Structural and pharmacological diversity of 1,4-naphthoquinone glycosides in recent 20 years.

1,4-naphthoquinones are the most widespread naphthoquinone compounds. Recently, many 1,4-naphthoquinone glycosides with different structural features have been obtained from both nature and synthesis, which has led to an increasing variety of naphthoquinone glycosides. In this paper, the structure variety and biological activity in recent 20 years are reviewed, and classified them according to the source and structure characteristics. Meanwhile the synthetic methods of O-, S-, C- and N-naphthoquinone glycosides and their structure activity relationships are also described. It was referred that the presence of polar groups of C2 and C5 and non-polar groups attached to C3 on the naphthoquinone ring are beneficial for their biological activities. It will provide more comprehensive literature resources for the future research of 1, 4-naphthoquinone glycosides and lay a theoretical foundation.

Research progress on the structure and biological diversities of 2-phenylindole derivatives in recent 20 years.

The privileged structure binds to multiple receptors with high affinity, which is helpful to the development of new bioactive compounds. Indole is classified as a privileged structure, which may be one of the most important structural categories in drug discovery. As a special subset of indole compounds, 2-phenylindole seems to be one of most promising forerunners of drug development. In this paper, 106 articles were referenced to review the structural changes, biological activities and structure-activity relationship of compounds in recent 20 years, and classified them according to their pharmacological activities, from several aspects, including anticancer, antibacterial, anti-inflammatory, analgesic, antiviral, anti-parasite, the biological activities target to central nervous system, et al. It also points out the importance of artificial intelligence (AI) technology in discovery of new 2-phenylindole compounds in a broader prospect. This review will provide some ideas for researchers to develop new indole drugs.

Synthesis of structurally diverse derivatives of aconitine-type diterpenoid alkaloids and their anti-proliferative effects on canine breast cancer cells.

As one of the most common malignancies in female dogs, no drugs have been developed specifically for the treatment of canine mammary carcinoma. In our previous study, a series of diterpenoid alkaloids derivatives were synthesized and exhibited good anti-proliferative activity in vitro against both normal and adriamycin-resistant human breast cancer cells lines. In this study, a series of structurally diverse aconitine-type alkaloids derivatives were also synthesized basing on the minimal modification principle, by modifying on A-ring, C-ring, D-ring, N-atom or salt formation on aconitine skeleton. Their anti-proliferative effects and mechanism on canine mammary cancer cells were investigated, exhibiting the importance of the substitution at A ring, the long chain ester at the C8, the hydroxyl group at the C13, the phenyl ring at the C14 and the N-ethyl group, while the methoxy group at the C1 and C16 showed little effect on the activity. The results of the proliferation, apoptosis and ultrastructure tests of the treated canine mammary carcinoma cells referred that the representative compound, aconitine linoleate (25) could block the cell cycle of canine mammary carcinoma cells in the G0/G1 phase, and exhibit the anti-proliferative effect by inducing apoptosis.

Cinnamaldehyde Restores Ceftriaxone Susceptibility against Multidrug-Resistant Salmonella.

In recent years, infections caused by multidrug-resistant (MDR) bacteria have greatly threatened human health and imposed a burden on global public health. To overcome this crisis, there is an urgent need to seek effective alternatives to single antibiotic therapy to circumvent drug resistance and prevent MDR bacteria. According to previous reports, cinnamaldehyde exerts antibacterial activity against drug-resistant Salmonella spp. This study was conducted to investigate whether cinnamaldehyde has a synergistic effect on antibiotics when used in combination, we found that cinnamaldehyde enhanced the antibacterial activity of ceftriaxone sodium against MDR Salmonella in vitro by significantly reduced the expression of extended-spectrum beta-lactamase, inhibiting the development of drug resistance under ceftriaxone selective pressure in vitro, damaging the cell membrane, and affecting its basic metabolism. In addition, it restored the activity of ceftriaxone sodium against MDR Salmonella in vivo and inhibited peritonitis caused by ceftriaxone resistant strain of Salmonella in mice. Collectively, these results revealed that cinnamaldehyde can be used as a novel ceftriaxone adjuvant to prevent and treat infections caused by MDR Salmonella, mitigating the possibility of producing further mutant strains.

Response surface methodology for optimization of the extraction of polysaccharide from the roots of onosma hookeri clarke. var. longiforum duthie and its antioxidant capacity and immune activity.

Onosma hookeri Clarke. var. longiforum Duthie (OHC-LD), one of the traditional Tibetan medicine, has been found many functions, including removing heat to cool blood, nourishing lung and inhibiting bacteria. In order to study the polysaccharides in OHC-LD water extract, the optimal extraction progress of polysaccharides of the roots of OHC-LD by response surface method designed with three-factor three-level Box-Behnken method and the antioxidant capacity and immune activity of the crude polysaccharide were studied in this investigation. Under the best conditions, the extraction yield of polysaccharide was 3.19±0.09% (n = 3). After purification, the crude polysaccharide was obtained with polysaccharide contents of 42.57%, which demonstrated stronger DPPH scavenging activity than BHT at low concentrations (<625 µg/mL), and comparable ABTS radical scavenging activity as BHT at high concentrations (≥1250 µg/mL). Additionally, it also exhibited a certain cell proliferation activity and an enhancement of the phagocytic ability of RAW264.7 cells. This study revealed that the crude polysaccharide from the roots of OHC-LD might be exploited as a natural antioxidant and immune enhance agent in the future in both medical and food industry.

Isolation, structure identification, and immunostimulatory effects in vitro and in vivo of polysaccharides from Onosma hookeri Clarke var. longiforum Duthie.

BACKGROUND: This study characterized an acidic polysaccharide (OHC-LDPA) isolated from the medicinal and edible homologous plant Onosma hookeri Clarke var. longiforum Duthie. The structure of OHC-LDPA was elucidated based on the analysis of infrared, one-/two-dimensional nuclear magnetic resonance, and gas chromatography-mass spectrometry data. The immunostimulatory effects of OHC-LDPA were identified by both in vitro and in vivo models. RESULTS: The structure of OHC-LDPA was elucidated as a typical pectin polysaccharide, consisting of galacturonic acid, galactose, arabinose, and rhamnose as the primary sugars, with linear galacturonic acid as the main chain and arabinogalacturonic acid as the main branched components. OHC-LDPA could significantly stimulate the proliferation and phagocytosis of RAW264.7 macrophages and the release of nitric oxide in vitro. Also, it could accelerate the recovery of spleen and thymus indexes, enhance the splenic lymphocyte proliferation responses, and restore the levels of interleukin-2, interleukin-10, interferon-γ, and immunoglobulin G in the serum in a cyclophosphamide-induced immunosuppressed-mice model. In addition, OHC-LDPA could restore the intestinal mucosal immunity and reduce the inflammatory damage. CONCLUSION: OHC-LDPA could improve the immunity both in vitro and in vivo and could be used as a potential immunostimulant agent. © 2022 Society of Chemical Industry.

The synthesis review of the approved tyrosine kinase inhibitors for anticancer therapy in 2015-2020.

In the 21st century, cancer is the major public health problem worldwide. Based on the important roles of protein tyrosine kinase, the accelerated hunt for potent small-molecule tyrosine kinase inhibitors has led to the success of 30 newly inhibitors in this family for the cancer therapy in last five years. In this review, we updated their synthesis methods, and compared the original research routes with the optimized routes for each PTK inhibitor against different target, in order to make an outlook on the future synthesis of potential PTK inhibitors for anticancer therapy.

Synthesis and structure-activity relationship of lipo-diterpenoid alkaloids with potential target of topoisomerase IIα for breast cancer treatment.

Aconitine linoleate (11) isolated from the Aconitum sinchiangense W. T. Wang exhibited significant anti-tumor activity. Based on this, a series of novel lipo-diterpenoid alkaloids were synthesized and evaluated for their anticancer activities against MCF-7 and MCF-7/ADR cell lines. Seventeen compounds, including 18-20, 22, 24-32, 36, 39, 41-42 possessed higher anti-proliferative activities (IC50 < 20 µM) against MCF-7 cell lines, which were better than the reference drug etoposide (IC50 = 18.01 ± 1.64 µM), among which compound 24 (IC50 = 4.00 ± 0.30 µM) was found to be the most potent derivative, being 4.5-fold more active than etoposide. Meanwhile, eighteen compounds, including 18-22, 24, 26-32, 36, 38-39, 41-42 presented excellent activities (IC50 < 20 µM) against MCF-7/ADR cell lines, better than etoposide (IC50 = 35.48 ± 0.29 µM) and doxorubicin (IC50 = 67.61 ± 6.5 µM). The most potent compound (19) was 13.5- and 25.7-fold more active than etoposide and doxorubicin against MCF-7/ADR cell lines, respectively. The structure-activity relationship (SAR) studies indicated that the 3-OH, 8-lipo, 14-benzene ring, and nitrogen atom with proper alkaline are crucial elements for anti-proliferative activity of target lipo-diterpenoid compounds. The proper length, the double bonds or di-fluoro-substituted at C-8 fatty acid chain, the para-donating electron group on 14-benzene group, and 13-OH are all favorable for the enhancement of anti-proliferative activities. In conclusion, the introduction of the 8-lipo group into aconitine leads to significant increase of anti-proliferative activity against MCF-7 and MCF-7/ADR cells, which suggests these kinds of lipo-alkaloids are powerful and promising antitumor compounds for breast cancer, especially for drug-resistant breast cancer.

The antiviral activity of kaempferol against pseudorabies virus in mice.

BACKGROUND: Pseudorabies virus (PRV), a member of the Alphaherpesviruses, is one of the most important pathogens that harm the global pig industry. Accumulated evidence indicated that PRV could infect humans under certain circumstances, inducing severe clinical symptoms such as acute human encephalitis. Currently, there are no antiviral drugs to treat PRV infections, and vaccines available only for swine could not provide full protection. Thus, new control measures are urgently needed. RESULTS: In the present study, kaempferol exhibited anti-PRV activity in mice through improving survival rate by 22.22 %, which was higher than acyclovir (Positive control) with the survival rate of 16.67 % at 6 days post infection (dpi); meanwhile, the survival rate was 0 % at 6 dpi in the infected-untreated group. Kaempferol could inhibit the virus replication in the brain, lung, kidney, heart and spleen, especially the viral gene copies were reduced by over 700-fold in the brain, which was further confirmed by immunohistochemical examination. The pathogenic changes induced by PRV infection in these organs were also alleviated. The transcription of the only immediate-early gene IE180 in the brain was significantly inhibited by kaempferol, leading to the decreased transcriptional levels of the early genes (EPO and TK). The expression of latency-associated transcript (LAT) was also inhibited in the brain, which suggested that kaempferol could inhibit PRV latency. Kaempferol-treatment could induce higher levels of IL-1ß, IL-4, IL-6, TNF-α and IFN-γ in the serum at 3 dpi which were then declined to normal levels at 5 dpi. CONCLUSIONS: These results suggested that kaempferol was expected to be a new alternative control measure for PRV infection.

Characterization of inulin-type fructans from two species of Radix Codonopsis and their oxidative defense activation and prebiotic activities.

BACKGROUND: Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. RESULTS: It was confirmed that the neutral polymers CPPN and CTPN were ß-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. CONCLUSION: The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.

Antibacterial effect of Blumea balsamifera DC. essential oil against Haemophilus parasuis.

Haemophilus parasuis (H. parasuis), the cause of the Glasser's disease, is a potentially pathogenic gram-negative organism that colonizes the upper respiratory tract of pigs. The extraction of Blumea balsamifera DC., as a traditional Chinese herb, has shown great bacteriostatic effect against several common bacteria. To study the antibacterial effect on H. parasuis in vitro, this study evaluated the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Blumea balsamifera DC. essential oil (BBO) as well as morphological changes in H. parasuis treated with it. Furthermore, changes in expression of total protein and key virulence factors were also assessed. Results showed that the MIC and MBC were 0.625 and 1.25 µg/mL, respectively. As the concentration of BBO increased, the growth curve inhibition became stronger. H. parasuis cells were damaged severely after treatment with BBO for 4 h, demonstrating plasmolysis and enlarged vacuoles, along with broken cell walls and membranes. Total protein and virulence factor expression in H. parasuis was significantly downregulated by BBO. Taken together, these results indicated a substantial antibacterial effect of BBO on H. parasuis.

Nocardia seriolae: a serious threat to the largemouth bass Micropterus salmoides industry in Southwest China.

Nocardia seriolae is the causative agent of nocardiosis in both marine and freshwater fish. Here, we report on multiple outbreaks of nocardiosis associated with elevated mortality (23-35%) in farmed largemouth bass in Sichuan, China, from 2017 to 2018. A total of 9 strains isolated from diseased largemouth bass were identified as N. seriolae by phenotypic characterization, 16S rRNA and hsp65 gene sequence analysis. The clinical signs of infected largemouth bass included hemorrhage, skin ulcers and prominent tubercles varying in size in the gill, liver, spleen and kidney. Experimental infection indicated that these isolates were the pathogens responsible for the mortalities. In vitro antibacterial activities of 12 antibiotics against N. seriolae isolates were determined as minimum inhibitory concentrations. Histopathological observation of diseased fish infected with N. seriolae showed necrotizing granulomatous hepatitis, nephritis, splenitis, epithelial hypertrophy and hyperplasia with degenerative changes of the epithelium in the gill. Large quantities of bacterial aggregates were found in the necrotic area of the granuloma by Lillie-Twort Gram stain and immunocytochemistry. Our findings indicated that N. seriolae is a serious threat to the largemouth bass Micropterus salmoides industry in Southwest China.

Oral exposure of pregnant rats to copper nanoparticles caused nutritional imbalance and liver dysfunction in fetus.

Copper nanoparticles (Cu NPs) are increasingly used as an animal feed additive in China. In previous studies, it was determined that Cu NPs can penetrate the placental barrier, however, its toxic effects on the fetus have not yet been elucidated. Therefore, in this study, we investigated the potential fetal toxic effects of Cu NPs. Cu NPs were orally administered to pregnant Sprague-Dawley rats from gestation days (GDs) 3-18 at a dose of 60, 120, and 180 mg/kg/day. Cesarean sections were conducted on GD 19. During fetal examination, no toxicities were observed regarding general clinical signs, however, Cu NPs significantly decreased fetal body weight, body length, and liver weights. Cu ions and Cu MPs exhibited similar effects on the fetal development. Cu NPs increased the liver concentration of Cu, and decreased protein levels and Fe in fetuses. Cu NPs also increased oxidative stress and inflammation in the fetus after pregnant rats were exposed to high doses of Cu NPs. Oral exposure to Cu NPs during pregnancy increased Cu concentrations in the fetus, which not only affected fetal development, but also significantly induced oxidative stress and inflammatory responses in fetal liver. Taken together, these findings are valuable to evaluate fetal risk assessment after oral exposure of Cu NPs during pregnancy. Additional comprehensive toxicity studies are deemed necessary to clarify the underlying mechanisms involved.

High prevalence of multi-drug resistances and diversity of mobile genetic elements in Escherichia coli isolates from captive giant pandas.

The purpose of this study was to characterize the antimicrobial resistance produced by mobile genetic elements and integron gene cassettes in Escherichia coli isolated from the feces of captive giant pandas. We performed a standard disk diffusion antimicrobial susceptibility test with 84 E. coli isolates and further evaluated the mobile genetic elements and integron gene cassettes. The antimicrobial susceptibility test demonstrated that 43.37% (36/84) of the isolates showed multiple drug resistances. The E. coli isolates mainly showed resistance to aztreonam (86.90%, 73/84) and amoxicillin/clavulanic acid (80.95%, 68/84). The most frequently observed resistance patterns were ampicillin/amoxicillin-clavulanic acid (13.10%, n = 11), and doxycycline/amoxicillin-clavulanic acid (4.76%, n = 4). Further analyses detected 11 mobile genetic elements, of which merA (54/84, 64.30%) had the highest frequency. All isolates were negative for intI3, traA, tnpU, traF, tnp513, tnsA, ISkpn7, ISpa7, ISkpn6, and ISCR1. We further analyzed antimicrobial resistance-related integrons among 30 E. coli isolates (the 27 intI1-positive isolates and the 3 intI2-positive isolates); six gene cassette profiles (dfrA17+aadA5, aadA2, dfrA12+aadA2, dfrA1+aadA1, dfrA1, and aadA1) were identified in the 27 intI1-positive isolates, but not in the three intI2-positive ones. Our study sheds light on the prevalence of multiple drug resistances and the diversity of mobile genetic elements in E. coli isolates, and highlights the necessity to monitor antibiotic resistance in more E. coli strains from captive giant pandas.

Anticoccidial effect of Fructus Meliae toosendan extract against Eimeria tenella.

CONTEXT: Fructus Meliae toosendan extracts (FMTE) have a good therapeutic effect on coccidiosis, but there is no relevant research on its prophylactic effect on coccidiosis. OBJECTIVE: This study comprehensively evaluates the anticoccidial effect of FMTE. MATERIALS AND METHODS: In vitro, the unsporulated oocysts were treated with serial dilutions of FMTE and incubated for 7 d, and the sporulated oocysts were counted for calculating the median lethal concentration (LC50) of FMTE. In vivo, 180 10-day-old broiler chickens free of coccidiosis were weighted and randomly distributed into six groups: normal group, untreated group, 4 protective groups (positive group and three FMTE groups). From day 10 to day 21, chickens in the three FMTE groups were pre-treated with FMTE at the dosage of 2.5, 5 and 10 g/kg/d, respectively, and chickens in the positive group were pre-treated with qiuliling (10 g/kg/d). On day 14, chickens in all groups except the normal group were orally infected with 1.5 × 104 sporulated oocysts. The clinical symptoms were observed from day 10 to day 21, the anticoccidial index (ACI), tissue lesions, and intestinal microflora were determined on day 21. RESULTS: FMTE showed anti-sporulation effect against E. tenella and the LC50 value was 245.83 µg/mL in vitro. In vivo, FMTE at the dosage of 10 g/kg/d was effective against E. tenella infection, and its ACI value was 162.56, which was higher than the value of positive drug qiuliling (128.81). Discussion and conclusions: FMTE have potent anticoccidial effects, and it presents an alternative anticoccidial agent for avian coccidiosis control.

Preparation of resveratrol dry suspension and its immunomodulatory and anti-inflammatory activity in mice.

Context: Resveratrol is a natural polyphenol compound. It exhibits antitumor, immunostimulatory, and antiviral activities. However, poor water solubility and structural instability limit its administration and storage.Objective: A resveratrol dry suspension (RDS) was prepared and immunomodulatory effect in immunosuppressive mice induced by cyclophosphamide and anti-inflammatory activities in mice were evaluated.Materials and methods: The preparation of RDS was optimized by the orthogonal design method. To evaluate the immunomodulatory effects, SPF Kunming mice were divided into seven groups comprising of nine males and nine females for each group. The RDS supplemented group was administrated doses of 3.33, 1.67, and 0.83 g/kg/d. Then visceral index, lymphocyte proliferation, the ratio of CD3+ CD4+/CD3+ CD8+, and the contents of cytokines in serum were tested. To ameliorate effects of acetic acid induced capillary permeability, xylene-based ear oedema, and cotton pellet granuloma, RDS as anti-inflammatory agent was administered at doses of 1, 0.33, and 0.1 g/kg/d as compared to indomethacin (IM) provided as a positive control at 10 mg/kg.Results: RDS inhibited the degradation of resveratrol and enhanced the CD3+ CD4+/CD3+ CD8+ ratio, spleen index, IL-2 level, and splenic lymphocytes in immunosuppressive mice. RDS (0.1 g/kg/d) significantly inhibited the acetic acid-induced capillary permeability, and at doses of 0.33 and 1 g/kg/d repressed the ear swelling and granuloma formation in immunocompromised mice.Discussion and Conclusion: RDS is a stable, cheaper, and suitable preparation with potent immunoregulatory and anti-inflammatory activities. Keeping in view these remarkable properties, RDS could be an appropriate preparation for clinic use of resveratrol.

Multiplex genome editing by natural transformation in Vibrio mimicus with potential application in attenuated vaccine development.

Vibrio mimicus (V. mimicus) is a significant pathogen in freshwater catfish, though knowledge of virulence determinants and effective vaccine is lacking. Multiplex genome editing by natural transformation (MuGENT) is an easy knockout method, which has successfully used in various bacteria except for V. mimicus. Here, we found V. mimicus strain SCCF01 can uptake exogenous DNA and insert it into genome by natural transformation assay. Subsequently, we exploited this property to make five mutants (△Hem, △TS1, △TS2, △TS1△TS2, and △II), and removed the antibiotic resistance marker by Flp-recombination. Finally, all of the mutants were identified by PCR and RT-PCR. The results showed that combination of natural transformation and FLP-recombination can be applied successfully to generate targeted gene disruptions without the antibiotic resistance marker in V. mimicus. In addition, the five mutants showed mutant could be inherited after several subcultures and a 668-fold decrease in the virulence to yellow catfish (Pelteobagrus fulvidraco). This study provides a convenient method for the genetic manipulation of V. mimicus. It will facilitate the identification and characterization of V. mimicus virulence factors and eventually contribute to a better understanding of V. mimicus pathogenicity and development of attenuated vaccine.

Kaempferol alleviates LPS-ATP mediated inflammatory injury in splenic lymphocytes via regulation of the pyroptosis pathway in mice.

Background: The pharmacological application of kaempferol, a natural flavonol present in different plant species, has been demonstrated to have extensive anti-inflammatory, anti-apoptotic, anti-oxidative, and anti-cancer effects. Pyroptosis is an inflammatory form of programed cell death by membranolysis and associated leakage of cytoplasm. This study investigated the molecular mechanism of kaempferol-induced effects on the pyroptosis in splenic lymphocytes (SLCs) isolated from mice. Methods: Lipopolysaccharide (LPS)-primed and adenosine triphosphate (ATP)-stimulated SLCs were used to establish the pyroptosis model. The kaempferol pretreatment was tested in the model. Results: The results show that kaempferol alleviates LPS-ATP mediated damage by increasing cell viability, improving membrane integrity, and decreasing the release of IL1b and IL-18. Kaempferol reduces pyroptosis by suppressing the expression and activity of caspase-1, increasing the protein expression of Toll-like receptor 4 (TLR4) and NOD-like receptor 3 (NLRP3), and inhibition of the decomposition of gasdermin D (GSDMD). Conclusions: Our data suggest that kaempferol exhibits anti-pyroptosis activities, which warrants further detailed investigation.

Protective Effects of Salidroside against Carbon Tetrachloride (CCl4)-Induced Liver Injury by Initiating Mitochondria to Resist Oxidative Stress in Mice.

The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on liver injury induced by carbon tetrachloride (CCl4) in vivo. Mice were pretreated with salidroside (60 mg/kg, intraperitoneally injected, i.p.) once per day for 14 consecutive days and then administered with CCl4 (15.95 g/kg, i.p.) for 24 h to produce a liver injury model. Salidroside attenuated hepatic transaminase elevation in serum and ameliorated liver steatosis and necrosis, thereby suggesting its protective effect on the liver. Salidroside antagonized CCl4-induced toxicity by equilibrating antioxidation system, thereby inhibiting reactive oxygen species accumulation, and restoring mitochondrial structure and function. Salidroside exerts antioxidant and liver-protective effects by selectively inhibiting the activation of genes, including growth arrest and DNA -damage-inducible 45 α (Gadd45a), mitogen-activated protein kinase 7 (Mapk7), and related RAS viral oncogene homolog 2 (Rras2), which induce oxidative stress in the mitogen-activated protein kinase pathway. These results revealed that salidroside can protect the liver from CCl4-induced injury by resisting oxidative stress and protecting mitochondrial function.

A Polysaccharide Isolated from Codonopsis pilosula with Immunomodulation Effects Both In Vitro and In Vivo.

In this study, an acidic polysaccharide from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-ß-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of ß-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-ß (TGF-ß), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4+/CD8+ T lymphocyte ratio. These results suggest that ß-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.