Effect of Cistanche Tubulosa Extracts on Male Reproductive Function in Streptozotocin–Nicotinamide-Induced Diabetic Rats

Diabetes is a chronic disorder characterized by hyperglycemia due to decreased levels of insulin or the inefficiency of the tissue to use it effectively. Infertility is known as a major outcome of diabetes and affects the male reproductive system by causing sperm impairment and gonadal dysfunction. Cistanche tubulosa is a parasitic plant which has the capacity to improve memory, immunity, and sexual ability, reduce impotence, and minimize constipation. This study was focused on the investigation of the anti-inflammatory and protective effects of echinacoside (ECH) in Cistanche tubulosa extract (CTE) on the male reproductive system of the diabetic rats. The antioxidant, anti-inflammatory, and protective effects of CTE were evaluated by both in vitro and in vivo methods. The in vitro results show that the ECH inhibited reactive oxygen species (ROS) production and improved StAR, CYP11A1, CYP17A1, and HSD17β3 protein expression. The in vivo analysis was carried out with three doses of echinacoside (ECH) (80, 160, and 320 mg/kg) in CTE. In total, 0.571 mg/kg of rosiglitazone (RSG) was administered as a positive control. Diabetes was induced by streptozotocin (STZ) (65 mg/kg) and nicotinamide (230 mg/kg) in combination with a high-fat diet (45%). The in vivo studies confirmed that the ECH improved blood sugar levels, insulin resistance, leptin resistance, and lipid peroxidation. It can restore kisspeptin 1 (KiSS1), G protein-coupled receptor GPR 54, suppressor of cytokine signaling 3 (SOCS-3), and sirtuin 1 (SIRT1) messenger ribonucleic acid (mRNA) expression in the hypothalamus and recover sex hormone level. Thus, this study confirmed the antioxidant, anti-inflammatory, and steroidogenesis effects of CTE.

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The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis

Scientific Reports ◽

10.1038/s41598-021-87353-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wuyang Huang ◽

Ky Young Cho ◽

Di Meng ◽

W. Allan Walker

Keyword(s):

Lactic Acid ◽

Mechanistic Model ◽

Transcriptomic Analysis ◽

Dependent Manner ◽

Protective Effects ◽

Very Preterm Infants ◽

Anti Inflammatory ◽

The Impact

AbstractAn excessive intestinal inflammatory response may have a role in the pathogenesis of necrotizing enterocolitis (NEC) in very preterm infants. Indole-3-lactic acid (ILA) of breastmilk tryptophan was identified as the anti-inflammatory metabolite involved in probiotic conditioned media from Bifidobacteria longum subsp infantis. This study aimed to explore the molecular endocytic pathways involved in the protective ILA effect against inflammation. H4 cells, Caco-2 cells, C57BL/6 pup and adult mice were used to compare the anti-inflammatory mechanisms between immature and mature enterocytes in vitro and in vivo. The results show that ILA has pleiotropic protective effects on immature enterocytes including anti-inflammatory, anti-viral, and developmental regulatory potentials in a region-dependent and an age-dependent manner. Quantitative transcriptomic analysis revealed a new mechanistic model in which STAT1 pathways play an important role in IL-1β-induced inflammation and ILA has a regulatory effect on STAT1 pathways. These studies were validated by real-time RT-qPCR and STAT1 inhibitor experiments. Different protective reactions of ILA between immature and mature enterocytes indicated that ILA’s effects are developmentally regulated. These findings may be helpful in preventing NEC for premature infants.

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Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation

The American Journal of Chinese Medicine ◽

10.1142/s0192415x17500458 ◽

2017 ◽

Vol 45 (04) ◽

pp. 847-861 ◽

Cited By ~ 15

Author(s):

Chia-Yang Li ◽

Katsuhiko Suzuki ◽

Yung-Li Hung ◽

Meng-Syuan Yang ◽

Chung-Ping Yu ◽

...

Keyword(s):

Ex Vivo ◽

Aloe Vera ◽

Peritoneal Macrophages ◽

Mitogen Activated Protein Kinase ◽

Protective Effects ◽

Raw264.7 Macrophages ◽

Mitogen Activated Protein ◽

Anti Inflammatory

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

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Injectable mechanical pillows for attenuation of load-induced post-traumatic osteoarthritis

Regenerative Biomaterials ◽

10.1093/rb/rbz013 ◽

2019 ◽

Vol 6 (4) ◽

pp. 211-219

Author(s):

Derek T Holyoak ◽

Tibra A Wheeler ◽

Marjolein C H van der Meulen ◽

Ankur Singh

Keyword(s):

Knee Joint ◽

Joint Damage ◽

Mechanical Trauma ◽

Protective Effects ◽

Post Injury ◽

On Demand ◽

Post Traumatic ◽

Anti Inflammatory

Abstract Osteoarthritis (OA) of the knee joint is a degenerative disease initiated by mechanical stress that affects millions of individuals. The disease manifests as joint damage and synovial inflammation. Post-traumatic osteoarthritis (PTOA) is a specific form of OA caused by mechanical trauma to the joint. The progression of PTOA is prevented by immediate post-injury therapeutic intervention. Intra-articular injection of anti-inflammatory therapeutics (e.g. corticosteroids) is a common treatment option for OA before end-stage surgical intervention. However, the efficacy of intra-articular injection is limited due to poor drug retention time in the joint space and the variable efficacy of corticosteroids. Here, we endeavored to characterize a four-arm maleimide-functionalized polyethylene glycol (PEG-4MAL) hydrogel system as a ‘mechanical pillow’ to cushion the load-bearing joint, withstand repetitive loading and improve the efficacy of intra-articular injections of nanoparticles containing dexamethasone, an anti-inflammatory agent. PEG-4MAL hydrogels maintained their mechanical properties after physiologically relevant cyclic compression and released therapeutic payload in an on-demand manner under in vitro inflammatory conditions. Importantly, the on-demand hydrogels did not release nanoparticles under repetitive mechanical loading as experienced by daily walking. Although dexamethasone had minimal protective effects on OA-like pathology in our studies, the PEG-4MAL hydrogel functioned as a mechanical pillow to protect the knee joint from cartilage degradation and inhibit osteophyte formation in an in vivo load-induced OA mouse model.

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Heme Oxygenase-1, a Key Enzyme for the Cytoprotective Actions of Halophenols by Upregulating Nrf2 Expression via Activating Erk1/2 and PI3K/Akt in EA.hy926 Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7028478 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 6

Author(s):

Xiu E. Feng ◽

Tai Gang Liang ◽

Jie Gao ◽

De Peng Kong ◽

Rui Ge ◽

...

Keyword(s):

Heme Oxygenase ◽

Antioxidant Activities ◽

Heme Oxygenase 1 ◽

Protective Effects ◽

Key Enzyme ◽

Ea.Hy926 Cells ◽

Anti Inflammatory ◽

Mechanistic Basis

Increasing evidence has demonstrated that heme oxygenase-1 (HO-1) is a key enzyme triggered by cellular stress, exhibiting cytoprotective, antioxidant, and anti-inflammatory abilities. Previously, we prepared a series of novel active halophenols possessing strong antioxidant activities in vitro and in vivo. In the present study, we demonstrated that these halophenols exhibited significant protective effects against H2O2-induced injury in EA.hy926 cells by inhibition of apoptosis and ROS and TNF-αproduction, as well as induction of the upregulation of HO-1, the magnitude of which correlated with their cytoprotective actions. Further experiments which aimed to determine the mechanistic basis of these actions indicated that the halophenols induced the activation of Nrf2, Erk1/2, and PI3K/Akt without obvious effects on the phosphorylation of p38, JNK, or the expression of PKC-δ. This was validated with the use of PD98059 and Wortmannin, specific inhibitors of Erk1/2 and PI3K, respectively. Overall, our study is the first to demonstrate that the cytoprotective actions of halophenols involve their antiapoptotic, antioxidant, and anti-inflammatory abilities, which are mediated by the upregulation of Nrf2-dependent HO-1 expression and reductions in ROS and TNF-αgeneration via the activation of Erk1/2 and PI3K/Akt in EA.hy926 cells. HO-1 may thus be an important potential target for further research into the cytoprotective actions of halophenols.

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Anti-Inflammatory Effect of Targeted Delivery of SOD to Endothelium: Mechanism, Synergism with NO Donors and Protective Effects In Vitro and In Vivo

PLoS ONE ◽

10.1371/journal.pone.0077002 ◽

2013 ◽

Vol 8 (10) ◽

pp. e77002 ◽

Cited By ~ 29

Author(s):

Vladimir V. Shuvaev ◽

Jingyan Han ◽

Samira Tliba ◽

Evguenia Arguiri ◽

Melpo Christofidou-Solomidou ◽

...

Keyword(s):

Targeted Delivery ◽

Protective Effects ◽

No Donors ◽

Anti Inflammatory ◽

Inflammatory Effect

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Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus

Frontiers in Immunology ◽

10.3389/fimmu.2021.733808 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jialing Liu ◽

Yanmei Zhang ◽

Hongqin Sheng ◽

Chunling Liang ◽

Huazhen Liu ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

Macrophage Polarization ◽

Fasting Blood Glucose ◽

Therapeutic Effects ◽

Protective Effects ◽

Monocyte Chemoattractant Protein 1 ◽

Anti Inflammatory

Accumulating evidence reveals that both inflammation and lymphocyte dysfunction play a vital role in the development of diabetic nephropathy (DN). Hyperoside (HPS) or quercetin-3-O-galactoside is an active flavonoid glycoside mainly found in the Chinese herbal medicine Tu-Si-Zi. Although HPS has a variety of pharmacological effects, including anti-oxidative and anti-apoptotic activities as well as podocyte-protective effects, its underlying anti-inflammatory mechanisms remain unclear. Herein, we investigated the therapeutic effects of HPS on murine DN and the potential mechanisms responsible for its efficacy. We used C57BLKS/6J Lepdb/db mice and a high glucose (HG)-induced bone marrow-derived macrophage (BMDM) polarization system to investigate the potentially protective effects of HPS on DN. Our results showed that HPS markedly reduced diabetes-induced albuminuria and glomerular mesangial matrix expansion, accompanied with a significant improvement of fasting blood glucose level, hyperlipidaemia and body weight. Mechanistically, pretreatment with HPS effectively regulated macrophage polarization by shifting proinflammatory M1 macrophages (F4/80+CD11b+CD86+) to anti-inflammatory M2 ones (F4/80+CD11b+CD206+) in vivo and in bone marrow-derived macrophages (BMDMs) in vitro, resulting in the inhibition of renal proinflammatory macrophage infiltration and the reduction in expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) while increasing expression of anti-inflammatory cytokine Arg-1 and CD163/CD206 surface molecules. Unexpectedly, pretreatment with HPS suppressed CD4+ T cell proliferation in a coculture model of IL-4-induced M2 macrophages and splenic CD4+ T cells while promoting their differentiation into CD4+IL-4+ Th2 and CD4+Foxp3+ Treg cells. Taken together, we demonstrate that HPS ameliorates murine DN via promoting macrophage polarization from an M1 to M2 phenotype and CD4+ T cell differentiation into Th2 and Treg populations. Our findings may be implicated for the treatment of DN in clinic.

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Protective Effects of Ginkgo Biloba Dropping Pills Against Liver Ischemia/reperfusion Injury in Mice

10.21203/rs.3.rs-59585/v1 ◽

2020 ◽

Author(s):

Zheng Wang ◽

Ping Zhang ◽

Qingqing Wang ◽

Xueping Sheng ◽

Jianbing Zhang ◽

...

Keyword(s):

Cell Viability ◽

Ginkgo Biloba ◽

Ischemia Reperfusion ◽

Protective Effects ◽

Liver Ischemia ◽

Primary Hepatocytes ◽

Injury Model ◽

Anti Inflammatory

Abstract Background: Liver ischemia-reperfusion (I/R) injury is an inevitable pathological phenomenon in various clinical conditions, such as liver transplantation, resection surgery, or shock, which is the major cause of morbidity and mortality after operation. Ginkgo Biloba Dropping Pill (GBDP) is a unique Chinese Ginkgo Biloba leaf extract preparation that exhibits a variety of beneficial biological activities. The aim of this study is to investigate the protective effects of GBDP on the liver I/R injury both in vitro and in vivo. Methods: Hypoxia/reoxygenation (H/R) experiments were performed in AML-12 cells and primary hepatocytes, which were pretreated with GBDP (60 or 120 μg/mL) followed by incubation in a hypoxia chamber. Cell viability and cell apoptosis were detected by MTT assay and annexin V staining respectively. C57BL/6 mice were used to establish liver I/R injury model, and were pretreated with GBDP (100 or 200 mg/kg/day, i.g.) for two weeks. Liver damage was detected by plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST). Liver necrosis and neutrophil infiltration were determined by H&E and myeloperoxidase immunohistochemistry staining. Finally, TUNEL staining and western blot analysis of apoptosis-related proteins were used to investigate the anti-apoptotic effect of GBDP. Results: In the in vitro study, GBDP pretreatment improved the cell viability of AML-12 cells in H/R injury model. Similarly, the same result was found in the primary hepatocytes isolated from C57BL/6 mice. Moreover, GBDP decreased the number of apoptotic cells induced by H/R. In the in vivo study, oral administration of GBDP ameliorated liver injury evidenced by a significant decline in the levels of ALT and AST. Furthermore, the result of H&E staining showed that GBDP reduced the size of necrosis area. In addition, the decreased infiltration of neutrophils indicated that GBDP may play an anti-inflammatory effect. More importantly, GBDP reduced TUNEL-positive cells and the expression of Bax and caspase-3 in liver indicating GBDP has anti-apoptotic effects.Conclusion: Our findings elucidated that GBDP has potential effects for protecting against liver I/R injury characterized by its anti-apoptotic, anti-necrotic, and anti-inflammatory properties, which would promisingly make a contribution to the exploration of therapeutic strategies in the liver I/R injury.

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Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3457890 ◽

2020 ◽

Vol 2020 ◽

pp. 1-21

Author(s):

Márcia Fernanda Correia Jardim Paz ◽

Marcus Vinícius Oliveira Barros de Alencar ◽

Rodrigo Maciel Paulino de Lima ◽

André Luiz Pinho Sobral ◽

Glauto Tuquarre Melo do Nascimento ◽

...

Keyword(s):

Genomic Instability ◽

Neutrophil Infiltration ◽

Protective Effects ◽

Pharmacological Effects ◽

Self Medication ◽

Study Objective ◽

Anti Inflammatory

Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six in vitro, and 76 in vivo studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.

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Curcumin loaded and co-loaded nanosystems: A review from a biological activity enhancement perspective

Pharmaceutical Nanotechnology ◽

10.2174/2211738508666201228150659 ◽

2020 ◽

Vol 08 ◽

Author(s):

Andrea Mariela Araya-Sibaja ◽

Krissia Wilhelm ◽

Gustavo Adolfo González-Aguilar ◽

José Roberto Vega-Baudrit ◽

Norma Julieta Salazar-López ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Aqueous Solubility ◽

Nanostructured Lipid Carrier ◽

Protective Effects ◽

Cell Internalization ◽

Low Toxicity ◽

Anti Inflammatory

Background: Curcumin is a natural phenolic compound exhibiting multiple bioactivities that have been evaluated in vitro, in vivo as well as through clinical studies in humans. Some of them include antimicrobial, antioxidant, anti-inflammatory and central nervous system protective effects. Further, curcumin is considered a Generally Recognized as Safe substance because of its low toxicity. However, its molecular structure is susceptible to changes in pH, oxidation, photodegradation, low aqueous solubility and biotransformation compromising its bioavailability, drawbacks that have been successfully addressed through nanotechnology. Objective: The present review systematizes findings on the enhancement of curcumin’s beneficial effects when it is loaded and co-loaded into different types of nanosystems covering liposomes, polymeric and solid-lipid nanoparticles, nanostructured lipid carrier, lipid-polymeric hybrids, self-assembled and protein-based core-shell systems in relation to its antimicrobial, antioxidant, anti-inflammatory and central nervous system protective bioactivities. Conclusion: Curcumin is a versatile molecule capable of exerting antimicrobial, antioxidant, anti-inflammatory and central nervous system protective effects in an enhanced manner using the possibilities offered by the nanotechnology - based approach. Its enhanced bioactivities are associated with increments in solubility, stability, bioavailability as well as in improved intracellular uptake and cell internalization. These advantages, in addition to curcumin’s low toxicity, indicate the potential of curcumin to be loaded and co-loaded into nanosystems capable to provide a controlled release and targeted administration.

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The N-Terminal Domain of Thrombomodulin Sequesters HMGB1: A Novel Anti-Inflammatory Mechanism.

Blood ◽

10.1182/blood.v104.11.3435.3435 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3435-3435

Author(s):

Kazuhiro Abeyama ◽

Yasushi Yoshimoto ◽

Ikuro Maruyama

Keyword(s):

Protein C ◽

Statistical Significance ◽

Dependent Manner ◽

Protective Effects ◽

Binding Studies ◽

Terminal Domain ◽

Anti Inflammatory ◽

Dose Dependent

Abstract Thrombomodulin (TM) is an endothelial anticoagulant cofactor that promotes thrombin-mediated formation of activated protein C (APC), the latter an enzyme with potent anti-coagulant and anti-inflammatory properties. We have found that the N-terminal, lectin-like domain (D1) of thrombomodulin has unique anti-inflammatory properties. Thrombomodulin, via D1, binds high mobility group-B1 DNA binding protein (HMGB1), a factor closely associated with necrotic cell damage following its release from the nucleus, thereby preventing leukocyte activation in vitro, and ultraviolet radiation-induced cutaneous inflammation and lipopolysaccharide-induced lethality in vivo. Our data also demonstrate anti-inflammatory properties of a peptide spanning the D1 domain of TM and suggest its therapeutic potential. These findings highlight a novel mechanism through which an endothelial cofactor, TM, suppresses inflammation; i.e., sequestration of mediators thereby preventing their interaction with cell surface receptors on effector cells in the vasculature. Results: TM binds HMGB1 and prevents expression of pro-inflammatory activity. Our co-culture studies of leukocytes and HUVEC, and results in the cutaneous irritation model suggested that early release of a mediator, such as HMGB1, might contribute importantly to cellular activation in inflammation at later time points. In this context, TM might have the ability to decrease HMGB1-mediated inflammatory events. Binding studies using surface plasmon resonance (SPR), performed to directly assess the interaction of TM and immobilized HMGB1, demonstrated dose-dependent binding in the nanomolar range (Kd ~232 nM). Furthermore, addition of rhs-TM decreased, in a dose-dependent manner, the binding of HMGB1 to RAGE through the its N-terminal domain, but not anti-coagulant domain. TM and the N-terminal-derived TM peptide have anti-inflammatory effects in settings where HMGB1 is a likely key mediator. In HMGB1-mediated skin inflammation model, systemic administration of rhs-TM, its lectin-like domain and sRAGE resulted in a significant blunting of the inflammatory response. In contrast, the effect of anti-coagulant domain, although showing a trend toward decreased ear swelling, did not achieve statistical significance (anticoagulant domain has anti-inflammatory effects in vivo that probably reflect its ability to support thrombin-mediated activation of protein C; the latter does not occur in vitro after inactivation of the protein C zymogen by heat treatment). In view of recent data suggesting a link between HMGB1 released from injured tissue and endotoxin-induced lethality in mice, we also tested whether rhs-TM and its lectin-like domain might also have protective effects in this model. We employed a dose of intraperitoneal (IP) LPS (10 mg/kg) resulting in 100% lethality by 96 hrs. Systemic (IP) treatment of animals with anti-HMGB1 IgY had a protective effect with respect to lethality at 4 days, whereas the same regimen of nonimmune IgY was without effect. Similarly, IP administration of rhs-TM and its N-teminal lectin domain, but not anti-coagulant domain had complete protective effects compared with anti-HMGB1 IgY. Conclusion: Our findings have elucidated an unexpected anti-inflammatory property of TM residing in the D1 domain, namely binding of HMGB1.

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