Yinbo Niu

An apple oligogalactan prevents against inflammation and carcinogenesis by targeting LPS/TLR4/NF-κB pathway in a mouse model of colitis-associated colon cancer

Evidence strongly supported a link between inflammation and cancer. Patients with colitis have high risk for development of colon cancer. Nuclear factor-kappa B (NF-κB), partially induced by lipopolysaccharide (LPS) binding to Toll-like receptor (TLR) 4, is a vital molecule in supervising the transformation of colitis to colon cancer. It could be a good strategy to prevent colitis carcinogenesis for targeting LPS/TLR4/NF-κB pathway. In the present study, we obtained an oligogalactan composed of five galacturonic acids from apple pectin and evaluated its protective efficacy on intestinal toxicities and carcinogenesis in a mouse model of colitis-associated colon cancer induced by 1,2-dimethylhydrazine and dextran sodium sulfate (DSS). The apple oligogalactan (AOG) was highly effective against intestinal toxicities and carcinogenesis and decreased the elevated levels of TLR4 and tumor necrosis factor-α (TNF-α) induced by inflammation in vivo in this model system. In vitro studies, AOG alone only slightly increased the levels of protein expression and messenger RNA of TLR4, phosphorylation of IκBα and production of TNF-α in HT-29 cells. However, AOG significantly decreased the elevation of all the biomarkers induced by LPS when it was combined with LPS. The effect of AOG may be related to membrane internalization and redistribution of TLR4 from cell membrane to cytoplasm. AOG is active against inflammation and carcinogenesis through targeting LPS/TLR4/NF-κB pathway. Both AOG and LPS are agonists of TLR4 for sharing the same ligand but AOG has a much lower intrinsic activity than that of LPS. AOG may be useful for treatment of colitis and prevention of carcinogenesis in the clinics.

Asperosaponin VI, A Saponin Component from Dipsacus asper Wall, induces Osteoblast Differentiation through Bone Morphogenetic Protein‐2/p38 and Extracellular Signal‐regulated Kinase 1/2 Pathway

Osteoporosis is a reduction in skeletal mass because of the loss of osteoblastic activity or an increase in osteoclastic activity. The survival of osteoblast cells plays a crucial role in the development of osteoporosis. Asperosaponin VI (ASA VI) is a kind of saponin in the medicinal herb Dipsacus asper Wall which has long been used as an antiosteoporosis drug. The assay of cell proliferation, alkaline phosphatase (ALP) activity and measurement of mineralized matrix, showed that ASA VI exhibited a significant induction of proliferation, differentiation and mineralization in MC3T3‐E1 and primary osteoblastic cells. Induction of differentiation by ASA VI was associated with increased bone morphogenetic protein‐2 (BMP‐2), indicating that BMP‐2 is essential in ASA VI to mediate osteoblast maturation and differentiation. In addition, ASA VI may induce differentiation by increasing the activity of p38 and ERK1/2. In conclusion, ASA VI may induce osteoblast maturation and differentiation, and then increase bone formation via increasing BMP‐2 synthesis, and activating p38 and ERK1/2. Copyright

Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconitine and skimmianine on the ulcerative colitis rats induced by trinitrobenzene-sulfonic acid.

Ulcerative colitis involves complicated etiology and presents diverse symptoms including intestine inflammation, bowel pain and diarrhea. Anti-inflammatory drugs are the mainstay in patient care, accompanied with antidiarrhea and analgesic agents used as symptomatic treatment. A classic traditional Chinese medicine formula, Fructus Mume pill (FMP), showed remarkable therapeutic efficacy in treating ulcerative colitis. However, since it contains many herbs and countless chemicals, the underlying mechanism is not clear. In this study, we selected three alkaloids from FMP, namely, berberine, hypaconitine and skimmianine to study the individual drug effect and compare these results with the BHS combination on: 1) The recovery of ulcerative colitis rats induced by trinitrobenzene-sulfonic acid. 2) Mice with xylene-induced acute exudative edema and acetic acid-induced writhing. 3) Gastrointestinal transit inhibition, and 4) the response of HT29 cells after treatment with lipopolysaccharide. We found that the compound hypaconitine showed a potent analgesic effect, while skimmianine acted as an antidiarrhea agent and the component berberine was the key agent exerting anti-inflammatory effect. However, since berberine killed the commensal bacteria and induced lipopolysaccharide release, it could at the same time aggravate colon inflammation. The three-alkaloid combination BHS produced complementary and synergistic effects in colon inflammation recovery, relieving acetic acid-induced bowel pain and xylene-induced acute exudative edema. BHS also decreased lipopolysaccharide production and enhanced the therapeutic efficacy. It is hoped that this study will lay the foundation to further dissect and understand the FMP formula to improve the treatment with simplified and well defined drug combinations for this dreadful disease.

Modified apple polysaccharide prevents against tumorigenesis in a mouse model of colitis-associated colon cancer: role of galectin-3 and apoptosis in cancer prevention.

BackgroundColorectal cancer (CRC) is one of the most common and preventable cancers. Regular consumption of apples is conducive to reduction in CRC risk.Aim of the studyTo evaluate effects of modified apple polysaccharide (MAP) on tumorigenesis in a mouse model of colitis-associated colon cancer.MethodsOne hundred male ICR mice were administered with 1, 2-dimethyl-hydrazine (DMH) and dextran sodium sulfate (DSS). Forty mice were given no further treatment, the rest were fed basal diet blended with three different doses of MAP; 2.5, 5, and 10% (20 mice in each group).ResultsMAP significantly protected ICR mice against DMH/DSS-induced tumorigenesis. The incidence of tumor development was 90% (18/20) in the mice treated with DMH/DSS, but that was reduced to 25% (5/20), 15% (3/20), and 5% (1/20), respectively, in the mice treated with basal diets plus 2.5, 5, and 10% of MAP. Study of apoptosis of colonic epithelial cells revealed that MAP moderately increased apoptosis, suggesting that the anti-tumor potency of MAP was probably attributed to its ability to induce apoptosis. Western blot analysis demonstrated that carbohydrate-binding protein galectin-3 changed in both the nucleus and the cytoplasm during the process from colitis to colon cancer in the model. And MAP could inhibit the binding of galectin-3 to its ligand: this is, at least in part, the possible mechanism of MAP by enhancing apoptosis and preventing tumorigenesis.ConclusionsThese data suggest that MAP has a potential role in clinical prevention and treatment for colon cancer.

Role of phytochemicals in colorectal cancer prevention

Although the incidence of colorectal cancer (CRC) has been declining in recent decades, it remains a major public health issue as a leading cause of cancer mortality and morbidity worldwide. Prevention is one milestone for this disease. Extensive study has demonstrated that a diet containing fruits, vegetables, and spices has the potential to prevent CRC. The specific constituents in the dietary foods which are responsible for preventing CRC and the possible mechanisms have also been investigated extensively. Various phytochemicals have been identified in fruits, vegetables, and spices which exhibit chemopreventive potential. In this review article, chemopreventive effects of phytochemicals including curcumin, polysaccharides (apple polysaccharides and mushroom glucans), saponins (Paris saponins, ginsenosides and soy saponins), resveratrol, and quercetin on CRC and the mechanisms are discussed. This review proposes the need for more clinical evidence for the effects of phytochemicals against CRC in large trials. The conclusion of the review is that these phytochemicals might be therapeutic candidates in the campaign against CRC.

Immunomodulation of Rheum tanguticum polysaccharide (RTP) on the immunosuppressive effects of dexamethasone (DEX) on the treatment of colitis in rats induced by 2,4,6-trinitrobenzene sulfonic acid

Dexamethasone (DEX) is still the main choice for colitis, although the immunosuppressive side effects are still the troublesome problems to overcome. In our previous study, Rheum tanguticum polysaccharide (RTP), extracted from traditional Chinese medicine rhubarb, targeted mannose receptor, showed immunoregulatory effect on the balance of Th1 and Th2 polarization in colitis rats. For the present study, we hypothesized that RTP could regulate the immunosuppressive effects of DEX. Taking advantage of the colon delivery ability of the polysaccharide, we prepared the double emulsion of RTP microsphere containing DEX to investigate the potential immunoregulatory effects of RTP on DEX immunosuppression in TNBS-induced colitis in rats. As expected, DEX-RTP microsphere showed not only significant immunomodulatory effects, but also strong anti-inflammation. The microsphere balanced enteric bacteria disorder, decreased TLR4 activation and promoted the balance of Th1 and Th2 polarization, inhibited NF-kappaB activity. Especially, DEX-RTP showed significant colon injury reparation. DEX alone exhibited a strong anti-inflammatory effect by suppressing MPO activity, down-regulate NF-kappaB activity and Th1 cytokines production. However, DEX showed severe immunosuppressive effects. It aggravated the intestinal commensal bacteria disorder, induced thymus atrophy and the further imbalance of Th1/Th1 cytokine polarization. RTP showed significant immunoregulatory effects. A significant protection on the intestinal bacterial balance, TLR4 and NF-kappaB activation decreased, and Th1/Th2 cytokine production balance were showed in RTP. In conclusion, DEX-RTP microsphere delivered DEX directly to the colon avoiding the absorption at the upper intestinal tract and showed synergistic effects on colitis both from the strong anti-inflammatory effects of DEX and from the immunoregulation of RTP.

Medicinal Herbs in the Prevention and Treatment of Osteoporosis

Osteoporosis is a common disease with wide prevalence, especially in the elderly population. Osteoporosis induced fractures not only decrease the patients life quality, but also cause heavy financial burden to the society. Although current medications for osteoporosis are effective, numerous adverse effects have been observed accompanying their clinical applications. Effective prevention and therapy strategies with high safety are critical, which benefit both individual patients and the whole society. Traditional Chinese medicines have been used for thousands of years to treat bone related diseases in China and a number of modern preparations have been developed that are currently commercially available. In addition, several medicinal herbs demonstrated therapeutic effects against osteoporosis in animal models. This paper reviewed the anti-osteoporotic effects of traditional Chinese formulas, medicinal herbs and bioactive constituents based on clinical trials and in vivo animal studies. Due to the lack of rigorous studies to compare the effectiveness with conventional interventions, traditional formulas are recommended as alternative medications or supplements to treat osteoporosis at the current stage. Although there are abundant natural resources with anti-osteoporotic effects, either in the form of medicinal herbs or bioactive components, much work need to be accomplished before they are developed into potential drugs.

The possible mechanisms of Fructus Mume pill in the treatment of colitis induced by 2,4,6-trinitrobenzene sulfonic acid in rats.

ETHNOPHARMACOLOGICAL RELEVANCE Fructus Mume pill (FMP) has been used as a folk remedy for gastrointestinal diseases in China over thousands of years. FMP was approved for the treatment of gastrointestinal diseases in 2001 by the State Food and Drug Administration (SFDA) of China. Although FMP had significant efficacy for treatment of the patients with inflammatory bowel disease (IBD) in the clinic, the mechanism of action is still unclear. AIM OF THE STUDY In the present study, the effects and possible mechanism of FMP on colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) were investigated. MATERIALS AND METHODS Fifty-four SD rats were divided into six groups. Nine rats for each group from three independent experiments were investigated for the effects of FMP. RESULTS FMP protected against diarrhea, colon weight increase, colonic accretion, ulceration and myeloperoxidase (MPO) activity elevation. The effects of FMP on recovery of colonic damage and restoration of the normal structures of colorectums were superior to dexamethasone (DEX). FMP promoted the restoration of abnormal cytokine secretion after TNBS treatment. FMP was effective in restoring the balance of intestinal bacteria population from the imbalance of G(+)/G(-) in rats with colitis. CONCLUSIONS The results indicated that FMP is effective in treatment of colitis in an experimental rat model. The possible mechanisms may be through down-regulation of Th1-polarized immune response and opsonic effect of intestinal commensal bacteria in this model system.

Low molecular weight apple polysaccharides induced cell cycle arrest in colorectal tumor.

Dietary components play an important role in cancer prevention. Many ingredients from apples have been proven to have antitumor potency. We thus made low molecular weight apple polysaccharides (LMWAP) and evaluated the effects of it on colorectal cancer (CRC). The effects of LMWAP on human colon carcinoma cells (HT-29) were evaluated using a microarray. Then, cell-cycle distribution was measured by flow cytometric analysis. A colitis-associated colorectal cancer mouse model was used to assess the effect of LMWAP on in vivo CRC prevention. Treatment of HT-29 cells with LMWAP resulted in 333 genes expression over cutoff values (≥2-fold). Further analysis demonstrated that pathways of cell cycle were mainly influenced. At the concentrations from 0.001 to 0.1 mg/mL, LMWAP induced a G0/G1 phase block in HT-29 cells in a dose-dependent way. In vivo studies revealed that administration of LMWAP could protect ICR mice against CRC effectively. The results of Western blot suggested LMWAP induced cell-cycle arrest in a p53 independent manner. These data indicate that LMWAP could inhibit the development of CRC through affecting cell cycle, and it has potential for clinical prevention for colon cancer.

The importance of the prenyl group in the activities of osthole in enhancing bone formation and inhibiting bone resorption in vitro.

Osteoporosis treatment always aimed at keeping the balance of bone formation and bone resorption. Recently, prenyl group in natural products has been proposed as an active group to enhance the osteogenesis process. Osthole has both the prenyl group and bone-protective activities, but the relationship is still unknown. In this study we found that osthole exerted a potent ability to promote proliferation and osteogenic function of rat bone marrow stromal cells and osteoblasts, including improved cell viability, alkaline phosphatase activity, enhanced secretion of collagen-I, bone morphogenetic protein-2, osteocalcin and osteopontin, stimulated mRNA expression of insulin-like growth factor-1, runt-related transcription factor-2, osterix, OPG (osteoprotegerin), RANKL (receptor activator for nuclear factor-κB ligand), and the ratio of OPG/RANKL, as well as increasing the formation of mineralized nodules. However, 7-methoxycoumarin had no obvious effects. Osthole also inhibited osteoclastic bone resorption to a greater extent than 7-methoxycoumarin, as shown by a lower tartrate-resistant acid phosphatase activity and lower number and smaller area of resorption pits. Our findings demonstrate that osthole could be a potential agent to stimulate bone formation and inhibit bone resorption, and the prenyl group plays an important role in these bone-protective effects.