Curcumin-treated Group Research Articles

Histopathological examination of the hepatoprotective effect of curcumin with piperine on thioacetamide induced hepatotoxicity in rats

Piperine possesses bio-enhancer characteristics, while curcumin has a long history of traditional use in reviving the liver and treating illnesses and dysfunction of the liver. Thus, the goal of the current investigation was to ascertain the hepatoprotective potential of curcumin and piperine after oral administration on albino rat liver damage caused by thioacetamide. In this study, the animals were divided into five groups, each containing four rats. Groups II (received thioacetamide on the eighth day), III (received curcumin orally for seven days), IV, and V received a single dose of thioacetamide on the eighth day of the experiment. For seven days, a group I received normal saline as a control. For seven days, Group III received 200 mg of curcumin per kg of body weight. Groups IV and V received piperine for 7 days combined with curcumin at doses of 200 and 400 mg per kg of body weight, respectively. Rats of all the groups were sacrificed on the 10th day of the study. The thioacetamide treated group showed severe necrosis, hemosiderosis, and mononuclear cell infiltration around the central vein. The curcumin-treated group showed minimal hepatic necrosis and mild degenerative changes indicating restoration of normal architecture due to the hepatoprotective property of respective treatments against thioacetamide. The histo-architecture of the kidney treated with thioacetamide showed pathological changes as evidenced by tubular degeneration and distorted architecture. Treatment groups showed improvement in renal pathology. Hence, the study concluded that curcumin provided hepatoprotection against thioacetamide-induced hepatotoxicity and in combination with piperine hepatoprotective activity of curcumin was observed to be reduced.

Curcumin Involve the Myofibrosis Process of Rabbit Valve Interstitial Cells based on Expression Alpha- Smooth Muscle Actin: Experimental Posttest-only Control Group Design

Introduction: Following an acute rheumatic fever infection brought on by an inflammatory reaction to streptococcal bacteria, rheumatic heart valve disease results in valve degeneration. Elements of the immune system play an important role, in facilitating myofibroblast transdifferentiation and clearing damaged tissue of apoptotic cells. Myelofibrosis arising in valve components is the main cause of valve dysfunction. Valve myelofibrosis showed a significantly increased collagen, proteoglycan, and elastin content in myofibrotic valves compared to healthy valves. Objective: To establish curcumin’s capacity to prevent rabbit valve interstitial cells (VIC) from differentiating into myofibroblasts after being stimulated by TGF-1 by comparing the results to controls. Method: This study uses a posttest-only control group design for an in-vitro laboratory experiment. Heart VIC of a New Zealand rabbit were isolated (Oryctolagus cuniculus), and induced fibrosis by administration of TGF-β1 5 ng/mL. VIC pretreated with TGF-β1 were treated with low-dose curcumin (20 nanoM/L) and high-dose curcumin (50 nanoM/L). The immunocytochemical method based on SMA expression observed the inhibition of myofibroblastic differentiation. Statistical significance was analyzed by Kruskal-Wallis statistical test with a p-value < 0.05 as the limit of significance. Result: Administration of curcumin with low doses (20 nanoM/L) and high doses (50 nanoM/L), significantly decreased TGF-β1-induced myofibroblastic differentiation of VIC, which was characterized by decreased SMA expression in all low-dose curcumin treatment groups (20 nanoM/L) (1.40 ± 6.30) and high-dose curcumin (50 nanoM/L) (1.40 ± 8.30). Conclusion: Curcumin potentially prevent the development of SMA-expressing VIC into myofibroblasts.

Curcumin protects islet beta cells from streptozotocin‑induced type 2 diabetes mellitus injury via its antioxidative effects.

Streptozotocin (STZ)-induced diabetes rodent models are widely used to study the pathogenesis and metabolic function in diabetes (DM). The aim of this study was to assess the antioxidant effect of curcumin in STZ-induced type 2 diabetes mellitus (T2DM). In this research, rats were randomly divided into 3 groups (8 in each group): a nondiabetic group (Control), a diabetic group (DM), and a curcumin treatment group (DM + Cur 200 mg/kg group). Meanwhile, after intraperitoneal injection (i.p.), associated-oxidative stress parameters were observed, malondialdehyde (MDA) was decreased, and glutathione peroxidase (GPX) and super oxide dismutase (SOD) were restored in pancreatic tissues of curcumin-treated DM rats. In addition, curcumin improved the survival and function of islet cells with decreased cell apoptosis in Langerhans islet and increased insulin secretion in the STZ-induced T2DM rat model. Our findings suggest that curcumin is a potent candidate for the prevention and therapy of DM.

Effect of Curcumin on Interleukin-6 Expression and Malondialdehyde Levels in Liver Fibrosis

BACKGROUND: Chronic inflammation and excessive oxidative stress are the main mechanisms causing liver fibrosis. It releases anti-inflammatory cytokines, namely, interleukin 6 (IL-6), nitric oxide, and malondialdehyde (MDA). Curcumin acts as an anti-inflammatory, antioxidant, and antifibrotic. AIM: This study is aimed to analyze differences in IL-6 expression and MDA levels in (Deutschland, Denken, and Yoken) DDY mice with liver fibrosis after common bile duct ligation between the curcumin-treated and control groups. METHODS: This research is an experimental study with a post-test-only control group design. Seventy-five male DDY mice 20–30g were used in this study (n = 5). Mice were randomly divided into five groups, each consisting of 15 mice. The first group healthy control (HC) was the HC group given phosphate-buffered saline (PBS) solution and did not perform the CBDL. The second group negative control (NC) was a NC group given PBS solution and completed the CBDL. The third group positive control (PC) was a PC group given oral ursodeoxycholic acid (UDCA) and performed CBDL. The fourth group (P1) was assigned oral curcumin and performed the CBDL. The fifth group (P2) was given oral curcumin and UDCA and performed the CBDL. Seven, fourteen, and 21 days after ligation, liver samples were taken to examine IL-6 expression and MDA levels. RESULTS: There was a significant difference between the NC and PC groups (p = 0.00), NC and P1 (p = 0.00), NC with P2 (p = 0.00), PC with P1 (p = 0.04), PC with P2 (p = 0.04), on day 21 between the NC and PC groups (p = 0.00), NC with P1 (p = 0.00), and PC with P2 (p = 0.00). Statistical analysis of the comparison of MDA levels on days 7 and 14 found no significant difference. On day 21, there was a substantial difference between the NC group and P1 (p = 0.02). CONCLUSION: This study concluded that curcumin effectively reduced IL-6 expression and MDA levels in liver fibrosis.

Protective effects of intranasal curcumin on silica-induced lung damage

ObjectiveBeing anti-inflammatory and an antioxidant in nature, curcumin has been studied for its anti-asthmatic effects, but its impact on silicosis has not been investigated before. It is a form of occupational lung illness caused by inhaling crystalline silica. It is particularly common among those who work in construction-related sectors. Therefore, present study has been undertaken to investigate impact of intranasal curcumin on silica induced lung damage in mice model of silicosis. Materials and methodsMice model of silicosis was developed by intranasal silica instillation (2.5 mg/mice) for different durations mainly 7, 14 and 21 days, where the longest duration of silica exposure (21 days) mimics chronic occupational exposure of silica dust leading to silicosis. Curcumin (5 mg/kg,i.n) and /or dexamethasone, a known corticosteroid (10 mg/kg,i.p) was administered an hour prior to silica administration. ResultsPresent study revealed silica induced lung damage in the mice model of silicosis characterized by airway inflammation, collagen deposition and enhanced expression of fibrosis markers (MMP-9, α-SMA, Hydroxyproline), which were significantly reduced in curcumin treatment groups. Inhibitory effects of curcumin were compared with standard drug, dexamethasone, a corticosteroid and was found better in protecting structural alterations in the lung.Damaged and abnormal mitochondria (enlarged and irregular shapes) were observed in silicosis group which were reduced in curcumin and dexamethasone treatment groups as revealed in transmission electron microscopic studies. ConclusionsPresent study shows protective effects of intranasal curcumin on silica-induced airway inflammation and structural changes thereby lung damage. Hence, it can be considered as an alternative and complementary medication for silicosis.

Effect of Curcumin on Hippocampal Neurons, Learning, and Spatial Memory in a Model of Global Cerebral Ischemia

Background: Curcumin is a natural antioxidant known for its neuroprotective properties against cerebral ischemic reperfusion injury (CIRI). Stroke has the greatest impact on the hippocampus CA1 region and leads to cognitive impairment. Objective: This study aimed to investigate the effect of pretreatment with turmeric extract before induction of cerebral ischemia on the structure of the hippocampus CA1 region, learning, and spatial memory. Methods: A total of 32 adult male Wistar rats were randomly divided into four groups: 1) control group, 2) sham group (received DMSO), 3) ischemia group (15 min bilateral carotid artery), and 4) curcumin group (received 100 mg/kg of curcumin daily for five days before induction of ischemia). A Morris water maze test was performed to evaluate memory impairment in mice 48 h after ischemia induction. The animals were then anesthetized, and their blood samples were taken for malondialdehyde measurement. Subsequently, the animals’ brains were removed, and the number of neurons and the volume of the layers were examined using cresyl violet staining. Results: The results of stereology showed a significant increase in the volume of the CA1 region and its substrates in the curcumin treatment group compared to the ischemia group. In addition, the number of pyramidal neurons in the treatment group showed a significant increase compared to the ischemia group. Moreover, curcumin administration reduced spatial memory impairment in the treatment group compared to the ischemia group. Conclusion: These results suggest that pretreatment with curcumin can improve memory and learning disorders and hippocampal neuron damage following ischemia.

Metabolomics study on liver of db/db mice treated with curcumin using UPLC-Q-TOF-MS

A metabolomics method based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to study the metabolic changes of liver in db/db mice administered with curcumin. After one week of acclimating to feeding, 20 db/db mice were randomly divided into two groups: curcumin non-treatment group and curcumin treatment group. After eight weeks of treatment, plasma and liver were collected for biochemical analysis and metabolomics analysis, as well as liver oxidative stress and histopathology examination. Serum biochemical indicators such as blood glucose, triglycerides, fasting insulin, and aspartate aminotransferase decreased significantly in the curcumin treatment group compared to the curcumin non-treatment group, whereas hepatic pathological levels and antioxidation levels improved. There were several different potential biomarkers in two groups, including sphingomyelin (SM) (d18:0/20:0), eicosapentaenoic acid (EPA), docosapentaenoic acid (22n-6) (DPAn-6), arachidonic acid (AA), dihomo-gamma- linolenic acid (DGLA), leukotriene C4 (LTC4), lysophosphatidylethanolamine (LysoPE) (16:1(9Z)/0:0), LysoPE (18:1(9Z)/0:0), LysoPE (0:0/18:0), LysoPE (0:0/20:1(11Z)), LysoPE (20:1(11Z)/0:0), 3-sulfinoalanine, alpha-tocotrienol (α-T3) and pantetheine 4′-phosphate (4′-PP). The mechanism might be related to biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, phospholipid metabolism, and taurine and hypotaurine metabolism. The effects of curcumin on type 2 diabetes mellitus (T2DM) include antioxidant, delaying development of T2DM, preventing β-cell death, decreasing insulin resistance, alleviating hepatic damage, and improving metabolic disturbances. Our results provide novel insights and ideas for prevention and treatment of curcumin on T2DM and its complications.

Efficacy of Nanocurcumin with application of Iontophoresis on Inflammatory arthritis patients.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory systemic disorder that primarily affects smaller joints characterized by periods of severe pain, stiffness, and swelling and destruction of the bones and cartilage. As indicated by past investigations, oral organization of curcumin results in calming impact regardless of its low bioavailability in patients. Objective: This study aims to measure the efficacy of nanocurcumin particles with iontophoresis in inflammatory arthritis patients. Methodology: Nanocurcumin were prepared by a process based on a wet-milling technique. In vitro anti inflammatory assay of nanocurcumin was determined by Bradford assay using bovine serum albumin (BSA) as the standard. The prospective study was done among a 10 patients from the reports obtained from March 2020 to October 2020 in Physiotherapy clinic, Madurai. Results: All the curcumin-treated groups showed significant alleviation of inflammatory arthritic condition (p<0.05) when compared with inflammatory arthritic controls. Conclusion: Iontophoretic administration of curcumin may ameliorate arthritic symptoms significantly, and the effect is assumed to be due to better penetration and enhanced bioavailability. Geriatrics patients are supposed to be benefited fairly by this technique.

Potentiality of curcumin on ISHAK scoring system and the expressions of BAX, IL-17A, and EGF in the treatment ofSchistosoma mansoni infection using Swiss albino mice.

The present study evaluated the antiparasitic effect of curcumin extract on Schistosoma mansoni in Swiss albino mice. The experimental design included four groups of S. mansoni - infected mice; without treatment (controls), curcumin-treated, Praziquantel (PZQ)-treated, and PZQ +curcumin treated mice. The results showed that curcumin improved ISHAK confluent necrosis score up to zero. PZQ +curcumin showed a significant reduction in portal inflammation. Both activity and fibrosis demonstrated lower scores in all treated groups, however, PZQ revealed a marked increase in confluent necrosis and interface hepatitis. Besides, the lobular inflammation revealed worsening in the overall ISHAK score in all treated groups compared with the control. Few periocular granulomas were recovered by PZQ +curcumin treatment at day 35 post-treatment (6±1.2), P-value <0.05. Curcumin revealed a mild reduction (60±7.376). Curcumin-treated groups, with and without PZQ, resulted in higher significant Immunoreactivity score (IRS) for Bcl-2-associated X (BAX) and lower Interleukine- 17A (IL-17A), and Human epidermal growth factor (EGF), compared to the control. However, PZQ revealed a lower mean IRS value in BAX, higher IL-17A and EGF in the periovulatory granuloma. It was concluded that PZQ +curcumin treatment had a potent synergistic outcome through lessening the number of granulomas, the inflammatory events, and the expression of EGF, and amelioration of apoptosis in the periovulatory granulomas if compared with either PZQ or curcumin alone.

No persistent effects of intracerebral curcumin administration on seizure progression and neuropathology in the kindling rat model for temporal lobe epilepsy

Curcumin is known for its neuroprotective, anti-inflammatory and anti-oxidant properties and has been investigated as a potential therapeutic drug for Temporal Lobe Epilepsy (TLE). We previously found anti-epileptogenic properties of curcumin in an in vitro brain slice model for epileptogenesis, and inhibitory effects on the MAPK-pathway in vivo after intracerebrally applying curcumin in post-status epilepticus rats. Here, we investigated whether the intracerebral application of curcumin could be anti-epileptogenic in the rapid kindling rat model for TLE. Curcumin or vehicle was injected directly into the brain through an intracerebral ventricular cannula at 5 consecutive days during the kindling process. Kindling consisted of repeated electrical stimulations of the angular bundle (12 times a day with a 30min interval) every other day, until rats were fully kindled or until 36 stimulations were administered. One week after kindling acquisition, additional kindling stimulations were applied in a re-test in the absence of curcumin- or vehicle treatment. Curcumin-treated rats required more stimulations compared to vehicle-treated rats to reach Racine stage IV seizures, indicating that curcumin delayed seizure development. However, it did not prevent the fully kindled state as shown in the re-test. Increasing the dose of curcumin did not produce a delay in seizure development. Immunohistochemistry showed that kindling produced cell loss, astrogliosis, mossy fiber sprouting and neurogenesis in the dentate gyrus, which were not different between vehicle- and curcumin-treated groups. Although curcumin's effects on neuropathology were not detected and the delay of kindling development was transient, the data warrant further exploration of its anti-epileptogenic potential using formulations that further increase its bioavailability.

Co-expression network analysis for renal cell carcinoma genes and in vitro confirmation of their expression in cell model in the presence of curcumin

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and accounts for 2 to 3% of adult malignant tumors. This study proposed novel co-expression genes in RCC and investigated the curcumin effect on the expression of this gene in human cancer cells (ACHN). In this experimental study, the co-expression networks were predicted from different criteria for RCC by bioinformatics methods and employing RT-qPCR analysis; the mRNA levels of the selected genes were compared between curcumin-treated (24, 48, and 72 h) and untreated groups. The lncRNA-miRNA-mRNA interaction was created. RT-qPCR showed that the expression of c-Maf and LINC01077 in curcumin-treated ACHN was different from that of the un-treated ACHN. Our results suggest that the newly identified molecular pathway was affected by curcumin, proving that this drug has an anti-cancer effect.

Mechanism of curcumin inhibiting pyroptosis in infectious acute lung injury through NLRP3 inflammatory pathway

Purpose of this study the mechanism of curcumin inhibiting pyroptosis in infectious acute lung injury through NLRP3 inflammatory pathway. In this study, SPF SD male rats were randomly divided into blank control group, curcumin group, lipopolysaccharide (LPS) group, LPS + curcumin group, LPS + Nigerin treatment group, LPS + Nigerin + curcumin treatment group. Three in each group. Animal models were established according to the experimental design. Blood samples were collected after anesthesia, and the lung wet/dry weight ratio was calculated. TUNEL was used to detect pyroptosis of alveolar macrophages in left lower lobe, and Elisa was used to detect the expression levels of inflammatory factors IL-1β and IL-18 in left lung tissue. Western Blot was used to detect the expression of pyroptosis-related proteins such as NLRP3, Caspase1 and GSDMD in right lung alveolar lavage fluid. Compared with the blank control group, the lung wet weight and lung dry weight of the curcumin group were significantly increased (P < 0.01, P < 0.05). Compared with the LPS group, the lung wet weight and lung dry weight of the curcumin group There was a statistical difference in weight increase (P < 0.01). Compared with the blank control group, the apoptosis rate of lung tissue in the curcumin group, LPS group and LPS+ nigericin group was significantly increased (P < 0.01). Compared with the LPS + nigericin group, the lung tissue apoptosis rate in the LPS + curcumin + nigericin group was decreased, but there was no statistical difference (P > 0.05). LPS and LPS combined with Nigerian bacteriocin can cause pyroptosis in lung tissue. Curcumin can inhibit pyroptosis of lung tissue macrophages caused by LPS and LPS combined with Nigerian bacteriocin, and reduce inflammatory response.

Curcumin protects human umbilical vein endothelial cells against high oxidized low density lipoprotein-induced lipotoxicity and modulates autophagy.

Objective(s):Endothelial dysfunction is a precursor of cardiovascular disease, and protecting endothelial cells from damage is a treatment strategy for atherosclerosis (AS). Curcumin, a natural polyphenolic compound, has been shown to protect endothelial cells from dysfunction. In the present study, we investigated whether curcumin could ameliorate high oxidized low-density lipoprotein (ox-LDL)-induced endothelial lipotoxicity by inducing autophagy in human umbilical vein endothelial cells (HUVECs).Materials and Methods:HUVECs were treated with 50 μM high ox-LDL alone or in combination with 5 μM curcumin for 24 hr. Cell viability and function were assessed by the cell counting kit-8 (CCK-8) assay, tube formation assay and cell migration experiments. Oil red O staining was used to detect lipid droplet accumulation in HUVECs. The change in reactive oxygen species (ROS) levels in HUVECs was measured with the probe DCFH-DA. Quantitative real-time PCR (qPCR) and Western blotting were used to evaluate the mRNA and protein levels of several inflammatory and autophagy-related factors.Results:Cell viability was restored, tube formation and migration ability were increased, and lipid accumulation, oxidative stress and inflammatory responses were decreased in the curcumin-treated group compared with the high ox-LDL group. Furthermore, high ox-LDL inhibited HUVEC autophagy, and this effect was reversed by curcumin. Moreover, curcumin regulated the expression of several key proteins involved in the AMPK/mTOR/p70S6K signaling pathway.Conclusion:Our findings suggest that curcumin is able to reduce endothelial lipotoxicity and modulate autophagy and that the AMPK/mTOR/p70S6K pathway might play a key role in these effects.

Curcumin induces apoptosis through caspase dependent pathway in human colon carcinoma cells

We investigated the apoptotic effects of curcumin in the colon carcinoma cell line SW480. Cells were treated with 40-200μM curcumin for 24, 48, and 72h, and the IC50 values were determined for each time interval. BrdU, caspase-3, and TUNEL staining results and the gene expression of FADD, CASP8, and CASP3 were evaluated. Curcumin treatments significantly inhibited cell proliferation and significantly induced apoptosis for 24, 48, and 72h. The proportion of BrdU-stained cells in the control groups were 58%, 57% and 61% and 28%, 27%, and 30% in the curcumin treatment groups at 24, 48, and 72h, respectively. The proportion of apoptotic cells was 28%, 29%, and 28% in the control groups and 59%, 61%, and 60% in the curcumin treatment groups at 24, 48, and 72h, respectively. As expected, caspase-3 staining also revealed a higher number of apoptotic cells in curcumin treatment groups at 24, 48, and 72h compared to controls. The proportion of Caspase-3-stained cells in the control groups were 23%, 25%, and 24% and 59%, 60%, and 62% in the curcumin treatment groups at 24, 48, and 72h, respectively. To prove caspase-3 staining results, FADD, CASP8, and CASP3 gene expressions were evaluated by real-time qPCR. Unlike the immunohistochemical results, no statistically significant upregulation was found at 24 and 48h, while relative gene expressions of FADD, CASP8, and CASP3 was significantly upregulated at 72h. The expression level increase was 0.88-, 1.19-, and 2.11-fold for FADD, 1.25-, 1.29-, and 1.59-fold for CASP8, and 1.33-, 1.46-, and 3.00-fold for CASP3 at 24, 48, and 72h, respectively. These results suggest that curcumin may be a potential protective or treatment agent against colon cancer; however, further studies on curcumin-rich diets and curcumin bioavailability are required.

Curcumin ameliorates hypertension via gut-brain communication in spontaneously hypertensive rat

Gut dysbiosis and dysregulation of gut–brain communication have been identified in hypertensive patients and animal models. Previous studies have shown that probiotic or prebiotic treatments exert positive effects on the pathophysiology of hypertension. This study aimed to examine the hypothesis that the microbiota-gut-brain axis is involved in the antihypertensive effects of curcumin, a potential prebiotic obtained from Curcuma longa. Male 8- to 10-week-old spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were divided into four groups: WKY rats and SHRs treated with vehicle and SHRs treated with curcumin in dosage of 100 or 300 mg/kg/day for 12 weeks. Our results show that the elevated blood pressure of SHRs was markedly decreased in both curcumin-treated groups. Curcumin treatment also altered the gut microbial composition and improved intestinal pathology and integrity. These factors were associated with reduced neuroinflammation and oxidative stress in the hypothalamus paraventricular nucleus (PVN). Moreover, curcumin treatment increased butyrate levels in the plasma, which may be the result of increased butyrate-producing gut microorganisms. In addition, curcumin treatment also activated G protein-coupled receptor 43 (GPR 43) in the PVN. These results indicate that curcumin reshapes the composition of the gut microbiota and ameliorates the dysregulation of the gut-brain communication to induce antihypertensive effects.

Curcumin, an Inhibitor of p300-HAT Activity, Suppresses the Development of Hypertension-Induced Left Ventricular Hypertrophy with Preserved Ejection Fraction in Dahl Rats.

We found that curcumin, a p300 histone acetyltransferase (HAT) inhibitor, prevents cardiac hypertrophy and systolic dysfunction at the stage of chronic heart failure in Dahl salt-sensitive rats (DS). It is unclear whether curcumin suppresses the development of hypertension-induced left ventricular hypertrophy (LVH) with a preserved ejection fraction. Therefore, in this study, we randomized DS (n = 16) and Dahl salt-resistant (DR) rats (n = 10) at 6 weeks of age to either curcumin or vehicle groups. These rats were fed a high-salt diet and orally administrated with 50 mg/kg/d curcumin or its vehicle for 6 weeks. Both curcumin and vehicle treatment groups exhibited similar degrees of high-salt diet-induced hypertension in DS rats. Curcumin significantly decreased hypertension-induced increase in posterior wall thickness and LV mass index, without affecting the systolic function. It also significantly reduced hypertension-induced increases in myocardial cell diameter, perivascular fibrosis and transcriptions of the hypertrophy-response gene. Moreover, it significantly attenuated the acetylation levels of GATA4 in the hearts of DS rats. A p300 HAT inhibitor, curcumin, suppresses the development of hypertension-induced LVH, without affecting blood pressure and systolic function. Therefore, curcumin may be used for the prevention of development of LVH in patients with hypertension.

Curcumin Improved Glucose Intolerance, Renal Injury, and Nonalcoholic Fatty Liver Disease and Decreased Chromium Loss through Urine in Obese Mice

Obesity-associated hyperglycemia underlies insulin resistance, glucose intolerance, and related metabolic disorders including type 2 diabetes, renal damage, and nonalcoholic fatty liver disease. Turmeric root is commonly used in Asia, and curcumin, one of its pharmacological components, can play a role in preventing and treating certain chronic physiological disorders. Accordingly, this study examined how high-fat diet (HFD)-induced hyperglycemia and hyperlipidemia are reduced by curcumin through changes in fatty liver scores, chromium distribution, and renal injury in mice. Relative to the control group, also fed an HFD, the curcumin group weighed less and had smaller adipocytes; it also had lower daily food efficiency, blood urea nitrogen and creatinine levels, serum alanine aminotransferase and aspartate aminotransferase levels, serum and hepatic triglyceride levels, and hepatic lipid regulation marker expression. The curcumin-treated obese group exhibited significantly lower fasting blood glucose, was less glucose intolerant, had higher Akt phosphorylation and glucose transporter 4 (GLUT4) expression, and had greater serum insulin levels. Moreover, the group showed renal damage with lower TNF-α expression along with more numerous renal antioxidative enzymes that included superoxide dismutase, glutathione peroxidase, and catalase. The liver histology of the curcumin-treated obese mice showed superior lipid infiltration and fewer FASN and PNPLA3 proteins in comparison with the control mice. Curcumin contributed to creating a positive chromium balance by decreasing the amount of chromium lost through urine, leading to the chromium mobilization needed to mitigate hyperglycemia. Thus, the results suggest that curcumin prevents HFD-induced glucose intolerance, kidney injury, and nonalcoholic fatty liver disease.

Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a.

PurposeThe mechanism underlying curcumin’s protective effect on osteoarthritis (OA) has not been clarified. This study aimed to determine whether curcumin exerts a chondroprotective effect by inhibiting apoptosis via upregulation of E2F1/PITX1 and activation of autophagy via the Akt/mTOR pathway by targeting microRNA-34a (miR-34a).MethodsMale Sprague–Dawley rats were fed a normal diet (ND) or high-fat diet (HFD) for 28 weeks. Five rats from each diet group were selected randomly for histological analysis of OA characteristics. Rats fed a HFD were given a single intra-stifle joint injection of the miR-34a mimic agomir-34a or negative control agomir (NC), followed by weekly low-dose (200 μg/kg body weight) or high-dose (400 μg/kg body weight) curcumin intra-joint injections from weeks 29 to 32. The rats’ stifle joints were submitted to histological analysis and to an apoptotic assay. Expression of miR-34a was detected using a real-time RT-PCR. E2F1 and PITX1 protein levels were determined by Western blot analysis, and the expressions of Beclin1, LC3B, p62, phosphorylated (p)-Akt, and p-mTOR were measured using immunofluorescence analysis.ResultsWe found that rats fed a HFD had OA-like lesions in their articular cartilage and had increased apoptosis of chondrocytes and decreased autophagy compared to rats fed a ND. Curcumin treatment alleviated OA changes, inhibited apoptosis, and upregulated autophagy. Agomir-34a treatment reduced E2F1, PITX1, Beclin1, and LC3B expression and increased p62, p-Akt, and p-mTOR expression in HFD-fed rats given low- or high-dose curcumin. Greater numbers of apoptotic cells, lesser expression of p62, p-Akt, and p-mTOR, and greater expression of E2F1, PITX1, and LC3B were observed in the agomir-34a and high-dose curcumin-treated group than in agomir-34a and low-dose curcumin-treated group.ConclusionCurcumin’s chondroprotective effect was mediated by its suppression of miR-34a, apparently by reducing apoptosis, via upregulation of E2F1/PITX1, and by augmenting autophagy, likely via the Akt/mTOR pathway.

Unraveling the biomechanistic role of Rac1/TWEAK/Fn14/NF-κB intricate network in experimentally doxorubicin-induced cardiotoxicity in rats: The role of curcumin.

Doxorubicin (DOX) is an important chemotherapeutic drug. Cardiotoxicity diminishes its clinical efficacy. We aimed to focus on the mechanism of DOX-induced cardiotoxicity, in addition, to evaluate curcumin's protective effect against it. Twenty-eight rats were divided into the normal control group I, curcumin-treated (200 mg/kg body weight [b.w.]) group II, DOX-treated (4 mg/kg b.w.) group III, and DOX + curcumin group IV. Cardiac injury markers, heart tissue oxidative stress indices, interferon-gamma (INF-γ), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), upregulated modulator of apoptosis (PUMA), p53 and nuclear factor kappa-B p65 (NF-κB p65) levels as well as messenger RNA gene expression of Rac1 and fibroblast growth factor-inducible protein 14 (Fn14) were assayed, besides the assay of DNA damage, histopathological changes, survivin immunohistochemistry and electron microscopic examination. Curcumin significantly downregulated Rac1 and Fn14 gene expression and significantly decreased p53, NF-κB p65, INF-γ, and PUMA levels in the cardiac tissue. In addition, curcumin improved oxidative stress indices, DNA damage, and cardiac toxicity markers in the form of lactate dehydrogenase (LD), creatine kinase isoenzyme-MB (CK-MB), and cardiac troponin-I (cTn-I). Meanwhile, upregulated antiapoptotic marker survivin was observed. Light and electron microscopic findings confirmed our biochemical and molecular outcomes. The current study established the antioxidant, anti-inflammatory, and antiapoptotic roles of curcumin against DOX cardiotoxicity.

Therapeutic effect of modulating the NLRP3-regulated transforming growth factor-β signaling pathway on interstitial cystitis/bladder pain syndrome

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder with complex pathogenesis and lacks effective treatment. Chronic inflammation is the main pathogenesis of Hunner-type IC/BPS. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome-related transforming growth factor-β (TGF-β)/Smad signaling pathway plays a crucial role in inflammation-related tissue fibrosis. Lipopolysaccharide (LPS) and protamine sulfate (LPS/PS) were instilled into the mouse bladder twice a week for 5 consecutive weeks to establish a chronic inflammation-induced IC/BPS model (LPS/PS model). Following LPS/PS treatment, curcumin (oral, 100 mg/kg; a potent NLRP3 modulator) was administered for 2 weeks in the curcumin treatment group, and normal saline was used for the sham group. Bladder function was evaluated by performing the voiding spot assay and examining the status of urothelial denudation and fibrosis in bladder tissues. The expression of NLRP3 inflammasome, interleukin-1β, TGF-β, Smad, vimentin, and E-cadherin in bladder tissues was evaluated through immunohistochemistry staining. Results revealed that the repeated instillation of LPS/PS leads to voiding dysfunction, bladder urothelium denudation, and detrusor muscle fibrosis through the upregulation of the NLRP3 inflammasome/IL-1β-related TGF-β/Smad pathway and the increased epithelial–mesenchymal transition process in bladder tissues. The downregulation of the NLRP3 inflammasome/IL-1β-related TGF-β/Smad pathway in bladder tissues through curcumin effectively mitigated bladder injury in the LPS/PS model. In conclusion, the NLRP3 inflammasome/IL-1β-related TGF-β/Smad pathway plays a crucial role in bladder injury in the LPS/PS model, and modulation of this pathway, such as by using curcumin, can effectively mitigate the sequelae of chronic inflammation-induced IC/BPS.