MyMedR

Fulltext Construction of a novel quinoxaline as a new class of Nrf2 activator

Kandasamy M, Mak KK, Devadoss T, Thanikachalam PV, Sakirolla R, Choudhury H, et al.

BMC Chem, 2019 Dec;13(1):117.

PMID: 31572984 DOI: 10.1186/s13065-019-0633-4

Background: The transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2) and its principal repressive regulator, Kelch-like ECH-associated protein 1 (KEAP1), are perilous in the regulation of inflammation, as well as maintenance of homeostasis. Thus, NRF2 activation is involved in cytoprotection against many inflammatory disorders. N'-Nicotinoylquinoxaline-2-carbohdyrazide (NQC) was structurally designed by the combination of important pharmacophoric features of bioactive compounds reported in the literature.

Methods: NQC was synthesised and characterised using spectroscopic techniques. The compound was tested for its anti-inflammatory effect using Lipopolysaccharide from Escherichia coli (LPSEc) induced inflammation in mouse macrophages (RAW 264.7 cells). The effect of NQC on inflammatory cytokines was measured using enzyme-linked immune sorbent assay (ELISA). The Nrf2 activity of the compound NQC was determined using 'Keap1:Nrf2 Inhibitor Screening Assay Kit'. To obtain the insights on NQC's activity on Nrf2, molecular docking studies were performed using Schrödinger suite. The metabolic stability of NQC was determined using mouse, rat and human microsomes.

Results: NQC was found to be non-toxic at the dose of 50 µM on RAW 264.7 cells. NQC showed potent anti-inflammatory effect in an in vitro model of LPSEc stimulated murine macrophages (RAW 264.7 cells) with an IC50 value 26.13 ± 1.17 µM. NQC dose-dependently down-regulated the pro-inflammatory cytokines [interleukin (IL)-1β (13.27 ± 2.37 μM), IL-6 (10.13 ± 0.58 μM) and tumor necrosis factor (TNF)-α] (14.41 ± 1.83 μM); and inflammatory mediator, prostaglandin E2 (PGE2) with IC50 values, 15.23 ± 0.91 µM. Molecular docking studies confirmed the favourable binding of NQC at Kelch domain of Keap-1. It disrupts the Nrf2 interaction with kelch domain of keap 1 and its IC50 value was 4.21 ± 0.89 µM. The metabolic stability studies of NQC in human, rat and mouse liver microsomes revealed that it is quite stable with half-life values; 63.30 ± 1.73, 52.23 ± 0.81, 24.55 ± 1.13 min; microsomal intrinsic clearance values; 1.14 ± 0.31, 1.39 ± 0.87 and 2.96 ± 0.34 µL/min/g liver; respectively. It is observed that rat has comparable metabolic profile with human, thus, rat could be used as an in vivo model for prediction of pharmacokinetics and metabolism profiles of NQC in human.

Conclusion: NQC is a new class of NRF2 activator with potent in vitro anti-inflammatory activity and good metabolic stability.

Matched MeSH terms: Mice

Fulltext Computational approaches: discovery of GTPase HRas as prospective drug target for 1,3-diazine scaffolds

Kumar S, Sharma D, Narasimhan B, Ramasamy K, Shah SAA, Lim SM, et al.

BMC Chem, 2019 Dec;13(1):96.

PMID: 31355369 DOI: 10.1186/s13065-019-0613-8

Heterocyclic 1,3-diazine nucleus is a valuable pharmacophore in the field of medicinal chemistry and exhibit a wide spectrum of biological activities. PharmMapper, a robust online tool used for establishing the target proteins based on reverse pharmacophore mapping. PharmMapper study is carried out to explore the pharmacological activity of 1,3-diazine derivatives using reverse docking program. PharmMapper, an open web server was used to recognize for all the feasible target proteins for the developed compounds through reverse pharmacophore mapping. The results were analyzed via molecular docking with maestro v11.5 (Schrodinger 2018-1) using GTPase HRas as possible target. The molecular docking studies displayed the binding behavior of 1,3-diazine within GTP binding pocket. From the docking study compounds s3 and s14 showed better docked score with anticancer potency against cancer cell line (HCT116). Hence, the GTPase HRas may be the possible target of 1,3-diazine derivatives for their anticancer activity where the retrieved information may be quite useful for developing rational drug designing. Furthermore the selected 1,3-diazine compounds were evaluated for their in vitro anticancer activity against murine macrophages cell line. 1,3-Diazine compounds exhibited good selectivity of the compounds towards the human colorectal carcinoma cell line instead of the murine macrophages. The toxicity study of the most active compounds was also performed on non cancerous HEK-293 cell line.

Matched MeSH terms: Mice

Fulltext Low dose triterpene-quinone fraction from Ardisia crispa root precludes chemical-induced mouse skin tumor promotion

Yeong LT, Abdul Hamid R, Saiful Yazan L, Khaza'ai H, Mohtarrudin N

BMC Complement Altern Med, 2015;15(1):431.

PMID: 26638207 DOI: 10.1186/s12906-015-0954-3

Drastic increment of skin cancer incidence has driven natural product-based chemoprevention as a promising approach in anticancer drug development. Apart from its traditional usages against various ailments, Ardisia crispa (Family: Myrsinaceae) specifically its triterpene-quinone fraction (TQF) which was isolated from the root hexane extract (ACRH) was recently reported to exert antitumor promoting activity in vitro. This study aimed at determining chemopreventive effect of TQF against chemically-induced mouse skin tumorigenesis as well as elucidating its possible pathway(s).

Matched MeSH terms: Mice, Inbred ICR; Mice

Fulltext Elucidation of in-vitro anti-inflammatory bioactive compounds isolated from Jatropha curcas L. plant root

Othman AR, Abdullah N, Ahmad S, Ismail IS, Zakaria MP

BMC Complement Altern Med, 2015;15:11.

PMID: 25652309 DOI: 10.1186/s12906-015-0528-4

BACKGROUND: The Jatropha curcas plant or locally known as "Pokok Jarak" has been widely used in traditional medical applications. This plant is used to treat various conditions such as arthritis, gout, jaundice, wound and inflammation. However, the nature of compounds involved has not been well documented. Hence, this study was conducted to investigate the anti-inflammatory activity of different parts of J. curcas plant and to identify the active compounds involved.
METHODS: In this study, methanol (80%) extraction of four different parts (leaves, fruits, stem and root) of J. curcas plant was carried out. Phenolic content of each part was determined by using Folin-Ciocalteau reagent. Gallic acid was used as the phenol standard. Each plant part was screened for anti-inflammatory activity using cultured macrophage RAW 264.7 cells. The active plant part was then partitioned with hexane, chloroform, ethyl acetate and water. Each partition was again screened for anti-inflammatory activity. The active partition was then fractionated using an open column chromatography system. Single spots isolated from column chromatography were assayed for anti-inflammatory and cytotoxicity activities. Spots that showed activity were subjected to gas chromatography mass spectrophotometry (GC-MS) analysis for identification of active metabolites.
RESULTS: The hexane partition from root extract showed the highest anti-inflammatory activity. However, it also showed high cytotoxicity towards RAW 264.7 cells at 1 mg/mL. Fractionation process using column chromatography showed five spots. Two spots labeled as H-4 and H-5 possessed anti-inflammatory activity, without cytotoxicity activity. Analysis of both spots by GC-MS showed the presence of hexadecanoic acid methyl ester, octadecanoic acid methyl ester and octadecanoic acid.
CONCLUSION: This finding suggests that hexadecanoic acid methyl ester, octadecanoic acid methyl ester and octadecanoic acid could be responsible for the anti-inflammatory activity of the J. curcas root extract.

Matched MeSH terms: Mice

Fulltext Anti-inflammatory effect of the sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden, the Tiger Milk mushroom

Lee SS, Tan NH, Fung SY, Sim SM, Tan CS, Ng ST

BMC Complement Altern Med, 2014;14:359.

PMID: 25256382 DOI: 10.1186/1472-6882-14-359

The sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) is used as a traditional medicine to relieve cough, asthma and chronic hepatitis. The traditional uses of the sclerotium are presumably related to its anti-inflammatory effect. The present study was carried out to evaluate the anti-inflammatory activity of the sclerotial powder of L. rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) cultivar TM02.

Matched MeSH terms: Mice

Fulltext Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8

Abood WN, Fahmi I, Abdulla MA, Ismail S

BMC Complement Altern Med, 2014;14:205.

PMID: 24969238 DOI: 10.1186/1472-6882-14-205

Immunomodulators are substances that modify immune system response to a threat. Immunomodulators modulate and potentiate the immune system, keeping it highly prepared for any threat. The immunomodulatory effect of the traditional medicine Tinospora crispa is investigated in this work.

Matched MeSH terms: Mice

Fulltext Ardisia crispa roots inhibit cyclooxygenase and suppress angiogenesis

Hamsin DE, Hamid RA, Yazan LS, Taib CN, Yeong LT

BMC Complement Altern Med, 2014;14:102.

PMID: 24641961 DOI: 10.1186/1472-6882-14-102

In our previous studies conducted on Ardisia crispa roots, it was shown that Ardisia crispa root inhibited inflammation-induced angiogenesis in vivo. The present study was conducted to identify whether the anti-angiogenic properties of Ardisia crispa roots was partly due to either cyclooxygenase (COX) or/and lipoxygenase (LOX) activity inhibition in separate in vitro studies.

Matched MeSH terms: Mice, Inbred ICR

Fulltext In vitro and ex-vivo cellular antioxidant protection and cognitive enhancing effects of an extract of Polygonum minus Huds (Lineminus™) demonstrated in a Barnes Maze animal model for memory and learning

George A, Ng CP, O'Callaghan M, Jensen GS, Wong HJ

BMC Complement Altern Med, 2014;14:161.

PMID: 24886679 DOI: 10.1186/1472-6882-14-161

Polygonum minus Huds.is a culinary flavouring that is common in South East Asian cuisine and as a remedy for diverse maladies ranging from indigestion to poor eyesight. The leaves of this herb have been reported to be high in antioxidants. Flavonoids which have been associated with memory, cognition and protection against neurodegeneration were found in P. minus.

Matched MeSH terms: Mice, Inbred C57BL

Fulltext Antinociceptive activity of methanolic extract of Muntingia calabura leaves: further elucidation of the possible mechanisms

Zakaria ZA, Mohd Sani MH, Cheema MS, Kader AA, Kek TL, Salleh MZ

BMC Complement Altern Med, 2014;14:63.

PMID: 24555641 DOI: 10.1186/1472-6882-14-63

Muntingia calabura (Elaecoparceae) is a medicinal plant traditionally used, particularly, by the Peruvian people to alleviate headache and cold, pain associated with gastric ulcers or to reduce the prostate gland swelling. Following the recent establishment of antinociceptive activity of M. calabura leaf, the present study was performed to further elucidate on the possible mechanisms of antinociception involved.

Matched MeSH terms: Mice, Inbred ICR

Fulltext Piper betle induces phase I & II genes through Nrf2/ARE signaling pathway in mouse embryonic fibroblasts derived from wild type and Nrf2 knockout cells

Wan Hasan WN, Kwak MK, Makpol S, Wan Ngah WZ, Mohd Yusof YA

BMC Complement Altern Med, 2014;14:72.

PMID: 24559113 DOI: 10.1186/1472-6882-14-72

Nuclear factor-erythroid 2 p45 related factor 2 (Nrf2) is a primary transcription factor, protecting cells from oxidative stress by regulating a number of antioxidants and phase II detoxifying enzymes. Dietary components such as sulforaphane in broccoli and quercetin in onions have been shown to be inducers of Nrf2. Piper betle (PB) grows well in tropical climate and the leaves are used in a number of traditional remedies for the treatment of stomach ailments and infections among Asians. The aim of this study was to elucidate the effect of Piper betle (PB) leaves extract in Nrf2 signaling pathway by using 2 types of cells; mouse embryonic fibroblasts (MEFs) derived from wild-type (WT) and Nrf2 knockout (N0) mice.

Matched MeSH terms: Mice

Fulltext Methanol extract of Melastoma malabathricum leaves exerted antioxidant and liver protective activity in rats

Mamat SS, Kamarolzaman MF, Yahya F, Mahmood ND, Shahril MS, Jakius KF, et al.

BMC Complement Altern Med, 2013;13:326.

PMID: 24267313 DOI: 10.1186/1472-6882-13-326

Melastoma malabathricum L. (Melastomaceae) is a small shrub with various medicinal uses. The present study was carried out to determine the hepatoprotective activity of methanol extract of M. malabathricum leaves (MEMM) against the paracetamol-induced liver toxicity in rats model.

Matched MeSH terms: Mice, Inbred ICR

Fulltext Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3T3

Phan CW, David P, Naidu M, Wong KH, Sabaratnam V

BMC Complement Altern Med, 2013;13:261.

PMID: 24119256 DOI: 10.1186/1472-6882-13-261

Mushrooms are not only regarded as gourmet cuisine but also as therapeutic agent to promote cognition health. However, little toxicological information is available regarding their safety. Therefore, the aim of this study was to screen selected ethno-pharmacologically important mushrooms for stimulatory effects on neurite outgrowth and to test for any cytotoxicity.

Matched MeSH terms: Mice

Fulltext Syzygium campanulatum korth methanolic extract inhibits angiogenesis and tumor growth in nude mice

Aisha AF, Ismail Z, Abu-Salah KM, Siddiqui JM, Ghafar G, Abdul Majid AM

BMC Complement Altern Med, 2013;13:168.

PMID: 23842450 DOI: 10.1186/1472-6882-13-168

Syzygium campanulatum Korth (Myrtaceae) is an evergreen shrub rich in phenolics, flavonoid antioxidants, and betulinic acid. This study sought to investigate antiangiogenic and anti-colon cancer effects of S.C. standardized methanolic extract.

Matched MeSH terms: Mice, Nude; Mice

In vitro and in vivo anti-colon cancer effects of Garcinia mangostana xanthones extract

Aisha AF, Abu-Salah KM, Ismail Z, Majid AM

BMC Complement Altern Med, 2012;12:104.

PMID: 22818000

BACKGROUND: Xanthones are a group of oxygen-containing heterocyclic compounds with remarkable pharmacological effects such as anti-cancer, antioxidant, anti-inflammatory, and antimicrobial activities.
METHODS: A xanthones extract (81% α-mangostin and 16% γ-mangostin), was prepared by crystallization of a toluene extract of G. mangostana fruit rinds and was analyzed by LC-MS. Anti-colon cancer effect was investigated on HCT 116 human colorectal carcinoma cells including cytotoxicity, apoptosis, anti-tumorigenicity, and effect on cell signalling pathways. The in vivo anti-colon cancer activity was also investigated on subcutaneous tumors established in nude mice.
RESULTS: The extract showed potent cytotoxicity (median inhibitory concentration 6.5 ± 1.0 μg/ml), due to induction of the mitochondrial pathway of apoptosis. Three key steps in tumor metastasis including the cell migration, cell invasion and clonogenicity, were also inhibited. The extract and α-mangostin up-regulate the MAPK/ERK, c-Myc/Max, and p53 cell signalling pathways. The xanthones extract, when fed to nude mice, caused significant growth inhibition of the subcutaneous tumor of HCT 116 colorectal carcinoma cells.
CONCLUSIONS: Our data suggest new mechanisms of action of α-mangostin and the G. mangostana xanthones, and suggest the xanthones extract of as a potential anti-colon cancer candidate.

Matched MeSH terms: Mice, Nude; Mice

Fulltext Antipsychotic-like activity of noni (Morinda citrifolia Linn.) in mice

Pandy V, Narasingam M, Mohamed Z

BMC Complement Altern Med, 2012;12:186.

PMID: 23082808 DOI: 10.1186/1472-6882-12-186

Noni fruit is widely consumed in tropical regions of Indonesia to the Hawaiian Islands. The noni plant has a long history of use as a medicinal plant to treat a wide variety of ailments including CNS disorders. The present investigation was designed to evaluate the antipsychotic effect of noni fruits (Morinda citrifolia Linn.) using mouse models of apomorphine-induced climbing behaviour and methamphetamine-induced stereotypy (licking, biting, gnawing and sniffing).

Matched MeSH terms: Mice

Fulltext 1'-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations

In LL, Arshad NM, Ibrahim H, Azmi MN, Awang K, Nagoor NH

BMC Complement Altern Med, 2012;12:179.

PMID: 23043547 DOI: 10.1186/1472-6882-12-179

Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1'S-1'-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes.

Matched MeSH terms: Mice, Nude; Mice

Fulltext Antioxidant, anti-inflammatory and cytotoxicity of Phaleria macrocarpa (Boerl.) Scheff Fruit

Hendra R, Ahmad S, Oskoueian E, Sukari A, Shukor MY

BMC Complement Altern Med, 2011;11:110.

PMID: 22070850 DOI: 10.1186/1472-6882-11-110

Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae) originates from Papua Island, Indonesia and grows in tropical areas. The different parts of the fruit of P. macrocarpa were evaluated for antioxidant, anti-inflammatory, and cytotoxic activities.

Matched MeSH terms: Mice

Fulltext Cytotoxic and antibacterial activities of endophytic fungi isolated from plants at the National Park, Pahang, Malaysia

Hazalin NA, Ramasamy K, Lim SM, Wahab IA, Cole AL, Abdul Majeed AB

BMC Complement Altern Med, 2009;9:46.

PMID: 19930582 DOI: 10.1186/1472-6882-9-46

Endophytes, microorganisms which reside in plant tissues, have potential in producing novel metabolites for exploitation in medicine. Cytotoxic and antibacterial activities of a total of 300 endophytic fungi were investigated.

Matched MeSH terms: Mice

Fulltext Glucan-rich polysaccharides from Pleurotus sajor-caju (Fr.) Singer prevents glucose intolerance, insulin resistance and inflammation in C57BL/6J mice fed a high-fat diet

Kanagasabapathy G, Kuppusamy UR, Abd Malek SN, Abdulla MA, Chua KH, Sabaratnam V

BMC Complement Altern Med, 2012;12:261.

PMID: 23259700 DOI: 10.1186/1472-6882-12-261

BACKGROUND: Pleurotus sajor-caju (P. sajor-caju) has been extremely useful in the prevention of diabetes mellitus due to its low fat and high soluble fiber content for thousands of years. Insulin resistance is a key component in the development of diabetes mellitus which is caused by inflammation. In this study, we aimed to investigate the in vivo efficacy of glucan-rich polysaccharide of P. sajor-caju (GE) against diabetes mellitus and inflammation in C57BL/6J mice fed a high-fat diet.
METHODS: Diabetes was induced in C57BL/6J mice by feeding a high-fat diet. The mice were randomly assigned to 7 groups (n=6 per group). The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120 and HFD240 (for high-fat), where the mice were administrated with three dosages of GE (60, 120, 240 mg GE/kg b.w respectively). Metformin (2 mg/kg b.w) served as positive control. The glucose tolerance test, glucose and insulin levels were measured at the end of 16 weeks. Expressions of genes for inflammatory markers, GLUT-4 and adiponectin in the adipose tissue of the mice were assessed. One-way ANOVA and Duncan's multiple range tests (DMRT) were used to determine the significant differences between groups.
RESULTS: GE treated groups improved the glucose tolerance, attenuated hyperglycemia and hyperinsulinemia in the mice by up-regulating the adiponectin and GLUT-4 gene expressions. The mice in GE treated groups did not develop insulin resistance. GE also down-regulated the expression of inflammatory markers (IL-6, TNF-α, SAA2, CRP and MCP-1) via attenuation of nuclear transcription factors (NF-κB).
CONCLUSION: Glucan-rich polysaccharide of P. sajor-caju can serve as a potential agent for prevention of glucose intolerance, insulin resistance and inflammation.

Matched MeSH terms: Mice, Inbred C57BL; Mice

Fulltext The hexane fraction of Ardisia crispa Thunb. A. DC. roots inhibits inflammation-induced angiogenesis

Hamsin DE, Hamid RA, Yazan LS, Taib CN, Ting YL

BMC Complement Altern Med, 2013;13:5.

PMID: 23298265 DOI: 10.1186/1472-6882-13-5

Ardisia crispa (Myrsinaceae) is used in traditional Malay medicine to treat various ailments associated with inflammation, including rheumatism. The plant's hexane fraction was previously shown to inhibit several diseases associated with inflammation. As there is a strong correlation between inflammation and angiogenesis, we conducted the present study to investigate the anti-angiogenic effects of the plant's roots in animal models of inflammation-induced angiogenesis.

Matched MeSH terms: Mice, Inbred ICR; Mice

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