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  1. Ali Khan MS, Mat Jais AM, Afreen A
    Biomed Res Int, 2013;2013:185476.
    PMID: 24350249 DOI: 10.1155/2013/185476
    The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br. flowers. T. divaricata flower methanolic extract (TDFME) was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses--125, 250, and 500 mg/kg--orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization--high resolution mass spectral (ESI-HRMS) analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous.
  2. Ali Khan MS, Nazan S, Mat Jais AM
    Arq Gastroenterol, 2017 Jul-Sep;54(3):183-191.
    PMID: 28492713 DOI: 10.1590/S0004-2803.201700000-21
    BACKGROUND: Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. from family Combretaceae is used in Ayurveda and Siddha traditional systems of medicine to heal ulcers.

    OBJECTIVE: The present study was conducted to assess the gastroprotective effect and understand the fundamental mechanism of action of Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. Leaf Methanolic Extract.

    METHODS: The test extract was screened for anti-ulcer activity by Aspirin induced ulcerogenesis in pyloric ligation and ethanol induced gastric ulcers at three doses - 125, 250, and 500 mg/kg, p.o. using Ranitidine 50 mg/kg and Misoprostol 100 μg/kg as standard drug in respective models. Seven parameters were carefully examined, that is, ulcer index, total protein, mucin, catalase, malondialdehyde, and superoxide dismutase levels and histopathology. High Performance Liquid Chromatographic - Ultra Violet profiling and Liquid Chromatography - Mass Spectral analysis of crude Terminalia coriacea leaves methanolic extract were carried out as a part of chemical characterization to identify bioactive compounds.

    RESULTS: All the test doses exhibited significant gastroprotective function, particularly the higher doses demonstrated improved action. The results revealed a significant increase in the levels of catalase, superoxide dismutase, and Mucin with reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also illustrated the gastroprotective effect of Terminalia coriacea leaves methanolic extract.

    CONCLUSION: Terminalia coriacea leaves methanolic extract exhibited strong anti-oxidant and anti-secretory activities mediated gastroprotection besides inducing the gastric mucosal production. The observed pharmacological response can be attributed to the flavonoidal compounds namely - Quercetin-3-O-rutinoside, Luteolin-7-O-glucoside, Myricetin hexoside, Quercetin-3-O-glucoside, Isorhamnetin-3-O-rhamnosylglucoside and Isorhamnetin-3-O-glucoside identified in the extract for the first time with High Performance Liquid Chromatographic - Ultra Violet and Liquid Chromatography - Mass Spectral analysis.
  3. Ali Khan MS, Mat Jais AM, Hussain J, Siddiqua F, Gopala Reddy A, Shivakumar P, et al.
    ISRN Pharmacol, 2014;2014:327606.
    PMID: 24977051 DOI: 10.1155/2014/327606
    Channa striata (Bloch.) is a fresh water fish belonging to the family Channidae. The stripped snakehead fish possesses wide range of medicinal properties. In view of traditional use of C. striata for wound healing, the present study was undertaken to investigate the beneficial effects of orally administered freeze dried aqueous extract of Channa striata (AECS) in experimentally induced gastric ulcers in Wistar rats. Aspirin induced ulcerogenesis in pyloric ligation model was used for the assessment of antiulcer activity and Ranitidine (50 mg/kg) was employed as the standard drug. The various gastric parameters like volume of gastric juice, pH, free and total acidities, ulcer index, and levels of antioxidant enzymes like catalase, superoxide dismutase, and lipid peroxidation marker malondialdehyde were determined. AECS at concentrations of 40% and 50% w/v significantly decreased the volume of gastric juice and increased the levels of catalase while considerable decrease in free and total acidities and increase in superoxide dismutase were observed with the treatment of standard drug and AECS (50% w/v). All the test doses of AECS markedly decreased ulcer index and malondialdehyde compared to the standard drug whereas AECS 30% w/v did not alter volume of gastric juice, pH, free and total acidities, catalase, and superoxide dismutase. From these findings, it can be concluded that AECS is devoid of acid neutralizing effects at lower doses and possesses antisecretory and antiulcer activities and this could be related to its antioxidant mechanism.
  4. Shirley Ding SL, Kumar S, Ali Khan MS, Ling Mok P
    Front Cell Neurosci, 2018;12:190.
    PMID: 30108483 DOI: 10.3389/fncel.2018.00190
    Retinal degeneration is a prominent feature in ocular disorders. In exploring possible treatments, Mesenchymal Stem Cells (MSCs) have been recognized to yield therapeutic role for retinal degenerative diseases. Studies have also displayed that erythropoietin (EPO) administration into degenerative retina models confers significant neuroprotective actions in limiting pathological cell death. In this study, we aimed to use MSCs to deliver EPO and to evaluate the ability of EPO to rescue retinal neurons from dying upon reactive oxidative stress induction. We derived human MSCs from Wharton's jelly (hWJMSCs) of the umbilical cord and cells were transduced with lentivirus particles encoding EPO and a reporter gene of green fluorescent protein (GFP). The supernatants of both transduced and non-transduced cells were collected and used as a pre-conditioning medium for Y79 retinoblastoma cells (retinal neuron cell line) following exposure to glutamate induction. Retinal cells exposed to glutamate showed reduced mitochondrial depolarization and enhanced improvement in cell viability when incubated with pre-conditioned media of transduced cells. Our results established a proof-of-concept that MSCs could be used as a candidate for the delivery of EPO therapeutic gene in the treatment of retinal degenerations.
  5. Ali Khan MS, Misbah, Ahmed N, Arifuddin M, Rehman A, Ling MP
    Food Chem Toxicol, 2018 Jun 05.
    PMID: 29883785 DOI: 10.1016/j.fct.2018.06.007
    Flowers of Tabernaemontana divaricata (L.) R. Br., (Apocynaceae) are used in traditional medicine for analgesic property. The present study was performed to isolate the active principles and investigate the mechanisms involved in the anti-nociception caused by T. divaricata flower methanolic extract (TDFME). The extract in the doses of 125, 250 and 500 mg/kg, p.o was subjected to various assays in acetic acid induced abdominal writhing and formalin induced paw licking test models. Naloxone, L-Arginine, Glibenclamide and Glutamate were used as inducers while Morphine, L-NAME, Methylene blue and Aspirin served as standard drugs. The phytochemical analysis led to the isolation of three indole alkaloids namely Voacangine, Catharanthine and O-acetyl Vallesamine. The anti-nociception produced by TDFME was attenuated significantly (p< 0.001) by the intra-peritoneal pretreatment of naloxone, L-Arginine and glibenclamide. The nociception produced by glutamate was inhibited by TDFME. TDFME also enhanced the antinociceptive activity of L-NAME when given in combination. However TDFME co-administration did not produce significant results with methylene blue indicating lack of cGMP involvement. These results indicate that TDFME produces anti-nociception action mediated by opioid, nitric oxide, K+-ATP and glutamate mechanisms and the effect is largely related to the indole alkaloids.
  6. Ding SLS, Koh AE, Kumar S, Ali Khan MS, Alzahrani B, Mok PL
    PMID: 31060031 DOI: 10.1016/j.jphotobiol.2019.04.008
    Dysfunctional or death of retinal photoreceptors is an irreversible phenomenon that is closely associated with a broad range of retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD), resulting in successive loss of visual function and blindness. In search for viable treatment for retinal degenerative diseases, mesenchymal stem cells (MSCs) has demonstrated promising therapeutic capabilities to repair and replace damaged photoreceptor cells in both in vitro and in vivo conditions. Nevertheless, the dearth of MSC differentiation capacity into photoreceptors has limited its use in cell replacement therapy. Erythropoietin (EPO) has vital role in early neural retinal cell differentiation and demonstrated rescue potential on dying photoreceptor cells. Hence, we aimed to evaluate the differentiation capacity of MSCs into photoreceptor cells in the presence of human EPO protein. We derived the MSC from human Wharton's jelly of umbilical cord and transduced the cells with lentivirus particles encoding EPO and green fluorescent protein (GFP) as reporter gene. The transduced cells were selectively cultured and induced to differentiate into photoreceptors by exposing to photoreceptor differentiation cocktail. Our preliminary results showed that transduced cells exposed to induction medium had an enhanced differentiation capacity when compared to non-transduced cells. Our results demonstrated a novel strategy to increase the yield of in vitro photoreceptor differentiation and may be potentially useful in improving the efficiency of stem cell transplantation for ocular disorders.
  7. Ali Khan MS, Ahmed N, Misbah, Arifuddin M, Zakaria ZA, Al-Sanea MM, et al.
    Food Chem Toxicol, 2018 May;115:523-531.
    PMID: 29555329 DOI: 10.1016/j.fct.2018.03.021
    In view of the report on anti-nociceptive activity of Leathery Murdah, Terminalia coriacea {Roxb.} Wight & Arn. (Combretaceae) leaves, the present study was conducted to isolate the active constituents and identify the underlying mechanisms. The methanolic extract of T. coriacea leaves (TCLME) at doses 125, 250 and 500 mg/kg orally, was subjected to various in-vivo assays in acetic acid induced writhing and formalin induced paw-licking tests with aspirin (100 mg/kg) and morphine (5 mg/kg) as reference drugs. Three flavonoids, rutin, robinin and gossypetin 3-glucuronide 8-glucoside were isolated and characterized from TCLME for the first time. The extract showed significant (p 
  8. Al-Sanea MM, Ali Khan MS, Abdelazem AZ, Lee SH, Mok PL, Gamal M, et al.
    Molecules, 2018 Jan 31;23(2).
    PMID: 29385071 DOI: 10.3390/molecules23020297
    A new series of 1-phenyl-3-(4-(pyridin-3-yl)phenyl)urea derivatives were synthesized and subjected to in vitro antiproliferative screening against National Cancer Institute (NCI)-60 human cancer cell lines of nine different cancer types. Fourteen compounds 5a-n were synthesized with three different solvent exposure moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure. Substituents with different π and σ values were added on the terminal phenyl group. Compounds 5a-e with a 4-hydroxymethylpiperidine moiety showed broad-spectrum antiproliferative activity with higher mean percentage inhibition values over the 60-cell line panel at 10 µM concentration. Compound 5a elicited lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose mode to determine median inhibitory concentration (IC50) values. The data revealed that urea compounds 5a and 5d are the most active derivatives, with significant efficacies and superior potencies than paclitaxel in 21 different cancer cell lines belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than gefitinib in 38 and 34 cancer cell lines, respectively, particularly colon cancer, breast cancer and melanoma cell lines.
  9. Koh AE, Alsaeedi HA, Rashid MBA, Lam C, Harun MHN, Saleh MFBM, et al.
    J. Photochem. Photobiol. B, Biol., 2019 Jul;196:111514.
    PMID: 31154277 DOI: 10.1016/j.jphotobiol.2019.111514
    Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration.
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