Humans ; Inflammation ; drug therapy ; metabolism ; MicroRNAs ; metabolism ; Stilbenes ; pharmacology ; therapeutic use

Increased arterial stiffness is an independent predictor of cardiovascular disease independent from blood pressure. Recent studies have shed new light on the importance of inflammation on the pathogenesis of arterial stiffness. Arterial stiffness is associated with the increased activity of angiotensin II, which results in increased NADPH oxidase activity, reduced NO bioavailability and increased production of reactive oxygen species. Angiotensin II signaling activates matrix metalloproteinases (MMPs) which degrade TGFbeta precursors to produce active TGFbeta, which then results in increased arterial fibrosis. Angiotensin II signaling also activates cytokines, including monocyte chemoattractant protein-1, TNF-alpha, interleukin-1, interleukin-17 and interleukin-6. There is also ample clinical evidence that demonstrates the association of inflammation with increased arterial stiffness. Recent studies have shown that reductions in inflammation can reduce arterial stiffness. In patients with rheumatoid arthritis, increased aortic pulse wave velocity in patients was significantly reduced by anti tumor necrosis factor-alpha therapy. Among the major classes of anti hypertensive drugs, drugs that block the activation of the RAS system may be more effective in reducing the progression of arterial stiffness. Thus, there is rationale for targeting specific inflammatory pathways involved in arterial stiffness in the development of future drugs. Understanding the role of inflammation in the pathogenesis of arterial stiffness is important to understanding the complex puzzle that is the pathophysiology of arterial stiffening and may be important for future development of novel treatments.
Angiotensin II/metabolism ; Humans ; Inflammation/drug therapy/metabolism/*physiopathology ; Matrix Metalloproteinases/metabolism ; Vascular Stiffness/drug effects/*physiology

It is reported, in the process of diabetic nephropathy (DN), inflammatory-related p38 mitogen-activated protein kinase (MAPK) signaling pathway has a close relationship with renal injury. On the one hand,many factors in the upstream including hyperglycemia, abnormal hemodynamics, oxidative stress, and pro-inflammatory cytokines could activate p38MAPK signaling pathway. On the other hand,the activated p38MAPK signaling pathway could lead to renal damage via activating inflammatory cells, inducing the expression of inflammatory mediators, and intervening cytokines production. CHM could intervene p38MAPK signaling pathway through multi-ways, including inhibiting inflammatory cytokines expression, regulating phosphorylated p38MAPK (p-p38MAPK) expression, and reducing fibrogenic factors expression.
Diabetic Nephropathies ; drug therapy ; enzymology ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Inflammation ; drug therapy ; metabolism ; Inflammation Mediators ; pharmacology ; Kidney ; drug effects ; enzymology ; metabolism ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; metabolism

Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are common features in hospitalized patients. Specific nutrients with immunological and pharmacological effects, when consumed in amounts above the daily requirement, are referred to as immune-enhancing nutrients or immunonutrients. Supplementation of immunonutrients is important especially for patients with immunodeficiency, virus or overwhelming infections accompanied by a state of malnutrition. Representative immunonutrients are arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids. Glutamine is the most abundant amino acid and performs multiple roles in human body. However, glutamine is depleted from muscle stores during severe metabolic stress including sepsis and major surgery. Therefore it is considered conditionally essential under these conditions. This review discusses the physiological role of glutamine, mode and dose for glutamine administration, as well as improvement of certain disease state after glutamine supplementation. Even though immunonutrition has not been widely assimilated by clinicians other than nutritionists, immunonutrients including glutamine may exert beneficial influence on diverse patient populations.
Animals ; Critical Illness ; Glutamine/blood/metabolism/*therapeutic use ; Humans ; Immunity/drug effects ; Inflammation/drug therapy/metabolism ; Malnutrition

Asthma ; drug therapy ; metabolism ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Inflammation Mediators ; metabolism ; Phytotherapy ; Signal Transduction

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.
Animals ; Asthma/drug therapy* ; Bronchoalveolar Lavage Fluid ; Inflammation/metabolism* ; Lung ; Male ; Permeability ; Rats

To study the effect of dihydroartemisinin(DHA) on hepatic inflammation and lipid metabolism in weaned piglets, a liver injury model of weaned piglets was established by lipopolysaccharide(LPS)-induced method. In this study, 30 healthy weaned piglets were selected and randomly divided into control group(CON), model group(LPS) and treatment group(LD, LPS+DHA), with 10 in each group. The CON group and the LPS group were fed with a basal diet, and the LD group was fed with a basal diet+80 mg·kg~(-1) DHA. The test period was 21 days. The LPS group and the LD group were intraperitoneally injected with 100 μg·kg~(-1) LPS at 4 hours before slaughter, and the CON group was injected with the same dose of sterile physiological saline. The results showed that compared with the CON group, contents of TC, AST activity and AST/ALT ratio were significantly increased in the serum of LPS piglets(P<0.05), content of HDL-c was significantly decreased(P<0.05). In addition, in the liver, the levels of TG, NEFA, IL-1β, IL-6 and TNF-α were increased significantly(P<0.05), and activities of LPL, HL and TL were decreased significantly(P<0.05). Compared with LPS group, content of TC, activities of AST and ALT and the AST/ALT ratio were decreased significantly(P<0.05), and HDL-c content increased significantly in the serum of LD piglets(P<0.05). The contents of TG, NEFA, IL-1β, IL-6 and TNF-α and activity of FAS in the liver were decreased significantly(P<0.05), and the activities of LPL, HL and TL were increased significantly(P<0.05). Compared with the CON group, the mRNA expressions of IL-1β, IL-6, TNF-α, ACCβ and SREBP-1 c in the LPS group were significantly increased(P<0.05), the mRNA expressions of AMPKα, SIRT1, CPT-1 and SCD were decreased significantly(P<0.05). The above indicators were improved in the LD group compared with the LPS group. These results indicated that DHA had a certain effect in recovering LPS-induced liver inflammation and abnormal lipid metabolism.
Animals ; Artemisinins/therapeutic use* ; Dietary Supplements ; Inflammation/drug therapy* ; Lipid Metabolism ; Lipopolysaccharides ; Liver/physiopathology* ; Swine

Studies have shown that chronic inflammatory response plays a key role in intracranial aneurysms (IA) formation and progression, and macrophages regulate the formation and progression of IA through a variety of pathways. Bone marrow monocyte-derived macrophages and resident-tissue macrophages infiltrate the vessel wall, after infiltration macrophages are polarized into various polarization phenotypes dominated by M1-like and M2-like cells. Polarized phenotypes of macrophages can regulate the formation and progression of intracranial aneurysms by releasing cytokines and regulating the inflammatory response of other immune cells, as well as release different cytokines to regulate the process of extracellular matrix remodeling. Some important progresses have been made in the clinical detection and treatment in targeting macrophages. This review provides a summary on the pathogenesis of IA and potential drug targets to prevent the formation and rupture of intracranial aneurysms.
Cytokines ; Disease Progression ; Humans ; Inflammation ; Intracranial Aneurysm ; complications ; drug therapy ; pathology ; Macrophages ; metabolism

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.
Animals ; NF-kappa B/metabolism* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Acupuncture Therapy ; Cytokines ; Disease Models, Animal ; Inflammation/therapy*

OBJECTIVETo investigate the anti-fibrosis effects and mechanisms of fenofibrate on hepatic fibrosis using a mouse model of fibrosis induced by carbon tetrachloride (CCl4).

METHODSTwenty-six male C57BL mice were divided into the following three groups: CCL4-induced untreated model control (n = 10), CCl4-induced fenofibrate-treated model (n = 10), and uninduced/untreated normal control (n = 6). All animals were sacrificed after the 5 weeks of induction and treatment. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA) and procollagen III amino-terminal peptide (PIIINP) were determined by routine biochemistry assays. Liver content of hydroxyproline (HYP) was measured by spectrophotometry. Liver content of malonic aldehyde (MDA) and superoxide dismutase (SOD) was measured by enzymatic assays. mRNA expression levels of liver fibrosis-associated factors were determined by PCR, and included alpha-smooth muscle actin (a-SMA), transforming growth factor-beta1 (TGFbeta1), type I collagen-alpha (Collagen1a), peroxisome proliferator-activated receptor-alpha (PPARa), and the inflammatory cytokines tumor necrosis factor alpha (TNFa) and interleukin-6 (IL-6). Finally, the degree of inflammation and fibrosis were assessed by histological analysis using hematoxylin-eosin and Sirius red staining.

RESULTSCompared to the untreated model group, the fenofibrate-treated model group showed significantly lower levels of serum ALT (55.72+/-1.20 vs. 38.72+/-1.25 IU/L), HA (236.20+/-17.57 vs. 152.9+/-13.06 mug/L) and PIIINP (41.66+/-1.89 vs. 34.32+/-1.53 mug/L) (all P less than 0.05). The fenofibrate-treated group also showed a significantly higher level of hepatic SOD content (untreated model: 67.00+/-4.65 vs. 101.1+/-5.32) but significantly lower level of hepatic MDA content (14.67+/-0.93 vs. 10.17+/-0.60 nmol/mg) and lower level of hepatic HYP content (0.67+/-0.80 vs. 0.41+/-0.50 mg/g) (all, P less than 0.05). In addition, the fenofibrate-treated group showed significantly reduced mRNA expression levels of a-SMA (6.83+/-0.88 vs. untreated model: 11.57+/-1.31), TGFbeta1 (67.83+/-4.65 vs. 112.30+/-4.81), Collagen1a (67.83+/-4.65 vs. 112.30+/-4.81), TNFa (17.43+/-2.32 vs. 37.83+/-4.69), and IL-6 (4.00+/-0.49 vs. 5.62+/-0.54), but significantly increased PPARa (0.30+/-0.03 vs. 0.18+/-0.03) (all, P less than 0.05). Finally, the degree of CCL4-induced hepatic fibrosis was attenuated by the fenofibrate treatment.

CONCLUSIONFenofibrate can reduce the degree of liver fibrosis in mice induced by CCl4. The mechanism may involve up-regulation of PPARa, inhibition of the inflammatory response, and enhancement of SOD antioxidant activity.

Animals ; Fenofibrate ; therapeutic use ; Inflammation ; drug therapy ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; PPAR alpha ; metabolism ; Superoxide Dismutase ; metabolism