Jack Ho Wong

Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications.

Chitosan is a natural polycationic linear polysaccharide derived from chitin. The low solubility of chitosan in neutral and alkaline solution limits its application. Nevertheless, chemical modification into composites or hydrogels brings to it new functional properties for different applications. Chitosans are recognized as versatile biomaterials because of their non-toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the recent research, trends and prospects in chitosan. Some special pharmaceutical and biomedical applications are also highlighted.

Review of research on Dendrobium, a prized folk medicine.

Medicinal plants of the Dendrobium genus are highly prized, and hence, methodologies have been developed to authenticate Dendrobium drugs from its adulterants. Many bioactive constituents of Dendrobium species have been identified. The macromolecules included lectins; the enzymes chalcone synthase, sucrose synthase, and cytokinin oxidase; and polysaccharides. The polysaccharides display immunomodulatory and hepatoprotective activities. Alkaloids exhibit antioxidant, anticancer, and neuroprotective activities. Other compounds manifest antioxidant, anticancer, and immunomodulatory.

A Review of Defensins of Diverse Origins

Defensins are a family of peptides with potent antimicrobial activity. They are found in various organisms. The intent of this article is to review the structures and mechanisms of antimicrobial actions of defensins produced by different organisms including humans, other mammals, birds, reptiles, fish, mollusks, arthropods, plants and fungi. The evolution and possible applications of these defensins are discussed.

Proteins with antifungal properties and other medicinal applications from plants and mushrooms

Living organisms produce a myriad of molecules to protect themselves from fungal pathogens. This review focuses on antifungal proteins from plants and mushrooms, many of which are components of the human diet or have medicinal value. Plant antifungal proteins can be classified into different groups comprising chitinases and chitinase-like proteins, chitin-binding proteins, cyclophilin-like proteins, defensins and defensin-like proteins, deoxyribonucleases, embryo-abundant protein-like proteins, glucanases, lectins, lipid transfer proteins, peroxidases, protease inhibitors, ribonucleases, ribosome-inactivating proteins, storage 2S albumins, and thaumatin-like proteins. Some of the aforementioned antifungal proteins also exhibit mitogenic activity towards spleen cells, nitric oxide inducing activity toward macrophages, antiproliferative activity toward tumor cells, antibacterial activity, and inhibitory activity toward HIV-1 reverse transcriptase. In contrast to the large diversity of plant antifungal proteins, only a small number of mushroom antifungal proteins have been reported. Mushroom antifungal proteins are distinct from their plant counterparts in N-terminal sequence. Nevertheless, some of the mushroom antifungal proteins have been shown to inhibit HIV-1 reverse transcriptase activity and tumor cell proliferation.

Gymnin, a potent defensin-like antifungal peptide from the Yunnan bean (Gymnocladus chinensis Baill).

From the seeds of the Yunnan bean, we purified an antifungal peptide using affinity chromatography on Affi-gel blue gel, FPLC-ion exchange chromatography on Mono S, and FPLC-gel filtration on Superdex 75. The antifungal peptide was adsorbed on Affi-gel blue gel at pH 7.8 and Mono S at pH 4.5. It exhibited a molecular mass of 6.5 kDa in both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its N-terminal sequence closely resembled defensin-related peptides. The peptide exerted antifungal activity toward the fungal species Fusarium oxysporum and Mycosphaerella arachidicola, with an IC50 of 2 microM for the former fungus and 10 microM for the latter. It manifested a weaker mitogenic activity toward murine splenocytes than Concanavalin A. It also displayed antiproliferative activity on a murine leukemia (L1210), a hepatoma (HepG2), and a murine leukemia (M1) cell line. It inhibited human immunodeficiency virus-1 reverse transcriptase with an IC50 of 200 microM.

Marine Peptides: Bioactivities and Applications

Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products.

Momordica Charantia Lectin, a Type II Ribosome Inactivating Protein, Exhibits Antitumor Activity toward Human Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

The incidence of nasopharyngeal carcinoma (NPC) remains high in endemic regions, including southern China, northern Africa, and North America. One of the promising therapeutic approaches on NPC is drug screening from natural products, such as components from traditional Chinese medicine. In this study, the antitumor activity of Momordica charantia lectin (MCL), a type II ribosome inactivating protein from bitter gourd, on NPC was investigated. MCL evinced potent cytotoxicity toward NPC CNE-1 (IC50 = 6.9) and CNE-2 (IC50 = 7.4) cells but minimally affected normal NP 69 cells. Further investigation disclosed that MCL induced apoptosis, DNA fragmentation, G1-phase arrest, and mitochondrial injury in both types of NPC cells. The reduction of cyclin D1 and phosphoretinoblastoma (Rb) protein expression contributed to arrest at G1-phase of the cell cycle. These events were associated with regulation of mitogen-activated protein kinases (MAPK; including p38 MAPK, JNK, and ERK) phosphorylation and promoted downstream nitric oxide (NO) production. Concurrent administration of the p38 MAPK inhibitor SB-203580 significantly diminished NO production and lethality of MCL toward NPC cells. Further studies revealed that MCL increased cytochrome c release into the cytosol, activated caspases-8, -9, and -3, and enhanced production of cleaved PARP, subsequently leading to DNA fragmentation and apoptosis. Finally, an intraperitoneal injection of MCL (1.0 mg/kg/d) led to an average of 45% remission of NPC xenograft tumors subcutaneously inoculated in nude mice. This is the first article that unveils the potential of a type II RIP, MCL, for prevention and therapy of NPC. Cancer Prev Res; 5(1); 109–21. ©2011 AACR.

Effects of cathelicidin and its fragments on three key enzymes of HIV-1.

Cathelicidins exhibit anti-HIV activity but it is not known if they reduce the activity of enzymes crucial to the life cycle of the retrovirus. It is shown in this investigation that human cathelicidin LL37 and its fragments LL13-37 and LL17-32 inhibited HIV-1 reverse transcriptase dose-dependently with an IC50 value of 15μM, 7μM, and 70μM, respectively. The three peptides inhibited HIV-1 protease with a weak potency, achieving 20-30% inhibition at 100μM. The mechanism of inhibition was protein-protein interaction as revealed by surface plasmon resonance. The peptides were devoid of the ability to inhibit translocation of HIV-1 integrase, which has been labeled with green fluorescent protein, into the nucleus. The peptides did not exert toxicity on human peripheral blood mononuclear cells.

Purification and Characterization of a Lectin from Phaseolus vulgaris cv. (Anasazi Beans)

A lectin has been isolated from seeds of the Phaseolus vulgaris cv. “Anasazi beans” using a procedure that involved affinity chromatography on Affi-gel blue gel, fast protein liquid chromatography (FPLC)-ion exchange chromatography on Mono S, and FPLC-gel filtration on Superdex 200. The lectin was comprised of two 30-kDa subunits with substantial N-terminal sequence similarity to other Phaseolus lectins. The hemagglutinating activity of the lectin was stable within the pH range of 1–14 and the temperature range of 0–80°C. The lectin potently suppressed proliferation of MCF-7 (breast cancer) cells with an IC50 of 1.3 μM, and inhibited the activity of HIV-1 reverse transcriptase with an IC50 of 7.6 μM. The lectin evoked a mitogenic response from murine splenocytes as evidenced by an increase in [3H-methyl]-thymidine incorporation. The lectin had no antifungal activity. It did not stimulate nitric oxide production by murine peritoneal macrophages. Chemical modification results indicated that tryptophan was crucial for the hemagglutinating activity of the lectin.

Recent Progress in Research on Ribosome Inactivating Proteins

The intent of this article is to review recent literature on ribosome inactivating proteins (RIPs) including isolation and characterization of new RIPs, studies on the crystal structures and mechanisms of actions of RIPs, the use of saporin-based neurotoxins to selectively lesion cholinergic neurons in neuroscience research, and the use of RIP-based conjugates and immunotoxins in anticancer therapy.