Abstract:

Abstract:InflammationSis a defense mechanism that protects human body from harmful stimuli. However, uncontrolled inflammationScan lead to damage to tissues locally or systemically. Studies, including ours, have shown that Chinese traditional medicines (CTM) exert significant anti-inflammatory effects through the inhibition of cAMP-PDEs activity. We aimed to provide an overview of cAMP-mediated modulatory effects of cAMP-PDEs-selective CTM on key proteins of inflammatory signaling pathways, mainly involving inhibition of NF-κB, MAPKs (p38, ERK, or JNK), TLR, MyD88, and STAT3, and activation of Nrf2, HO-1, AMPK, and PPARγ. Among them, inhibition of NF-κB is the most important way to play anti-inflammatory roles for all cAMP-PDEs-selective CTM.

Abstract:Luteolin is able to inhibit the adhesion of neutrophils to microvascular endothelial cells (MEC) and plays an anti-inflammatory role through regulating vascularScellSadhesion molecule (VCAM)-1 in MEC. The inhibitory mechanism is related to three signaling pathways: mitogen activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB)/IκB, and phosphatidylinositol-3-kinase (PI3K) /Akt pathways. The pathways (MAPK and NF-κB/IκB) are involved in the positive regulation of VCAM-1, and the PI3K/Akt pathway participates in the negative regulation. We determined the effects of luteolin on phosphorylation of p38 MAPK, p65 NF-κB, and p85 PI3K, which are key proteins in the mentioned pathways, respectively. Luteolin promotes the phosphorylation of p38 MAPK at different time intervals (30 s, and 1 min) and p85 PI3K (30 s, 1 min, and 5 min); but significantly inhibits the phosphorylation of p65 NF-κB (30 s, 1 min, 5 min, and 30 min) in MEC. As our results show, inhibition of p38 MAPK pathway induces downregulation of VCAM-1. Furthermore, inhibition of the phosphorylation of p38 MAPK via SB203580, a p38 MAPK inhibitor, also downregulates VCAM-1, suggesting that the regulation of VCAM-1 in the presence of luteolin in MEC is independent upon the p38 MAPK phosphorylation. This is to say luteolin regulates VCAM-1 expression in MEC through either inhibiting p65 NF-κB phosphorylation or promoting p85 PI3K phosphorylation. This work may provide an insight for the molecular mechanism in the anti-inflammatory effect of luteolin.

Abstract:Herba Epimedii (yinyanghuo in Chinese) is a commonly used traditional Chinese medicine. Flavonoids are the major effective ingredient of Herba Epimedii, icariin is the most abundant component in Epimedium flavonoids, and icaritin is the metabolite of icariin. In the last decade, a number of studies on the pharmacological effects of Epimedium extracts have been conducted. Emerging evidence has shown that Epimedium flavonoids, especially icariin and its derivatives, have anti-inflammatory effects in the animal and cellular models on a variety of diseases related to chronic inflammation, including osteoporosis, osteoarthritis, neurological and psychiaric disorders, atherosclerosis, asthma and lung diseases, inflammatory bowel diseases, kidney diseases, skin diseases, autoimmune diseases, and cancer. The molecular mechanisms involved in anti-inflammation effects of icariin and its derivatives include reducing inflammatory cytokines, down-regulating NF-κB signaling, NLRP3/caspase-1/IL-1β axis, STAT signaling and MAPK pathway, as well as up-regulating Nrf2/ARE/HO-1 pathway and increasing glucocorticoid receptor and estrogen receptor signaling. In this review, we have updated the recent advances in this field, and these studies have suggested that Epimedii and its active compounds have potential to treat multiple diseases related to chronic inflammation.

Abstract:Inflammation plays a vital role in the pathophysiology of ischemic stroke. Resident microglia are the first to respond to inflammatory response in cerebral ischemia. Traditionally, Microglia are regard as an important contributor to inflammation to aggravate brain injury. However, Recent studies have found that activated microglia exert anti-inflammatory production against ischemic injury. Future therapies targeting microglia may not exclusively aim at suppressing microglia activation, but also at modulating microglia polarization at different stages of ischemic stroke. With lacking effective therapy strategies for stroke, considerable attention has been attracted by Chinese Traditional Medicine (TCM). Many studies have reported that TCM protects ischemic injury by inhibiting activation of microglia and promote the different polarization of microglia phenotypes. The effects of TCM in mediating microglia activation and polarization during cerebral ischemia need to be further studied.

Abstract:Alzheimer's disease (AD) is the most common neurodegenerative disorders of the central nervous system (CNS). Its pathogenesis is complex and needs to be further studied. Recent findings have shown that inflammation, which is characterized by the excessive activation of microglias to produce inflammatory factors, is closely related to the pathogenesis of AD. Improper regulation of microglial receptors and their downstream pathways impair immune homeostasis in AD patients and AD experimental animals. Natural small-molecule compounds reverse the immune imbalance and retard the progresses of AD via inhibting the microglial pro-inflammatory receptors, activating microglial anti-inflammatory receptors and regulating the receptors involved in Aβ clearance. In this paper, we reviewed the mechanisms of chronic inflammation caused by microglias in AD, and summarized the beneficial effects of natural small-molecule compounds in AD immune homeostasis by regulating microglial receptors and their downstream pathways.

Abstract:This review summarizes recent progress of the anti-inflammatory effect of traditional Chinese medicine on neurocognitive disorders caused by Alzheimer"s disease (AD) and Parkinson’s disease (PD), and discusses some novel molecular mechanisms of traditional Chinese medicine (such as Xylocoside G, Formononetin, Honokiol, Sodium oligomannate and safflower flavonoid extract), including the regulation on Aβ generation and aggregation, tau phosphorylation, gut-brain axis and gut microbiota, autophagy, microglia polarization, extracellular space, neurogenesis and neurotransmission, for the treatment of AD and PD related neurocognitive disorders.

Abstract:Diabetes mellitus is one of the most devastating metabolic disorders affecting physiology of several organs. Type 2 diabetes (T2D) is the most prevalent type of diabetes worldwide, and . T2D usually affects elder population. and cClinical and basic studies have highlighted its involvement in cognition decline especially learning and memory. T2D individuals are at high risk to develop dementia as compare to normal population. This paper reviews highlighted the recent studies which demonstrated cognitive decline among T2D individuals and in animal models, including the related mechanisms and, the therapies, to make a better knowledge on T2D cognitive complication.

Abstract:Background: The continuous development of deep space exploration, the potential threat of war, and the occurrence of nuclear accidents increase our exposure to irradiation. Irradiation-induced neuroinflammation is one of the important aspects. The occurrence of neuroinflammation is closely related to neurodegenerative diseases such as Alzheimer"s disease (AD) and Parkinson"s disease (PD). The development of traditional Chinese medicines (TCM) with antioxidant and anti-inflammatory effects has positive implications for irradiation-induced damage to the central nervous system (CNS). Conclusion: Traditional Chinese medicine dragon"s blood has a good effect on the treatment of radiation-induced neuroinflammation. This review summarizes the role of dragon"s blood in reducing oxidative stress levels, expression of related inflammatory factors, and mitochondrial damage. At the same time, we propose that endogenous neurotoxins may aggravate brain-induced neuroinflammation which might be alleviated by dragon"s blood.

Abstract:Cognitive deficits were one of the core symptoms of depression, which has become a major challenge in the treatment of depression. Ormosia henryi Prain (OHP) is a green perennial tree widely distributed in southern China. Previous studies demonstrated that it has antidepressant effects. However, the effect of OHP on cognitive deficits has not been elucidated. The aim of the present study was to investigate the effect of OHP on cognitive deficits caused by chronic stress. A mice model of chronic unpredictable mild stress (CUMS) was established to evaluate the cognitive improvement effect of OHP. Cognitive behavior was assessed with novel object recognition and Morris water maze test. The levels of GFAP and Aβ protein in the hippocampus were analyzed by immunohistochemistry. The results showed that OHP significantly improved the short-term memory which presented as the increased discrimination index, and also alleviated the deficits of spatial learning and memory manifested as a decrease in the escape latency to reach the platform and an increase in the number of platform crossing. OHP could significantly increase the levels of 5-HT and DA、NE in hippocampal tissue. Moreover, it increased the levels of GFAP and reduced Aβ-positive cells in the CA1 region of the hippocampus of stressed mice. In short, this study demonstrates for the first time that OHP significantly improves the learning and memory abilities of chronic stress mice which may be related to the up-regulation of GAFP and down-regulation Aβ in the hippocampus, indicating that OHP may be a new potential drug for the treatment of cognitive disorders caused by chronic stress.

Abstract:Fibronectin (FN) is an important molecule that participates in hepatitis B infection and fibrosis. Lumbrokinase (LK) is synthesized by earthworms containing a group of proteolytic isozymes, which were used to hydrolyze fibrin in the treatment of clotting disease. One of the isozymes purified from the LK compound was verified as a hydrolase to degrade FN in vitro and was called earthworm fibronectin hydrolase (EFNase). However, whether LK functions to prevent the deterioration of hepatitis B virus (HBV) infection has not been clarified. In this study, we used HepG2.2.15 cells to investigate the effect of LK on the level of hepatitis B surface antigen (HBsAg) or FN, used C57BL/6J-HBV transgenic mice to explore the effect on the level of HBsAg, FN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, the pathological changes in livers. The results indicated that LK could inhibit HBsAg production in vitro and in vivo; decreased FN in serum and liver. Compared with physiological saline, LK improved the state of the livers. Those data provided valuable information to understand the therapeutic role of LK as a potentially effective medicine to treat chronic hepatitis B (CHB).

Abstract:Liver is the largest substantial organ in the abdominal cavity and it provides an essential role in maintaining the basic physiological functions. Liver diseases have become one of the common and frequently-occurring diseases that affect 10% of the population worldwide, usually with liver fibrosis as the late stage pathological characteristic. Due to the complexity of pathogenesis, there is no effective synthetic drug to treat liver fibrosis up to date. Traditional Chinese medicine (TCM) has the advantages of multiple targets and small side effects in the treatment of liver fibrosis. This article reviews the pathological mechanism of liver fibrosis and its relationship with inflammation. The application of the active herbal ingredients in TCM, medicinal plants and traditional Chinese formulae to treat liver fibrosis, and their mechanisms of action to inhibit inflammation associated with liver fibrosis are also discussed.

Abstract:As the prevalence of obesity and related diseases continues to rise, obesity accompanied chronic inflammation becomes a non-neglect public health problem. Innovative treatment options and strategies for obesity-related chronic inflammation are urgently needed. Fatty acid synthase (FAS) is a multiple enzyme complex which has been recognized as a potential therapeutic target for obesity, inflammation, diabetes, non-alcohol fatty liver disease (NAFLD), and cancer. Research on FAS inhibitors has attracted increasing attention in recent years. Several key inflammatory markers have been consistently associated with obesity, which suggests that a persistent inflammatory response is a potentially modifiable risk factor. In China, traditional Chinese medicines (TCMs) have been applied clinically to treat inflammation. Among them there are several TCMs with strong inhibitory effect on FAS. This brief review aims at summarizing literatures concerning the recognized role of FAS as a biomarker and therapeutic target in obesity and related inflammation as well as providing evidence to support the anti-inflammation potential of TCMs with FAS inhibitory activities. FAS has emerged as a crucial target in anti-obesity therapies, and FAS inhibition might contribute to the treatment of inflammation.

Abstract:With increasing incidences of diabetes, diabetic nephropathy (DN) becomes the leading cause of chronic kidney disease and end-stage (ESRD) renal disease worldwide. However, the current pharmacological treatments for glycemic control and inhibitors of the renin-angiotensin system cannot effectively prevent the progression of DN. Recent studies show that the chronic low-grade inflammation and activation of the immune system have emerged as a paramount role in the development and progression of DN. Understanding the inflammatory cascade and mechanisms in the progression of DN will enable identification of new potential targets and facilitate the design of innovation anti-inflammatory therapeutic strategies. Growing evidence has demonstrated that the treatment of Chinese herbal medicines for DN improves hyperglycemia and proteinuria interrupting progression to ESRD. Chinese herbal medicines including herbal formulas, single herbal medicines, extracts of herbs, and compounds from herb, have been proved to regulate inflammation in DN animal and cell line models. In this review, we focus on inflammatory molecules and pathways in relation to renal injury of DN, and discuss potential traditional Chinese medicine (TCM) strategies to treat DN via targeting inflammatory factors.

Abstract:The gut microbiota is closely related to the energy metabolism, and the disorder of its composition and metabolism can lead to insulin resistance, obesity and type 2 diabetes (T2DM) through multiple pathways. Berberine is used as an adjuvant treatment for metabolic diseases, such as obesity, T2DM, and nonalcoholic fatty liver disease, due to its effects on weight loss, hypoglycemia, lipid regulation, and other physiological parameters. Recent studies have shown that berberine can regulate the composition and metabolism of the gut microbiota, improve the gut micro-ecological environment, thereby ameliorating insulin resistance and metabolism. This review clarifies how the gut microbiota induces systemic low-grade inflammation and the development of metabolic diseases. It also explores berberine intervention in metabolic diseases, affecting the intestinal microbiota-inflammation axis, in order to find new therapeutic strategies for the treatment of such diseases and to provide important guidance for in-depth research in this field.

Abstract:Here, we review nitric oxide (NO) free radical as a driving force for Qi-blood circulation; antioxidants’ scavenging oxygen free radicals, protecting NO and helping NO to drive Qi-blood circulation, as well as their protecting cardiovascular and cerebrovascular health together with NO. NO and natural antioxidants can improve the longevity, and synergistically eliminate the damage caused by inflammation. Traditional Chinese medicines (TCM) including natural antioxidants ensure health via activating Qi-blood circulation and removing blood stasis, in which NO plays an important role in the invigoration of Qi-blood circulation.

Abstract:Chronic cough is a common disease in pediatric respiratory outpatient clinics with diverse etiology and age differences. Modern medicine believes that neurogenic airway inflammation is an important cause of chronic cough. Anti-inflammatory,and anti-allergic drug are used for chronic cough. Traditional Chinese medicine (TCM) treatment of chronic cough in children according to the overall concept and dialectical treatment, mainly from wind, phlegm and deficiency treatment, has a definite effect. Through consulting the literature, this paper summarizes the TCM for the treatment of chronic cough in children, and summarizes its anti-inflammatory mechanism. Clinical studies have found that treating children with chronic cough according to the theory of Fuyang of TCM can obtain good curative effect, so here this is accompanied by a brief description.

Abstract:With the acceleration of aging population in the world, the incidence of age-related bone loss has shown an obvious rising trend. It is of great significance to find effective approaches to relieve senile osteoporosis. Nobiletin is one of the most abundant flavonoids in citrus genus with many important biological properties. Herein, 20-month naturally aging mice were used as senile osteoporosis model and were treated with nobiletin by consecutive intraperitoneal injection for 15 days. Micro-CT results showed that nobiletin significantly improved the bone microstructure featured by increased bone volume fraction and decreased trabecular separation. HE staining results indicated that nobiletin increased the number of osteoblasts of trabecular bone surface. Serum osteocalcin (gene Bglap) level was also found to be significantly increased in mice by nobiletin treatment. We then tested the effect of nobiletin in mouse pre-osteoblast (MC3T3-E1 cells) model and found that nobiletin significantly up-regulated Mki67 expression, increased Bglap expression and alkaline phosphatase enzyme activity, and markedly enhanced the alizarin red S staining, suggesting that nobiletin can promote osteoblast proliferation, differentiation and mineralization. Further study of the underlying mechanism showed that nobiletin increased the retinoic acid receptor-related orphan receptor α (RORα, gene Rora), down-regulated sclerostin (SOST, gene Sost) and up-regulated osteocalcin, while knocking down of Rora significantly compromised the regulation of nobiletin on Sost and Bglap, indicating that the improving effect of nobiletin on age-related bone loss depends on RORα. To our knowledge this is the first report that nobiletin shows improvement effect on bone loss in naturally aging mice and the first report that nobiletin down-regulates Sost through Rora. These results provide a new mechanism of nobiletin in age-related bone loss and a new potential strategy to improve the senile osteoporosis.

Abstract: _{Gefitinib induced rash is a common sequellae during cancer treatment. The mechanism and treatment of these rashes are unclear, therefore we investigated the anti-inflammatory effect of Sanliangsan on gefitinib induced rashes. Brown Norway (BN) rats were randomly selected and divided into five groups: control group, gefitinib rash model control group(model group), Sanliangsan model groups of low-dose, medium-dose, and high-dose(low,medium and high dose). Gifitinib was administered in the morning and Sanliangsan in the afternoon on the same day for 4 weeks .The BN model rats in the low-dose, medium-dose and high-dose groups were given 2 mg/kg/day, 4 mg/kg/day and 8 mg/kg/day of Sanliangsan respectively. The control group was given pure water. Macrophages were classified by flow cytometry. Protein expression was detected by immunohistochemistry. Protein chip array was used to detect the signaling pathways and inflammatory factors associated with inflammation. The results showed that the expressions of macrophage inflammatory protein (MIP)-1, MIP-2, myelocyte triggered receptor-1 (TREM-1) and IL-17A were significantly increased in the gefitinib rash model control group compared with the control group. The expressions of MIP-1, MIP-2, TREM-1 and IL-17A were significantly reduced in the Sanliangsan groups compared with the gefitinib rash model control group. It was also discovered that the anti-inflammatory effect of Sanliangsan on gefitinib-induced rash was closely related to the signaling pathway of IL-17A.}

Abstract:Acupuncture is an ancient and important part of traditional Chinese medicine. As a non-pharmacological intervention recommended by the World Health Organization (WHO), acupuncture is widely used in the treatment of a variety of diseases. A large number of clinical and experimental evidences show that acupuncture can improve cognition by regulating neuroinflammation. Inflammation is a common pathological reaction of many neurodegenerative diseases, such as the activation of glial cells, the increase and release of inflammatory factors. Currently, a great deal of work progresses in the field of acupuncture in the field of anti-inflammation. To summarize the role of acupuncture in improving neuroinflammation in dementia, this review focuses on brain diseases and discusses the mechanism of acupuncture in the activation of glial cells in Alzheimer"s disease (AD), vascular dementia (VD), Parkinson"s disease (PD). Those acupoints distributed in 14 meridians and concentrated in the head and the distal extremities, are closely related to the activation and regulation of microglia. As described by recent studies, the inhibition of M1 microglial activation mediated by TLRs/NF- κ B and MAPKs pathways may be one of the key mechanisms of acupuncture regulating neuroinflammatory response and improving cognitive impairment in AD, VD and PD.

Abstract:In previous studies, it was found that blocking the low hydraulic resistance channel (LHRC) along meridian in mini-pigs could lead to the hyperalgesia, a series of abnormal behavioral changes, traditional Chinese medicine (TCM) syndromes and abnormal autopsy in internal organs. The objective of this paper is to investigate the pathology of these changes. Mini-pigs were randomly divided into a stomach meridian blocking group (SBG, n=8), a kidney meridian blocking group (KBG, n=8) and a control group (CG, n=6). The hydraulic gel was injected separately into LHRCs along the stomach meridian and the kidney meridian. The pigs were then fed 7 to 9 weeks, and several indexes were observed. The results showed that the blood serum creatinine increased extremely in all 3 groups and the level in the KBG was lower than that in the SBG by 13.76% (p＜0.05) and in the CG by 14.51% (p＜0.01). HE staining results showed that more than half of the pigs had the heart abnormalities in the CG, the liver abnormalities in the SBG and the kidney and testicles abnormalities in the KBG. Intestinal sections in the SBG showed that the intestinal crypt depth of the duodenum and the colon, and the total mucosal thickness of the large intestine were significantly higher than those of the CG. The jejunal V/C and the ileal crypt depth were significantly lower than those of the KBG, and the ileal V/C was significantly higher than that of the KBG. Compared with the CG, intestinal sections of the KBG showed that the duodenal crypt depth and the thickness of the colon was significantly higher than that of the CG. The GAS in the KBG was significantly higher than those of the CG and the SBG. The results verify that the blockage of LHRC along the stomach meridian and the kidney meridian can lead to different pathological phenomena, which provided a scientific basis for the syndromes induced by meridian stasis.