scholarly journals Protective Effect of a Novel Highly Bioavailable Formulation of Curcumin in Experimentally Induced Osteoarthritis Rat Model

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1765-1765
Author(s):  
Kazim Sahin ◽  
Cemal Orhan ◽  
Besir Er ◽  
Ali Said Durmus ◽  
Ibrahim Hanifi Ozercan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synovial Tissue ◽  
Rat Model ◽  
Cartilage Damage ◽  
Herbal Remedies ◽  
Cartilage Tissue ◽  
Dependent Manner ◽  
Physical Damage ◽  
Health Technologies ◽  
Experimentally Induced

Abstract Objectives Osteoarthritis (OA) of the knee is a chronic and painful debilitating disease. OA of the knee is initiated by physical damage and accumulated oxidative stress, followed by exaggerated inflammation leading to cartilage damage. Currently, no effective pharmacotherapy capable of restoring the cartilage tissue and joint architecture is available. Hence, there has been an attempt in developing alternative therapeutic approaches including herbal remedies. Curcumin from turmeric root used extensively in traditional medicine is a well-known anti-inflammatory agent. We have developed a novel, improved intestinal pH stable and highly bioavailable formulation of curcumin which is called Advanced Ultrasol Curcumin (AUC) and here we present data to demonstrate the efficacy of AUC in a rat model of knee OA. Methods Female Wistar rats were used to induce OA of the knee by intra-articular injection of sodium monoiodoacetate followed by recovery for 14 days. Seven rats were included in each group. Animals were supplemented with AUC for 4 weeks at two different concentrations (20 and 40 mg/kg of total curcuminoids) and assessment of disease was carried out by histopathology including integrity of joint architecture, and effect of supplementation on oxidative stress, inflammation and on extracellular matrix proteinases levels in joint tissue using western blot technique. Results We observed a significant restoration of joint architecture and reduction in swelling of joint as demonstrated by X-ray images and histopathology after 4 weeks of AUC administration. There was a significant reduction in serum and synovial tissue malondialdehyde levels and increased superoxide dismutase, glutathione peroxidase; and catalase levels. Further, there was a significant reduction in synovial inflammatory markers (IL-1β, IL-6, IL-10, TNF-α and CRP) and markers of cartilage damage such as COMP, collagen type 2 and MMP3 levels in synovial tissue. Conclusions Curcumin is a well-established herbal ingredient for inflammatory diseases such as OA and AUC, a novel formulation of curcumin with enhanced intestinal stability and bioavailability is effective in ameliorating pathophysiology of OA in experimentally induced rat OA model in a dose dependent manner. Funding Sources OmniActive Health Technologies Limited.

scholarly journals Efficacy of a Novel Integrated Active Herbal Formulation in Experimentally Induced Osteoarthritis Rat Model

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1762-1762
Author(s):  
Muralidhara Padigaru ◽  
Abhijeet Morde ◽  
Omer Ersin Muz ◽  
Cemal Orhan ◽  
Fusun Erten ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synovial Tissue ◽  
Health Care Professionals ◽  
Cartilage Damage ◽  
Dependent Manner ◽  
Pharmaceutical Drugs ◽  
Herbal Supplement ◽  
Health Technologies ◽  
Funding Sources ◽  
Herbal Formulation

Abstract Objectives Osteoarthritis (OA) is a debilitating chronic illness that affects millions across the globe. Current medical treatment approaches that focus on the reduction of pain and inflammation using pharmaceutical drugs are moderately effective and associated with significant adverse events. Hence health care professionals are exploring alternative approaches that are effective and safe to treat osteoarthritis. We developed a novel integrated active formulation to alleviate symptoms of osteoarthritis using improved plant extracts from Curcumin, Ashwagandha and Boswellia and validated the efficacy of the formulation using a well-established animal model for osteoarthritis. Methods We induced OA in female Wistar rats by intra-articular injection of sodium monoiodoacetate followed by recovery for 14 days. Seven rats were included in each group. Animals were supplemented with integrated active herbal formulation of enriched extracts of Curcumin, Boswellia and Ashwagandha for 4 weeks at two different concentrations (100 and 200 mg/kg body weight) and assessment of disease was carried out by histopathology including integrity of joint architecture, and effect of supplementation on oxidative stress, inflammation and on extracellular matrix proteinases levels in joint tissue using western blot technique. Results We observed a significant restoration of joint architecture and reduction in swelling of joint as demonstrated by X-ray images and histopathology after 4 weeks of administration integrated active herbal supplement. There was a significant reduction in serum and synovial tissue malondialdehyde levels and increased superoxide dismutase, glutathione peroxidase; and catalase levels. Synovial inflammatory markers (IL-1β, IL-6, IL-10, TNF-α and CRP) and markers of cartilage damage such as COMP, collagen type 2 and MMP-3 levels were significantly reduced in synovial tissue in response to supplementation. Conclusions Our data indicate that our integrated active herbal formulation has a strong protective effect against OA in a dose dependent manner by acting through multi-modal pathways as substantiated by significant effects on histopathology, inflammation, oxidative stress and collagen degradation. Funding Sources OmniActive Health Technologies Limited.

scholarly journals Efficacy of a Novel Integrated Active Herbal Formulation in Experimentally Induced Rat Model for Dry Eye Disease

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 441-441
Author(s):  
Abhijeet Morde ◽  
Omer Ersin Muz ◽  
Cemal Orhan ◽  
Fusun Erten ◽  
Mehmet Tuzcu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dry Eye ◽  
Rat Model ◽  
Tear Film ◽  
Oral Dosage ◽  
Eye Drops ◽  
Dependent Manner ◽  
Dry Eyes ◽  
Health Technologies ◽  
Active Formulation

Abstract Objectives Dry eye is common condition of eye with insufficient production of tears leading to inadequate lubrication of eyes. It is chronic in nature & may be associated with discomfort & eye redness, blurred vision & tear film instability leading to potentially damaged ocular surfaces. Inflammation & oxidative stress play significant role in pathogenesis of disease by causing ocular surface disruption. Traditional Rx for dry eyes such as artificial tears, punctual plugs, prescription eye drops, etc. doesn't adequately address underlying causes of dry eyes. Further many of treatments are in form of eye drops that require regular administration to eyes, which is inconvenient & contains preservatives that further irritate eyes. We evaluated integrated active formulation administered orally to alleviate symptoms of dry eyes in rat model. Methods We used proprietary formulation technology to blend multiple ingredients into an integrated oil suspension (OS) that can be conveniently used in an oral dosage form. Ingredients included bioavailable form of Curcumin, Lutein/Zeaxanthin (L/Z) and Vit D3 formulated as an integrated product. Dry eye condition was created by administration of BAK (benzalkonium chloride) to eyes of female Wistar rat twice daily for 14 days, followed by initiation of supplementation by administering integrated dry eye formulation by oral gavage for 4 weeks at dose of 100 & 200 mg/kg b.w. to evaluate effect of this novel formulation. 7 rats were included in each group. Results There was significant improvement in tear volume, tear breakup time, tear film integrity & reduced overall inflammation, histopathological examination with supplementation. Our formulation helped in lowering oxidative stress as evidenced by significant reduced serum & corneal MDA, increased corneal SOD & corneal GPx. Levels of inflammatory cytokines such as NF-κB, TNF-α, IL-1β, IL-6 & IL-8 were significantly reduced & protective proteins such as MUC1, MUC4, MUC5AC and MMP-9 were restored by supplementation with integrated dry eye formulation which were otherwise lowered in dry eye condition. Conclusions Our results strongly suggest that our novel integrated active formulation of Curcumin, L/Z, Vit D3 is effective in alleviating symptoms of dry eye condition with multi-modal mechanism of action in dose dependent manner. Funding Sources OmniActive Health Technologies Limited.

scholarly journals Intra-articular Injection of Baicalein Inhibits Cartilage Catabolism and NLRP3 Inflammasome Signaling in a Posttraumatic OA Model

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hui Bai ◽  
Rui Yuan ◽  
Zhiheng Zhang ◽  
Lin Liu ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Nlrp3 Inflammasome ◽  
Type Ii Collagen ◽  
Cartilage Degeneration ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Nlrp3 Inflammasome Activation ◽  
Immunochemical Staining

Baicalein has been shown to have chondroprotective potential in vitro. However, its effect on disease modification in osteoarthritis (OA) is largely unknown. The present study is aimed at determining whether baicalein could slow the progression of OA and inhibit OA-related inflammation in a rat model of destabilization of the medial meniscus (DMM) and the underlying mechanisms. The rats subjected to DMM surgery were treated with baicalein (0.8, 1.6, and 3.2 μg/L, 50 μL, once a week) by intra-articular injection for 6 weeks. Dexamethasone (0.4 mg/mL, 50 μL, once a week) was used as a positive control. Histologic grading of cartilage degeneration was performed using the Osteoarthritis Research Society International (OARSI) recommended grading system (on a scale of 0-6). The expression levels of molecules associated with cartilage homeostasis and inflammatory cytokines were analyzed; moreover, the NLRP3 inflammasome activation and cartilage oxidative stress-associated molecules were determined. Baicalein treatment reduced the OARSI score and slowed OA disease progression in a dose-dependent manner within a certain range. Compared with DMM rats, intra-articular injection of baicalein led to (1) reduced levels of inflammatory mediates such as IL-1β and TNF-α, (2) reduced immunochemical staining of MMP-13 and ADAMTS-5, (3) suppressed immunochemical staining loss of type II collagen, (4) reduced expression of cartilage degradation markers including CTX-II and COMP in urine, and (5) inhibited NLRP3 inflammasome activation rather than regulated expression of SOD, GSH, and MDA. In contrast to the administration of baicalein, dexamethasone injection showed similar effects to slow OA progression, while dexamethasone inhibited NLRP3 inflammasome partly through decreasing levels of SOD, GSH, and MDA. This study indicated that baicalein may have the potential for OA prevention and exerts anti-inflammatory effects partly via suppressing NLRP3 inflammasome activation without affecting oxidative stress-associated molecules, and inhibition of cartilage catabolism enzymes in an OA rat model.

scholarly journals Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhuming Chen ◽  
Huan Zhong ◽  
Jinsong Wei ◽  
Sien Lin ◽  
Zhixian Zong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synovial Tissue ◽  
Subchondral Bone ◽  
Nlrp3 Inflammasome ◽  
Cell Model ◽  
Cruciate Ligament ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Pathological Changes ◽  
Medial Meniscectomy

Abstract Introduction Osteoarthritis (OA) is an inflammatory disease of the joints that causes progressive disability in the elderly. Reactive oxygen species (ROS) play an important role in OA development; they may activate the NLRP3 inflammasome, thereby inducing the secretion of proinflammatory IL-1β and IL-18, leading to the aggravation of the downstream inflammatory response. Nrf2 is a key transcription factor that regulates the expression of antioxidant enzymes that protect against oxidative stress and tissue damage. We aimed to explore the underlying mechanism of OA development by investigating NLRP3, ASC, Nrf2, and HO-1 expression in synovia and their regulatory networks in OA. Methods Human total knee replacement samples were subjected to histology and micro-CT analysis to determine the pathological changes in the cartilage and subchondral bone and to assess the expression of inflammation-related markers in the synovial tissue by immunohistochemistry (IHC), qRT-PCR, and Western blot. To investigate these pathological changes in an OA animal model, adult Sprague-Dawley rats were subjected to anterior cruciate ligament transection and medial meniscectomy. Articular cartilage and subchondral bone changes and synovial tissue were also determined by the same methods used for the human samples. Finally, SW982 cells were stimulated with lipopolysaccharide (LPS) as an in vitro inflammatory cell model. The correlation between NLRP3 and Nrf2 expression was confirmed by knocking down NLRP3 or Nrf2. Results Cartilage destruction and subchondral bone sclerosis were found in the OA patients and OA model rats. Significantly increased expression levels of NLRP3, ASC, Nrf2, and HO-1 were found in the synovial tissue from OA patients. NLRP3, ASC, Nrf2, and HO-1 expression in the synovium was also upregulated in the OA group compared with the sham group. Furthermore, the NLRP3, Nrf2, HO-1, IL-1β, and IL-18 expression in LPS-treated SW982 cells was increased in a dose-dependent manner. As expected, the expression of NLRP3 was upregulated, and the expression of IL-1β and IL-18 was downregulated after Nrf2 silencing. However, knocking down NLRP3 did not affect the expression of Nrf2. Conclusions ROS-induced oxidative stress may be the main cause of NLRP3 inflammasome activation and subsequent release of downstream factors during OA development. Nrf2/HO-1 signaling could be a key pathway for the activation of the NLRP3 inflammasome, which may contribute to the progression of OA. Herein, we discovered a novel role of Nrf2/HO-1 signaling in the production of NLRP3, which may facilitate the prevention and treatment of OA.

scholarly journals A Next Generation Formulation of Curcumin Ameliorates Experimentally Induced Osteoarthritis in Rats via Regulation of Inflammatory Mediators

2021 ◽  
Vol 12 ◽  
Author(s):  
Mehmet Yabas ◽  
Cemal Orhan ◽  
Besir Er ◽  
Mehmet Tuzcu ◽  
Ali Said Durmus ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Therapeutic Option ◽  
Cartilage Damage ◽  
Cartilage Tissue ◽  
Next Generation ◽  
Physical Damage ◽  
Knee Oa ◽  
Tnf Α ◽  
Monosodium Iodoacetate ◽  
Histopathological Images

Osteoarthritis (OA) is a chronic and debilitating disease of the knee joint. OA of the knee is initiated by physical damage and accumulated oxidative stress, followed by an exaggerated inflammation leading to cartilage damage. Currently, no effective and safe therapeutic option capable of restoring articular cartilage tissue and joint architecture is available. We here report a novel and highly bioavailable formulation of curcumin, labeled as Next Generation Ultrasol Curcumin (NGUC), which was 64.7 times more bioavailable than natural 95% curcumin extract as demonstrated in rat bioavailability studies. We further investigated the protective effect of NGUC against monosodium iodoacetate (MIA)‐induced knee OA in rats. Analysis of X-ray and histopathological images revealed that NGUC supplementation restored joint architecture and reduced swelling of joints induced by MIA. NGUC treatment caused a significant reduction in the levels of inflammatory mediators such as TNF-α, IL-1β, IL-6, COMP, and CRP, and expressions of MMP-3, 5-LOX, COX-2, and NFκB in synovial tissue of rats with MIA-induced OA. NGUC also decreased serum MDA level and increased the levels of antioxidant enzymes SOD, CAT, and GPX. Thus, our results indicate that a novel formulation of curcumin with enhanced bioavailability effectively ameliorates the pathophysiology of OA.

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

Non-canonical Functions of Telomerase Reverse Transcriptase: Emerging Roles and Biological Relevance

2020 ◽  
Vol 20 (6) ◽  
pp. 498-507 ◽  
Author(s):  
Connor A.H. Thompson ◽  
Judy M.Y. Wong
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Reverse Transcriptase ◽  
Cancer Cells ◽  
Telomere Length ◽  
Telomere Maintenance ◽  
Telomerase Reverse Transcriptase ◽  
Alternative Mechanism ◽  
Dependent Manner ◽  
Mitochondrial Integrity

Increasing evidence from research on telomerase suggests that in addition to its catalytic telomere repeat synthesis activity, telomerase may have other biologically important functions. The canonical roles of telomerase are at the telomere ends where they elongate telomeres and maintain genomic stability and cellular lifespan. The catalytic protein component Telomerase Reverse Transcriptase (TERT) is preferentially expressed at high levels in cancer cells despite the existence of an alternative mechanism for telomere maintenance (alternative lengthening of telomeres or ALT). TERT is also expressed at higher levels than necessary for maintaining functional telomere length, suggesting other possible adaptive functions. Emerging non-canonical roles of TERT include regulation of non-telomeric DNA damage responses, promotion of cell growth and proliferation, acceleration of cell cycle kinetics, and control of mitochondrial integrity following oxidative stress. Non-canonical activities of TERT primarily show cellular protective effects, and nuclear TERT has been shown to protect against cell death following double-stranded DNA damage, independent of its role in telomere length maintenance. TERT has been suggested to act as a chromatin modulator and participate in the transcriptional regulation of gene expression. TERT has also been reported to regulate transcript levels through an RNA-dependent RNA Polymerase (RdRP) activity and produce siRNAs in a Dicer-dependent manner. At the mitochondria, TERT is suggested to protect against oxidative stress-induced mtDNA damage and promote mitochondrial integrity. These extra-telomeric functions of TERT may be advantageous in the context of increased proliferation and metabolic stress often found in rapidly-dividing cancer cells. Understanding the spectrum of non-canonical functions of telomerase may have important implications for the rational design of anti-cancer chemotherapeutic drugs.

Combination of Histone Deacetylase Inhibitor with Cu(II) 5,5- diethylbarbiturate Complex Induces Apoptosis in Breast Cancer Stem Cells: A Promising Novel Approach

2020 ◽  
Vol 21 ◽  
Author(s):  
Merve Erkisa ◽  
Nazlihan Aztopal ◽  
Elif Erturk ◽  
Engin Ulukaya ◽  
Veysel T. Yilmaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Histone Deacetylases ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Tumor Formation ◽  
Dependent Manner

Background: Cancer stem cells (CSC) are subpopulation within the tumor that acts a part in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy. Objective: In our study we scope out the effects of combination of a histone deacetylases inhibitor, valproic acid (VPA), and Cu(II) complex [Cu(barb-κN)(barb-κ2N,O)(phen-κN,N’)]·H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7). Methods: Viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2ˈ,7ˈ–dichlorofluorescein diacetate staining. Results: The VPA combined with Cu(II) complex showed anti proliferative activity on MCF-7s cells in a dose- and time-dependently. Treatment with combination of 2.5 mM VPA and 3.12 μM Cu(II) complex induces oxidative stress in a time-dependent manner, as well as apoptosis that is evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels. Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy that further analysis is required.

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