Nordin H. Lajis

Synthesis and biological evaluation of curcumin-like diarylpentanoid analogues for anti-inflammatory, antioxidant and anti-tyrosinase activities.

A series of 46 curcumin related diarylpentanoid analogues were synthesized and evaluated for their anti-inflammatory, antioxidant and anti-tyrosinase activities. Among these compounds 2, 13 and 33 exhibited potent NO inhibitory effect on IFN-gamma/LPS-activated RAW 264.7 cells as compared to L-NAME and curcumin. However, these series of diarylpentanoid analogues were not significantly inhibiting NO scavenging, total radical scavenging and tyrosinase enzyme activities. The results revealed that the biological activity of these diarylpentanoid analogues is most likely due to their action mainly upon inflammatory mediator, inducible nitric oxide synthase (iNOS). The present results showed that compounds 2, 13 and 33 might serve as a useful starting point for the design of improved anti-inflammatory agents.

Antiviral, Cyototoxic And Antimicrobial Activities Of Anthraquinones Isolated From The Roots Of Morinda Elliptica

2-Formyl-1-hydroxyanthraquinone, along with ten other known anthraquinones (1-hydroxy-2-methylanthraquinone, nordamnacanthal, damnacanthal, lucidin-?-methyl ether, rubiadin, rubiadin-1-methyl ether, soranjidiol, morindone, morindone-5-methyl ether and alizarin-1-methyl ether), isolated from the roots of Morinda elliptica , were assayed for anti-HIV, cytotoxic and antimicrobial activites. Only damnacanthal showed moderate activity against HIV. It was cytotoxic towards the MCF-7 (breast carcinoma) and CEM-SS (T-lymphoblastic leukaemia) cell line. Nordamnacanthal was very cytotoxic against the CEM-SS cell lines. Other anthraquinones that showed strong cytotoxicity towards the cell lines tested were lucidin-?-methyl ether (CEM-SS and MCF-7) and rubiadin (CEM-SS). Three anthraquinones viz., nordamnacanthal, damnacanthal and morindone, were found to have strong antimicrobial activity.

Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G1 arrest and apoptosis

Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death.

Antinociceptive activity of the essential oil of Zingiber zerumbet.

In the present study, the rhizome essential oil from Zingiber zerumbet (Zingiberaceae) was evaluated for antinociceptive activity using chemical and thermal models of nociception, namely, the acetic acid-induced abdominal writhing test, the hot-plate test and the formalin-induced paw licking test. It was demonstrated that intraperitoneal administration of the essential oil of Z. zerumbet (EOZZ) at the doses of 30, 100 and 300 mg/kg produced significant dose-dependent inhibition of acetic acid-induced abdominal writhing, comparable to that of obtained with acetylsalicylic acid (100 mg/kg). At the same doses, the EOZZ produced significant dose-dependent increases in the latency time in the hot-plate test with respect to controls, and in the formalin-induced paw licking test, the EOZZ also significantly reduced the painful stimulus in both neurogenic and inflammatory phase of the test. In addition, the antinociceptive effect of the EOZZ in the formalin-induced paw licking test as well as hot-plate test was reversed by the nonselective opioid receptor antagonist, naloxone suggesting that the opioid system was involved in its analgesic mechanism of action. On the basis of these data, we concluded that the EOZZ possessed both central and peripheral antinociceptive activities which justifying its popular folkloric use to relieve some pain conditions.

Semisynthesis and cytotoxic activities of andrographolide analogues

Andrographolide 1, a diterpenoid lactone of the plant Andrographis paniculata, known to possess antitumour activity in in vitro and in vivo breast cancer models was subjected to semisynthesis leading to the preparation of a number of novel compounds. These compounds exhibited in vitro antitumour activity with moderate to excellent growth inhibition against MCF-7 (breast) and HCT-116 (colon) cancer cells. Compounds 3,19-(2-chlorobenzylidene)andrographolide(5), 3,19-(3-chlorobenzylidene)andrographolide(6), 3,19-(3-fluorobenzylidene)andrographolide(7), 3,19-(4-fluorobenzylidene)andrographolide(8), 3,19-(2-fluorobenzylidene)andrographolide(10), 3,19-(2-chloro-5-nitrobenzylidene)andrographolide (21), 3,19-(4-chlorobenzylidene)andrographolide(30) and 3,19-(2-chloro-4-fluorobenzylidene) andrographolide(31) were also screened against 60 NCI (National Cancer Institute, USA) human tumour cell lines derived from nine cancer cell types.

Anthraquinones from Morinda elliptica

Phytochemical studies on roots of Morinda elliptica have resulted in the isolation of a new anthraquinone, 2-formyl-1-hydroxyanthraquinone, and 10 known anthraquinones. The structures of the anthraquinones were established based on spectral studies.

A synthetic curcuminoid derivative inhibits nitric oxide and proinflammatory cytokine synthesis

Curcumin is a highly pleiotropic molecule with significant regulatory effects upon inflammation and inflammatory related diseases. However curcumin has one major important limitation in which it has poor bioavailability. Design of synthetic structural derivatives of curcumin is but one approach that has been used to overcome its poor bioavailability while retaining, or further enhancing, its drug-like effects. We have synthesized a series of curcumin analogues and describe the effects of 2,6-bis-4-(hydroxyl-3-methoxy-benzylidine)-cyclohexanone or BHMC upon nitric oxide and cytokine synthesis in cellular models of inflammation. BHMC showed a significant dose-response inhibitory action upon the synthesis of NO and we have shown that this effect was due to suppression of both iNOS gene and enzyme expression without any effects upon scavenging of nitrite. We also demonstrated that BHMC has a very minimal effect upon iNOS activity with no effect at all upon the secretion of PGE(2) but has a strong inhibitory effect upon MCP-1 and IL-10 secretion and gene expression. Secretion and gene expression of TNF-alpha and IL-6 were moderately inhibited whereas IL-8 and IL-1beta were not altered. We conclude that BHMC selectively inhibits the synthesis of several inflammatory mediators. BHMC should be considered a promising drug lead for preclinical and further pharmacological studies.

Zerumbone-Induced Antinociception: Involvement of the l-Arginine-Nitric Oxide-cGMP -PKC-K+ATP Channel Pathways

This study investigated the antinociceptive effects of zerumbone in chemical behavioural models of nociception in mice. Zerumbone given through intraperitoneal route (i.p.) produced dose-related antinociception when assessed on acetic acid-induced abdominal writhing test in mice. In addition, the i.p. administration of zerumbone exhibited significant inhibition of the neurogenic pain induced by intraplantar (i.pl.) injection of capsaicin and bradykinin. Likewise, zerumbone given by i.p. route reduced the nociception produced by i.pl. injection of glutamate and phorbol myristate acetate (PMA). The antinociception caused by zerumbone in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with l-arginine (nitric oxide precursor) and glibenclamide (ATP-sensitive K(+) channel inhibitor). However, the antinociception of zerumbone was enhanced by methylene blue (non-specific gyanylyl cyclase inhibitor). Together, these results indicate that zerumbone produces pronounced antinociception against chemical models of nociception in mice. It also strongly suggests that the l-arginine-nitric oxide-cGMP-PKC-K(+) ATP channel pathways, the TRPV1 and kinin B2 receptors play an important role in the zerumbone-induced antinociception.

Epi-Sarsasapogenin and epi-smilagenin: two sapogenins isolated from the rumen content of sheep intoxicated by Brachiaria decumbens

Spectroscopic examination of purified extracts of the rumen content of sheep intoxicated by Brachiaria decumbens revealed the presence of two spirostanes, identified as epi-sarsasapogenin and epi-smilagenin. Sarsasapogenone was obtained by the oxidation of sarsasapogenin. The reduction of sarsasapogenone using lithium aluminum hydride yielded isomeric products, sarsasapogenin (20%) and epi-sarsasapogenin (80%).

Discrimination of Three Pegaga (Centella) Varieties and Determination of Growth-Lighting Effects on Metabolites Content Based on the Chemometry of 1H Nuclear Magnetic Resonance Spectroscopy

The metabolites of three species of Apiaceae, also known as Pegaga, were analyzed utilizing (1)H NMR spectroscopy and multivariate data analysis. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) resolved the species, Centella asiatica, Hydrocotyle bonariensis, and Hydrocotyle sibthorpioides, into three clusters. The saponins, asiaticoside and madecassoside, along with chlorogenic acids were the metabolites that contributed most to the separation. Furthermore, the effects of growth-lighting condition to metabolite contents were also investigated. The extracts of C. asiatica grown in full-day light exposure exhibited a stronger radical scavenging activity and contained more triterpenes (asiaticoside and madecassoside), flavonoids, and chlorogenic acids as compared to plants grown in 50% shade. This study established the potential of using a combination of (1)H NMR spectroscopy and multivariate data analyses in differentiating three closely related species and the effects of growth lighting, based on their metabolite contents and identification of the markers contributing to their differences.