The role of lipid peroxidation in modulating immune function / 药学学报

The immune system plays a pivotal role in the pathogenesis and progression of diseases. Lipid peroxidation, as a key effector molecule in the execution of ferroptosis, exerts critical effects on the functionality and survival of various immune cells and is involved in the pathological processes of multiple diseases. There is accumulating evidence suggesting the presence of ferroptosis in immune cells as well. Lipid peroxidation is closely associated with immune cell function. Accumulation of lipid peroxidation products in immune cells can lead to ferroptosis, directly impacting immune cell function. Non-immune cells, through lipid peroxidation-mediated cell death, release signaling molecules that regulate immune cell function. They jointly influence the body's homeostasis. This article provides a comprehensive review of the latest research progress on the regulatory role of lipid peroxidation in immune function. It analyzes the relationship between lipid peroxidation and immune cells, and provides a theoretical foundation for potential strategies targeting cellular lipid peroxidation and immunotherapy in the treatment of diseases.

Phospholipid remodeling and Parkinson's disease / 药学学报

The remodeling of phospholipid includes two processes: deacylation and reacylation. It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids, which is a key step in phospholipid metabolism. Phospholipids are not only the basic components of biological membranes, but also participate in the transduction of many molecular signals in cells. Therefore, phospholipid remodeling disorders can affect the structure and function of cell membranes, as well as the activity of membrane proteins, causing a series of intricate signaling cascades, and finally lead to many pathological changes including neurodegeneration. This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes, calcium independent group VIA phospholipase A2 (iPLA2β), peroxiredoxin 6 (PRDX6), calcium independent group VIB phospholipase A2 (iPLA2γ) as well as acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) in the pathology of Parkinson's disease. The mutations in the gene encoding iPLA2β, PLA2G6, have been widely reported to be directly related to hereditary Parkinson disease-14 (PARK14). Here we focus on the molecular mechanism of iPLA2β in the development of Parkinson's disease, mainly involving phospholipid fatty acid metabolism disorders, mitochondrial physiology abnormalities and α-synuclein aggregate formation and other aspects, which will help to understand the role of phospholipid remodeling in Parkinson's disease, and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.

Research progress on the detection methods and their application in ferroptosis / 药学学报

Ferroptosis is a novel type of cell death, which is distinguished from the traditional cell death pathways such as apoptosis, proptosis, necrosis and autophagy in terms of morphology, biochemistry and genetics. The main features of ferroptosis are the iron accumulation and lipid peroxidation. The regulation mechanism of ferroptosis involves glutathione metabolism, lipid peroxidation reactions and iron metabolism, which are closely related to the pathological process of tumor, aging, neurodegenerative diseases, ischemia reperfusion injury, cardiovascular and cerebrovascular diseases, kidney injury, hepatic fibrosis and so on. How to effectively study the role of ferroptosis regulation mechanism in the treatment of diseases becomes the hot spot and focus of the ferroptosis research. In recent years, with the in-depth study of ferroptosis, the identification, confirmation and the mechanism of ferroptosis have been developed significantly and have come forth continuously, in the meantime, techniques based on the morphology, biochemistry, molecular biology and genetics have been widely applied in the detection of ferroptosis. In order to deepen readers' understanding of ferroptosis and its detection methods, this paper will mainly review the current research progress on the detection methods and their application in ferroptosis, summarize and discuss their advantages and disadvantages in the detection of ferroptosis, this knowledge are crucial for better understanding and studying the biological function of ferroptosis.

The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.

Qingre Xiaoyanning Capsules alleviate HSV-1 susceptibility induced by emotional stress / 中国中药杂志

In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.

Phospholipid peroxidation: a key factor in "susceptibility" to neurodegenerative diseases / 药学学报

The biochemical integrity of the brain is necessary to maintain normal function. Oxidative damage is one of the mortal important reasons leading to the destruction of this integrity. The nervous system is enriched in phospholipid and polyunsaturated fatty acids (PUFAs). Due to the nature of high oxygen-consumption and rich lipids, brain is particularly vulnerable to oxidative damages. Phospholipid peroxidation is one of the results of imbalance in oxidation-antioxidant system. Once the antioxidant system is insufficient to resist oxidative damage, membrane phospholipids will be prone to free radical attack. Phospholipid peroxidation leads to a variety of toxic oxidation products, including membrane damage, mitochondrial dysfunction, rapid accumulation of amyloid, etc. Multiple proteins and nucleic acids can be covalently modified by peroxidation products, resulting in the loss of the protein functions, which eventually triggers programmed cell death and general neuroinflammation in brain, and ends up with an increased susceptibility to neurodegenerative diseases. Based on the knowledge of mechanisms of phospholipid peroxidation, this review focuses on the characteristics of phospholipid peroxidation as a key factor in the development of neurodegenerative diseases, in order to provide theoretical basis for targeted intervention of phospholipid peroxidation as a potential strategy to prevent neurodegenerative diseases.

Inhibitory effects of baicalein against herpes simplex virus type 1

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and widespread human pathogen, which gives rise to a range of diseases, including cold sores, corneal blindness, and encephalitis. Currently, the use of nucleoside analogs, such as acyclovir and penciclovir, in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains. Therefore, new anti-herpetic drugs and strategies should be urgently developed. Here, we reported that baicalein, a naturally derived compound widely used in Asian countries, strongly inhibited HSV-1 replication in several models. Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue (an acyclovir-resistant strain)

Fuzheng Yanggan Fomula alleviates liver injury through inhibiting NLRP3 inflammasome / 药学学报

In this study, the model of Propionibacterium acnes/lipopolysaccharide (P. acnes/LPS)-induced acute liver injury in mice was employed to investigate the protective effects of Fuzheng Yanggan Fomula (FYF) on acute liver injury. The effects of FYF on the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin-1β (IL-1β) in the serum, and the levels of malondialdehyde (MDA), oxygen radical absorbance capacity (ORAC), and glutathione (GSH) were examined in the livers of mice treated with P. acnes/LPS; The protein expression levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in liver tissues were detected by Western blot; Furthermore, hematoxylinendash-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical assay were used to observe pathological changes, apoptosis index, and inflammation infiltration of the liver tissue sections. All animal welfare and experimental procedures were followed by the Animal Ethics Committee of Jinan University. We conclude that FYF could alleviate P. acnes/LPS induced pathological damage and inflammatory infiltration in the liver of mice. Meanwhile, FYF decreases the contents of ALT, AST, IL-1β, and MDA, increases the contents of ORAC and GSH, and downregulates the expression of caspase-1 and IL-1β proteins. Collectively, these findings suggested that FYF could alleviate P. acnes/LPS induced acute liver injury in mice by inhibiting the activation of NLRP3 inflammasome, which provides a theoretical basis and a new drug target for the prevention and treatment of liver injury.

Disturbed Yin-Yang balance: stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1

Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, is able to establish a lifelong latent infection in the human host. Following primary replication in mucosal epithelial cells, the virus can enter sensory neurons innervating peripheral tissues nerve termini. The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny, and thus latency is established in the cell. Yin-Yang balance is an essential concept in traditional Chinese medicine (TCM) theory. Yin represents stable and inhibitory factors, and Yang represents the active and aggressive factors. When the organism is exposed to stress, especially psychological stress caused by emotional stimulation, the Yin-Yang balance is disturbed and the virus can re-engage in productive replication, resulting in recurrent diseases. Therefore, a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of HSV-1. Here we reviewed the recent advances in the studies of HSV-1 susceptibility, latency and reactivation. We included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections.

The prospects of ferroptosis in the pathogenesis of liver disease / 药学学报

Ferroptosis is a novel type of cell death which induced by iron-dependent lipid peroxidation accumulation. This type of cell death is significantly different from other cell death in terms of morphology, genetics and biochemistry. It has been reported that ferroptosis is involved in a variety of human diseases, particularly in liver diseases. Therefore, screening and studying of inhibitors or activators of ferroptosis may provide novel strategies for prevention and treatment of liver diseases. This review provides the biological characteristics and regulatory signaling pathways of ferroptosis, as well as the relationship between ferroptosis and liver diseases, which will contribute to new insight into the pathogenesis of liver diseases.

Anti-inflammatory effects of Reduning Injection on lipopolysaccharide-induced acute lung injury of rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the protective effects of Reduning Injection (, RDN), a patent Chinese medicine, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and its underlying mechanisms of action.</p><p><b>METHODS</b>Sixty male Sprague-Dawley rats were randomly divided into 6 groups, including normal control, model, dexamethasone (DEX, 5 mg/kg), RDN-H (720 mg/kg), RDN-M (360 mg/kg) and RDN-L (180 mg/kg) groups, with 10 rats in each group. Rats were challenged with intravenous injection of LPS 1 h after intraperitoneal treatment with RDN or DEX. At 6 h after LPS challenge, lung tissues and bronchoalveolar lavage fluid (BALF) were collected, and the number of inflammatory cells was determined. The right lungs were collected for histopathologic examination, measurement of gene and protein expressions, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities.</p><p><b>RESULTS</b>In vivo pretreatment of RDN (360, 720 mg/kg) significantly reduced the weight of wet to dry (W/D) ratio of lung, protein content in BALF, and led to remarkable attenuation of LPS-induced histopathological changes in the lungs. Meanwhile, RDN enormously decreased BALF total inflammatory cells, especially neutrophil and macrophage cell numbers. Moreover, RDN increased SOD activity, inhibited MPO activity, alleviated LPS-induced tumor neurosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression in lung tissues. Furthermore, RDN (720 mg/kg) efficiently weakened nuclear factorkappa B (NF-κB) gene and protein expression.</p><p><b>CONCLUSION</b>Anti-inflammatory effects of RDN was demonstrated to be preventing pulmonary neutrophil infiltration, lowering MPO activity, TNF-α and iNOS gene expression by inhibiting NF-κB activity in LPS-induced ALI.</p>

Anti-angiogenetic effect of arenobufagin in vitro and in vivo / 药学学报

This study is to investigate the anti-angiogenetic effect of arenobufagin in vitro and in vivo. The anti-proliferation effect of arenobufagin on CNE-2, Hep2, SH-SY5Y, LOVO, PC-3 and DU145 cells as well as human umbilical vein endothelial cells (HUVECs) was determined by MTT assay. Cell morphological changes of LOVO and HUVECs after arenobufagin treatment were observed by microscopy. Arenobufagin inhibited the proliferation of CNE-2, Hep2, SH-SY5Y, LOVO, PC-3, DU145 and HUVECs in a dose-dependent manner. Furthermore, it was obviously observed that the subcytotoxic concentration of arenobufagin in human carcinoma cells induced a marked decrease in the viability of HUVECs. Chick embryo chorioallantoic membrane (CAM) model was used to detect the anti-angiogenetic effect of arenobufagin in vivo. Arenobufagin significantly suppressed the angiogenesis of CAM. Cell cycle analysis demonstrated that G2/M phase was arrested and the sub-G1 peak appeared with the increase of arenobufagin concentration. PI/Annexin V double staining assay further demonstrated that arenobufagin could induce apoptosis in a dose- and time-dependent manner. Mitochondrial potential collapse detected by flow cytometric analysis was increased after arenobufagin treatment. It also observed that PARP was cleaved to p85 active form by Western blotting. Taken together, arenobufagin has significant anti-angiogenetic effect in vitro and in vivo, and the action mechanisms behind its anti-angiogenesis may be associated with cell cycle arrest and apoptosis of vein endothelial cells.

Anti-angiogenetic effect of arenobufagin in vitro and in vivo / 药学学报

This study is to investigate the anti-angiogenetic effect of arenobufagin in vitro and in vivo. The anti-proliferation effect of arenobufagin on CNE-2, Hep2, SH-SY5Y, LOVO, PC-3 and DU145 cells as well as human umbilical vein endothelial cells (HUVECs) was determined by MTT assay. Cell morphological changes of LOVO and HUVECs after arenobufagin treatment were observed by microscopy. Arenobufagin inhibited the proliferation of CNE-2, Hep2, SH-SY5Y, LOVO, PC-3, DU145 and HUVECs in a dose-dependent manner. Furthermore, it was obviously observed that the subcytotoxic concentration of arenobufagin in human carcinoma cells induced a marked decrease in the viability of HUVECs. Chick embryo chorioallantoic membrane (CAM) model was used to detect the anti-angiogenetic effect of arenobufagin in vivo. Arenobufagin significantly suppressed the angiogenesis of CAM. Cell cycle analysis demonstrated that G2/M phase was arrested and the sub-G1 peak appeared with the increase of arenobufagin concentration. PI/Annexin V double staining assay further demonstrated that arenobufagin could induce apoptosis in a dose- and time-dependent manner. Mitochondrial potential collapse detected by flow cytometric analysis was increased after arenobufagin treatment. It also observed that PARP was cleaved to p85 active form by Western blotting. Taken together, arenobufagin has significant anti-angiogenetic effect in vitro and in vivo, and the action mechanisms behind its anti-angiogenesis may be associated with cell cycle arrest and apoptosis of vein endothelial cells.

Effects of Sarcandra glabra extract on immune activity in restraint stress mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the protective effect of Sarcandra glabra extract (SGE) on immune system in restrained mice.</p><p><b>METHOD</b>The male C57BL/6 mice were randomly divided into normal control group, stress control group, 125, 500 mg x kg(-1) SGE group. The spleen lymphocyte suspensions of each group were prepared. The parameters of spleen T cells subsets, NK cell and NKT cell proportion and number was detected by Flow cytometry.</p><p><b>RESULT</b>SGE regulated the balance of T cell subsets, increased the percent of NK cells and NKT cell proportion and number in restrained mice.</p><p><b>CONCLUSION</b>SGE has immunologic protective effect in restrained mice probably via the amelioration of immune cells proportion and number.</p>

Beneficial effects of oolong tea consumption on diet-induced overweight and obese subjects / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the anti-obesity effects of oolong tea on diet-induced overweight or obesity.</p><p><b>METHODS</b>A total of 8 g of oolong tea a day for 6 weeks was ingested by 102 diet-induced overweight or obese subjects. The body fat level of the subjects was determined at the same time by taking body weight, height and waist measurements. The thickness of the subcutaneous fat layer was also determined on the abdomen 3 cm to the right of the navel by the ultrasonic echo method. On the other hand, effects of oolong tea ingestion on plasma triglyceride (TG) and total cholesterol (TC) were determined. Inhibitions of pancreatic lipase by oolong tea extract and catechins in vitro were also determined.</p><p><b>RESULTS</b>A total of 70% of the severely obese subjects did show a decrease of more than 1 kg in body weight, including 22% who lost more than 3 kg. Similarly, 64% of the obese subjects and 66% of the overweight subjects lost more than 1 kg during the experiment, and the subcutaneous fat content decreased in 12% of the subjects. The correlation between weight loss and subcutaneous fat decrease in men (r=0.055) was obviously lower than that in women (r=0.440, P<0.01). Body weight loss was signifificantly related to the decrease of the waist size in men (r=0.730, P<0.01) and women (r=0.480, P<0.01). Also, the correlation between subcutaneous fat reduction and decreased waist size was signifificant in women (r=0.554, P<0.01), but not in men (r=0.050, P>0.05). Moreover, the plasma levels of TG and TC of the subjects with hyperlipidemia were remarkably decreased after ingesting oolong tea for 6 weeks. In vitro assays for the inhibition of pancreatic lipase by oolong tea extract and catechins suggest that the mechanism for oolong tea to prevent hyperlipidemia may be related to the regulative action of oolong tea catechins in lipoprotein activity.</p><p><b>CONCLUSIONS</b>Oolong tea could decrease body fat content and reduce body weight through improving lipid metabolism. Chronic consumption of oolong tea may prevent against obesity.</p>

Effects of xiaoyan lidan pian extract on mice with stressive liver injury / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of Xiaoyan Lidan Pian extract (XLP) on restraint stress induced liver injury in mice.</p><p><b>METHODS</b>Liver injury mouse model was established by restraint stress. Sixty mice were equally divided into 6 groups, the normal control group, the model group, the Thiopronin group, and the three XLP groups treated with low (125 mg/kg), moderate (250 mg/kg) and high dose (500 mg/kg) XLP respectively. Effect of various treatments was evaluated by assessing alanine aminotransferase (ALT) in plasma; malondialdehyde (MDA) content in liver by thiobarbituric acid method; content of nitric oxide (NO) by Griess chemical method; hepatic antioxidant capacity index (ORAC) by fluorescent enzyme immunoassay; glutathione (GSH) content by HPLC; activity of glutathione peroxidase (GPX-Px) and glutathione S-transferase (GST) by colorimetry; activity of hepatic mitochondrial respiratory chain complex enzyme (MRCCE) by ultraviolet spectrophotometry; and contents of cytochrome a, b, c, and c1 by the redox differential spectra.</p><p><b>RESULTS</b>As compared with the model group, in the XLP groups, level of plasma ALT activity, liver content of MDA and NO, and contents of cytochromes were lower, while levels of ORAC index, GSH, GPX-Px and GST in liver, and MRCCE activity were higher.</p><p><b>CONCLUSION</b>XLP has definite protective effects on stressive liver injury in mice, which may be related to its action in alleviating the oxidative stress condition in mice.</p>

Protective effects of Guangdong Liangcha grandes on restraint stress-induced liver damage in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Guangdong Liangcha Keli on restraint stress-induced liver damage in mice.</p><p><b>METHOD</b>Thirty-five male C57BL/6J mice of 7 weeks old were divided into 5 groups randomly with 7 mice in each group: normal group, restraint stress group, 250 mg kg(-1) Vitamin C, Guangdong Liangcha Keli 500 mg kg(-1) and 250 mg kg(-1). After 18 hr restraint stress, the ALT acitivity in plasma, MDA level in plasma and liver, GSH content, GSH-PX and GST activities, NO level and ORAC value in liver were determined.</p><p><b>RESULT</b>Compared with restraint model group, Guangdong Liangcha Keli could markedly reduce ALT activity (92.75 +/- 1.91 vs 39.29 +/- 2.56, 32.69 +/- 1.46) U L(-1), and protect the liver damage induced by oxidative stress. In addition, Guangdong Liangcha Keli could effectively increase the ORAC value, GSH content, GSH-PX activity and GST activity and reduce the MDA level and NO level in liver.</p><p><b>CONCLUSION</b>Oral treatment of Guangdong Liangcha Keli is found to reduce restraint stress-induced liver damage in terms of above mentioned biochemical parameters, and these protective effects may be related to its free radical scavenging activity and lipid peroxidation inhibitory effects.</p>

Effect of Wanglaoji Cool Tea on plasma gluco metabolism and peroxidative state in stress mice / 中成药

AIM:To study the effect of Wanglaoji cool tea(WLJ)(Ilex asprella,Oroxylum indicum,polygnum chinese,Desmadium Styracifolium,Microcos Paniculata,Lophatherum gracile,Lygodium japonicum,Vitex negundo,Helicteres angustifolia,Rosa laevigate) on plasma gluco-metabolism and peroxidative state in stress mice. METHODS: The male BALB/c mice were randomly divided into normal control group,stress control group,positive control group,125 and 500 mg/kg WLJ group,which were administered samples once a day successively for 5 days.After oral administration 2 g/kg glucose into the 20 h stress mice,the elimination rate of plasma glucose,plasma ketone bodies and liver glycogen were determined.The peroxidative state in plasma and antioxidtive capacity of plasma was also measured. RESULTS: As compared with the control groups,WLJ accelerated the basic glucose metabolism of plasma,reduced the plasma ketone body and elevated the liver glycogen synthesis in stress mice.And it also decreased the level of MDA and increased the antioxidant capacity of plasma. CONCLUSION: WLJ improves the glucometabolic dysfunction in stress mice,and the mechanism might be related to the amelioration of peroxidative state in plasma.

The role of histamine in immune reactions / 中国药理学通报

Immunologic cells not only express histamine receptors, most of them but also have the abilities to produce histamine. Histamine possesses extensive biologic effects on the components of the immune system, including the antigen presenting cells, T lymphocytes and antibody isotypes, and accordingly affects the pathological processes of the inflammation, immunological diseases and tumor. On the other hand, the various cytokines produced during immune responses can regulate the synthesis and release of histamine, as well as the expressions of histamine receptors.