Investigation of antinociceptive, anti-inflammatory and thrombolytic activity of Caesalpinia digyna (Rottl.) leaves by experimental and computational approaches

Nazim Uddin Emon,Israt Jahan,Mohammed Aktar Sayeed 경희대학교 융합한의과학연구소 2020 Oriental Pharmacy and Experimental Medicine Vol.20 No.3

The study aimed to report in vitro thrombolytic and in vivo anti-nociceptive activity of methanolic extract of Caesalpinia digyna (MECD) followed by in silico PASS prediction, ADME analysis with toxicity and molecular docking study of antinociception (Cox-1, Cox-2) and thrombolytic (Tissue plasminogen activator). The clot lysis of human blood for thrombolytic study, acetic acid induced writing and formalin-induced licking in mice at several doses (50, 100, 200 and 400 mg/kg, b.w.; p.o.) of MECD for anti-inflammatory and antinoceptive activities were performed. In thrombolytic study, a significant 32.78% (P < 0.001) of the blood clot lysis revealed by MECD, while 70.32% (P < 0.001) and 3.84% were yields for positive control (streptokinase) and negative control (saline water), respectively. MECD developed a significant dose-dependent antinociception in acetic acid-induced abdominal writhing experiment while the 400 mg/kg exhibited maximum inhibition (59.27%; P < 0.001). Similarly at comparable dose concentrations, MECD produced significant (P < 0.001) dose-dependent activity in both neurogenic and inflammatory which was generated by intraplantar injections of formalin (2.5%, 20 μL/paw). In PASS prediction, isolated compounds caesalpinine A and caesalpinine C exhibited potential thrombolytic and antinociceptive activity followed by Lipinski rule for drug—like property where the compounds found to be effective in molecular docking study. The current finding suggesting MECD have potential thrombolytic and anti-nociceptive activity.

The protein kinase TOUSLED facilitates RNAi in <i>Arabidopsis</i>

Uddin, Mohammad Nazim,Dunoyer, Patrice,Schott, Gregory,Akhter, Salina,Shi, Chunlin,Lucas, William J.,Voinnet, Olivier,Kim, Jae-Yean Oxford University Press 2014 Nucleic acids research Vol.42 No.12

<P>RNA silencing is an evolutionarily conserved mechanism triggered by double-stranded RNA that is processed into 21- to 24-nt small interfering (si)RNA or micro (mi)RNA by RNaseIII-like enzymes called Dicers. Gene regulations by RNA silencing have fundamental implications in a large number of biological processes that include antiviral defense, maintenance of genome integrity and the orchestration of cell fates. Although most generic or core components of the various plant small RNA pathways have been likely identified over the past 15 years, factors involved in RNAi regulation through post-translational modifications are just starting to emerge, mostly through forward genetic studies. A genetic screen designed to identify factors required for RNAi in <I>Arabidopsis</I> identified the serine/threonine protein kinase, TOUSLED (TSL). Mutations in <I>TSL</I> affect exogenous and virus-derived siRNA activity in a manner dependent upon its kinase activity. By contrast, despite their pleiotropic developmental phenotype, <I>tsl</I> mutants show no defect in biogenesis or activity of miRNA or endogenous <I>trans</I>-acting siRNA. These data suggest a possible role for TSL phosphorylation in the specific regulation of exogenous and antiviral RNA silencing in <I>Arabidopsis</I> and identify TSL as an intrinsic regulator of RNA interference.</P>

Inhibition of the autophagy flux by gingerol enhances TRAIL-induced tumor cell death

NAZIM, UDDIN,JEONG, JAE-KYO,SEOL, JAE-WON,HUR, JIN,EO, SEONG-KUG,LEE, JOHN-HWA,PARK, SANG-YOUEL Spandidos Publications 2015 ONCOLOGY REPORTS Vol.33 No.5

<P>Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a primary anticancer agent and a member of the tumor necrosis factor family that selectively induces apoptosis in various tumor cells, but not in normal cells. Gingerol is a major ginger component with anti-inflammatory and anti?tumorigenic activities. Autophagy flux is the complete process of autophagy, in which the autophagosomes are lysed by lysosomes. The role of autophagy in cell death or cell survival is controversial. A549 adenocarcinoma cells are TRAIL-resistant. In the present study, we showed that treatment with TRAIL slightly induced cell death, but gingerol treatment enhanced the TRAIL-induced cell death in human lung cancer cells. The combination of gingerol and TRAIL increased accumulation of microtubule-associated protein light chain 3-II and p62, confirming the inhibited autophagy flux. Collectively, our results suggest that gingerol sensitizes human lung cancer cells to TRAIL-induced apoptosis by inhibiting the autophagy flux.</P>

Genistein enhances TRAIL-induced cancer cell death via inactivation of autophagic flux

NAZIM, UDDIN MD.,PARK, SANG-YOUEL Spandidos Publications 2015 ONCOLOGY REPORTS Vol.34 No.5

<P>Tumor necrosis factor-related apoptosis-inducing ligand??(TRAIL) is a transmembrane cytokine that is a promising anticancer agent as it selectively induces apoptosis in various types of tumor cells. Autophagic flux, which includes the complete process of autophagy, and suppression of autophagic flux has been increasingly recognized as a favorable and novel therapeutic approach for cancer treatment. Here, we showed that genistein, a major isoflavone compound that exerts its anticancer properties by inhibiting tumor cell proliferation, can induce TRAIL-mediated apoptotic cell death in TRAIL???resistant human adenocarcinoma A549 cells. Notably, genistein treatment led to a marked increase in the accumulation of microtubule-associated protein??1 light chain??3??(LC3)-II and p62 protein levels. The combination of genistein and TRAIL increased LC3-II, p62, activated caspase-3 and activated caspase-8 accumulation, confirming the inhibition of autophagic flux. Taken together, our results revealed that genistein enhanced TRAIL-induced tumor cell death in TRAIL-resistant A549 adenocarcinoma cells by inhibiting autophagic flux.</P>

PPARγ activation of anti-diabetic agent, troglitazone enhances TRAIL-induced apoptosis via autophagy flux

Nazim Uddin,Rasheduzzaman,Ji Hong Moon,Ju Hee Lee,You Jin Lee,Jae Won Seol,Sang Youel Park 대한수의학회 2016 대한수의학회 학술대회발표집 Vol.2016 No.-

Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS

Nazim, Uddin MD.,Park, Sang-Youel UNKNOWN 2019 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.43 No.2

<P>Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and is an antitumor drug that induces apoptosis in tumor cells with minimal or no effects on normal cells. Here, it is demonstrated that 6-shogaol (6-sho), a bioactive component of ginger, exerted anti-inflammatory and anticancer properties, attenuated tumor cell propagation and induced TRAIL-mediated cell death in liver cancer cells. The current study identified a potential pathway by revealing that TRAIL and 6-sho or chloroquine acted together to trigger reactive oxygen species (ROS) production, to upregulate tumor-suppressor protein 53 (p53) expression and to change the mitochondrial transmembrane potential (MTP). Treatment with <I>N</I>-acetyl-L-cysteine reversed these effects, restoring the MTP and attenuated ROS production and p53 expression. Interestingly, treatment with 6-sho increased p62 and microtubule-associated proteins 1A/1B light chain 3B-II levels, indicating an inhibited autophagy flux. In conclusion, attenuation of 6-sho-induced autophagy flux sensitized cells to TRAIL-induced apoptosis via p53 and ROS, suggesting that the administration of TRAIL in combination with 6-sho may be a suitable therapeutic method for the treatment of TRAIL-resistant Huh7 liver cells.</P>

Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL-induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species

Nazim, Uddin Md,Yin, Honghua,Park, Sang-Youel D.A. Spandidos 2019 MOLECULAR MEDICINE REPORTS Vol.19 No.2

<P>Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is well known as a transmembrane cytokine and has been proposed as one of the most effective anti-cancer therapeutic agents, owing to its efficiency to selectively induce cell death in a variety of tumor cells. Suppression of autophagy flux has been increasingly acknowledged as an effective and novel therapeutic intervention for cancer. The present study demonstrated that the anti-cancer and anti-inflammatory drug celastrol, through its anti-metastatic properties, may initiate TRAIL-mediated apoptotic cell death in lung cancer cells. This sensitization was negatively affected by <I>N</I>-acetyl-l-cysteine, which restored the mitochondrial membrane potential (ΔΨm) and inhibited reactive oxygen species (ROS) generation. Notably, treatment with celastrol caused an increase in microtubule-associated proteins 1A/1B light chain 3B-II and p62 levels, whereas co-treatment of celastrol and TRAIL increased active caspase 3 and 8 levels compared with the control, confirming inhibited autophagy flux. The combined use of TRAIL with celastrol may serve as a safe and adequate therapeutic technique for the treatment of TRAIL-resistant lung cancer, suggesting that celastrol-mediated autophagy flux inhibition sensitized TRAIL-initiated apoptosis via regulation of ROS and ΔΨm.</P>

Meat Quality Traits and Texture Profile Comparison of Frozen Hanwoo Beef

( Nazim Uddin ),( Inho Hwang ) 전북대학교 농업과학기술연구소 2016 농업생명과학연구 Vol.47 No.2

Meat and meat products provide vital nutrients like protein, fat, vitamins and minerals by making an essential role in dietary intake. The overall eating quality of meat and meat products is affected by physicochemical characteristics such as taste, texture, juiciness, appearance and odor. Texture is thought to be most vital attributes of all. In this study physicochemical quality traits and texture profile analysis, SDS-PAGE profile, Calpain activities comparison of frozen Longissimus thoracis (LT) and Biceps femoris (BF) muscles of Hanwoo were investigated. The BF muscle showed significantly (P<0.001) higher values of CIE a^* (Redness), cooking loss (%), Warner Bratzler Shear force (WBSF), tensile maximum force, hardness, and thiobarbituric acid reactive substances (TBARS) compared to LT muscle. LT muscle showed significant higher CIE L^* (Lightness) values than the BF muscle. There were no significant difference (P>0.05) in CIE b^* (Yellowness) and pH value m-calpain activities between LT and BF muscle. Myosin heavy chain, actin μ-calpain values were significantly (p<0.001) higher in BF muscle. Therefore, the result clearly visualize that physicochemical characteristics and texture profile varied within frozen muscle.

Meat Quality and Texture Profile Comparison Between Fresh and Frozen/Thawed Pork loin M. Longissimus thoracis et lumborum.

( Nazim Uddin ),( Inho Hwang ) 전북대학교 농업과학기술연구소 2016 농업생명과학연구 Vol.47 No.2

A comparison of the meat quality traits and texture profile attributes between fresh and frozen pork loins (Longissimus thoracis et lumborum) muscle was investigated. Three muscles were collected and distributed into two groups: fresh and frozen/thawed. Frozen vacuum-packed samples were kept at - 80°C refrigerator 24 hours and at 4°C 48 hours for thawing. The fresh sample had higher pH (p<0.05), cooking loss, CIE L^* (Lightness) (p<0.005), CIE a^* (Redness), Warner Braztler Shear force (WBSF) values (p<0.05) myosin heavy chain and actin activity and calpain activity than the frozen meat sample. The frozen meat sample had a greater tensile maximum force and tensile breaking load. The thiobarbituric acid reactive substances (TBARS) value and hardness as a texture profile analysis (TPA) attribute of frozen meat were significantly higher than the fresh meat. Therefore, the result in this comparison study could be used to explore the physicochemical trait alteration and texture profile analysis of fresh and frozen pork meat.

Evaluation of anti-nociceptive and anti-inflammatory activities of Piper sylvaticum (Roxb.) stem by experimental and computational approaches

Md. Nazim Uddin Chy,Md. Adnan,Akash Kumar Rauniyar,Md. Moksadul Amin,Mohuya Majumder,Md. Sahidul Islam,Shanta Afrin,Kaniz Farhana,Fayejun Nesa,Muazzem Ahmad Sany,Mohammad Akramul Hoque Tanim,Tanvir Iq 경희대학교 융합한의과학연구소 2020 Oriental Pharmacy and Experimental Medicine Vol.20 No.3

Piper sylvaticum Roxb., (Family: Piperaceae), commonly known as pahaari peepal, is used in traditional medicine for the treatment of rheumatic pain, headache, asthma, chronic cough, diarrhea, and wounds. To provide scientific proof for its traditional use, the present study was designed to investigate the antinociceptive and anti-inflammatory properties of methanol extract of P. sylvaticum stem (MEPSS) in pain models. Additionally, computational studies viz. molecular docking, ADME and toxicological property predictions were performed to identify the potent phytochemicals of this plant for antinociceptive and anti-inflammatory activities with good oral bioavailability and safety features. Quantitative phytochemical analysis of MEPSS was performed using established protocols. The antinociceptive activity was determined using acetic acid and formalin test in mice at the doses of 200 and 400 mg/kg while paw edema induced by carrageenan used for anti-inflammatory activity. Molecular docking study was performed by Schrödinger Maestro 10.1 whereas the SwissADME and admetSAR were used for ADME and toxicity prediction respectively. The total phenolic and flavonoid contents of MEPSS were 93.39 and 53.74 mg gallic acid and quercetin equivalent/g of extract respectively. The methanol extract exhibited significant and dosedependent antinociceptive and anti-inflammatory effects in experimental pain models. Also, our docking study showed that piperine, piperlonguminine, and sylvamide have the best binding affinities to cyclooxygenase enzymes with good ADME/T properties. This study confirmed that MEPSS possess significant antinociceptive and anti-inflammatory activities which could be due to the presence of phytochemicals and three bioactive compounds (piperine, piperlonguminine, and sylvamide) were found to be most effective in computational studies.