortened the lag culture time required to observe microscopical or DNA fragmentation traces. Increase of Fas/Apo-1 expression and caspase-8 and caspase-3 activation focused two typical steps in the pathway of the pro-apoptotic mechanism exhibited by polyamines, even if to a different extent: spermine > spermidine > putrescine. The possible role played by polyamines in the pathogenesis of periodontal disease by dysregulating apoptosis of gingival PMN is discussed.
TL;DR: It is suggested that JNK/SAPK is related to cAMP‐protective effect in SNP‐induced apoptosis, and cAMP relating agents protected SNP‐ induced cell death in neonatal rat ventricular cardiomyocytes.
Abstract: Cyclic adenosine monophosphate (cAMP) modulates various agent-induced apoptosis. In this study, we observed that cAMP had a significantly protective effect on nitric oxide (NO)-induced cytotoxicity in H9c2 cardiac muscle cells. Pretreatment with DBcAMP (cAMP analogue) or forskolin (adenylyl cyclase activator) also significantly prevented the SNP-induced apoptosis in H9c2 cells. In contrast, H-89 or KT5720 (PKA inhibitor) reversed the protective effects of DBcAMP. In this study, DBcAMP or forskolin reduced SNP-induced JNK/SAPK activation to the basal level, but KT5720 reversed the inhibitory effects of these two agents. In contrast to JNK/SAPK activation, DBcAMP and forskolin significantly enhanced SNP-activated p38 MAPK phosphorylation and did not affect SNP-mediated ERK activation. KT5720 reversed the effects of DBcAMP and forskolin on p38 MAPK phosphorylation. The inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK/SAPK markedly reduced the extent of SNP-induced cell death. Taken together, we suggest that JNK/SAPK is related to cAMP-protective effect in SNP-induced apoptosis. In addition, c-AMP relating agents protected SNP-induced cell death in neonatal rat ventricular cardiomyocytes. The cAMP-relating agent-induced protective effect is not restricted in H9c2 cardiac muscle cells.
TL;DR: The results revealed neither weight difference nor pathological change among the four groups, however, serum‐cytokine assay indicated that the cytokine modulation effects are consistent, and the most obvious cytokineModulation effect was observed in group D, which was the highest dosage employed for treating the mice.
Abstract: An experiment was conducted to investigate the effects of Yi-Fey Ruenn-Hou (YR) Tea, a combination of Chinese herbs, 10% licorice root, 10% American ginseng, 10% Radix Paeoniae alba and 70% green tea-soaked solution, on the cytokine modulation in Balb/C mice. Four groups of mice were administered either 1ml of drinking water (group A) or 2 mg/ml (group B), 8 mg/ml (group C), 40 mg/ml (group D) of a saturated solution of combined Chinese herbs daily for six months. The physiological and pathological characteristics of the mice were observed during the time, and the mice were weighed and at least two mice were sacrificed each month for pathological detection of the brain, heart, liver, spleen and kidney and cytokine analysis. The results revealed neither weight difference nor pathological change among the four groups, however, serum-cytokine assay indicated that the cytokine modulation effects are consistent, and the most obvious cytokine modulation effect was observed in group D, which was the highest dosage employed for treating the mice. TH2-pattern cytokines responded earlier and higher in group D than in groups B and C. Furthermore, the effect of YR Tea on cytokine modulation in vivo is predominantly TH2-pattern and is dependent on its dosage (P < 0.05).
TL;DR: It is indicated that CKBM may modulate the immune response by inducing the secretions of TNF‐alpha and IL‐6, which are cytokine mediators of innate immunity and inflammation preparing or “priming” the body to combat diseases.
Abstract: The current study investigated the immunomodulating effect of CKBM on cytokine induction in peripheral blood mononuclear cells (PBMCs) isolated from 20 healthy volunteers. Cytometric Bead Analysis (CBA) was used to study IL-2, IL-4, IL-6, IL10, TNF-alpha and IFN-gamma. TNF-alpha and IL-6 were significantly increased in a CKBM dose- and time-dependent manner. Flow cytometry analysis showed an increased intracellular staining of IL-6 but not of TNF-alpha in CKBM treated PBMCs. In addition, MTT cell cytotoxicity assay showed that CKBM concentrations below 5% did not significantly affect the metabolic activities of PBMCs. The current study indicated that CKBM may modulate the immune response by inducing the secretions of TNF-alpha and IL-6, which are cytokine mediators of innate immunity and inflammation preparing or ‘‘priming’’ the body to combat diseases.
TL;DR: The data suggest that the anti‐inflammatory mechanism of thalidomide is not related to events associated with the oxidative burst of PMNs or monocytes, and this effect on cell membranes is not affected after exposure to different concentrations of hypotonic NaCl solution.
Abstract: The anti-inflammatory effect of thalidomide has been well established. The mechanism of this anti-inflammatory action is still not completely understood. Certain drugs exert their anti-inflammatory action by stabilizing the membranes of polymorphonuclear neutrophils (PMN) thereby reducing the production of reactive oxygen intermediates. We evaluated the effect of thalidomide on cell membranes by using red blood cells (RBC), PMN and the monocyte-like cell line THP-1. Osmotic fragility of RBC showed that in vitro, thalidomide stabilized the membrane of RBC from plasma free blood; whereas, it did not affect RBCs from whole blood. Red blood cells taken from subjects before and after ingestion of thalidomide were not affected after exposure to different concentrations of hypotonic NaCl solution. Thalidomide did not affect the membrane stability of PMNs as well as THP-1 in a significant manner. These data suggest that the anti-inflammatory mechanism of thalidomide is not related to events associated with the oxidative burst of PMNs or monocytes.
TL;DR: Ethanol extracts‐DR and water extracts-DR were identified as potent inhibitor of cathepsins K and L and it is suggested that this increase in potency is probably due to an enhanced chemical reactivity of the extract mixtures toward the thiolate of the active site of the enzyme.
Abstract: Effects of traditional Korean (Hanbang) medicine, Drynariae rhizoma (DR), on the protease activity of bone loss‐initiation in rats and mice were investigated. Ethanol extracts‐DR (EE‐DR) and water extracts‐DR (WE‐DR) were identified as potent inhibitor of cathepsins K and L. The original WE‐DR inhibits cathepsins K and L with IC50 values of 3.7 µg/ml and 4.5 µg/ml, respectively. EE‐DR was more potent than that of WE‐DR, because the inhibitions of cathepsin K and L increased to 0.5 µg/ml and 0.8 µg/ml, respectively. The EE‐DR was proved to be the most potent. EE‐DR was found to be a potent inhibitor of cathepsins K with a Ki value of 5.0 µg/ml for cathepsin K. The activity was increased by 10‐fold when the assay is performed in the presence of glutathione at pH 7.0, which favors the formation of a GSH thiolate anion. Thus, it is suggested that this increase in potency is probably due to an enhanced chemical reactivity of the extract mixtures toward the thiolate of the active site of the enzyme. WE‐DR exhib...