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.

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>

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>

Extraction and Characterization of Pectin from Citrus sinensis Peel

Kamal Md. Mostafa,Kumar Jibon,Mamun Md. Akter Hamid,Ahmed Md. Nazim Uddin,Shishir Mohammad Rezaul Islamd,Mondal Shakti Chandra 한국농업기계학회 2021 바이오시스템공학 Vol.46 No.1

Purpose The industrial application of pectin is increasing although its production was far away from the demand, which exerts extra pressure on the existing pectin sources. The present study was focused on the extraction and quality evaluation of pectin from Citrus sinensis (sweet orange) peel as a potential pectin source. Methodology Pectin was extracted from sweet orange peel powder in a shaking water bath at three different extraction conditions, viz. temperatures (65, 75, 85, and 95 °C), pH (1.0, 1.5, 2, and 2.5), and time (45, 60, 75, and 90 min). The extracted pectin was dried to constant weight in a cabinet dryer at 50 °C and packed in the high-density polyethylene pouch and stored at 4 °C until used for quality analysis. After single factor experiments, optimization of process variables was done statistically using the response surface methodology (RSM), where the experimental data were fitted to a second-order polynomial model. Results The pectin yield was found to vary between 12.52 and 22.45% and the best extraction condition was recorded to be higher in yield at the temperature of 95 °C (21.53%), pH of 1.5 (21.28%), and extraction time of 90 min (22.45%) from the single factor optimization. The quality parameters of pectin, e.g., equivalent weight (1744.66~1899.33 g), methoxyl group content (5.02~5.64%), and degree of esterification (73.26~77.56%), were found to be in satisfactory levels. On the contrary, anhydrouronic acid content (38.47~41.30%) was very low compared to the existing data for various pectin sources. The developed polynomial model has effectively explained the data variation and adequately described the actual correlation between the independent and dependent variables. Results from both single factor experiments and RSM revealed that extraction temperature, pH, and time had a significant influence on the yield and quality of the extracted pectin. Fromthe optimization study, the optimum condition was found as the temperature of 94.13 °C, pH of 1.45, and time of 114.70 min, which yielded 23.64% pectin. Conclusion Conclusively, extraction of pectin from sweet orange peel could be of great interest for application in the food and pharmaceutical industries.

The potential health benefits of the isoflavone glycoside genistin

Anowarul Islam,Md Sadikul Islam,Md Nazim Uddin,Mir Md Iqbal Hasan,Md Rashedunnabi Akanda 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.4

Genistin is a type of isoflavone glycoside andhas a broad range of health benefits. It is found in a varietyof dietary plants, such as soybean, kudzu (Japanese arrowroot),and other plant-based products. Genistin has beendescribed to have several beneficial health impacts, suchas decreasing the risk of osteoporosis and post-menopausalsymptoms, as well as anti-cancer, anti-oxidative, cardioprotective,anti-apoptotic, neuroprotective, hepatoprotective,and anti-microbial activities. It may also assist individualswith metabolic syndrome. This review summarizes some ofthe molecular impacts and prospective roles of genistin inmaintaining and treatment of health disorders. The reviewcould help to develop novel genistin medicine with significanthealth benefits for application in the nutraceutical andpharmaceutical fields.

The pharmacological and biological roles of eriodictyol

Anowarul Islam,Md Sadikul Islam,Md Khalesur Rahman,Md Nazim Uddin,Md Rashedunnabi Akanda 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.6

Eriodictyol is a fl avonoid in the fl avanones subclass. It is abundantly present in a wide range of medicinalplants, citrus fruits, and vegetables that are considered tohave potential health importance. Having the considerablemedicinal properties, eriodictyol has been predicted toclarify the mode of action in various cellular and molecularpathways. Evidence for the existing therapeutic roles of eriodictyolincludes antioxidant, anti-infl ammatory, anti-cancer,neuroprotective, cardioprotective, anti-diabetic, anti-obesity,hepatoprotective, and miscellaneous. Therefore, this reviewaims to present the recent evidence regarding the mechanismsof action of eriodictyol in diff erent signaling pathwaysin a specifi c disease condition. In view of the immense therapeutic eff ects, eriodictyol may serve as a potential drugsource to enhance community health standards.

Evaluation of anxiolytic, sedative, and antioxidant activities of Vitex peduncularis Wall. leaves and investigation of possible lead compounds through molecular docking study

Auniq Reedwan Bin Jafar,Chy Md. Nazim Uddin,Adnan Md.,Chowdhury Md. Riad,Dutta Trishala,Ibban Sadab Sipar,Jahan Israt,Tona Marzia Rahman,Shima Mutakabrun,Sawon Md. Imtiajul Habib,Chakrabarty Nishan,Ho 경희대학교 융합한의과학연구소 2021 Oriental Pharmacy and Experimental Medicine Vol.21 No.3

Vitex peduncularis, belongs to the Verbenaceae family, locally known as ‘Boruna’, ‘Horina’, ‘Ashmul gaas’, is commonly used for treating various chronic diseases in the folk medicine such as malarial fevers, jaundice, diabetes, chest pain, joint ache, abnormality in eyes & face, and urethritis, etc. In the present study, we investigated the anxiolytic, sedative, and antioxidant activities of ethanol extract of V. peduncularis leaves (EEVP) in both in vivo and in vitro models. Then, a molecular docking analysis was carried out to determine the possible lead compounds of EEVP for the biological properties described above. The anxiolytic and sedative activity of EEVP was determined using hole board and hole cross tests, respectively. Antioxidant activity was measured using DPPH and FRPA assays, whereas docking was done by using the Schrödinger suite (Maestro v10.1). Our result demonstrated that EEVP has significant and dose-dependent anxiolytic and sedative activity at the doses of 200 and 400 mg/kg (b.w.) in both models. This study also exhibited that EEVP has significant antioxidant activity compared to reference standard ascorbic acid. The molecular docking study revealed that 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, and vitexilactone have the best binding affinities against the target receptors (potassium channel receptor, human gamma-aminobutyric acid receptor, and human peroxiredoxin 5) for anxiolytic, sedative, and antioxidant activities. The present study confirmed that EEVP has anxiolytic, sedative, and antioxidant properties, which could be because of the occurrence of various phytochemicals and three bioactive phytocompounds which found potential during molecular docking analysis.

Evaluation of Bonamia semidigyna (Roxb.) for antioxidant, antibacterial, anthelmintic and cytotoxic properties with the involvement of polyphenols

Md. Adnan,Md. Nazim Uddin Chy,Sajib Rudra,Afroza Tahamina,Raju Das,Mohammad Akramul Hoque Tanim,Tanvir Iqram Siddique,Asadul Hoque,Syeda Mashnia Tasnim,Arkajyoti Paul,A. T. M. Mostafa Kamal 경희대학교 융합한의과학연구소 2019 Oriental Pharmacy and Experimental Medicine Vol.19 No.2

This study was conducted to investigate the antioxidant, antibacterial, anthelmintic, and cytotoxic activities of the crude methanol extract of Bonamia semidigyna (Roxb.) leaves and its derived fractions in different experimental models. Leaves of B. semidigyna were extracted with methanol (MBS) and the resultant successively fractionated into n-hexane (NBS), petroleum ether (PBS), chloroform (CBS), and ethyl acetate (EBS) soluble fractions. Later, the plant extractives were investigated for antioxidant, antibacterial, anthelmintic and cytotoxic properties. Phytochemical study was carried out using standard methods and polyphenols content were determined by spectrophotometric techniques. Antioxidant activity was evaluated by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity, hydrogen peroxide ( H2O2) scavenging activity, ferric reducing power, and total antioxidant capacity assays. Disc diffusion technique used to evaluate the antibacterial efficacy and anthelmintic activity was determined using aquarium worm (Tubifex tubifex) whereas cytotoxicity was evaluated using brine shrimp lethality bioassay. The phytochemical study revealed the presence of alkaloids, flavonoids, terpenoids, tannins, saponins, phenolic, steroids, sterols, quinones, oxalate, coumarins, and emodins in the plant extractives. In addition, the quantitative phytochemical analysis showed the significant amount of polyphenol contents. In antioxidant assays, the crude methanol extract and EBS fraction exhibited the most potent antioxidant activity among all the extractives. The crude methanol extract and EBS fraction also possessed significant antibacterial and anthelmintic potentials while moderate cytotoxic activities were found for all the plant extractives. The present study confirmed that the crude methanol extract of B. semidigyna and its EBS fraction, possibly due to its high polyphenol contents possess significant antioxidant, antibacterial, and anthelmintic properties.

Litter-mediated allelopathic effects of kudzu (Pueraria montana) on Bidens pilosa and Lolium perenne and its persistence in soil

Rashid, Md. Harun,Asaeda, Takashi,Uddin, Md. Nazim The Korean Society of Weed Science and The Turfgra 2010 Weed Biology and Management Vol.10 No.1

This study investigated the allelopathic effects of kudzu litter on the seed germination and early growth of Bidens pilosa and Lolium perenne. The bioassays, with various concentrations (10, 20, 30, 40, and 50 $g\;L^{-1}$) of aqueous kudzu litter leachate, significantly affected the germination percentages and radicle growth of both species. These parameters decreased progressively when the seedlings were exposed to increasing concentrations of leachate. The root and shoot length, dry weight, and chlorophyll concentration of the B. pilosa and L. perenne seedlings also were significantly affected when they were grown in leachate-amended soil. However, the chlorophyll fluorescence values of the seedlings subjected to different concentrations of aqueous kudzu litter leachate indicated that the mere presence of leachate in the soil was not stressful for the plants. The seedlings of both species were under stressful conditions only when they were grown in the soil that was treated with higher concentrations of leachate (30, 40, or 50 $g\;L^{-1}$). A 6 week decomposition study of the kudzu litter in soil was conducted to observe the retention of phenolic content in the soil. The results showed that, although the concentration of dissolved organic carbon decreased with increasing decomposition, the phenolic concentration was not significantly affected when the observation period ended. This suggests that the phytotoxic properties of kudzu litter remain stable in soil systems for a considerable amount of time after incorporation into the soil.