Cur Treatment Research Articles

Curcumin triggers the Wnt/β-catenin pathway and shields neurons from injury caused by intermittent hypoxia

The objective of this study was to explore the molecular basis through which Curcumin (Cur) mitigates neuronal damage caused by obstructive sleep apnea (OSA). HT22 was used to simulate intermittent hypoxia (IH) injury and explore the effect of Cur on these cells. We evaluated the cell viability, cytotoxicity, apoptosis, proliferation, and Wnt/β-catenin (WβC) pathway. IWR-1 was used to block the pathway and investigate the protective mechanism of Cur. We constructed an in vivo model of IH to validate the results of the cellular experiments. IH accelerated apoptosis and cytotoxicity, suppressed proliferation, and decreased the activity of the WβC pathway. Cur can significantly improve cell viability, reduce apoptosis rate and cell toxicity, promote cell proliferation, and up-regulate the WβC. After blocking the WβC pathway, the proliferative effect of Cur was observably weakened. In vivo, IH caused hippocampal damage and inhibited WβC pathway activity in mice, which was ameliorated by Cur treatment. This implies that Cur could be a novel treatment option for neurological impairment brought on by OSA.

Network pharmacology, molecular docking and experimental study on the mechanism of Curcumin's anti-ferroptosis in melanocytes

Ferroptosis is a form of regulated nonapoptotic cell death associated with iron-dependent lipid peroxidation, closely associated with Vitiligo. Although the impact of Curcumin (Cur), a polyphenolic compound derived from the plant Curcuma longa Linn, on vitiligo has been established, the specific role and potential mechanistic pathways through which Cur modulates ferroptosis in vitiligo remain elusive. In this study, the critical targets and potential mechanisms of Cur in treating vitiligo were predicted by network pharmacology and molecule docking. Then, the effects of Cur on Erastin-induced ferroptosis were investigated in melanocytes induced by Erastin in vitro. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of Cur acting on Vitiligo found that these intersection genes are associated with the vitiligo oxidative stress pathway, including nuclear factor erythroid 2-related factor 2(Nrf2)/Heme Oxygenase 1(HO-1) signaling pathway. Further molecular docking shows that Cur has a good binding effect with Nrf2(the binding energy of Cur and Nrf2 protein is −6 kcal/mol). Through the CCK8 assay, showed that 10 μM Cur treatment 24 h after Erastin significantly improved cell viability In vitro. Then we found that Erastin induced cell death, ROS production, the mitochondrial membrane potential(MMP) decreased, Superoxide dismutase (SOD) and Glutathione (GSH) levels reduced, Malonaldehyde (MDA) and iron ion accumulation in melanocytes. In addition, the expression of glutathione peroxidase 4(GPX4) mRNA and protein was inhibited, while the expression of acyl-CoA synthetase long-chain family member 4(ACSL4), Transferrin Receptor Protein 1(TFR1) mRNA and protein was increased. However, the damage induced by Erastin was significantly relieved by Cur and Fer-1 treatment. Mechanistically, Cur treatment significantly promoted nuclear translocation of transcriptional factor Nrf2 and HO-1 expression. Interestingly, pretreatment with ML385, a selective Nrf2 inhibitor, counteracted anti-ferroptosis effects induced by Cur treatment. Taken together, these results demonstrate that Cur inhibits ferroptosis by regulating the Nrf2/HO-1 pathway to protect melanocytes.

New curcumin-loaded nanocapsules as a therapeutic alternative in an amnesia model.

This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations' effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10mg/kg), group III (Cur EUD Nc 10mg/kg), group IV (free Cur 10mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30min of treatment, the animals received the SCO and were subjected to behavioral tests 30min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice.

Curcumin alleviates Alzheimer’s disease by inhibiting inflammatory response, oxidative stress and activating the AMPK pathway

BackgroundAlzheimer’s disease (AD) is a common degenerative brain disorder with limited therapeutic options. Curcumin (Cur) exhibits neuroprotective function in many diseases. We aimed to explore the role and mechanism of Cur in AD. Materials and MethodsFirstly, we established AD mice by injecting amyloid-β1–42 (Aβ1–42) solution into the hippocampus. Then, the AD mice received 150 mg/kg/d Cur for 10 consecutive days. The Morris water maze test was conducted to evaluate the cognitive function of the mice by hidden platform training and probe trials. To assess the spatial memory of the mice, spontaneous alternation behavior, the number of crossing the novel arm and the time spent in the novel arm during the Y-maze test was recorded. Hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNAL) assay were performed to assess the pathological damage and apoptosis of brain tissues. The number of damaged neurons was inspected by Nissl staining. Immunohistochemical staining was then performed to detect Aβ1–42 deposition. The levels of tumor necrosis factor-α (TNF-a), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum and hippocampus, the contents of super oxide dismutase (SOD) and malondialdehyde (MDA) in brain tissues were assessed by enzyme-linked immunosorbent assay (ELISA). Additionally, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), RelA (p65) protein expressions and Adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation were tested using Western blot. ResultsCur not only improved cognitive function and spatial memory, but also alleviated the pathological damage and apoptosis of brain tissues for AD mice. Meanwhile, upon Cur treatment, the number of damaged neurons in AD mice was decreased, the level of Aβ1–42 in AD mice was significantly decreased. Furthermore, the AD mice treated with Cur exhibited lower TNF-a, IL-6, IL-1β and MDA levels and a higher SOD content. Besides, Cur also downregulated p65 expression and upregulated AMPK phosphorylation. ConclusionCur may improve AD via suppressing the inflammatory response, oxidative stress and activating the AMPK pathway, suggesting that Cur may be a potential drug for AD.

Curcumin promotes renewal of intestinal epithelium by miR-195-3p

Ethnopharmacological relevanceTurmeric (Curcuma longa) has been used to treat gastrointestinal disorders in the Indian Ayurvedic medical system. According to the theory behind traditional Chinese medicine, turmeric can be distributed in the spleen meridian, for which it has been used as a digestive aid. Curcumin (Cur), a natural polyphenol compound originally derived from turmeric, has anti-inflammatory activity and can assist in treating inflammatory bowel disease. Aims of the studyTo investigate curcumin's protective effects on intestinal epithelium and explore the underlying miR-195-3p-related mechanisms. Materials and methodsThe miR-195-3p mimics were used to over-express miR-195-3p. The in vitro effects of Cur and miR-195-3p on the intestine were shown utilizing intestinal cryptlike epithelial cell line-6 (IEC-6) cells. By fasting for 48 h, an intestinal mucosal atrophy model of SD rats was created in vivo. Cur (25 or 50 mg/kg) was assessed for its protective effect on intestinal epithelium. Glycyrrhetinic acid (GA) with an intestinal protective effect reported in our previous research was adopted as a positive drug for the in vivo and in vitro bioactivity evaluation since there is no universally positive drug for either intestinal mucosal restitution or miR-195-3p modulation. ResultsCur protects the intestinal epithelium and promotes its repair after injury via down-regulating miR-195-3p. In vitro experiments showed that Cur inhibited the apoptosis of IEC-6 cells, stimulated their growth, and down-regulated the level of miR-195-3p in cells. When miR-195-3p was overexpressed, the viability of IEC-6 cells decreased while the apoptosis rate increased. All the above detrimental effects were alleviated after curcumin intervention. Moreover, Cur reversed the effect of miR-195-3p on its downstream occludin. In vivo, results showed that 48-h fasting impaired the integrity of the small intestinal mucosa (abnormal crypt structure and reduced goblet cell number), which was ameliorated by Cur treatment. In addition, the Cur treatment reversed both the increased expression level of miR-195-3p and decreased levels of ki-67 and occludin caused by fasting. ConclusionsCur could promote the proliferation and repair after injury of the intestinal mucosa by down-regulating miR-195-3p.

Curcumin alleviated dextran sulfate sodium-induced colitis by recovering memory Th/Tfh subset balance.

Restoration of immune homeostasis by targeting the balance between memory T helper (mTh) cells and memory follicular T helper (mTfh) cells is a potential therapeutic strategy against ulcerative colitis (UC). Because of its anti-inflammatory and immunomodulatory properties, curcumin (Cur) is a promising drug for UC treatment. However, fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis. To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium (DSS) in mice by regulating the mTh and mTfh immune homeostasis. Balb/c mice were administered 3% and 2% DSS to establish the UC model and treated with Cur (200 mg/kg/d) by gavage on days 11-17. On the 18th d, all mice were anesthetized and euthanized, and the colonic length, colonic weight, and colonic weight index were evaluated. Histomorphological changes in the mouse colon were observed through hematoxylin-eosin staining. Levels of Th/mTh and Tfh/mTfh cell subsets in the spleen were detected through flow cytometry. Western blotting was performed to detect SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in colon tissues. Cur effectively mitigates DSS-induced colitis, facilitates the restoration of mouse weight and colonic length, and diminishes the colonic weight and colonic weight index. Simultaneously, it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane. While the percentage of Th1, mTh1, Th7, mTh7, Th17, mTh17, Tfh1, mTfh1, Tfh7, mTfh7, Tfh17, and mTfh17 cells decreased after Cur treatment of the mice for 7 d, and the frequency of mTh10, Th10, mTfh10, and Tfh10 cells in the mouse spleen increased. Further studies revealed that Cur administration prominently decreased the SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in the colon tissue. Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage, potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.

Curculigoside attenuates Helicobacter pylori-induced inflammation and apoptosis of gastric mucosal epithelial cells via NF-κB pathway

Purpose: To investigate the possible effects and mechanisms of action of curculigoside (Cur) on gastric ulcers.
 Methods: Human gastric mucosal epithelial GES-1 cells were infected with Helicobacter pylori and then treated with Cur. Cell counting kit 8 (CCK-8), flow cytometry, and immunofluorescence assays were used to investigate the effect of Cur on cell viability and apoptosis after exposure to H. pylori. Inflammation status and reactive oxygen species (ROS) were assessed using enzyme-linked immunoassay (ELISA) and dichlorodihydrofluorescein (DCF) staining, respectively, while immunoblot and immunofluorescence assays were performed to determine the effect of Cur on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway.
 Results: Cur significantly increased H. pylori-induced cell viability and inhibited H. pylori-induced inflammatory cytokine production (p < 0.01). Furthermore, Cur significantly suppressed H. pylori-induced ROS production and apoptosis (p < 0.01). Through the NF-κB pathway, Cur attenuated H. pylori-induced inflammation and apoptosis of gastric mucosal epithelial cells.
 Conclusion: In H. pylori infection, Cur treatment increases cell viability, reduces inflammatory cytokine production, suppresses ROS production, and inhibits apoptosis via NF-κB pathway. Further investigation using whole animal experiments would be needed to establish the role of Cur in the management of H. pylori-induced gastric ulcers.

Curcumin alleviates experimental colitis via a potential mechanism involving memory B cells and Bcl-6-Syk-BLNK signaling

Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease (IBD), which is mainly related to lymphocytes (T or B cells, incl-uding memory B cells), mast cells, activated neutrophils, and macrophages. As the precursor of B cells, the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells, whose dysfunction can easily lead to autoimmune diseases, including IBD. To investigate whether or not curcumin (Cur) can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling. Colitis was induced in mice with a dextran sulphate sodium (DSS) solution in drinking water. Colitis mice were given Cur (100 mg/kg/d) orally for 14 con-secutive days. The colonic weight, colonic length, intestinal weight index, occult blood scores, and histological scores of mice were examined to evaluate the curative effect. The levels of memory B cells in peripheral blood of mice were measured by flow cytometry, and IL-1β, IL-6, IL-10, IL-7A, and TNF-α expression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay. Western blot was used to measure the expression of Bcl-6, BLNK, Syk, and other signaling pathway related proteins. After Cur treatment for 14 d, the body weight, colonic weight, colonic length, colonic weight index, and colonic pathological injury of mice with colitis were ameliorated. The secretion of IL-1β, IL-6, TNF-α, and IL-7A was statistically decreased, while the IL-35 and IL-10 levels were considerably increased. Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM, IgG, IgA, FCRL5, CD103, FasL, PD-1, CD38, and CXCR3 on the surface of CD19+ CD27+ B cells, while the number of CD19+ CD27+ IL-10+ and CD19+ CD27+ Tim-3+ B cells increased significantly. In addition, Cur significantly inhibited the protein levels of Syk, p-Syk, Bcl-6, and CIN85, and increased BLNK and p-BLNK expression in colitis mice. Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.

Curculigoside Represses the Proliferation and Metastasis of Osteosarcoma via the JAK/STAT and NF-κB Signaling Pathways.

Curculigoside (Cur) is a natural component from Curculigo orchioides Gaertn, with various bioactivities. The function of Cur in the nervous system and osteoarthritis has been reported. However, its role in osteosarcoma (OS) needs to be investigated. Hence, we focus on probing the impact of Cur on OS. In vitro, cell counting kit 8 (CCK-8), flow cytometry and Transwell assay were used to investigate the effects of Cur on OS cell proliferation, apoptosis, migration and invasion. In vivo, we developed a xenograft model to figure out the effect of Cur on tumor growth in nude mice. Western blotting (WB) was conducted to compare the levels of Cur on apoptosis-related proteins (C-caspase-3, Bax, and Bcl-2), epithelial-mesenchymal transition (EMT)-related proteins (N-cadherin, Snail, and E-cadherin) and the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and nuclear factor-κB (NF-κB) pathways in vitro and in vivo. In-vitro data testified that Cur treatment markedly hampered OS cells' growth, migration and invasion and intensified their apoptosis compared to that of the control group. In vivo, Cur treatment notably hampered the growth of OS tumors in mice. In addition, both in vitro and in vivo experiments demonstrated that the phosphorylation of JAK2, STAT3, and NF-κB were inhibited through Cur treatment. Furthermore, the inhibition of Cur in OS cells was demonstrated by up-regulating the expression of JAK/STAT and NF-κB pathways protein levels. In summary, the data suggest that Cur curbs OS growth by down-regulating the JAK/STAT and NF-κB pathways, which is an underlying therapeutic option for OS treatment.

Curcumin Suppresses Lead-Induced Inflammation and Memory Loss in Mouse Model and In Silico Molecular Docking.

This study examined the efficacy of curcumin (Cur) against lead (Pb)-induced oxidative damage, inflammation, and cholinergic dysfunction. Institute for Cancer Research (ICR) mice received Pb (II) acetate in drinking water (1%) with or without Cur via oral gavage. Blood and brain tissues were collected for investigation. Pb increased the inflammatory markers and oxidative parameters, which were ameliorated by Cur administration. Cur treatment also improved memory loss, learning deficit, and cholinergic dysfunction via elevating acetylcholinesterase (AChE) enzymatic activity and protein expression. In silico molecular docking supported the results; Cur had a potent binding affinity for AChE receptors, tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), phosphorylations of IκB kinase (IKK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38). According to the chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile, Cur could serve as a potential candidate for Pb detoxication substance via exerting antioxidant activity. Taken together, our results suggest that Cur is a natural compound that could be used for the treatment of neurodegenerative disorders via suppressing lead-induced neurotoxicity.

Curcumin treatment attenuates cisplatin-induced gastric mucosal inflammation and apoptosis through the NF- κ B and MAPKs signaling pathway.

To investigate the protective effects of curcumin (Cur) on gastric mucosal injury induced by cisplatin (DDP), and explore possible molecular mechanisms. A mouse of gastric mucosal injury was established by intraperitoneal injection of DDP (27mg/kg). Thirty mice were randomly divided into control group, DDP group and DDP + Cur group. Serum and gastric mucosal samples were collected on the 7th day after Cur treatment. The index of gastric mucosa injury was calculated, and the expression levels of inflammation, apoptosis and signaling pathway proteins were evaluated using hematoxylin and eosin staining, ELISA and western blotting analysis. These data showed that Cur treatment significantly attenuated DDP-induced decrease in body weight, food intake, fat and muscle ratios, and improved the gross gastric injury, scores of ulcer index, and histopathology changes triggered by DDP (p < .05). Meanwhile, Cur significantly decreased serum IL-23 and IL-17 proteins, reduced the expression levels of gastric mucosal IL-1β, TNF- α and MPO, and restored the level of IL-10 protein (p < .05). Moreover, Cur treatment significantly inhibited the expression levels of Caspase-3, PARP and Bax, and increased the expression of Bcl-2 protein. Furthermore, Cur treatment significantly decreased the expression levels of IL-1R, MyD88 and TAK1, and also repressed the activation of NF-κB and nuclear translocation of NF-κB p65. And more importantly, Cur treatment significantly inhibited DDP-induced gastric mucosal JNK1/2, ASK1, P38 and JUN phosphorylation, and promoted the phosphorylation of ERK1/2 and C-Myc proteins. Our data suggest that Cur treatment alleviates DDP-induced gastric mucosal inflammation and apoptosis, which may be mediated through the NF- κ B and MAPKs signaling pathway.

Curcumin Affects Parkinson Protein 7 (PARK7; DJ-1) Expression and Regulates Proliferation and Apoptosis of Breast Cancer Cells by Up-Regulating miR-203

PTEN can inhibit PI3 K/AKT signaling pathway and DJ-1 negatively regualtes PTEN. Curcumin (Cur) regulates PTEN-PI3 K/AKT pathway. Bioinformatics analysis showed a targeting relationship between miR-203 and DJ-1, but it is unclear whether Cur regulates DJ-1-PTEN/PI3 K/AKT pathway through miR-203. We assessed Cur’s role in breast cancer cells. MCF-10A and MDA-MB-231 cells were cultured and expression of miR-203, DJ-1 and PTEN mRNA was measured by qRT-PCR. MDA-MB-231 cells were treated with 0, 10 μM Cur followed by analysis cell proliferation by CCK-8 assay, cell apoptosis by flow cytometry, miR-203, DJ-1 and PTEN mRNA level by qRT-PCR. MDA-MB-231 cells were divided into 3 groups: 0 μM, 10 μM Cur+miR-NC treatment group, 10 μM+miR-203 inhibitor group to measure cell apoptosis and proliferation. Compared with MCF-10A cells, miR-203 and DJ-1 mRNA in MDA-MB-231 cells was significantly upregulated and PTEN mRNA expression was decreased. Cur treatment significantly decreased cell proliferation, promoted caspase-3 activity and cell apoptosis, as well as elevated miR-203 and PTEN mRNA level and decreased DJ-1 mRNA level. miR-203 inhibitor transfection can antagonize Cur’s effect on upregulation of miR-203, increase DJ-1 expression, decrease PTEN expression, enhance PI3 K/AKT pathway activity, and antagonize Cur’s anti-tumor effect. Curcumin increases miR-203 expression, down-regulates DJ-1 expression, affects PTEN-PI3 K/AKT pathway activity, and play an anti-tumor effect through inhibiting breast cancer cell proliferation and promoting apoptosis.

Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway.

Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 μM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-β-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 μM~10 μM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene (Atg) 7 and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs.

Curcumin plays a protective role against septic acute kidney injury by regulating the TLR9 signaling pathway.

BackgroundThis study aims to evaluate the inhibitory effect of curcumin (Cur) on the progression of septic acute kidney injury (SAKI), in order to improve the survival rate in this patient population.MethodsAcute kidney injury (AKI) was induced by cecal ligation perforation (CLP) in Sprague-Dawley (SD) rats. Using this AKI animal model, the survival rate of the rats was evaluated at different time points after Cur treatment to explore whether Cur can improve survival in an animal model of AKI. The expression levels of inflammatory factors (NF-κB, TNF-α, and IL-10), organ injury markers [urea nitrogen (UN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, creatine kinase (CK), and lactate dehydrogenase (LDH)], and disease progression markers [neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C (CysC)] were determined using an enzyme-linked immunosorbent assay (ELISA).ResultsThe serum levels of UN, Cr, NF-κB, ALT, AST, amylase, CK, LDH, inflammatory factors TNF-α and IL-10, and markers of early diagnosis of SAKI (NGAL, CysC, KIM-1) were significantly lower in the curcumin group than those in the placebo group (P<0.05). In addition, serum levels of TLR9 and its downstream molecules MyD88, IRF5, and IRF7 in the curcumin group were significantly lower than those in the placebo group (P<0.05). The application of TLR9-specific inhibitors to experimental rats led to similar results as those obtained in the curcumin group, whose detection indexes were significantly lower than those in the placebo treatment group (P<0.05).ConclusionsGiven the excellent performance of Cur in anti-tumor, anti-oxidation, anti-inflammatory, and other clinical trials, it is very likely to be further developed as a potential drug for the clinical treatment of AKI.

Exosome derived from bone marrow mesenchymal stem cells pre-treated with curcumin alleviates osteoporosis by promoting osteogenic differentiation via regulating the METTL3/microRNA-320/RUNX2 signaling pathway

IntroductionCurcumin (CUR) was reported to stimulate the expression of methyltransferase‐like 3 (METTL3), a potential new target for the replacement therapy of osteoporosis. Besides, marrow stem cells (MSC)-derived exosomes (EXO) were proven to improve osteoporosis by promoting the proliferation of osteoblasts. In this study, we aimed to study the effect of CUR and BMSC-derived exosomes in the treatment of osteoporosis.Material and methodsMicroscopy was used to characterize exosomes derived from bone marrow stem cells (BMSCs). MicroCT was carried out to analyze the parameters of bone formation. Western blot was carried out to analyze the expression of surface markers on BMSC-derived exosomes and METTL3/Runt-related transcription factor 2 (RUNX2) proteins under different conditions. Real-time PCR was used to assess the gene expression under different circumstances.ResultsThe exosomes derived from CUR-treated BMSCs showed an enhanced therapeutic effect on osteoporosis mice compared with exosomes derived from untreated BMSCs. Mechanistically, the effect of BMSC-derived exosomes on restoring the de-regulated expression of METTL3, miR-320 and RUNX2 was significantly enhanced by CUR treatment upon BMSCs. Besides, CUR treatment upon BMSCs showed an obvious effect on enhancing the stimulatory role of BMSC-derived exosomes in the expression of METTL3, miR-320, RUNX2, BGLAP and LAP in BMSCs. Furthermore, luciferase assay demonstrated that miR-320 was capable of suppressing the expression of RUNX2 through binding to the 3’ UTR of RUNX2.ConclusionsOur study demonstrated that BMSC-derived exosomes could modulate the METTL3/miRNA-320/RUNX2 axis to attenuate osteoporosis by promoting osteogenic differentiation of BMSCs. Moreover, the CUR treatment upon BMSCs promoted the therapeutic effect of BMSC-derived exosomes.

Curcumin Reduces Neuroinflammation and Improves the Impairments of Anesthetics on Learning and Memory by Regulating the Expression of miR-181a-5p

Objective: The purpose of this study was to explore the role of curcumin (Cur) in isoflurane (ISO)-induced learning and memory dysfunction in Sprague-Dawley rats and further elucidate the mechanism of the protective effect produced by Cur. Methods: Rat models of cognitive impairment were established by inhaling 3% ISO. The Morris water maze test was used to assess the cognitive function of rats. ELISA and qRT-PCR were used to analyze the protein levels of pro-inflammatory cytokines and expression levels of miR-181a-5p, respectively. Results: Cur significantly improved the ISO-induced cognitive dysfunction in rats and alleviated the ISO-induced neuroinflammation. miR-181a-5p was overexpressed in ISO-induced rats, while Cur treatment significantly reduced the expression of miR-181a-5p. Overexpression of miR-181a-5p promoted the cognitive impairment and the release of inflammatory cytokines and reversed the neuroprotective effect of Cur. Conclusion: Cur has a protective effect on ISO-induced cognitive dysfunction, which may be achieved by regulating the expression of miR-181a-5p.

Cardioprotective effect of pioglitazone and curcumin against diabetic cardiomyopathy in type 1 diabetes mellitus: impact on CaMKII/NF-κB/TGF-β1 and PPAR-γ signaling pathway.

Diabetic cardiomyopathy (DCM) is a leading cause of death in diabetic patients, which is currently without available specific treatment. This study aimed to investigate the potential protective effects of pioglitazone (Pio) and curcumin (Cur) against DCM in type 1 diabetes mellitus (T1DM), with pointing to their role on Ca+2/calmodulin-dependent protein kinase II (CaMKII) and peroxisome proliferator-activated receptor gamma (PPAR-γ) expression. Diabetes was induced in adult male Sprague Dawley rats by administration of single intraperitoneal injection of streptozotocin (STZ) (52.5mg/kg). Diabetic rats were administered either Pio (20mg/kg/day) or Cur (100mg/kg/day) orally for 6weeks. Treatment with Pio and/or Cur markedly reduced serum cardiac injury markers and lipid profile markers in diabetic animals. Additionally, Pio and/or Cur treatment mitigated oxidative stress and fibrosis in diabetic rats as evident from the significant suppression in myocardial lipid peroxidation and tumor growth factor beta 1 (TGF-β1) level, with concomitant significant elevation in total antioxidant capacity (TAC) and improvement in histopathological architecture of heart tissue. Pio/Cur treatment protocol accomplished its cardioprotective effect by depressing cardiac CaMKII/NF-κB signaling accompanied by enhancement in PPAR-γ expression. Conclusively, these findings demonstrated the therapeutic potential of Pio/Cur regimen in alleviating DCM in T1DM through modulation of CaMKII and PPAR-γ expression. Graphical Abstract.

Curcumin alleviates neuroinflammation, enhances hippocampal neurogenesis, and improves spatial memory after traumatic brain injury

Cognitive decline is one of the most obvious symptoms of traumatic brain injury (TBI). Previous studies have demonstrated that cognitive decline is related to substantially increased neuroinflammation and decreased neurogenesis in the hippocampus in a rat model of TBI. Using this model, we explored the role of curcumin (Cur) in ameliorating TBI-impaired spatial memory because Cur has been shown to exhibit anti-chronic-neuroinflammatory, neurogenesis-promoting, and memory-improving properties.Animals received daily Cur or vehicle treatment for 28 days after TBI and also received 50-bromodeoxyuridine(BrdU) for the first 7 days of the treatment for assaying neurogenesis. An optimal Cur dose of 30 mg/kg, selected from a range of 10–50 mg/kg, was used for the present study. Neuroinflammation was evaluated by astrocyte hypertrophy, activated microglia, and inflammatory factors in the hippocampus. Behavioral water-maze studies were conducted for 5 days, starting at 35-day post-TBI. The tropomyosin receptor kinase B (Trkb) inhibitor, ANA-12, was used to test the role of the brain-derived neurotrophic factor (BDNF)/ TrkB/Phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in regulating inflammation and neurogenesis in the hippocampus.Treatment with Cur ameliorated the spatial memory of TBI rats, reduced TBI-induced chronic inflammation, typified by diminished astrocyte hypertrophy, reduction in activated microglia, declined inflammatory factors, and increased neurogenesis in the hippocampus. We also found that BDNF/Trkb/PI3K/Akt signaling was involved in the effects of Cur in TBI rats.Thus, Cur treatment can ameliorate the spatial memory in a murine model of TBI, which may be attributable to decreased chronic neuroinflammation, increased hippocampal neurogenesis, and/or BDNF/Trkb/PI3K/Akt signaling.

Effects of curcuminoids on cognitive deficits in young audiovisually overstimulated mice

Constant audiovisual exposure from digital media devices can cause overstimulation (OS) of the infant brain, which negatively impacts cognition. Curcuminoids (Cur, the principal component of turmeric) have shown neuroprotective qualities, however, their effects on overstimulated brain are unknown. This study aimed to determine the effects of audiovisual OS on cognitive functions in young mice, and to investigate if Cur offered neuroprotection. Ten day old mice were exposed to flashing lights and sound 8 h/day for 5 days/wk along with Cur (1 or 20 mg/kg in feed) for 42 days. Cognitive functions were measured using behaviour tests. Cholinergic function was determined using hippocampal and cortical acetylcholine levels and muscarinic acetylcholine receptors (M1, M3 and M5) gene expression. It was observed that OS did not affect spatial learning and memory, but reduced cued and contextual fear learning (p < 0.001) and impaired short-term memory retrieval (p < 0.05) as compared to control. The OS led to elevated anxiety (p < 0.05), but did not alter acetylcholine levels in the cortex and hippocampus. The OS significantly reduced gene expression in the cortex (M1: p < 0.05 and M3: p < 0.001) and hippocampus (M1: p < 0.001, M3: p < 0.05 and M5: p < 0.001), compared to control. The Cur treatment along with OS not only worsened spatial learning, exploratory activity and social behaviour, but also reduced acetylcholine levels in the cortex and hippocampus, as compared to control and OS groups. It was concluded that OS has a negative impact on behaviour and cholinergic function. Further studies on Cur usage in developing children's brain are needed for its cautious use.

Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling

This study evaluates the protective effects of Thymoquinone (Tq) and Curcumin (Cur) in models of cisplatin-induced renal toxicity. Proliferation studies were carried out in HEK-293 cells. Cisplatin(ip) 5 mg/kg BW was used to induce renal injury in Sprague–Dawley rats. 50 mg/kg BW Tq + 100 mg/kg BW Cur, with or without cisplatin-treatment were administered for 5 days. Tq + Cur combination synergistically reduced the proliferation inhibition of HEK-293 cells resulted from cisplatin treatment and brought down cisplatin-induced apoptosis in these cells. In vitro studies revealed serum levels of BUN, creatinine, CK and pro-inflammatory cytokines like TNF-α, IL-6 and MRP-1 to be elevated in the cisplatin-treated group while reducing glomerular filtration rate. Tq + Cur treatment significantly improved these conditions. The antioxidant enzyme levels and mitochondrial ATPases were restored upon treatment, which were lessened in the cisplatin-treated group. Cisplatin induced the expression of KIM-1, which was brought down by the combination treatment. Tq + Cur treatment increased the expressions of phosphorylated Akt, Nrf2 and HO-1 proteins while decreasing the levels of cleaved caspase 3 and NFκB in kidney homogenates. In summary, Tq + Cur had protective effects on cisplatin-induced nephrotoxicity and renal injury, which could be mediated by up-regulation of survival signals like Akt, Nrf2/HO-1 and attenuation of KIM-1, NFκB.