Systematic Chemical Analysis of Crude Glycan Isolates from the Seven-Herb Decoction Quanzhenyiqitang with Anti-COPD Activity.

The classical Chinese Medicine prescription, Quanzhenyiqitang (QZYQT), containing seven tonic herbs (Shudi, Dangshen, Maidong, Baizhu, Niuxi, Fuzi, and Wuweizi) is clinically used to treat chronic obstructive pulmonary disease (COPD). Although there are studies on the pharmacological effects of QZYQT, little attention has been paid to its active carbohydrate ingredients. We performed a systematic chemical analysis of the crude glycan isolates from the seven-herb decoction (GI-QZYQT) after confirming its anti-COPD activity. GI-QZYQT could enhance lung function, reduce lung damage, and alleviate inflammatory response in mice with COPD. Moreover, two monosaccharides (fructose and glucose) and six oligosaccharides (sucrose, melibiose, 1-kestose, raffinose, mannotriose, and stachyose), accounting for 40.23 % of GI-QZYQT, were discovered using hydrophilic interaction liquid chromatography-evaporative light-scattering detection. Inulin-type fructan with an average molecular weight of 2112 Da was identified using high-performance gel-permeation chromatography in combination with monosaccharide mapping analysis, accounting for 20.10 % of GI-QZYQT in mass. The comparison study showed that the identified monosaccharides, oligosaccharides, and the inulin-type fructan of GI-QZYQT were mainly derived from herbs of Shudi, Dangshen, Maidong, Baizhu, and Niuxi. These findings provide crucial information on the chemical composition of GI-QZYQT, which is vital for the in-depth understanding of its bioactivity, mechanism, and product development.

Synthetic Iowaite Can Effectively Remove Inorganic Arsenic from Marine Extract.

For the removal of arsenic from marine products, iowaite was prepared and investigated to determine the optimal adsorption process of arsenic. Different chemical forms of arsenic (As(III), As(V)) with varying concentrations (0.15, 1.5, 5, 10, 15, and 20 mg/L) under various conditions including pH (3, 5, 7, 9, 11) and contact time (1, 2, 5, 10, 15, 30, 60, 120, 180 min) were exposed to iowaite. Adsorption isotherms and metal ions kinetic modeling onto the adsorbent were determined based on Langmuir, Freundlich, first- and second-order kinetic models. The adsorption onto iowaite varied depending on the conditions. The adsorption rates of standard solution, As(III) and As(V) exceeded 95% under proper conditions, while high complexity was noted with marine samples. As(III) and As(V) from Mactra veneriformis extraction all decreased when exposed to iowaite. The inclusion morphology and interconversion of organic arsenic limit adsorption. Iowaite can be efficiently used for inorganic arsenic removal from wastewater and different marine food products, which maybe other adsorbent or further performance of iowaite needs to be investigated for organic arsenic.

Overview on biological activities and molecular characteristics of sulfated polysaccharides from marine green algae in recent years.

Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits.

Characterization of ACE inhibitory peptides from Mactra veneriformis hydrolysate by nano-liquid chromatography electrospray ionization mass spectrometry (Nano-LC-ESI-MS) and molecular docking.

Food-derived bioactive compounds are gaining increasing significance in life sciences. In the present study, we identified angiotensin I-converting enzyme (ACE)-inhibitory peptides from Mactra veneriformis hydrolysate using a nano-LC-MS/MS method. Mactra veneriformis hydrolysate was first separated into four fractions (F1-F4) based on molecular weight by ultrafiltration. The fraction with molecular weight lower than 1 kDa (F1) showed the highest ACE inhibitory activity. F1 was then analyzed by a high throughput nano-LC-MS/MS method and sequences of peptides in F1 were calculated accordingly. The 27 peptides identified as above were chemically synthesized and tested for ACE-inhibitory activity. The hexapeptide VVCVPW showed the highest potency with an IC50 value of 4.07 µM. We then investigated the interaction mechanism between the six most potent peptides and ACE by molecular docking. Our docking results suggested that the ACE inhibitory peptides bind to ACE via interactions with His383, His387, and Glu411 residues. Particularly, similar to the thiol group of captopril, the cysteine thiol group of the most potent peptide VVCVPW may play a key role in the binding of this peptide to the ACE active site.

A Gellan Gum/Sodium Alginate-based gastric-protective hydrogel loaded with a combined herbal extract consisting of Panax notoginseng, Bletilla striata and Dendrobium officinale.

One Chinese herbal combination consisting of Panax notoginseng, Bletilla striata and Dendrobium officinale (PBD) is an effective Traditional Chinese Medicine (TCM) prescription and is widely used in clinics to treat gastric ulcers due to their safety and effectiveness compared with chemical agents, such as aspirin and omeprazole. Herein, an in situ forming gel (ISFG) based on Gellan Gum (GG) and Sodium Alginate (SA) was designed to deliver extracts of PBD prescription (EPBDP). The central composite design optimized prescription dosage was 0.1 % w/v of GG and 0.5 % w/v of SA. Gels prepared with this formulation demonstrated outstanding fluidity and instantaneous gel formation. In vitro release data showed that sustained drug release occurred in the gel, and the gel was pH-sensitive. The rheological tests confirmed the formation of stable gel, which exhibited strong viscosity and elasticity. In vitro adhesion assays revealed that the gel had strong gastric mucosal adhesion, while in vivo residual rate experiments of active ingredients revealed that the gel might greatly improve the gastric retention of active ingredients. Animal studies demonstrated that the gel was effective in treating gastric ulcers. Hence, the results of the study show that EPBDP-ISFG, a highly pH-sensitive sustained-release system, is effective.

Extra virgin olive oil-based phospholipid complex/self-microemulsion enhances oral absorption of salvianolic acid B through inhibition of catechol-O-methyltransferase-mediated metabolism.

The oral bioavailability of many phenolic acid drugs is severely limited due to the high hydrophilicity and extensive first-pass effect induced by catechol-O-methyltransferase (COMT) metabolism. The present study investigated the inhibitory activity of the pharmaceutical excipients of extra virgin olive oil (EVOO) against COMT and evaluated the potential of a self-microemulsion loaded with a phospholipid complex containing EVOO for oral absorption enhancement of salvianolic acid B (SAB), a model phenolic acid. In vitro COMT assay showed that EVOO could effectively inhibit enzyme activity in the rat liver cytosol. Next, the SAB phospholipid complex/self-microemulsion containing EVOO (named SP-SME1) was prepared and characterized (particle size, 243.60 ± 6.96 nm and zeta potential, -23.67 ± -1.36 mV). The phospholipid complex/self-microemulsion containing ethyl oleate (EO) (named SP-SME2) was taken as the control group. Compared with free SAB, the apparent permeability coefficient (Papp value) of the two SP-SMEs significantly increased (12.0-fold and 10.90-fold). Pharmacokinetic study demonstrated that the AUC0-∞ value of SAB for the SP-SME1 group significantly increased by 4.72 and 2.82 times compared to those for free SAB (p < 0.001) and SP-SME2 (p < 0.01), respectively. Moreover, the AUC0-∞ value of monomethyl-SAB (metabolite of SAB, MMS) for the SP-SME1 group decreased by 0.83 times compared to that for SP-SME2. In conclusion, the EVOO-based phospholipid complex/self-microemulsion greatly enhanced the oral absorption of SAB, which was mainly attributed to the inhibition of COMT activity induced by EVOO.

Excipient-free nanodispersions dominated by amphiphilic glycosides for bioavailability enhancement of hydrophobic aglycones, a case of glycyrrhetinic acid with diammonium glycyrrhizinate.

Natural aglycones, a major ingredient accompanied by glycosides in plants, have played an important role in the treatment of various diseases. However, their bioavailability is limited by their poor water solubility. In contrast to previous efforts that required the use of new exotic materials which may raise concerns about biocompatibility, we report the first case of excipient-free nanodispersions in which an insoluble glycyrrhetinic acid (GA) assembled with its amphiphilic parent drug diammonium glycyrrhizinate (DG) into water-dispersible nanodispersions (130.8 nm for particle size and 91.74% for encapsulation efficiency). This strategy largely increased GA's water apparent solubility by hundreds of times to 549.0 µg/mL with a high cumulative dissolution percentage in vitro greater than 80% in 5 min. The study on the formation mechanism showed that the OH, C-O and C=O group stretching peaks shifted in the FTIR spectra of GA-DG nanodispersions, while the COOH peak (δ COOH 12.19 ppm) disappeared in the 1H NMR spectrum of GA-DG nanodispersions, indicating that carboxyl groups on GA may interact with the hydroxyl groups of DG in solution. Molecular dynamics simulations suggested that both hydrophobic interactions and hydrogen-bond interactions contribute to the coassembly of GA and DG molecules in aqueous solution. Oral pharmacokinetic studies in rats demonstrated that such nanodispersions have a significant increase in Cmax and AUC0-t of 2.45- and 3.45-fold compared with those for GA, respectively. Therefore, this strategy, employing amphiphilic glycosides as excipients to prepare nanodispersions, not using new materials, paves the way for the further application of hydrophobic aglycone drugs.

A periodic review of chemical and pharmacological profiles of Tubiechong as insect Chinese medicine.

Tubiechong, in Chinese medicine, denotes the dried female insects of Eupolyphaga sinensis Walker (ESW) or Polyphaga plancyi Bolivar (PPB). As a traditional insect-type, in medicine, it has been historically utilized to treat bruises, fractures, amenorrhea, postpartum blood stasis, lumps and relieving pain. We herein have performed a systematic survey involving the chemical and biological studies in the past decades to reveal the value of such insect resources for their development and clinical utilization. Chemical studies indicated that Tubiechong generated many active compounds, including proteins, amino acids, peptides, fatty acids, alkaloids, nucleosides, polysaccharides, fat-soluble vitamins and mineral elements. Tubiechong or its extract has a wide range of activities including anticoagulation and anti-thrombosis, anti-tumor, antioxidant, immune regulation, blood lipid regulation and hepatoprotection. Finally, a periodic mini-review was conducted to summarize such chemical and pharmacological profiles of Tubiechong medicine. The active peptides in Tubiechong are majorly focused in this review and introduced as one important aspect since there is much literature and huge investigative interest in it. Traditional medical use of the insect was also stressed in this review associating with its disease-eliminating actions by promoting blood circulation or eliminating tissue-swelling pains, which might play important roles in anticancer practices or investigation. In accordance with the modern pharmacological progress, Tubiechong and its extracts indeed exerted antitumor actions through multiple pathways, such as interfering with tumor biological behaviors (growth, apoptosis, invasion, metastasis and angiogenesis), and regulating host immune function. To some extent, this knowledge would provide a basis for further research and application of Tubiechong medicine.

Improved efficacy of Panax notoginseng saponin loaded into BSP/alginate microspheres for the treatment of alcoholic gastric ulcers.

Previously, we have reported the evaluations of alginate and Bletilla striata polysaccharide (BSP) in formulation of microsphere, which is a muco-adhesive carrier and can achieve a long duration of gastric retention. The combination of Panax notoginseng (Burk.) and B. striata is a traditional Chinese herbal formula that is used to treat gastric ulcers. BSP, an effective ingredient of B. striata, possesses both medicinal and excipient functions. Panax notoginseng saponin (PNS), which can easily dissolve in water, is the main effective ingredient in P. notoginseng (Burk.) for the treatment of gastric ulcers. However, microspheres containing PNS could directly cause drug leakage, ultimately reducing the encapsulation rate. In this study, PNS was fabricated into a hydrophobic dispersion with slow-release characteristics. Subsequently, PNS was packaged into BSP/alginate microspheres to improve the encapsulation rate. The prepared PNS-loaded microspheres were round, the release characteristics aligned with the Weibull equation, and the active ingredients were released by diffusion and erosion. The developed microspheres improved the effects of PNS and synergistically exerted the pharmaceutical effects of BSP on acute gastric ulcers.

Mucoadhesive nanocrystal-in-microspheres with high drug loading capacity for bioavailability enhancement of silybin.

Nanocrystals, due to high drug loading efficiency, have drawn large attention as nanotechnology to enhance solubility and bioavailability of poorly soluble drugs. However, most nanocrystals still encountered low oral absorption percentage due to its insufficient retention time in the gastrointestinal tract (GI). In this work, silybin (SB) as model drug was fabricated to nanocrystals, and further loaded into a mucoadhesive microsphere to increase the GI retention. Such mucoadhesive microspheres were prepared with a wet media milling technique followed by coagulation and film coating. Nanocrystals and microspheres were thoroughly characterized by diverse complementary techniques. As results, such delivery system displayed an encapsulation efficiency of approximately 100 % and a drug loading capacity of up to 35.41 ± 0.31 %. In addition, mucoadhesiveness test ex vivo conducted with rat intestine showed that film-coated microspheres were retained for more than 1 h. Benefiting from nanocrystals technology, the drug cumulative release percentage of the microspheres was remarkable improved compared to unprocessed one in vitro. Finally, pharmacokinetics studies in rats showed a significant 3-fold increase of drug oral bioavailability compared to unprocessed SB. The current study demonstrates that the developed delivery vehicle can enhance the bioavailability of SB by increasing its dissolution percentage as well as through extending retention time in the GI tract, and achieve high drug loading capacity.

Protective Actions of Acidic Hydrolysates of Polysaccharide Extracted From Mactra veneriformis Against Chemical-Induced Acute Liver Damage.

The present study aimed to explore the hepatoprotective effects of acidic hydrolysates of polysaccharide extracted from the marine clam M. veneriformis (Ah-MVPS) against ethanol- and CCl4-induced liver damage. Moreover, we also seek to probe the mechanism associated with the liver protection effect of Ah-MVPS. A series of animal and cell experiments were executed to detect suitable serological and histological indicators in hepatic tissues. Ah-MVPS can significantly reduce liver damage by means of an increase in hepatocyte superoxidase dismutase and inhibition of leakages of alanine aminotransferase and aspartate transaminase, as well as through alleviation of malondialdehyde excalation. Ah-MVPS inhibited steatosis and water-like hepatic deterioration in histological examination. They can suppress membrane destruction in boundaries and the collapse of reticular scaffolds of injured mouse hepatocytes and can substantially reduce the inflammatory extent of liver tissue aroused by excessive intake of ethanol or CCl4. In cell assays, Ah-MVPS markedly elevated the viability of L-02 cells exposed to an intoxication of ethanol or H2O2. The beneficial effect of Ah-MVPS might arise, at least in part, because of the amelioration of peroxidation or oxidative stress. Taken together, our findings reveal that Ah-MVPS have potential for development as protective agents to attenuate acute liver injuries.

Mucoadhesive improvement of alginate microspheres as potential gastroretentive delivery carrier by blending with Bletilla striata polysaccharide.

As polysaccharide from Bletilla striata (BSP) was anticipated with mucoadhesive improvement in sodium alginate (SA) microspheres, BSP was mixed with SA to construct a composite microsphere to retain in the gastrointestinal tract for a long time. The morphological properties, particle size and thermodynamic properties of the microspheres in combination with comprehensive evaluations in the swelling properties, mucin adsorption, ex vivo and in vivo gastric retention were determined to characterize the mucoadhesion of SA-BSP blend microspheres. Results showed that the prepared microspheres were discrete and spherical. The addition of BSP increased flexibility and reduced rigidity of SA microsphere. Furthermore, the swelling property, mucin adsorption ability and the retention rate on the gastric mucosa of SA matrix were increased after blending with BSP. Mucoadhesion tests showed the SA-BSP microspheres stayed much longer in rats' stomach than the SA microsphere did. Above all, the SA-BSP microspheres with the enhanced mucoadhesion suggested being a potential drug carrier in developing the gastroretentive drug delivery system.

Resource, chemical structure and activity of natural polysaccharides against alcoholic liver damages.

Many natural polysaccharides from bio-resources hold advantages of multi-functions, high efficiency, non-toxicity or low side effect, and have strong potentials in protection against alcoholic liver damages. This review summarized the bio-resources, chemical and structural characteristics of natural polysaccharides with potentials in inhibition against alcoholic liver damages, and also emphasized knowledge on correlations between their chemical structure and function. Approximately 95 species were confirmed in generation of hepatoprotective polysaccharides. Products as crude polysaccharides originated from 17 species were sum up despite the indetermination of their accurate structure. Additional four polysaccharides were described for their known chemical structures. Possible roles of hepatoprotective polysaccharides were provided with evidence on antioxidant promotion, lipids regulation, apoptosis inhibition and anti-inflammation, as well as confirmations in immune enhancement, iron removal and anti-fibrosis when currently treated against the alcoholic liver damages. To sum up, this overview could serve to guide development and utilization of natural hepatoprotective polysaccharides.

Polyphenols of Chinese skullcap roots: from chemical profiles to anticancer effects.

Great efforts have been made to identify the principle bioactive constituents of Chinese herbs and to unravel the molecular mechanisms behind their anticancer effects. Scutellaria baicalensis (Huangqin or Chinese skullcap) is a widely consumed herbal medicine and has been historically used in anticancer therapy in China and other countries. Chinese skullcap generates many active chemicals in the root and is abundant in polyphenols, which act as its anti-cancer ingredients. It contains around 53 polyphenols in total: 50 flavonoids and 3 stilbenes. The polyphenols have similar chemical structures since they are derived from similar biochemical synthetic pathways. According to the literature, as the active chemicals of the skullcap root, 18 polyphenols exhibit evident anticancer activities. They can be developed not only as novel candidates and precursors in anticancer drug screening, but also as important tools and agents in cancer pharmacology. We comprehensively elaborated the anticancer pharmacological properties of crude polyphenolic extracts and 12 other single compounds excluding the six well-known polyphenols, i.e., baicalein, baicalin, wogonin, wogonoside, chrysin and verbascoside. In this review, we also discussed the possible mechanisms of the anticancer effect of several skullcap polyphenols. Overall, this paper provides a unique path to understand the anticancer properties of Chinese skullcap as well as guidance to find novel anticancer drugs from a natural polyphenolic reservoir.

Involvement of metabolism-permeability in enhancing the oral bioavailability of curcumin in excipient-free solid dispersions co-formed with piperine.

Curcumin (CUR) has gained increasing interest worldwide due to multiple biological activities. However, the therapeutic application remains limited because of its low aqueous solubility, intestinal metabolism and poor membrane permeability. In present study, an excipient-free CUR solid dispersion co-formed with piperine (PIP), the absorption enhancer involving metabolism-permeability, was successfully prepared by melting and quench cooling (co-amorphous CUR-PIP). The co-amorphous CUR-PIP exhibited superior performance in non-sink dissolution compared with crystalline and amorphous CUR, and showed physically stable at least 3 months, attributing to the strong molecular interactions between CUR and PIP as evaluated by FTIR spectra. Furthermore, the combination of PIP with CUR in the co-amorphous formulation could inhibit the glucuronidation of CUR, as exhibited in the in vitro assay of rat intestinal microsomes. The co-amorphous CUR-PIP would also exhibit higher gastrointestinal membrane permeability of CUR, as confirmed by Papp of CUR in Caco-2 model. After administration of co-amorphous CUR-PIP, the AUC of CUR significantly increased by 2.16- and 1.92-fold those in crystalline and amorphous CUR, respectively. This study demonstrates that the developed co-amorphous CUR-PIP can enhance the bioavailability of CUR by increasing its dissolution, inhibiting metabolic processes, and facilitating membrane permeability.

The formulation and immunisation of oral poly(DL-lactide-co-glycolide) microcapsules containing a plasmid vaccine against lymphocystis disease virus in Japanese flounder (Paralichthys olivaceus).

Nucleic acid-based immunotherapy is a new treatment option for fish immunisation in intensive culture. However, DNA-based vaccines would be hydrolyzed or denaturized because of the existence of nucleases and severe gastrointestinal conditions. Poly(DL-lactide-co-glycolide) (PLGA) microcapsules, loaded with plasmid DNA (pDNA) against lymphocystis disease virus (LCDV), were prepared by modified water in oil in water (W/O/W) double emulsion method in our laboratory. Encapsulation efficiency, loading percent and diameter of microcapsules were 78-88%, 0.5-0.7% and less than 10 mum, respectively. In simulated gastric fluid (SGF), less than 10% of pDNA was released from microcapsules in 12 h, and about 6.5% of pDNA was released in 12 h in simulated intestinal fluid (SIF). The content of the supercoiled of pDNA in microcapsules and control was 80% and 89% respectively, which indicated that a little supercoiled pDNA degradation occurred during encapsulation. RT-PCR showed that lots of RNA containing information of MCP gene existed in all tissues of fish vaccinated with microcapsules 10-90 days after oral administration. SDS-PAGE and immunoblots, as well as immunofluorescence images, displayed that major capsid protein (MCP) of LCDV was expressed in tissues of fish vaccinated with pDNA-loaded microcapsules. In addition, indirect enzyme-linked immunosorbent assay (ELISA) showed that the immune responses of sera were positive (O.D> or =0.3) from week 1 to week 24 for fish vaccinated with microcapsules, in comparison with fish vaccinated with naked pDNA. Our results suggested that PLGA microcapsules were promising oral carriers for pDNA delivery. This encapsulation technique had potential for drug delivery applications due to its ease of operation and notable immunisation efficacy.

Abundance of saccharides and scarcity of glycosaminoglycans in the soft tissue of clam, Meretrix meretrix (Linnaeus).

We investigated presence and distribution of glycosaminoglycans (GAGs) in Meretrix meretrix soft tissue by determining GAG composition in the different parts, namely, mantle edge, foot, gill, adductor muscle, and viscera. The occurrence of glycan ingredients was examined by histochemistry, whereas GAG and general polysaccharide contents in clam tissue were qualified through extraction and determination. Tissue sections stained with alcian blue or periodic acid-Schiff demonstrated the general existence of saccharides and trifling generation of GAGs in clam tissues. GAGs coexisting with glycogens appeared to be primarily produced in the mantle and foot tissues in mucus form by visualization. The GAG content of the polysaccharide extract ranged from 16.8 to 75.8 mg in 10 g of 5 dried tissue materials in comparison with total carbohydrate level in the range of 500-1760 mg, thereby indicating that GAGs were not the major components of polysaccharide extracts. GAG composition only accounted for approximately 4% of total glycan components, which consist of the determinations of amino sugar and uronic acid. The soft tissues of clam contained abundant saccharide compounds but sparse amounts of GAGs. The results will benefit the subsequent development of products made from the polysaccharide components of M. meretrix.

Rheological and mucoadhesive properties of polysaccharide from Bletilla striata with potential use in pharmaceutics as bio-adhesive excipient.

This study described the rheological and mucoadhesive properties of one natural water-soluble polysaccharide from Bletilla striata (BSP). The rheological characteristics of BSP in aqueous solutions and BSP mixed with other polymers were investigated under various conditions, including concentration, temperature, pH, and salt addition. Viscometric studies and ex vivo mucoadhesion tests were also conducted to examine the mucoadhesive properties of BSP. Results indicated that BSP behaved as a shear-thinning fluid at various concentrations, and its viscosity decreased at high temperatures. The viscous flow properties of the BSP mixtures changed at high pH (>5.0). Conversely, the viscosity of the BSP solutions was slightly affected by electrolytes. The viscosities of the BSP mixtures with four other commonly used polymers (sodium alginate, sodium carboxymethyl cellulose, hypromellose, and chitosan) were enhanced. The synergistic viscosity of BSP/mucin mixtures increased as BSP concentrations increased, and the maximum value was observed in the SIF medium without enzymes. The adhesive abilities of 5.0% and 10.0% BSP were almost equivalent to that of 0.5% sodium alginate, suggesting that BSP exhibited a certain mucoadhesive property, although it was weaker than that of the other commonly used mucoadhesive materials. BSP showed potential for pharmaceutical excipient applications in bioadhesive drug delivery systems.

Structural elucidation and immune-enhancing activity of peculiar polysaccharides fractioned from marine clam Meretrix meretrix (Linnaeus).

The marine clam Meretrix meretrix was subjected to extraction with a combined procedure of water decoction, ethanol precipitation, and deproteinization to yield a water-soluble polysaccharide coded as MMP. The product was fractionated with DEAE-52 cellulose and resulted in two soluble fractions designated as MMP-2 and -3. The structures of the fractions were determined by chemical and physicochemical analysis, and their immunomodulation activities and cytokine production were assayed by lymphopoiesis. Results showed that MMP-2 and -3 were glucomannan and glucogalactan homologs, respectively. They possess average molecular masses of 272 and 257 kDa, respectively, and were elucidated as branched copolymers, elaborated as α(1→4)-glucan branching with mannose or galactose via ß(1→6)-linkage. Bioassay indicated that MMP-2 and -3 held moderate potentials in restoring immune function because they augment splenocyte proliferation and enhance the cytokine secretion of lymphocytes dose-dependently. We speculated that their bioactivities are closely correlated with their peculiar structures.

High dispersed phyto-phospholipid complex/TPGS 1000 with mesoporous silica to enhance oral bioavailability of tanshinol.

Phenolic acids are widely distributed in the plant kingdom and possess a broad spectrum of pharmacological activity. However, low oral bioavailability restricts their application. In this study, a high dispersed phyto- phospholipid complex with mesoporous silica containing TPGS 1000 (TPC-SD) was fabricated using Tanshinol (Tan) as model drug. Phospholipid complex (PC) was employed to improve the n-octanol/water partition coefficient (log P) and apparent permeability coefficients (Papp) of Tan. Mesoporous silica was used to compensate for the negative effects of phospholipid on drug's dispersion and dissolution owing to its viscosity and poor water-solubility. TPGS 1000, a P-gp inhibitor, was used to block the efflux of Tan. Log P tests showed that the lipophilicity of Tan was significantly enhanced by Tanshinol phospholipid complex (TPC) formation. In vitro dissolution results showed that the cumulative dissolution percentage of Tan from TPC-SD was 4.33- fold of that from TPC in 120 min A Caco-2 permeability test confirmed that Papp (AP-BL) of TPC and TPC-SD increased approximately 2.22- and 3.53- fold compared to those of unformulated Tan, respectively (p < 0.01, p < 0.01). Pharmacokinetic studies demonstrated that the AUC0-∞ of TPC-SD was 2.23- and 1.47- fold compared with those of unformulated Tan and TPC, respectively (p < 0.01, p < 0.01). These results indicated that the high dispersed phyto- phospholipid complex/TPGS 1000 by mesoporous silica can be a promising drug delivery system to improve the oral bioavailability of free phenolic acids.