Evodiamine Lowers Blood Lipids by Up-Regulating the PPARγ/ABCG1 Pathway in High-Fat-Diet-Fed Mice.

The natural alkaloid evodiamine enhances cholesterol efflux from cultured THP-1-derived macrophages, but whether it has any impact on blood lipids in vivo remains unknown. In this study, the effect of evodiamine on hyperlipidemia induced by a high-fat diet (HFD) was investigated in mice. Intragastric administrations of evodiamine (10 and 20 mg/kg) for 8 weeks resulted in a significant improvement of metabolic lipid profiles by reducing the plasma levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Evodiamine also significantly decreased hepatic lipid accumulation and hepatic total bile acids (TBA). Mechanistically, evodiamine increased ATP-binding cassette transporter G1 (ABCG1) mRNA and protein expression and up-regulated peroxisome proliferator-activated receptor gamma (PPARγ) expression in the liver. Taken together, the natural product evodiamine lowers blood lipids in HFD-fed mice likely through promoting the PPARγ-ABCG1 signaling pathway.

Phytol: A review of biomedical activities.

Phytol (PYT) is a diterpene member of the long-chain unsaturated acyclic alcohols. PYT and some of its derivatives, including phytanic acid (PA), exert a wide range of biological effects. PYT is a valuable essential oil (EO) used as a fragrance and a potential candidate for a broad range of applications in the pharmaceutical and biotechnological industry. There is ample evidence that PA may play a crucial role in the development of pathophysiological states. Focusing on PYT and some of its most relevant derivatives, here we present a systematic review of reported biological activities, along with their underlying mechanism of action. Recent investigations with PYT demonstrated anxiolytic, metabolism-modulating, cytotoxic, antioxidant, autophagy- and apoptosis-inducing, antinociceptive, anti-inflammatory, immune-modulating, and antimicrobial effects. PPARs- and NF-κB-mediated activities are also discussed as mechanisms responsible for some of the bioactivities of PYT. The overall goal of this review is to discuss recent findings pertaining to PYT biological activities and its possible applications.

Lycopene and Vascular Health.

Lycopene is a lipophilic, unsaturated carotenoid, found in red-colored fruits and vegetables, including tomatoes, watermelon, papaya, red grapefruits, and guava. The present work provides an up to date overview of mechanisms linking lycopene in the human diet and vascular changes, considering epidemiological data, clinical studies, and experimental data. Lycopene may improve vascular function and contributes to the primary and secondary prevention of cardiovascular disorders. The main activity profile of lycopene includes antiatherosclerotic, antioxidant, anti-inflammatory, antihypertensive, antiplatelet, anti-apoptotic, and protective endothelial effects, the ability to improve the metabolic profile, and reduce arterial stiffness. In this context, lycopene has been shown in numerous studies to exert a favorable effect in patients with subclinical atherosclerosis, metabolic syndrome, hypertension, peripheral vascular disease, stroke and several other cardiovascular disorders, although the obtained results are sometimes inconsistent, which warrants further studies focusing on its bioactivity.

Eurycomalactone Inhibits Expression of Endothelial Adhesion Molecules at a Post-Transcriptional Level.

The C-19 quassinoid eurycomalactone (1) has recently been shown to be a potent (IC50 = 0.5 µM) NF-κB inhibitor in a luciferase reporter model. In this study, we show that 1 with similar potency inhibited the expression of the NF-κB-dependent target genes ICAM-1, VCAM-1, and E-selectin in TNFα-activated human endothelial cells (HUVECtert) by flow cytometry experiments. Surprisingly, 1 (2 µM) did not inhibit TNFα-induced IKKα/ß or IκBα phosphorylation significantly. Also, the TNFα-induced degradation of IκBα remained unchanged in response to 1 (2 µM). In addition, pretreatment of HUVECtert with 1 (2 µM) had no statistically significant effect on TNFα-mediated nuclear translocation of the NF-κB subunit p65 (RelA). Quantitative RT-PCR revealed that 1 (0.5-5 µM) exhibited diverse effects on the TNFα-induced transcription of ICAM-1, VCAM-1, and SELE genes since the mRNA level either remained unchanged (ICAM-1, E-selectin, and VCAM-1 at 0.5 µM 1), was reduced (VCAM-1 at 5 µM 1), or even increased (E-selectin at 5 µM 1). Finally, the time-dependent depletion of a short-lived protein (cyclin D1) as well as the measurement of de novo protein synthesis in the presence of 1 (2-5 µM) suggested that 1 might act as a protein synthesis inhibitor rather than an inhibitor of early NF-κB signaling.

Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases.

Arterial stiffness predicts an increased risk of cardiovascular events. Inflammation plays a major role in large arteries stiffening, related to atherosclerosis, arteriosclerosis, endothelial dysfunction, smooth muscle cell migration, vascular calcification, increased activity of metalloproteinases, extracellular matrix degradation, oxidative stress, elastolysis, and degradation of collagen. The present paper reviews main mechanisms explaining the crosstalk between inflammation and arterial stiffness and the most common inflammatory markers associated with increased arterial stiffness, considering the most recent clinical and experimental studies. Diverse studies revealed significant correlations between the severity of arterial stiffness and inflammatory markers, such as white blood cell count, neutrophil/lymphocyte ratio, adhesion molecules, fibrinogen, C-reactive protein, cytokines, microRNAs, and cyclooxygenase-2, in patients with a broad variety of diseases, such as metabolic syndrome, diabetes, coronary heart disease, peripheral arterial disease, malignant and rheumatic disorders, polycystic kidney disease, renal transplant, familial Mediterranean fever, and oral infections, and in women with preeclampsia or after menopause. There is strong evidence that inflammation plays an important and, at least, partly reversible role in the development of arterial stiffness, and inflammatory markers may be useful additional tools in the assessment of the cardiovascular risk in clinical practice. Combined assessment of arterial stiffness and inflammatory markers may improve non-invasive assessment of cardiovascular risk, enabling selection of high-risk patients for prophylactic treatment or more regular medical examination. Development of future destiffening therapies may target pro-inflammatory mechanisms.

Bupleurum chinense Roots: a Bioactivity-Guided Approach toward Saponin-Type NF-κB Inhibitors.

The roots of Bupleurum chinense have a long history in traditional medicine to treat infectious diseases and inflammatory disorders. Two major compounds, saikosaponins A and D, were reported to exert potent anti-inflammatory activity by inhibiting NF-κB. In the present study, we isolated new saikosaponin analogues from the roots of B. chinese interfering with NF-κB activity in vitro. The methanol-soluble fraction of the dichloromethane extract of Radix Bupleuri was subjected to activity-guided isolation yielding 18 compounds, including triterpenoids and polyacetylenes. Their structures were determined by spectroscopic methods as saikogenin D (1), prosaikogenin D (2), saikosaponins B2 (3), W (4), B1 (5), Y (6), D (7), A (8), E (9), B4 (10), B3 (11), and T (12), saikodiyne A (13), D (14), E (15) and F (16), falcarindiol (17), and 1-linoleoyl-sn-glycero-3-phosphorylcholine (18). Among them, 4, 15, and 16 are new compounds, whereas 6, previously described as a semi-synthetic compound, is isolated from a natural source for the first time, and 13-17 are the first reports of polyacetylenes from this plant. Nine saponins/triterpenoids were tested for inhibition of NF-κB signaling in a cell-based NF-κB-dependent luciferase reporter gene model in vitro. Five of them (1, 2, 4, 6, and 8) showed strong (> 50%, at 30 µM) NF-κB inhibition, but also varying degrees of cytotoxicity, with compounds 1 and 4 (showing no significant cytotoxicity) presenting IC50 values of 14.0 µM and 14.1 µM in the cell-based assay, respectively.

Amorpha fruticosa - A Noxious Invasive Alien Plant in Europe or a Medicinal Plant against Metabolic Disease?

Amorpha fruticosa L. (Fabaceae) is a shrub native to North America which has been cultivated mainly for its ornamental features, honey plant value and protective properties against soil erosion. It is registered amongst the most noxious invasive species in Europe. However, a growing body of scientific literature also points to the therapeutic potential of its chemical constituents. Due to the fact that A. fruticosa is an aggressive invasive species, it can provide an abundant and cheap resource of plant chemical constituents which can be utilized for therapeutic purposes. Additionally, exploitation of the biomass for medicinal use might contribute to relieving the destructive impact of this species on natural habitats. The aim of this review is to provide a comprehensive summary and systematize the state-of-the-art in the knowledge of the phytochemical composition and the potential of A. fruticosa in disease treatment and prevention, with especial emphasis on diabetes and metabolic syndrome. Also reviewed are aspects related to potential toxicity of A. fruticosa which has not yet been systematically evaluated in human subjects.

Screening of Vietnamese medicinal plants for NF-κB signaling inhibitors: assessing the activity of flavonoids from the stem bark of Oroxylum indicum.

ETHNOPHARMACOLOGICAL RELEVANCE: Seventeen plants used in Vietnamese traditional medicine for the treatment of inflammatory disorders were screened for NF-κB inhibitory activity. Oroxylum indicum, which exhibited activity, was investigated in detail. MATERIALS AND METHODS: Forty plant extracts from 17 species were prepared by maceration using dichloromethane and methanol and were tested (10µg/mL) to evaluate their ability to inhibit NF-κB activation using TNF-α-stimulated HEK-293 cells stably transfected with a NF-κB-driven luciferase reporter. The active extract of Oroxylum indicum was subsequently fractionated by different chromatographic techniques. After isolation, all single compounds were identified by spectroscopic methods and assessed for NF-κB inhibitory effects. RESULTS: The dichloromethane extracts obtained from Chromolaena odorata leaves and the stem bark of Oroxylum indicum showed distinct inhibitory effects on NF-κB activation at a concentration of 10µg/mL. The active extract of Oroxylum indicum was subjected to further phytochemical studies resulting in identification of four flavonoid aglyca and six flavonoid glycosides. Pharmacological evaluation of the obtained compounds identified oroxylin A as the most active substance (IC50=3.9 µM, 95% CI: 3.5-4.4 µM), while chrysin and hispidulin showed lower activity with IC50=7.2µM (95% CI: 6.0-8.8 µM) and 9.0 µM (95% CI: 7.9-10.2 µM), respectively. Interestingly, in this study the activity of baicalein (IC50=28.1 µM, 95% CI: 24.6-32.0 µM) was weak. The isolated glycosides showed no inhibitory activity when tested at a concentration of 30 µM. Quantification of the four active flavonoids in extracts and plant materials suggested that oroxylin A contributes to the NF-κB inhibitory activity of the stem barks of Oroxylum indicum to a greater extent than baicalein which was thought to be responsible for the anti-inflammatory activity of this plant. CONCLUSIONS: The screening presented in this study identified the dichloromethane extracts of Chromolaena odorata and Oroxylum indicum as promising sources for NF-κB inhibitors. Hispidulin, baicalein, chrysin and oroxylin A, isolated from Oroxylum indicum, were identified as inhibitors of NF- κB activation.

Polyyne hybrid compounds from Notopterygium incisum with peroxisome proliferator-activated receptor gamma agonistic effects.

In the search for peroxisome proliferator-activated receptor gamma (PPARγ) active constituents from the roots and rhizomes of Notopterygium incisum, 11 new polyacetylene derivatives (1-11) were isolated. Their structures were elucidated by NMR and HRESIMS as new polyyne hybrid molecules of falcarindiol with sesquiterpenoid or phenylpropanoid moieties, named notoethers A-H (1-8) and notoincisols A-C (9-11), respectively. Notoincisol B (10) and notoincisol C (11) represent two new carbon skeletons. When tested for PPARγ activation in a luciferase reporter assay with HEK-293 cells, notoethers A-C (1-3), notoincisol A (9), and notoincisol B (10) showed promising agonistic activity (EC50 values of 1.7 to 2.3 µM). In addition, notoincisol A (9) exhibited inhibitory activity on NO production of stimulated RAW 264.7 macrophages.

Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review.

Agonists of the nuclear receptor PPARγ are therapeutically used to combat hyperglycaemia associated with the metabolic syndrome and type 2 diabetes. In spite of being effective in normalization of blood glucose levels, the currently used PPARγ agonists from the thiazolidinedione type have serious side effects, making the discovery of novel ligands highly relevant. Natural products have proven historically to be a promising pool of structures for drug discovery, and a significant research effort has recently been undertaken to explore the PPARγ-activating potential of a wide range of natural products originating from traditionally used medicinal plants or dietary sources. The majority of identified compounds are selective PPARγ modulators (SPPARMs), transactivating the expression of PPARγ-dependent reporter genes as partial agonists. Those natural PPARγ ligands have different binding modes to the receptor in comparison to the full thiazolidinedione agonists, and on some occasions activate in addition PPARα (e.g. genistein, biochanin A, sargaquinoic acid, sargahydroquinoic acid, resveratrol, amorphastilbol) or the PPARγ-dimer partner retinoid X receptor (RXR; e.g. the neolignans magnolol and honokiol). A number of in vivo studies suggest that some of the natural product activators of PPARγ (e.g. honokiol, amorfrutin 1, amorfrutin B, amorphastilbol) improve metabolic parameters in diabetic animal models, partly with reduced side effects in comparison to full thiazolidinedione agonists. The bioactivity pattern as well as the dietary use of several of the identified active compounds and plant extracts warrants future research regarding their therapeutic potential and the possibility to modulate PPARγ activation by dietary interventions or food supplements.

Identification of isosilybin a from milk thistle seeds as an agonist of peroxisome proliferator-activated receptor gamma.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of glucose and lipid metabolism. Agonists of this nuclear receptor are used in the treatment of type 2 diabetes and are also studied as a potential treatment of other metabolic diseases, including nonalcoholic fatty liver disease. Silymarin, a concentrated phenolic mixture from milk thistle (Silybum marianum) seeds, is used widely as a supportive agent in the treatment of a variety of liver diseases. In this study, the PPARγ activation potential of silymarin and its main constituents was investigated. Isosilybin A (3) caused transactivation of a PPARγ-dependent luciferase reporter in a concentration-dependent manner. This effect could be reversed upon co-treatment with the PPARγ antagonist T0070907. In silico docking studies suggested a binding mode for 3 distinct from that of the inactive silymarin constituents, with one additional hydrogen bond to Ser342 in the entrance region of the ligand-binding domain of the receptor. Hence, isosilybin A (3) has been identified as the first flavonolignan PPARγ agonist, suggesting its further investigation as a modulator of this nuclear receptor.

Activity-guided isolation of NF-κB inhibitors and PPARγ agonists from the root bark of Lycium chinense Miller.

ETHNOPHARMACOLOGICAL RELEVANCE: The root bark of Lycium chinense Miller, Lycii radicis cortex, has been used in traditional Chinese medicine (TCM) to treat different inflammation-related symptoms, such as diabetes mellitus. The pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) is a key regulator of inflammation, while the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is a key modulator of genes involved in diabetes development. To identify putative active compound(s) from Lycii radicis cortex inhibiting NF-κB or activating PPARγ. MATERIAL AND METHODS: Using activity-guided fractionation, six extracts with different polarity, isolated fractions, and purified compounds from Lycii radicis cortex were tested for NF-κB inhibition and PPARγ activation in vitro. The structure of the purified compounds was elucidated by NMR and MS techniques. RESULTS: The ethyl acetate extract and the methanol extract of Lycii radicis cortex suppressed tumor necrosis factor alpha (TNF-α)-induced activation of NF-κB, while the dichloromethane extract activated PPARγ. Nine phenolic amide analogues, including trans-N-(p-coumaroyl)tyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), dihydro-N-caffeoyltyramine (4), three neolignanamides (5-7), and two lignanamide (8, 9), were isolated and their inhibitory potential on NF-κB was determined (1-4 were also contained in water decoction). Two of the nine isolated phenolic amides inhibited TNF-α-induced NF-κB activation. Trans-N-caffeoyltyramine was verified as the key component responsible for the NF-κB inhibition with an IC50 of 18.4µM in our cell-based test system. Activation of PPARγ was attributed to a palmitic-acid enriched fraction which displayed concentration-dependent effect ablated upon co-treatment with the PPARγ antagonist T0070907. CONCLUSIONS: Phenolic amides were confirmed as main components from Lycii radicis cortex responsible for NF-κB inhibition. Fatty acids were identified as the major plant constituent responsible for the PPARγ activation. Structure-activity relationship analysis suggests that the NF-κB inhibitory activity of trans-N-caffeoyltyramine may be attributed to its Michael acceptor-type structure (α,ß-unsaturated carbonyl group). The data of this study contribute to a better understanding of the molecular mechanism of action of Lycii radicis cortex extracts in the context of inflammation.

Identification of chromomoric acid C-I as an Nrf2 activator in Chromolaena odorata.

Activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) contributes to several beneficial bioactivities of natural products, including induction of an increased cellular stress resistance and prevention or resolution of inflammation. In this study, the potential of a crude leaf extract of Chromolaena odorata, traditionally used against inflammation and skin lesions, was examined for Nrf2 activation. Guided by an Nrf2-dependent luciferase reporter gene assay, the phytoprostane chromomoric acid C-I (1) was identified as a potent Nrf2 activator from C. odorata with a CD (concentration doubling the response of vehicle-treated cells) of 5.2 µM. When tested at 1-10 µM, 1 was able to induce the endogenous Nrf2 target gene heme oxygenase 1 (HO-1) in fibroblasts. Between 2 and 5 µM, compound 1 induced HO-1 in vascular smooth muscle cells (VSMC) and inhibited their proliferation in a HO-1-dependent manner, without eliciting signs of cytotoxicity.

NF-κB inhibitors from Eurycoma longifolia.

The roots of Eurycoma longifolia have been used in many countries of Southeast Asia to alleviate various diseases including malaria, dysentery, sexual insufficiency, and rheumatism. Although numerous studies have reported the pharmacological properties of E. longifolia, the mode of action of the anti-inflammatory activity has not been elucidated. Bioguided isolation of NF-κB inhibitors using an NF-κB-driven luciferase reporter gene assay led to the identification of a new quassinoid, eurycomalide C (1), together with 27 known compounds including 11 quassinoids (2-12), six alkaloids (13-18), two coumarins (19, 20), a squalene derivative (21), a triterpenoid (22), and six phenolic compounds (23-28) from the extract of E. longifolia. Evaluation of the biological activity revealed that C19-type and C20-type quassinoids, ß-carboline, and canthin-6-one alkaloids are potent NF-κB inhibitors, with IC50 values in the low micromolar range, while C18-type quassinoids, phenolic compounds, coumarins, the squalene derivative, and the triterpenoid turned out to be inactive when tested at a concentration of 30 µM. Eurycomalactone (2), 14,15ß-dihydroklaieanone (7), and 13,21-dehydroeurycomanone (10) were identified as potent NF-κB inhibitors with IC50 values of less than 1 µM.

Imbricaric acid and perlatolic acid: multi-targeting anti-inflammatory depsides from Cetrelia monachorum.

In vitro screening of 17 Alpine lichen species for their inhibitory activity against 5-lipoxygenase, microsomal prostaglandin E2 synthase-1 and nuclear factor kappa B revealed Cetrelia monachorum (Zahlbr.) W.L. Culb. & C.F. Culb. As conceivable source for novel anti-inflammatory compounds. Phytochemical investigation of the ethanolic crude extract resulted in the isolation and identification of 11 constituents, belonging to depsides and derivatives of orsellinic acid, olivetolic acid and olivetol. The two depsides imbricaric acid (4) and perlatolic acid (5) approved dual inhibitory activities on microsomal prostaglandin E2 synthase-1 (IC50 = 1.9 and 0.4 µM, resp.) and on 5-lipoxygenase tested in a cell-based assay (IC50 = 5.3 and 1.8 µM, resp.) and on purified enzyme (IC50 = 3.5 and 0.4 µM, resp.). Additionally, these two main constituents quantified in the extract with 15.22% (4) and 9.10% (5) showed significant inhibition of tumor necrosis factor alpha-induced nuclear factor kappa B activation in luciferase reporter cells with IC50 values of 2.0 and 7.0 µM, respectively. In a murine in vivo model of inflammation, 5 impaired the inflammatory, thioglycollate-induced recruitment of leukocytes to the peritoneum. The potent inhibitory effects on the three identified targets attest 4 and 5 a pronounced multi-target anti-inflammatory profile which warrants further investigation on their pharmacokinetics and in vivo efficacy.

Honokiol: a non-adipogenic PPARγ agonist from nature.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are clinically used to counteract hyperglycemia. However, so far experienced unwanted side effects, such as weight gain, promote the search for new PPARγ activators. METHODS: We used a combination of in silico, in vitro, cell-based and in vivo models to identify and validate natural products as promising leads for partial novel PPARγ agonists. RESULTS: The natural product honokiol from the traditional Chinese herbal drug Magnolia bark was in silico predicted to bind into the PPARγ ligand binding pocket as dimer. Honokiol indeed directly bound to purified PPARγ ligand-binding domain (LBD) and acted as partial agonist in a PPARγ-mediated luciferase reporter assay. Honokiol was then directly compared to the clinically used full agonist pioglitazone with regard to stimulation of glucose uptake in adipocytes as well as adipogenic differentiation in 3T3-L1 pre-adipocytes and mouse embryonic fibroblasts. While honokiol stimulated basal glucose uptake to a similar extent as pioglitazone, it did not induce adipogenesis in contrast to pioglitazone. In diabetic KKAy mice oral application of honokiol prevented hyperglycemia and suppressed weight gain. CONCLUSION: We identified honokiol as a partial non-adipogenic PPARγ agonist in vitro which prevented hyperglycemia and weight gain in vivo. GENERAL SIGNIFICANCE: This observed activity profile suggests honokiol as promising new pharmaceutical lead or dietary supplement to combat metabolic disease, and provides a molecular explanation for the use of Magnolia in traditional medicine.

Polyacetylenes from Notopterygium incisum--new selective partial agonists of peroxisome proliferator-activated receptor-gamma.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of glucose and lipid metabolism and therefore an important pharmacological target to combat metabolic diseases. Since the currently used full PPARγ agonists display serious side effects, identification of novel ligands, particularly partial agonists, is highly relevant. Searching for new active compounds, we investigated extracts of the underground parts of Notopterygium incisum, a medicinal plant used in traditional Chinese medicine, and observed significant PPARγ activation using a PPARγ-driven luciferase reporter model. Activity-guided fractionation of the dichloromethane extract led to the isolation of six polyacetylenes, which displayed properties of selective partial PPARγ agonists in the luciferase reporter model. Since PPARγ activation by this class of compounds has so far not been reported, we have chosen the prototypical polyacetylene falcarindiol for further investigation. The effect of falcarindiol (10 µM) in the luciferase reporter model was blocked upon co-treatment with the PPARγ antagonist T0070907 (1 µM). Falcarindiol bound to the purified human PPARγ receptor with a Ki of 3.07 µM. In silico docking studies suggested a binding mode within the ligand binding site, where hydrogen bonds to Cys285 and Glu295 are predicted to be formed in addition to extensive hydrophobic interactions. Furthermore, falcarindiol further induced 3T3-L1 preadipocyte differentiation and enhanced the insulin-induced glucose uptake in differentiated 3T3-L1 adipocytes confirming effectiveness in cell models with endogenous PPARγ expression. In conclusion, we identified falcarindiol-type polyacetylenes as a novel class of natural partial PPARγ agonists, having potential to be further explored as pharmaceutical leads or dietary supplements.

tert-Butyldimethylsilyl O-protected chitosan and chitooligosaccharides: useful precursors for N-modifications in common organic solvents.

An efficient and chemoselective procedure for preparing highly organosoluble 3,6-di-O-tert-butyldimethylsilyl (TBDMS)-chitosan and chitooligosaccharides is reported. The selective modification of the chitooligosaccharides with 0.50 degree of N-acetylation was achieved by using TBDMSCl as the reagent in combination with DMF/imidazole. These protocols yielded partly TBDMS-substituted chitooligosaccharides that were subsequently reacted with TBDMSOTf in dichloromethane in order to silylate the remaining, more sterically hindered hydroxyl groups. In the case of the chitosan polymer, a mesylate salt of chitosan was silylated using TBDMSCl in DMSO, yielding full silylation of the hydroxyl groups without using N-protection groups. The silyl-protected polymers displayed excellent solubility in a number of common organic solvents. The 3,6-di-O-TBDMS-chitosan and chitooligosaccharides were reacted with acetic anhydride, and deprotected to obtain the corresponding N-acetyl derivatives (chitin and chitinoligosaccharide). Our results show that the readily prepared 3,6-di-O-TBDMS-chitosan and chitooligosaccharides are useful precursors for selective N-modifications in common organic solvents.