Ginseng berry concentrate prevents colon cancer via cell cycle, apoptosis regulation, and inflammation-linked Th17 cell differentiation.

The Asian ginseng root (Panax ginseng C.A. Meyer) is a very commonly used herbal medicine worldwide. Ginseng fruit, including the berry (or pulp) and seed, is also valuable for several health conditions including immunostimulation and cancer chemoprevention. In this study, the anticancer and anti-proliferative effects of the extracts of ginseng berry and seed were evaluated. The ginsenosides in the ginseng berry concentrate (GBC) and ginseng seed extract (GSE) were analyzed. We then evaluated their anti-colorectal cancer potentials, including antiproliferation, cell cycle arrest, and apoptotic induction. Further investigation consisted of the berry's adaptive immune responses, such as the actions on the differentiation of T helper cells Treg, Th1, and Th17. The major constituents in GBC were ginsenosides Re and Rd, which can be compared to those in the root. The GBC significantly inhibited colon cancer cell growth, and its anti-proliferative effect involved mechanisms including G2/M cell cycle arrest via upregulation of cyclin A and induction of apoptosis via regulation of apoptotic related gene expressions. GBC also downregulated the expressions of pro-inflammatory cytokine genes. For the adaptive immune responses, GBC did not influence Th1 and Treg cell differentiation but significantly inhibited Th17 cell differentiation and thus regulated the balance of Th17/Treg for adaptive immunity. Although no ginsenoside was detected in the GSE, interestingly, it obviously enhanced colon cancer cell proliferation with the underlined details to be determined. Our results suggested that GBC is a promising dietary supplement for cancer chemoprevention and immunomodulation.

Role of intestinal microbiome in American ginseng-mediated colon cancer prevention in high fat diet-fed AOM/DSS mice [corrected].

OBJECTIVE: Chronic intestinal inflammation is a risk factor for colorectal cancer (CRC) initiation and development. Diets that are rich in Western style fats have been shown to promote CRC. This study was conducted to investigate the role of intestinal microbiome in American ginseng-mediated CRC chemoprevention in a mouse model. The population and diversity of enteric microbiome were evaluated after the ginseng treatment. METHODS: Using an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced gut inflammation and tumorigenesis mouse model, the effects of oral American ginseng on high fat diet-associated enteric pathology were determined. After establishment of a 16S rRNA illumina library from fecal samples, MiSeq sequencing was carried out to reveal the microbial population. The alpha and beta diversities of microbiome were analyzed. RESULTS: American ginseng significantly attenuated AOM/DSS-induced colon inflammation and tumorigenesis by reducing the colitis score and colon tumor multiplicity. The MiSeq results showed that the majority of sequences fell into three phyla: Firmicutes, Bacteroidetes and Verrucomicrobia. Further, two significant abundance shifts at the family level, Bacteroidaceae and Porphyromonadaceae, were identified to support ginseng's anti-colitis and anti-tumor effects. In addition, alpha and beta diversity data demonstrated that ginseng led to a profound recovery from the AOM/DSS-induced dysbiosis in the microbial community. CONCLUSION: Our results suggest that the CRC chemopreventive effects of American ginseng are mediated through enteric microbiome population-shift recovery and dysbiosis restoration. Ginseng's regulation of the microbiome balance contributes to the maintenance of enteric homeostasis.

Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure.

Because as many as half of glaucoma patients on intraocular pressure (IOP)-lowering therapy continue to experience optic nerve toxicity, it is imperative to find other effective therapies. Iron and calcium ions play key roles in oxidative stress, a hallmark of glaucoma. Therefore, we tested metal chelation by means of ethylenediaminetetraacetic acid (EDTA) combined with the permeability enhancer methylsulfonylmethane (MSM) applied topically on the eye to determine if this noninvasive treatment is neuroprotective in rat optic nerve and retinal ganglion cells exposed to oxidative stress induced by elevated IOP. Hyaluronic acid (HA) was injected into the anterior chamber of the rat eye to elevate the IOP. EDTA-MSM was applied topically to the eye for 3 months. Eyeballs and optic nerves were processed for histological assessment of cytoarchitecture. Protein-lipid aldehyde adducts and cyclooxygenase-2 (COX-2) were detected immunohistochemically. HA administration increased IOP and associated oxidative stress and inflammation. Elevated IOP was not affected by EDTA-MSM treatment. However, oxidative damage and inflammation were ameliorated as reflected by a decrease in formation of protein-lipid aldehyde adducts and COX-2 expression, respectively. Furthermore, EDTA-MSM treatment increased retinal ganglion cell survival and decreased demyelination of optic nerve compared with untreated eyes. Chelation treatment with EDTA-MSM ameliorates sequelae of IOP-induced toxicity without affecting IOP. Because most current therapies aim at reducing IOP and damage occurs even in the absence of elevated IOP, EDTA-MSM has the potential to work in conjunction with pressure-reducing therapies to alleviate damage to the optic nerve and retinal ganglion cells.

The safety and effectiveness of TM81, a Chinese herbal medicine, in the treatment of type 2 diabetes: a randomized double-blind placebo-controlled trial.

AIM: TM81 (or Tang-Min-Ling-Wan) is a Chinese medicine. Previous studies suggested that this medicine is effective for treating type 2 diabetes. This controlled trial evaluated the safety and effectiveness of TM81 in the treatment of type 2 diabetic patients. METHODS: This study was a large-scale controlled clinical trial to evaluate the safety and effectiveness of TM81 on type 2 diabetes. After a 2-week run-in period, 480 overweight type 2 early-stage diabetic patients [35-65 years old, HbA1c ≥ 7.0%, fasting plasma glucose (FPG) 7.0-13.9 mM or 2 h plasma glucose (PG) > 11.1 mM, body mass index (BMI) ≥ 24 kg/m(2)] were enrolled. These patients were divided into a TM81 group and placebo group in a 3 : 1 ratio. The subjects received 6 g TM81 or placebo, three times daily for 12 weeks. RESULTS: After treatment, the HbA1c decrease was 1.02% in the TM81 group versus 0.47% in the placebo group. The FPG decreased 0.8 ± 0.1 mM in the TM81 group versus an increase of 0.2 ± 0.2 mM in the placebo group. The PG decreased 2.7 ± 0.3 mM in the TM81 group versus a decrease of 0.9 ± 0.4 mM in the placebo group (all p < 0.05). The TM81 was more effective for patients with higher baseline HbA1c levels. The TM81 group also showed improved ß-cell function and increased homeostatic model assessment (HOMA)-ß. In addition, body weight, BMI and waist circumference of subjects in the TM81 group were reduced, and the symptoms related to diabetes were improved. There were no significant differences in the types and frequency of adverse reactions between the two groups. CONCLUSIONS: The data showed that TM81 is effective in controlling blood glucose level and is safe to use in patients with early-stage type 2 diabetes.

Chemosensory basis of behavioural plasticity in response to deterrent plant chemicals in the larva of the Small Cabbage White butterfly Pieris rapae.

Behavioural and electrophysiological responsiveness to three chemically different secondary plant substances was studied in larvae of Pieris rapae L. (Lepidoptera: Pieridae). Three groups of caterpillars were studied that during their larval development were exposed to different rearing diets: an artificial diet or one of two host-plants, cabbage, Brassica oleracea, or nasturtium, Tropaeolum majus. In dual-choice leaf disc assays, caterpillars reared on cabbage were strongly deterred by the phenolic chlorogenic acid, the flavonol glycoside naringin and the alkaloid strychnine. However, behavioural plasticity was found in caterpillars reared on nasturtium or artificial diet in that these did not discriminate against chlorogenic acid. Caterpillars reared on the artificial diet were also significantly less sensitive to naringin and strychnine in the behavioural assay. Electrophysiological studies of the maxillary sensilla styloconica revealed that the deterrent neuron in the medial sensillum, but not in the lateral sensillum, of cabbage-reared caterpillars was more sensitive than the same neuron type of caterpillars reared on nasturtium or artificial diet. We conclude that (1) the diet-induced behavioural habituation to deterrents can at least partly be explained by chemosensory desensitisation of a generalist type of maxillary deterrent neuron; (2) behavioural cross-habituation to the three structurally diverse deterrent compounds can be traced back to cross-sensitivity for these compounds in the same gustatory neuron.

American ginseng berry juice intake reduces blood glucose and body weight in ob/ob mice.

Diabetes is a serious chronic metabolic disease and has a significant impact on patients' lives and the health care system. We previously observed that the organic solvent extract of American ginseng berry possessed significant antidiabetic effects in obese diabetic ob/ob mice after intraperitoneal injection. If American ginseng berry is useful as a dietary supplement, simple preparation and oral intake would be a convenient, safe, and practical means for consumers. In this study, the simply prepared berry juice was first analyzed using high-performance liquid chromatography, and then administered orally in the ob/ob mice. The animals received daily berry juice 0.6 mL/kg or vehicle for 10 consecutive days. The results indicated that oral juice administration significantly lowered fasting blood glucose levels, and this effect continued for at least 10 d after cessation of the treatment. Data from intraperitoneal glucose tolerance test demonstrated that there was a notable improvement in glucose tolerance in the juice treated group. In addition, the berry juice significantly reduced body weight. Our data suggest that ginseng berry juice, as a dietary supplement, may have functional efficacy in consumers with diabetes.

Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells.

AIM: To investigate the anti-proliferative effects of Crocus sativus extract and its major constituent, crocin, on three colorectal cancer cell lines (HCT-116, SW-480, and HT-29). The cell growth inhibition effect was compared to that of non-small cell lung cancer (NSCLC) cells. In addition, Crocus sativus' effect on non-cancer cells was evaluated. METHODS: Using high performance liquid chromatography (HPLC), the purity of crocin and the content of crocin extract were determined. Anti-proliferative effects of Crocus sativus extract and crocin on test cells was evaluated by MTS assay. RESULTS: The purity of crocin was found to be 95.9% and the content of crocin in the extract was 22.9%. Significant concentration-related inhibition effects of the extract on all three colorectal cancer cell lines were observed (P<0.01). The proliferation was reduced most significantly in HCT-116 cells, to 45.5% at 1.0 mg/ml and to 6.8% at 3.0 mg/ml. Crocin at 1.0 mM, significantly reduced HCT-116, SW-480, and HT-29 cell proliferation to 2.8%, 52%, and 16.8%, respectively (P<0.01). Since 3.0 mg/ml Crocus sativus extract contained approximately 0.6 mM crocin, the observed effects suggest that crocin is a major responsible constituent in the extract. Significant anti-proliferative effects were also observed in non-small cell lung cancer cells. However, Crocus sativus extract did not significantly affect the growth of non-cancer young adult mouse colon cells. CONCLUSION: Data from this study demonstrated that Crocus sativus extract and its major constituent, crocin, significantly inhibited the growth of colorectal cancer cells while not affecting normal cells. Crocus sativus extract should be investigated further as a viable option in the treatment of colorectal cancer.

Simultaneous identification of Bulbus Fritillariae cirrhosae using PCR-RFLP analysis.

Bulbus Fritillariae (BF) is the most commonly used antitussive herb in China. There are nine species of Fritillaria recorded as the drug BF in the Chinese Pharmacopoeia. Bulbus Fritillariae cirrhosae (BF cirrhosae) is a group that includes four species of BF; these four species come from wild sources with higher efficiency and lower toxicity compared to the other five species of BF. Due to reasons of carelessness and reduced costs, the other five species are often sold as BF cirrhosae. Analysis through appearance, microscopic and chemical techniques has limitations. Identifying botanical resources is a primary step in the standardization of herbal medicine. In the present article, the internal transcribed spacer 1 (ITS1) regions of the nuclear ribosomal DNA (nrDNA) of nine species and one variety of Fritillaria genus have been sequenced. A mutation site in the ITS1 region among BF cirrhosae and other species of BF has been found and can be recognized by the restriction endonuclease SmaI. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the nuclear ribosomal ITS1 region was used to differentiate BF cirrhosae from other species of BF and is a successful method in distinguishing the subgroups.

Ganoderma lucidum extract inhibits proliferation of SW 480 human colorectal cancer cells.

AIM: Ganoderma lucidum is a commonly used Chinese herb and an important ingredient in traditional Chinese medicine herbal formulations for immune dysfunction related illnesses. The effects of this medicinal mushroom on human colorectal cancer cells have not yet been evaluated. In this study, we investigated the effects of Ganoderma lucidum extract using SW 480 human colorectal cancer cell line. MATERIALS AND METHODS: Two different fractions of Ganoderma lucidum extract, i.e., a fraction containing mainly polysaccharides (GLE-1), and a triterpenoid fraction without polysaccharides (GLE-2) were analyzed. Their antiproliferative activity was evaluated by cell proliferation assay and 3H-thymidine incorporation assay. Scavenging effects of DPPH radical were assessed using ESR-spectroscopy. RESULTS: Our data showed that both GLE-1 and GLE-2 significantly inhibited the proliferation of SW 480 cells. The inhibitory effect of GLE-2 was much stronger than that of GLE-1. GLE-1 inhibited DNA synthesis in the cells and reduced the formation of DPPH radicals. CONCLUSION: Ganoderma lucidum extract inhibits proliferation of human colorectal cancer cells and possesses antioxidant properties.

[Effect of Tripterygium wilfordii on Th1, Th2 cytokines production in asthma patients].

OBJECTIVE: To observe the effect of Tripterygium wilfordii on Th1, Th2 cytokines in asthma patients for further study on the therapeutic mechanism. METHODS: Twelve patients of middle or severe asthma were treated by Tripterygium polyglucoside 40 mg or 60 mg daily for 4 weeks. Blood of patients was colleted before and after treatment for serum and peripherol blood mononuclear cells (PBMC) preparation. The prepared PBMCs were stimulted in vitro with Concanavalin A (ConA) for 6 hrs and followed by culturing with Triptolide for 24 hrs and then the supernatant was collected. The concentration of interleukin-2(IL-2), -4(IL-4), -5(IL-5) and interferon-gamma(IFN-gamma) in serum and in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of IL-2, IL-4 and IL-5 of patients decreased significantly after treatment of Tripterygium polyglucoside (P < 0.01), but IFN-gamma level was under the detection sensitivity both before and after treatment. Triptolide could inhibit PBMC to secrete IL-2, IL-4 and IL-5 in vitro (P < 0.01), but IFN-gamma was also under the detection sensitivity. CONCLUSION: The marked inhibition of Th2 cytokine expression by Tripterygium was the important mechanism of it in treating asthma. But the fact that Tripterygium also showed inhibition on Th1 cytokine indicated that the inhibition of Tripterygium on Th2 and Th1 cytokines was non-specific.

Triterpenoid saponins from Aster auriculatus.

Three new triterpenoid saponins, auriculatusaponins A, B, and C, along with one known saponin, 3- O-beta-glucuronylolean-12-en-28-oic acid 28-( O-alpha-rhamnopyranosyl-(1-->2)-alpha-arabinopyranosyl) ester were isolated from roots of Aster auriculatus. On the basis of spectral and chemical evidence, auriculatusaponins A, B, and C were determined as 3beta- O-beta-glucuronyl-16-oxo-12-ene-28-noroleanane, 3beta- O-beta-glucuronyl-16alpha- trans-feruloyloxy-12-en-oleanane, and 3- O-beta-glucopyranosyl-16alpha-hydroxy-olean-12-ene-28-oic acid 28- O-carboxymethyl ester, respectively.

Neolignan glycosides from Pedicularis longiflora.

Four new neolignan glucosides, longiflorosides A, B, C and D, in addition to one known neolignan glucoside, dehydro-diconiferyl alcohol-4-O-beta-D-glucopyranoside were obtained from whole plants of Pedicularis longiflora. The structures of these compounds were determined mainly on spectral evidence.

Experimental studies on early treatment of schistosomal infection with artemether.

An early treatment with artemether given in appropriate regimens was tested in mice, rabbits and dogs for prevention purposes. Artemether was administered intragastrically (ig) to the hosts on day 7 after infection with Schistosoma japonicum cercariae at a single dose, and the same dose of artemether was repeated every 1 or 2 weeks for 2-4 times. As a result, most of the female worms were killed before their oviposition with female worm reduction rates of 90-100%, resulting in protection of the host from damage induced by schistosome eggs. When rabbits were treated ig with artemether 10 mg kg-1 on day 7 after infection, followed by repeated dosing every week for 4 times, some parameters related to acute schistosomiasis, such as temperature, eosinophil count and eggs in the feces were negative, and low specific antigen and antibody levels in serum were seen. Further study showed that the appropriate regimens of Artemether were also effective in early treatment of reinfection with cercariae. When rabbits infected with 48-52 cercariae once every other day for 5 times were treated ig with artemether 15 mg kg-1, followed by repeated dosing every 1 or 2 week for 2- 3 times, the female worm reduction rates were 92.1-98.4%. Histopathological examination of the livers showed that the above-mentioned early treatment with Artemether exhibited a promising protective effect on dogs and rabbits. The major features included normal appearance of the liver resembling those of uninfected dogs and rabbits; few or no dispersed miliary egg tubercles appeared on the surface of the liver; the structure of the hepatic lobules was normal with normal arrangement of the liver bundles; few or no eggs appeared in the portal vein area and there was apparent diminution of total egg granuloma, comprising inflammatory, fibrous or scarred egg granuloma. On the basis of above-mentioned results, early treatment with Artemether could be recommended for field trial for controlling acute schistosomiasis, reducing infection rate and intensity of infection.