• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.506-512
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• 2012

Although pruritus is the critical symptom of atopic dermatitis that profoundly affect the patients' quality of life, controlling and management of prurirtus still remains as unmet needs mainly due to the distinctive multifactorial pathogenesis of pruritus in atopic dermatitis. Based on the distinct feature of atopic dermatitis that psychological state of patients substantially influence on the intensity of pruritus, various psychotropic drugs have been used in clinic to relieve pruritus of atopic dermatitis patients. Only several psychotropic drugs were reported to show real antipruritic effects in atopic dermatitis patients including naltrexone, doxepin, trimipramine, bupropion, tandospirone, paroxetine and fluvoxamine. However, the precise mechanisms of antipruritic effect of these psychotropic drugs are still unclear. In human skin, serotonin receptors and serotonin transporter protein are expressed on skin cells such as keratinocytes, melanocytes, dermal fibroblasts, mast cells, T cells, natural killer cells, langerhans cells, and sensory nerve endings. It is noteworthy that serotonergic drugs, as well as serotonin itself, showed immune-modulating effect. Fenfluramine, fluoxetine and 2, 5-dimethoxy-4-iodoamphetamine significantly decreased lymphocyte proliferation. It is still questionable whether these serotonergic drugs exert the immunosuppressive effects via serotonin receptor or serotonin transporter. All these clinical and experimental reports suggest the possibility that antipruritic effects of selective serotonin reuptake inhibitors in atopic dermatitis patients might be at least partly due to their suppressive effect on T cells. Further studies should be conducted to elucidate the precise mechanism of neuroimmunological interaction in pruritus of atopic dermatitis.

• Journal of Pharmacopuncture
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• v.21 no.2
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• pp.90-97
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• 2018

Silymarin is a flavonoid complex extracted from the Silybum marianum plant with a wide range of pharmacological and biochemical effects. In the present study, the immunomodulatory effects of silymarin were investigated in BALB/c mice. Silymarin was administered daily by intraperitoneal injection at doses of 50, 100 and 150 mg/kg for 14 consecutive days. Following the exposure, host hematological parameters, spleen cellularity and histopathological examination, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), splenocyte cytokine production and lymphocyte proliferation assay were studied in all of the test groups of animals. The results showed that the low dose of silymarin (50 mg/kg) could stimulate both cellular and humoral immune functions in the treated hosts. In addition, silymarin at 100 mg/kg appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that silymarin has efficient immunostimulant properties. As a recommendation, the application of silymarin along with acupuncture technique (herbal acupuncture) can be thought as a good plan to modulate and enhance the immune system for the management of several immunodeficiency disorders. However, further studies are required to demonstrate this hypothesis.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.485-491
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• 2011

Previously, we have reported that apigenin, a natural flavonoid found in a variety of vegetables and fruits, stimulated melanogenesis through the activation of $K^+-Cl^-$-cotransport (KCC) in B16 melanoma cells. In this study we investigated the possible involvement of reactive oxygen species (ROS) in the mechanism of apigenin-induced melanogenesis in B16 cells. Apigenin elevated intracellular ROS level in a dose-dependent manner. Treatment with various inhibitors of NADPH oxidase, diphenylene iodonium (DPI), apocynin (Apo) and neopterine (NP) significantly inhibited both the generation of ROS and melanogenesis induced by apigenin. In addition these inhibitors profoundly inhibited apigenin-induced $Cl^-$-dependent $K^+$ efflux, a hallmark of KCC activity. However, the apigenin-induced ROS generation was not significantly affected by treatment with a specific KCC inhibitor R-(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]acetic acid (DIOA). These results indicate that the ROS production may be a upstream regulator of the apigenin-induced KCC stimulation, and in turn, melanogenesis in the B16 cells. Taken together, these results suggest that the NADPH oxidase-mediated ROS production may play an important role in the apigenin-induced melanogenesis in B16 cells. These results further suggest that NADPH oxidase may be a good target for the management of hyperpigmentation disorders.

• YAKHAK HOEJI
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• v.51 no.3
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• pp.169-173
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• 2007

The aim of this study was to investigate the effect of morin on the pharmacokinetics of nifedipine in rats. The pharmacokinetic parameters of nifedipine were measured after the oral administration of nifedipine (5 mg/kg) in the presence or absence of morin (1.5, 7.5 and 15 mg/kg, respectively). Compared to the control groups, the presence of 7.5 mg/kg and 15 mg/kg of morin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) of nifedipine by 48.5${\sim}$68.2%, and the peak concentration (C$_{max}$,) of nifedipine by 59.9~84.2%. The absolute bioavailability(AB%) of nifedipine was significantly (p<0.05) increased by 21.5${\sim}$24.5% compared to the control (14.5%). While there was no significant change in the time to reach the peak plasma concentration (T$_{max}$) and the terminal half-life (T$_{1/2}$) of nifedipine in the presence of morin. It might be suggested that morin altered disposition of nifedipine by inhibition of both the first-pass metabolism and p-glycoprotein (P-gp) efflux pump in the small intestine of rats. In conclusion, the presence of morin significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of morin or morin-containing dietary supplement with nifedipine should require close monitoring for potential drug interaction.

• YAKHAK HOEJI
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• v.55 no.4
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• pp.332-337
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• 2011

The purpose of this study was to investigate the effect of epigallocatechin gallate (EGCG) on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral and iv administration of nimodipine with or without EGCG and also the effect of EGCG on the cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) activity were evaluated. EGCG inhibited CYP3A4 and P-gp activity. EGCG significantly increased the area under the plasma concentration-time curve (AUC) and peak plasma concentration ($C_{max}$) of nimodipine. The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by EGCG were increased by 16% and by 48%, respectively, compared to the control. In contrast, EGCG did not affect the intravenous pharmacokinetics of nimodipine. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of CYP3A4 in the small intestine and/or in the liver and inhibition of P-gp in the small intestine by EGCG.

• Bulletin of the Korean Chemical Society
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• v.30 no.3
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• pp.573-576
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• 2009

The reaction of $(en)Pd(NO_3)_2$ (en = ethylenediamine) with 1,4-bis(dimethyl-4-pyridylsilyl)benzene (L) affords cyclodimer, $[(en)Pd(L)]_2(NO_3)_4$, whereas the reaction of $(tmeda)Pd(NO_3)_2$ (tmeda = N,N,N’,N’-tetramethylethylenediamine) with L gives cyclotrimer, $[(tmeda)Pd(L)]_3(NO_3)_6$. Both complexes exist as catenane in water. The catenated cyclodimer is rigid whereas the catenated cyclotrimer is dynamic in water. The catenated cyclotrimers afford hydrogel containing 98.5% water below 2 ${^{\circ}C}$. The hydrogel changes to its sol around 38 ${^{\circ}C}$, and to its clear solution at 78 ${^{\circ}C}$. Such a notable difference between $[(en)Pd(L)]_2(NO_3)_4$ and $[(tmeda)Pd(L)]_3(NO_3)_6$ might be explained by their different dynamic behavior via ring size effects.

• Natural Product Sciences
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• v.13 no.2
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• pp.105-109
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• 2007

Alcoholic extract of Terminalia arjuna [TA] was evaluated far its hepatoprotective activity against carbon tetrachloride (CCl$_4$)-induced hepatic damage in rats. The hepatoprotective activity of TA was evaluated by measuring levels of serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP). The serum levels of total proteins(TP), total albumins (TAL) and bilirubin (BILN) were also estimated. The histological studies were also carried out to support the above parameters. Silymarin (SM) was used as standard drug. Administration of TA (250 and 500 mg/kg/po) markedly prevented CCl$_4$-induced elevation of levels of SGOT, SGPT, SALP, TP, TAL and BILN. These biochemical observations were supplemented by histopathological examination of liver sections. Alcoholic extract of TA also shown significant in-vitro free radical scavenging activity against 1, 1-diphenyl-2-picryl hydrazyl (DPPH) and nitric oxide (NO) radicals. Thus, the present study provides a scientific rationale for the traditional use of this plant in the management of liver diseases.

• Natural Product Sciences
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• v.13 no.4
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• pp.289-294
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• 2007

Ethanolic extract (50% v/v) and alkaloid fraction of Tylophora indica leaves were examined for lysosomal enzyme inhibitory activity in adjuvant-induced arthritic rats. The alkaloid fraction showed statistically significant inhibition of arthritic lesions (p < 0.05) from day 18, (p < 0.025) from day 20 and (p < 0.001) from day 21 onwards in the adjuvant-induced arthritis, which was comparable to the response of standard drug Indomethacin. The ethanolic extract was less significant than the alkaloidal fraction in inhibition of arthritis. Alkaloid fraction showed significant (p < 0.001) inhibitory effect on the lysosomal enzyme activities in adjuvantinduced arthritic rats. It also significantly prevented decrease in collagen levels and synovial damage observed during arthritis and also inhibited increase in urinary excretion levels of collagen degradation products like hydroxyproline, hexosamine, hexuronic acid, etc. Both ethanolic extract as well as the alkaloid fraction, however, did not show any significant activity in normal nonarthritic rats. The ethanolic extract and the alkaloid fraction may thus be able to inhibit the progress of inflammation and inhibit the destructive activity of lysosomal enzymes on structural macromolecules like collagen etc. in the synovial capsule in joints during arthritic states. They may thus prevent synovial damage observed during arthritis.

• CELLMED
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• v.8 no.4
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• pp.19.1-19.5
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• 2018

A majority of the peoples in Indian cities depend on high fat diet, smoking, ghutka chewing and improper sleep, these all are lifestyle changes, can cause ischemic heart disease. Globally, ischemic heart disease (IHD) is the leading killer. Unani System of medicine not only provides well-based medical cures for diseases, but its holistic approaches as it possess unique principles of diet, lifestyle and particularly therapeutics, to balance and enrich all aspects of physiology and psyche. All diseases are the result of poor management of the six governing (or essential) factors, beyond the ability of physics or Tabiat to maintain and restore homeostasis. In this context, lifestyle diseases can be prevented by conscious changes to the person's diet, behavior and environment. The holistic approach of Unani medicine is well placed to cover the two main pillars of lifestyle diseases, namely, prevention and treatment. In this paper, we report on the prevalence of CAD in patients with known diagnosis of CAD and try to find out its relationship with different lifestyle changes.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.1-20
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• 2019

Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, $Wnt/{\beta}-catenin$ and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.