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Study of the Gastrointestinal Protective Effects of Polysaccharides from Angelica sinensis in Rats
Abstract
We studied the protective effects of polysaccharides isolated from the root of Angelica sinensis (Oliv.) (Danggui) on gastrointestinal damage induced by ethanol or indomethacin in rats. Oral administration of ethanol provoked a marked hemorrhagic damage in the glandular mucosa, which was accompanied with a significant increase of myeloperoxidase (MPO) activity, a marker enzyme for inflammation and neutrophil infiltration. An extract from Angelica, which mainly consisted of polysaccharides (95%) (AP), dose-dependently prevented gastric mucosal damage. This ulcer protective effect could last at least 12 h after administration. Prostaglandin E2 produced a similar anti-lesion effect. AP and prostaglandin E2 also reduced mucosal MPO activity. Indomethacin-induced gastrointestinal damage, another neutrophil-dependent lesion model in the gastrointestinal tract, was also prevented by AP pretreatment. The present findings suggest that polysaccharides from Angelica possess an anti-inflammatory action, perhaps through the inhibitory action on neutrophil infiltration in the gastrointestinal mucosa. AP could potentially be useful to prevent any neutrophil-dependent mucosal injury in the gastrointestinal tract.
... The antiulcer activity of various plants, including Panax ginseng [83,84], Angelica sinensis [47,85], Bupleurum falcatum [82], Cochlospermum tinctorium [33], and Strychnos potatorum [86], has been attributed to the polysaccharides present in the evaluated extracts. However, only Sun et al. [84] and Yamada [82] evaluated the gastric antiulcer activity of polysaccharides that were purified from P. ginseng and B. falcatum, respectively, and characterized as pectic polysaccharides containing high levels of galacturonic acid. ...
... However, only Sun et al. [84] and Yamada [82] evaluated the gastric antiulcer activity of polysaccharides that were purified from P. ginseng and B. falcatum, respectively, and characterized as pectic polysaccharides containing high levels of galacturonic acid. Other studies showed only the activity of crude extract mixtures containing polysaccharides [33,47,85,86]. Nergard et al. [33] linked antiulcer activity with the presence of arabinogalactan type II in the evaluated crude pectic extract. ...
The gastric mucosa is continuously exposed to damaging agents that are involved in the pathogenesis of gastric ulcers, the most common chronic gastrointestinal disease. Common habits such as stress, coffee ingestion, tobacco, alcohol, and nonsteroidal antiinflammatory drugs’ consumption contribute to the physiopathology of gastric ulcers. There is an ongoing search to discover novel bioactive gastroprotective and ulcer-healing compounds derived from medicinal plants. Among antiulcer studies using natural products, those focused on isolated compounds have brought promising results, which is important for developing new drugs against gastric ulcers. In this manuscript, we review the published antiulcer studies dedicated to isolated compounds, highlighting the chemical structure and mechanisms of action of each compound and trying to elucidate a structure–activity relationship for the tested compounds.
... Recent pharmacological studies demonstrated that APS had radio-protective effects in irradiated mice through modulation of proliferating response of hematopoietic stem cells . Gastrointestinal protective effects (Cho et al., 2000;Ye et al., 2003) and the mechanism of Angelica polysaccharide in rats have been reported and APS was known to be protective against ethanol-or indomethacin-induced mucosal damage (Choy et al., 1994). It was also reported that A. sinensis crude extract increased the proliferation of gastric epithelial cells through modulation of several proliferation-related genes, including epidermal growth factor (EGF) receptor and ornithine decarboxylase (ODC) and c-Myc (Ye et al., 2003. ...
... Effects of Angelica polysaccharide on blood coagulation and platelet aggregation and the protective effect of the polysaccharides-enriched fraction from A. sinensis on hepatic injury were also studied. In cancer cells, Angelica polysaccharide has been reported to possess anti-tumor effects (Shang et al., 2003;Tsai et al., 2005) and also exhibited immunostimulating activities both in vitro and in vivo (Cho et al., 2000). Cyclophosphamide (CY) is a cytostatic agent that produces systemic toxicity especially on cells with high proliferative capacity, while polysaccharides from Angelica polysaccharide have been shown to increase the turnover of hemopoietic stem cells (Hui et al., 2006). ...
To investigate the effects of Angelica polysaccharide on erythrocyte immunity and marrow hematopoiesis in chickens, Angelica polysaccharide was used for the study of immunity and hematinic mechanism in order to provide basis for clinical reference. In this experiment, three gradient dosages (50, 100, 150 mg/kg body weight) of Angelica polysaccharide were drenched to the control group and the anemia groups, respectively. The anemia chickling model was made by abdominal injection of cyclophosphamide (CY) for 6 days (80 mg/kg·day). Red blood cell-C3b receptor (RBC-CR1) and red blood cell-immune complex (RBC-IC) rosette rates were measured and analyzed. Ectogenetic semi-solid culture medium of bone marrow hemopoietic progenitor cells was used to observe Angelica polysaccharide and separated serum from Angelica polysaccharide treatment on the proliferation of colony-forming unit-erythrocyte (CFU-E), burst-forming unit-erythrocyte (BFU-E) and colony-forming unit-granulocyte macrophage (CFU-GM). The results showed that Angelica polysaccharide can significantly increase RBC-CR1 rosette rate in the healthy chicken groups (p 0.05). At the same time, Angelica polysaccharide can restore the RBCCR1 rosette rate and the RBC-IC rosette rate caused by cyclophosphamide to the normal level. Serum containing Angelica polysaccharide can significantly facilitate the proliferation on CFU-E (p<0.01), BFUE (p<0.01) and CFU-GM (p<0.01), but Angelica polysaccharide had no more direct proliferation on CFUE, BFU-E and CFU-GM. This indicated that Angelica polysaccharide had the proliferation on hemopoietic progenitor cells of marrow by the change of hemopoietic factor.
... ASP is primarily composed of the monosaccharides glucose, mannose, galactose, rhamnose, arabinose, and xylose. It utilizes alpha (1, 4)-Glc Glycosidic linkage in its backbone and has functions such as regulating immunity [41,42], anti-tumor effects [43], and protecting the gastrointestinal tract [44]. Although its specific composition and spatial conformation are not yet clear for studying its exact target, our work on the effectiveness of ASP can provide data support and research direction for pharmacological studies. ...
Angelica sinensis (AS) can improve the haematopoietic function, but the treatment mechanism is unknown. Transfusion dependency was estimated by Kaplan-Meier survival analyses and Cox proportional-hazard model in AS treated apalstic anemia (AA) patients. After that, the AA GEO database was analysed, the up differentially expressed genes (DEGs) of AA were combined with AS targets for the intersection of targets. After the AA mouse model was established, the effect of AS was confirmed by haematopoietic function tests. The same experiment plus mitochondrial apoptotic pathway tests in vivo were performed in Angelica sinensis polysaccharide (ASP)-treated mice, the key ingredient in AS. For in vitro experiment, bone marrow nucleated cells (BMNCs) were tested. Clinical data confirmed that the level of transfusion dependency and IL17A were lower in AS-users compared to non-AS users (p < 0.001). The intersection of targets between AA and AS most concentrated on inflammation and apoptosis. Then, the same effect was found in AS treated AA mice model. In both in vivo and in vitro tests, ASP demonstrated the ability to mitigate P38/MAPK-induced Bax-associated mitochondrial apoptosis, while also reducing the levels of activated Th17 cells and alleviating abnormal cytokine levels. So, the protective effect of AS and ASP on hematopoietic function lies in their ability to prevent apoptosis.
... Plants are important sources of natural polysaccharides, the functions of which are generally related to their structures, and include resistance to oxidation, tumors, and diabetes, immunomodulation, liver protection, hypoglycemia, and gastrointestinal protection [60][61][62][63][64][65][66]. As plants with medicinal value, Chinese herbal medicines are rich in polysaccharides, and data on the structures and functional activities of some of these polysaccharides have been generated. ...
Colorectal cancer (CRC) ranks third and second among the most widespread cancers worldwide and the most common causes of human death due to cancer, respectively. Further, for unknown reasons, numbers of young patients diagnosed with colon cancer has increased. Polysaccharides are important functional phytochemicals reported to have anti-CRC effects. Moreover, CRC development and progression is closely related to the gut microbiome. Although approaches for treating CRC have been the subject of some review papers, research into traditional Chinese medicine (TCM) treatments for CRC and the underlying mechanisms involving polysaccharides have not been reviewed. Here, we reviewed the mechanisms underlying treatment of CRC using TCM polysaccharides, based on the etiology of CRC, and common treatment methods applied. The relationship between intestinal microbes and CRC, the mechanism by which TCM polysaccharides induce CRC cell apoptosis, and how TCM polysaccharides promote immune responses are discussed, as well as TCM polysaccharide use in combination with chemotherapy. TCM polysaccharides provide options for CRC treatment, due to their advantages of having multiple targets, eliciting modest adverse reactions, and wide range of available sources.
... Another major ingredient Lithospermum has been proved to promote intestinal wound healing in vitro via induction of TGF-β [19]. Lithospermum extract has also anti-inflammatory and antibacterial effects, which promote blood circulation and epithelial growth and detoxication and strengthen local blood circulation [20,21]. Angelica polysaccharides increase the number of white blood cells and reticulocytes to prevent ethanol-or indomethacin-induced gastric mucosal damage [22]. ...
Background. Xuzhou Qufu Shengji Ointment (QFSJO) has been used in hospital and private medication for more than 30 years to treat the infective wounds after trauma. However, molecular investigation is lacking. This study used rats to explore the healing mechanism of QFSJO in promoting wound healing in human. Methods. One circular incision was individually generated on the back of 30 rats in three groups and challenged with 10⁸ CFU (0.3 mL) of Staphylococcus aureus. Then, one of the trauma groups was treated with QFSJO gauze, and the control group was covered with a piece of Vaseline gauze, while the western medicine group was treated with erythromycin in a similar way. The dressing change of all the groups was performed once a day for three weeks. The anti-inflammation and proangiogenesis of QFSJO were evaluated by enzyme-linked immunosorbent assay (ELISA). The levels of angiogenesis associated factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), hydroxyproline, and hemoglobin, were measured according to ELISA. The immunohistochemistry of CD31 and CD34 expression in granulation tissue was demonstrated and quantitatively analyzed for angiogenesis in granulation tissue in sites. Results. A faster wound healing ratio was observed in QFSJO-dressing-treated group than Vaseline- and erythrocin-treated groups. ELISA results showed that QFSJO promoted VEGF and b-FGF levels significantly in early stage of wound healing. QFSJO dressing group also showed an enhanced hydroxyproline and hemoglobin in granulation tissue. The expressions of CD31 and CD34 in granulation tissue of QFSJO group were higher than in the Vaseline and erythrocin groups. Conclusion. QFSJO improved the healing rate of the infective wounds by promoting the angiogenesis of granulation tissue and inhibiting the inflammation of the trauma tissue. Our finding suggests that QFSJO is able to help angiogenic capillary sprouts for collagen accumulates in the granulation tissue.
1. Introduction
The refractory infectious wound healing is a challenge in the surgical department, which is generally caused by accidental crush injury, bacterial contamination, exposure of callus after trauma, local defects of skin, and muscle necrosis. Tendons, nerves, and vascular injury can further enhance bacterial contamination [1]. Sometimes, the wound infection is triggered by lack of hygiene awareness or in patients who are long-term bedridden and with reduced immunity. According to the concept of traditional Chinese medicine (TCM), infectious wound belongs to “sore and ulcer” category and frequently need removal of slough to promote tissue regeneration through surgical methods. Xuzhou QFSJO has the functions of clearing heat (lower fever and reduce inflammation) and detoxifying (eliminating evil in body) and can be used in clinical treatment for crissum abscess, diabetic foot, and furuncle based on the herb ingredients and the TCM theory. The major contents of QFSJO are Astragalus membranaceus (AM), Lithospermum erythrorhizon (LE), commonly used as gromwell root’s (GR), Danggui (Angelica Sinensis, Radix), and others. AM is regarded as the major component in the formula because its tonifying function (Huang Qi in Chinese can be regarded as sufficient oxygen), which correct spleen deficiency, and then, it is used in diarrhea, fatigue, and loss of appetite as well as wound healing [2, 3]. The major components of AM are made of polysaccharides, flavonoids, and saponins. Because of their hydrophilic and hydrophobic functions, AM have been used for immunomodulating and as antioxidant, anti-inflammatory, and anticancer medications [4, 5]. Currently, AM has been applied in some western medication for restoring and strengthening the immune response, enhancing the number of white blood cells and neutrophils and increasing phagocytosis by macrophages to promote humoral and cellular immunity [6]. In recent studies, AM-based treatments have demonstrated significant amelioration in treatment of side effects induced by other orthodox drugs (e.g., cancer chemotherapeutics and some of immunosuppressants). GR, another important component of QFSJO, has been proved to protect against ultraviolet B-induced inflammatory in skin through apoptotic signals [4], increased ceramide production in atopic dermatitis [5], improve moisturization and barrier function, and promote wound healing. QFSJO, which originated from a private recipe with long history, has been affirmed the intangible cultural heritage of Jiangsu Province in 2016. From January 2014 to June 2020, Xuzhou QFSJO has been used to treat infective wound more than 200 clinical cases, and significant clinical effects were recorded. Compared with control cases, QFSJO promoted the growth of granulation tissue and the skin regeneration to accelerate the healing of infectious wound after trauma [1]. But, the mechanism of QFSJO remains unclear. Considering the pivotal role of QFSJO in treatment of infected wounds, in this study, we observed the efficacy of QFSJO in the treatment of infective full-thickness skin wound healing through a multicenter randomized double-blind controlled trial. In order to further clarify the mechanism of QFSJO in treating infected wounds, we collected the secretions of each group and determined the IL-6 and TNF-α by ELISA to detect the inflammation and anti-inflammatory effects. VEGF stimulates wound healing via multiple mechanisms including collagen deposition, angiogenesis and epithelization. We also detected the levels of VEGF and b-FGF in the tissue supernatant to clarify the angiogenesis effect of QFSJO. Furthermore, we measured the changes of hemoglobin and hydroxyproline in granulation tissue of the wound surface area. By using immunohistochemistry (IHC), the expression of CD31 and CD34 in the granulation tissue was evaluated for the angiogenesis. These approaches help us understand the molecular mechanism of QFSJO during the promotion of infective wound healing, which may further improve the effectiveness of QFSJO in dermatology and osteopathic medicine.
2. Materials and Methods
2.1. Preparation of Animals and Wound Healing Models
This study was approved by the ethnic committee of the Xuzhou Medical University (no. SYXK (Su) 2020–0048). Thirty Sprague Dawley (SD) male rats at week four (average weight 100 Gram) were anesthetized with 0.7% pentobarbital sodium via auricular veins (6 mL/Kg). Subsequently, their back hairs were shaved off (12 cm × 10 cm), and the wound sites were disinfected with povidone-iodine. A full-thickness circular excisional skin wound (20 mm in diameter and deep into the fascia) was created on the back of each SD rat with scissors and forceps. The wounds were covered with a circular gauze and infected with 0.3 mL Staphylococcus aureus (10⁸ CFU/mL). The rats were divided into three groups: the control group (Vaseline group), the treatment group (Xuzhou QFSJO), and the erythromycin group (western medicine group). During the study period, all the SD rats were kept in cages with free access to food and water. The day of wound operation was considered as day 0. The wounded areas were monitored by a camera (Fuji, S20 Pro, Japan) and measured on 3, 7, 14, and 21 postwound injury days. Wound healing rate [7] was calculated using the following formula: % of wound healing rate = (wound area on day 0–wound area on days)/wound area on day 0 × 100%. We followed the guidelines for Animal Care and Use of Xuzhou Medical University. One animal of each group was randomly selected and sacrificed at 3rd, 7th, 14th, and 21st postoperatory days, and the wound region was excised for subsequent detection the content of hydroxyproline and hemoglobin according to traditional and commercial protocols.
2.2. Composition and Processing Method of QFSJO
Xuzhou QFSJO (Jiangsu Medical Products Administration permit: Z04000706) was formulated and processed as follows: Astragalus (A. membranaceus) 12 g, Lithospermum 10 g, Angelica 12 g, blood charcoal 12 g, and raw gypsum 30 g were together pestled into 100-mesh sieve. Sesame oil (417 g) was boiled and added to the raw tortoise shells in a pot and fried until it became brown; then, the remaining sesame oil was added into the batch. Subsequently, sieved Angelica and Rehmannia glutinosa were added to the pot; frying was continued until deep fry to scorched. They were filtered (the residues were removed) and heated slightly to boiling point. Astragalus, comfrey, blood residual charcoal, calamine, and raw gypsum powder were added and they were stirred constantly and boiled slightly for 1.5 hours. The beeswax was melted in another pot until there was no foam, filtered into sesame oil pot with gauze, stirred about 10 minutes, and then left until the temperature dropped to 40°C. Stirring evenly was continued. It was packed and condensed and then stored at room temperature for use. QFSJO, erythromycin, and saline were provided by Preparation Laboratory of Xuzhou Traditional Chinese Hospital. Vaseline gauze was manufactured by Pharmaceutical Factory of Jiangsu Hospital of TCM (Jiangsu Pharmaceutical Approval Number 203201). The main active ingredients in the decoction are present in Table 1 and AM molecules in SMILES format (Table 2).
Active ingredient of AM [8]
Active ingredients of Angelica [9]
Active ingredients of Lithospermum [10]
Active ingredient of Rehmannia glutinosa Libosch [11]
Astragalus polysaccharides
Organic acids
Comfrey oil
Catalpol
Astragalus saponins
Polysaccharides
Shikonol
Rehmannia glutinosa polysaccharide
Astragalus flavone
Flavonoids
Alkannins
... Epimedium, Rehmannia glutinosa (RG), Panax ginseng, and Angelica sinensis (AS) are representative drugs in these four categories of tonics. Epimedium can nourish the kidneys and works as an aphrodisiac, strengthening muscles and bones; Rehmannia can nourish yin, enrich fluid production, ease pyrexia, and stem bleeding [7]; Ginseng is popular as a strong tonic in strengthening vitality, activating circulation, as well as calming the mind [8][9][10][11]; Angelica nourishes the blood, promoting good blood circulation, lubricating the intestine, and regulating bowel movement [12][13][14][15][16]. They are commonly used in traditional Chinese medicine in a variety of diseases and are mainly given by oral administration and are sometimes made into drops or given as injections. ...
Since time immemorial, plant derived natural products have been used for the treatment of various human diseases before the intervention of modern medicine. The basis of modern medicine is still being inspired from traditional medicine and therapies. However, despite their tremendous therapeutic potential, these natural drugs often have poor bioavailability, metabolic instability, and aqueous insolubility. These factors greatly impede a natural drug’s commercialization potential as a mainstream medicine. Therefore, the development of nanocarrier drug delivery systems is indispensable in overcoming the various constraints of the bottlenecks which occur with natural drugs. Of particular interest in this review are four plant materials endogenous to China with the common names of barrenwort or horny goat weed ( Epimedium ), Shu Di Huang ( Rehmannia glutinosa , RG), ginseng ( Panax ginseng ), and Dong Quai or female ginseng ( Angelica sinensis , AS), each having been scientifically investigated for a wide range of therapeutic uses as has been originally discovered from the long history of traditional usage and anecdotal information by local population groups in Asia. The integration of natural drugs from the East and nanocarrier drug delivery systems developed from the West is paving the way towards further accurate and efficient medicine therapy. We further discuss the potential benefits of these plants and the enhancement of their therapeutic efficacy by nanotechnology intervention.
... Angelica sinensis polysaccharide (ASP), which is extracted with water as the initial extraction solvent, consists of xylose, galactose, glucose, arabinose, rhamnose, fructose, and glucuronic acid [7][8][9]. Some studies have reported that ASP exhibits gastrointestinal protective effects, immunomodulatory effects [10], antitumor activity [11,12], and anti-inflammatory activity [13]. Furthermore, one study has shown the capacity of ASP to protect chondrocytes from H 2 O 2 -induced apoptosis via its antioxidant effects [14]. ...
Objective
Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism.
Method
Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP.
Results
The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway.
Conclusion
ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.
... ex Reg. is a plant that is widely used in the treatment of digestive diseases in traditional Chinese medicine. Rheum tanguticum was identified by Professor Ren Yi in Northwest University in Xi'an, China, the relevant research on RTP is extracted from rhizomes, which was extracted according to the methods described previously [22,23]. Polysaccarides extracted from R. tanguticum (RTP) consist of galactose, galacturonic acid, arabinose, glucose, glucuronic acid and sorbose [24]. ...
Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. The Nrf2/HO-1 pathway is a critical endogenous antioxidant stress pathway, but its precise role in radiation-induced enteritis remains to be clarified. Polysaccharides extracted from Rheum tanguticum (RTP) can protect the intestinal cells from radiation-induced damage, but the underlying mechanism is unknown. SD rats and IEC-6 cells were exposed to 12 or 10 Gy X-ray radiation. Rat survival, and histopathological and immunohistochemical profiles were analyzed at different time points. Indicators of oxidative stress and inflammatory response were also assessed. Cell viability, apoptosis and Nrf2/HO-1 expression were evaluated at multiple time points. Significant changes were observed in the physiological and biochemical indexes of rats after radiation, accompanied by significant oxidative stress response. The mRNA and protein expression of Nrf2 peaked at 12 h after irradiation, and HO-1 expression peaked at 48 h after irradiation. RTP administration reduced radiation-induced intestinal damage, upregulated Nrf2/HO-1, improved physiological indexes, significantly decreased apoptosis and inflammatory factors, and upregulated HO-1, particularly at 48 h after irradiation. In conclusion, Nrf2 is activated in the early stage of radiation-induced intestinal injury and plays a protective role. RTP significantly ameliorates radiation-induced intestinal injury via the regulation of Nrf2 and its downstream protein HO-1.
... d anti-ulcerogenic activity against induced ulcers (Sun et al.1991). The pectin-like bupleuran 2II from Bupleurum falcatum (Apiaceae) also exhibited significant anti-ulcer activity (Yamada et al 1991). Polysaccharides from dang gui -Angelica sinensis (Apiaceae) demonstrated protection of the gastrointestinal mucosa against ethanol and indomethacin (Cho, Mei et. al. 2000), while polysaccharide rich fractions of hot water extract of Actractylodes lancea stimulated proliferation of bone marrow cells medicated by Peyer's patch cells (Yu, Kiyohara et al. 1998). ...
... d anti-ulcerogenic activity against induced ulcers (Sun et al.1991). The pectin-like bupleuran 2II from Bupleurum falcatum (Apiaceae) also exhibited significant anti-ulcer activity (Yamada et al 1991). Polysaccharides from dang gui -Angelica sinensis (Apiaceae) demonstrated protection of the gastrointestinal mucosa against ethanol and indomethacin (Cho, Mei et. al. 2000), while polysaccharide rich fractions of hot water extract of Actractylodes lancea stimulated proliferation of bone marrow cells medicated by Peyer's patch cells (Yu, Kiyohara et al. 1998). ...
... ASP also inhibits the growth of transplanted sarcoma-180 tumors in mice. 63 Other biological activities have also been found in ASP, such as hematopoietic activity, anti-oxidant activity, hepatoprotective activity, anti-osteoarthritis activity, 60 gastrointestinal protection 66,90 and anti-diabetic activity. 47,66 ...
Most of traditional Chinese medicine substances come from herbal plants. The medicinal quality of herbal plants varies with the locations of cultivation, the parts of the herb collected, the season of the herb collected, and the herb processing method. Polysaccharides are major components of the herb plants and their biosynthesis is partly controlled by the genes but mostly influenced by the availability of the nutrition and determined by the various environmental factors. In recent decades, polysaccharides isolated from different kinds of Chinese herbs have received much attention due to their important biological activities, such as anti-tumor, anti-oxidant, anti-diabetic, radiation protecting, antiviral, hypolipidemic, and immunomodulatory activities. Interestingly, different batches of the same herb can obtain different polysaccharide fractions with subtle differences in molecular weight, monosaccharide compositions, glycosidic linkages, and biological functions. Even with these variations, a large number of bioactive polysaccharides from different kinds of traditional Chinese herbs have been purified, characterized, and reported. This review provides a comprehensive summary of the latest polysaccharide extraction methods and the strategies used for monosaccharide compositional analysis plus polysaccharide structural characterization. Most importantly, the reported chemical characteristics and biological activities of the polysaccharides from the famous traditional Chinese herbs including Astragalus membranaceus, Ginseng, Lycium barbarum, Angelica sinensis, Cordyceps sinensis, and Ophiopogon japonicus will be reviewed and discussed. The published studies provide evidence that polysaccharides from traditional Chinese herbs play an important role in their medical applications, which forms the basis for future research, development, and application of these polysaccharides as functional foods and therapeutics in modern medicine.
... The general preparation procedure of Astragalus membranaceus decoction (AMD) is as follows [11]. Briefly, 100 g the root of Astragalus membranaceus was extracted by refluxing with water (1:8, w/v) for 1.5 h following sonicating for 30 min, then the extraction solutions were combined to be filtered and concentrated to 100 mL under reduced pressure. ...
Background:
Astragalus membranaceus (Fisch.) Bunge is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer, and expectorant. The purpose of the study was to investigate the curative effects of the decoction obtained from Astragalus membranaceus root in intestinal mucosal injury induced by LPS in mice. An LPS-induced intestinal mucosal injury mice model was applied in the study.
Methods:
The mice were post-treated with Astragalus membranaceus decoction (AMD) for 4 days after 3 days LPS induction. ELISA kit was used to detect the content of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4,IL-6 and IL-8 in the serum of each group mice. The morphological changes in intestinal mucosa at the end of the experiments were observed. Both VH (villus height) and CD (crypt depth) were measured using H&E-stained sections.
Results:
There were significant differences in IL-1β, IL-4,IL-6, IL-8 and TNF-α levels in AMD-treated group on the 7th day compared to the controls group. The VH was lower in duodenum, jejunum and the ileum in LPS-treated mice compared to the control animals. Similarly, there was also decrease in V/C. Compared to the control mice, for AMD-treated mice, VH and CD had no significantly differences.
Conclusions:
Astragalus membranaceus reduced intestinal mucosal damage and promoted tissue repair by inhibiting the expression of inflammatory cytokine.
... The functions of polysaccharides are typically related to their structures. Polysaccharides in both simple and complex glycoconjugated forms support a variety of functions, including antioxidant [11], immunomodulatory [12], antitumor [13], hepatoprotective [14], hypoglycemic [15], antidiabetic [16], and gastrointestinal-protective activities [17]. ...
... protective effect, prevention of gastric mucosal damage, which contribute much to the therapeutic effects of ASR [7][8][9]. ...
To explore the nutrients in roots ofAngelica sinensis(Angelicae Sinensis Radix, ASR), a medicinal and edible plant, and evaluate its nutritional value, a rapid and reliable UHPLC-TQ-MS method was established and used to determine the potential nutritional compounds, including nucleosides, nucleobases and amino acids, in 50 batches of ASR samples obtained using two drying methods. The results showed that ASR is a healthy food rich in nucleosides, nucleobases and amino acids, especially arginine. The total average content of nucleosides and nucleobases in all ASR samples was 3.94 mg/g, while that of amino acids reached as high as 61.79 mg/g. Principle component analysis showed that chemical profile differences exist between the two groups of ASR samples prepared using different drying methods, and the contents of nutritional compounds in samples dried with the tempering-intermittent drying processing method (TIDM) were generally higher than those dried using the traditional solar processing method. The above results suggest that ASR should be considered an ideal healthy food and TIDM could be a suitable drying method for ASR when taking nucleosides, nucleobases and amino acids as the major consideration for their known human health benefits.
... Pharmacological studies of polysaccharides have shed some light on a novel aspect of functional foods in protecting the gastrointestinal mucosa. Polysaccharides promote tissue repair through different growth factors and produce anti-inflammatory effects by suppressing the neutrophil/cytokine cascade in the gastrointestinal tract (Cho et al., 2000;Hui, Wu, Shin, So, & Cho, 2006;Silva et al., 2012). Yue et al. (2015) previously reported that WJPS alleviated experimental inflammatory bowel disease (IBD) in rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis by enhancing the intestinal barrier function. ...
... Aqueous extraction of A. sinensis root caps was carried out in the Department of Physiology and Pharmacology, UAF. Polysaccharide fraction was isolated by the ethanol precipitation method as described by Cho et al. (2000) and modified by Ye et al. (2003). Angelica sinensis root caps (100 g) were boiled for 3-4 h periods with water for a total of 12 h. ...
Context: Angelica sinensis L. (Umbelliferae) has medicinal properties.
Objectives: The present study evaluates the haematopoietic effects of A. sinensis polysaccharides (ASP) against lisinopril-induced anaemia.
Materials and methods: Thirty healthy adult male albino rats were randomly divided into five groups (n = 6). Group I was control group. Group II was treated with angiotensin-converting enzyme inhibitor (ACEI, 20 mg/kg/day) to induce anaemia. In group III, erythropoietin (EPO, 100 IU/kg/each) was administered in combination with ACEI. Group IV was treated with ASP (1 g/kg/day), extracted from A. sinensis root caps. In Group V, ASP (1 g/kg/day) was treated with ACEI. After 28 days, blood and tissue samples were collected for haematological and histopathological analysis, respectively.
Results: The results showed that ACEI significantly reduced the haemoglobin (Hb, 10.0 g/dL), packed cell volume (PCV, 39.5%), red blood cells (RBCs, 6.2 million/mm³), mean corpuscular volume (MCV, 53.5 fL) and mean corpuscular haemoglobin (MCH, 16.2 pg/cell) values. In the group treated with ASP, the Hb (13.7 g/dL) and RBCs (7.8 million/mm³) increased significantly (p < 0.05). The combination of ASP and ACEI led to the significant (p < 0.05) reduction in Hb (10.7 g/dL), PCV (33.3%), RBCs (6.0 million/mm³), MCV (54.42 fL) and MCH (16.44 pg/cell) values. While histopathological examination of the liver and kidney cells showed a mild degree of toxicity in the ASP-treated group.
Conclusion: ASP has a potentiating effect on haematological parameters when given alone. However, when administered simultaneously with lisinopril, it showed an unfavourable effect with more complicated anaemia so it should not be used with ACEIs.
... Regel. Rheum tanguticum polysaccharide (RTP) was extracted according to the methods described previously [27] . In brief, Rheum tanguticum Maxim (1 kg) was fragmented and boiled 3 times,8 hours each time with absolute ethanol for 24 hours to extract the components dissolved in ethanol. ...
AIM: To study the effects of Rheum tanguticum polysaccharide-1 (RTP-1) on ulcerative colitis in rats induced by 2, 4, 6-trinitrophene sulphonic acid (TNBS) and their possible mechanism.
METHODS: RTP1 (200 mg·kg⁻¹, ig) extracted from Rheum tanguticum Maxim. ex Regel was administrated to rats with colitis induced by TNBS for 5 d, 7 d, 10 d and 14 d, respectively. The effects of RTP1 and dexamethasone (DX, 0.2 mg·kg⁻¹, ig) were contrastively investigated. The MPO level and SOD activity were determined by chromatometry. The expansion and protein expression of CD4⁺ T lymphocytes isolated from colon mucosae and mesenteric lymph nodes of colitis rats were performed by immunohistochemical analysis and Western-blot methods.
RESULTS: Treatments of RTP1 (200 mg·kg⁻¹, ig) significantly reduced diarrhea, mortality, colon mass, ulcer areas and MPO level in colon mucosae on days 5, 7, 10 and 14 (5.2 ± 1.4, 5.4 ± 0.7, 5.2 ± 1.8, P < 0.05. 3.4 ± 0.8, P < 0.01. 16.1 ± 12.1, P < 0.01. 31.8 ± 8.6, 17.7 ± 5.3, 12.7 ± 4.1, P < 0.05). The effects of RTP1 were similar to those noted above in DX group, but there were no immunosupressive effects of DX in RTP-1 group, such as body mass loss, thymus and spleen atrophy. The decreased number and down-regulated protein levels of CD4⁺ T cells isolated from the colon of colitis rats treated with RTP1 were found.
CONCLUSION: RTP1 shows significantly protective effects but lower side effects on rats with colitis induced by TNBS. The mechanism may be due to the resistance to over expansion of CD4.
Keywords: $[Keywords]
Citation: Liu L, Wang ZP, Xu CT, Pan BR, Mei QB, Long Y, Liu JY, Zhou SY. Effects of Rheum tanguticum polysaccharide on TNBS -induced colitis and CD4 ⁺ T cells in rats. World J Gastroenterol 2003; 9(10): 2284-2288
Colonic lesion and inflammation induced by TNBS-ethanol were accompanied by a drastic elevation of MPO activity in colonic tissues. This enzyme was used as an index of quantitative inflammation and a marker of neutrophil infiltration in the tissue (Gastroenterology 1989;96:795-811). In the present study, administration of RTP significantly attenuated the increase of colonic MPO activity, indicating its anti-inflammatory effect. SOD is an antioxidant enzyme that is cytoprotective in many tissues, because it scavenges the overproduced superoxide by stimulants. This study showed that the SOD activity in colonic tissue was significantly increased on days 5 and 7, but returned to normal level on days 10 and 14 after TNBS-enema. It is envisaged that the elevated SOD activity may be a protective reaction in the colonic tissue against the overproduction of superoxide during the early active phase of colonic inflammation. Administration of RTP markedly increased SOD activity after TNBS-enema and kept SOD at a higher level till 14 d. This result indicated that the therapeutic effectiveness of RTP on colitis might be at least in part, through its anti-oxidative effect. However, the underlying mechanisms of the therapeutic effectiveness of RTP need further studies. All these findings implicate that RTP has a very impressive therapeutic effectiveness on experimental colitis, and RTP may be the main component of Rheum Rheum tanguticum that is commonly used as a classic Chinese drug against inflammation in gut.
... Other activities. Other bioactivities such as anti-osteoarthritis activity (Wen et al., 2014), gastrointestinal protective (Cho et al., 2000), and anti-diabetic activities (Sun et al., 2005) also have been found in ASP. ...
In recent decades, the polysaccharides from the medicinal plants have attracted a lot of attention due to their significant bioactivities, such as anti-tumor activity, antioxidant activity, anticoagulant activity, antidiabetic activity, radioprotection effect, anti-viral activity, hypolipidemic and immunomodulatory activities, which make them suitable for medicinal applications. Previous studies have also shown that medicinal plant polysaccharides are non-toxic and show no side effects. Based on these encouraging observations, most researches have been focusing on the isolation and identification of polysaccharides, as well as their bioactivities. A large number of bioactive polysaccharides with different structural features and biological effects from medicinal plants have been purified and characterised. This review provides a comprehensive summary of the most recent developments in physiochemical, structural features and biological activities of bioactive polysaccharides from a number of important medicinal plants, such as polysaccharides from Astragalus membranaceus, Dendrobium plants, Bupleurum, Cactus fruits, Acanthopanax senticosus, Angelica sinensis (Oliv.) Diels, Aloe barbadensis Miller, and Dimocarpus longan Lour. Moreover, the article has also been forcused on the applications of bioactive polysaccharides for medicinal applications. Recent studies have provided evidence that polysaccharides from medicinal plants can play a vital role in bioactivities. The contents and data will serve as a useful reference material for further investigation, production and application of these polysaccharides in functional foods and therapeutic agents.
... Water extracts of AS strongly increase the CYP2D6 and CYP3A activity in the microsome fraction in the liver of male Wistar rat (Lin and Chiang 2008). One of the most active ingredients in AS is its polysaccharide (ASP), which exhibits a variety of pharmacological activities, including antioxidative, anti-inflammatory, and immunomodulatory effects (Mei et al. 1991;Cho et al. 2000). ...
This study aimed to investigate the effects of polysaccharide from Angelica and Astragalus (AAP) on carbon tetrachloride (CCl4) induced liver damage in mice. A total of 120 Kunming mice were randomly distributed among 6 groups comprising (i) the normal control mice, (ii) the CCl4 treatment group, (iii) the bifendate treatment group, (iv) the AAP treatment group, (v) the Angelica sinensis polysaccharide (ASP) treatment group, and (vi) the Astragalus membranaceus polysaccharide (AMP) treatment group. AAP, ASP and AMP were administered to mice treated with CCl4. The activities of alanine transaminase (ALT) and aspartate transaminase (AST) in the serum, and superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver tissues were quantified, as well as the liver index. Hepatic histological changes were observed by staining liver sections with hematoxylin and eosin. Our results show that bifendate, AAP, ASP, and AMP significantly decreased the activities of MDA, AST, and ALT, and enhanced the activity of SOD in CCl4-treated mice. Bifendate, AAP, ASP, and AMP consistently ameliorated the liver injuries induced with CCl4. Notably, the hepatoprotective effect of AAP was stronger than that of bifendate, ASP, or AMP. In addition, AAP alleviated liver inflammation and decreased the liver indexes of mice induced with CCl4. These effects were at least partly due to the antioxidant properties of AAP in scavenging free radicals to ameliorate oxidative stress and to inhibit lipid peroxidation.
... [32] Recently, a number of preclinical studies have shown the beneficial effects of Angelica sinensis in animal models of bacteria-induced pneumonia, carrageenaninduced edema, and ethanol-induced hemorrhagic tissue damage. [33] It has been demonstrated that a low molecular weight fraction of Radix Angelicae Sinensis extract dose dependently demolished LPS-induced HMGB1 release in macrophage cultures. Angelica sinensis extract inhibited HMGB1 release in part by interfering with its cytoplasmic translocation, thereby preserving its nuclear localization in LPS-stimulated cells. ...
Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein (HMGB1), are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGB1-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGB1-targeted Chinese herbal therapies in sepsis.
... Angelicae sinensis radix (AS) is commonly used in traditional Chinese medicine to treat several diseases, such as menopausal symptoms [15,16], gastric mucosal damage [17][18][19][20] and hepatic injury [21][22][23]. Previous literatures have shown that AS improves the level of therapeutic angiogenesis for the treatment of ischemic disease [24,25]. ...
Glioblastoma multiforme (GBM) is a highly vascularized and invasive neoplasm. The methanol extract of Angelica sinensis (AS-M) is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. In in vivo studies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.
... Diels (Umbelliferae), known as Dang-gui in Chinese and used widely as a tonic agent, is one of the most important traditional Chinese herbs (Hsu H Y, et al., 1976) and polysaccharides are amongst its principal pharmacologically active constituents. The pharmacological properties of A. sinensis include anti-oxidative, anti-inflammatory, and immunomodulatory activities (Cho C H., et al. 2000;Mei Q B, et al., 1991). ...
In this study, we have investigated the antiviral activity of GuiQi polysaccharides (GQP) upon enterovirus 71 (EV71) in vitro. An assay using methyl thiazolyl tetrazolium (MTT), and analyses of cytopathic effects (CPE) were used to examine the antiviral activity of GQP upon Vero cells infected with EV71. The results revealed that GQP at concentrations below 31.2 μg/mL exhibited significant antiviral effects upon EV71 when applied under three different experimental protocols. GQP was most strongly active in preventing the adsorption of EV71 to target cells and in this respect it was significantly more effective than ribavirin. In addition, it was clear that GQP could inhibit viral replication when added to cells 2 h after infection, but if added at the point of infection its effect was weak. GQP is considered to be less toxic than ribavirin, and may warrant further evaluation as a possible agent in the treatment of hand, foot and mouth disease (HFMD).
... WKY1 was produced by water extraction and ethanol precipitation as described previously [13]. In brief, Astragalus membranaceus and Lycium barbarum mixed at a certain proportion were boiled in 10-fold water for 1.5 h. ...
Kidney Yang Deficiency Syndrome (KDS-Yang), a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine), lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol), gut microbiota metabolism (indole-3-propionic acid), biosynthesis of catecholamine (norepinephrine), and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH), and urine 17-hydroxycorticosteroids (17-OHCS).
... With the rapid social development, it had reached its climax in Tang Dyansty and Song Dynasty, and has been formally authorized as a functional health liquor in 1998 by Ministry of Public Health in China. As a functional health liquor, it has various biological properties like anti-oxidant, anti-fatigue and immunoenhancement [4], and some reports also showed that most of the medical herbs it contains have the effect of hepatic injury protection [5], blood coagulation, antitumor, anti-inflammation, gastrointestinal protection, immunity regulation, anti-oxygen etc. [6][7][8][9] and some which have been used in TCM formulation on clinical practice for their hepatoprotective effects. Our laboratory has identified the main components in ZYQL through systematically chemical isolation and detected by HPLC-PDA detectors in previous study. ...
The study first evaluated the hepatoprotective effect of Zhuyeqing Liquor (ZYQL) against acute alcohol-induced liver injury in mice. Animals were administered orally with 50% alcohol 12 ml/kg at 4 h after the doses of ZYQL everyday for fourteen consecutive days except mice in normal group. The protective effect was evaluated by biochemical parameters including serum aspartate transaminase (AST), alanine transferase (ALT), total-bilirubin (TBIL) and reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissue. The result were confirmed histopathologically and the expression of TNF-alpha in mice liver was determined by immunohistochemistry analysis. HPLC-PDA was used for phytochemical analysis of ZYQL, and the plant source of each compound was claritied by UPLC-TOF-MS. The result showed that pretreatment with ZYQL exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes in a dose depended manner. HPLC analysis indicated that ZYQL contained flavonoids, iridoids, terpenoids and phenolic acids, which might be the active chemicals. This study demonstrated the hepatoprotective activity of ZYQL, thus scientifically supported the founction of its health care.
Polysaccharides from natural sources have the potentials in being used as substitutes of chemosynthetic drugs for gastroprotection because of its safety and efficacy. For giving a better understanding of gastroprotective polysaccharides, the research progress on preparation, structure, bioactivity, and their action mechanism is comprehensively summarized in this review. Moreover, the structure–activity relationship of gastroprotective polysaccharides is discussed. Accumulating evidence has indicated that natural polysaccharides, which were widely prepared by water extraction and column chromatography purifications, exhibited gastroprotective effects in vitro and in vivo. The action mechanism might be related to gastric secretions, promotion of gastric defensive factor releases, antioxidation, anti‐inflammatory, antiapoptosis, and facilitation of proliferation. Phenolic compounds, molecular weight and conformation, monosaccharide composition, backbone structure and side chain, and functional group have great influences on the gastroprotective activities of polysaccharides. This review gives comprehensive guidance to the exploitation and application of natural polysaccharides in food and other industries for gastroprotection. Gastroprotective potentials of polysaccharides from natural sources.
Prunus armeniaca gum exudate (PAGE) is obtained from the trunk branches of apricot trees. PAGE is a high‐molecular‐weight polysaccharide with arabinogalactan structure. The physicochemical and rheological characteristics of this gum have been investigated in various researches. PAGE offers a good potential for use as an emulsifying, binding, and stabilizing agent in food and pharmaceutical industries. It also can be used as an organic additive in tissue culture media, synthesizing of metallic nanoparticles, binding potential in tablets, antioxidant agent, and corrosion inhibitor. For desirable emulsifying, stabilizing, shelf life‐enhancing properties, and antioxidant activity of PAGE, it can be used as additive in many foods. We present here a comprehensive review on the existing literatures on characterization of this source of polysaccharide to explore its potential applications in various systems.
Objective
Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism.
Method
Human primary chondrocytes isolated from articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3)II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localisation and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-Methyladenine (3-MA), chloroquine (CQ) and a specific inhibitor of ERK1/2, SCH772984, were used respectively to confirm the autophagic effect of ASP.
Results
The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocytes proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of ERK1/2 pathway.
Conclusion
ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP a potential therapeutic supplementation for OA treatment.
Objective
Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism.
Method
Human primary chondrocytes isolated from articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3)-II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localisation and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile，activation of ERK 1/2 pathway was determined by western blot. The autophagy inhibitors 3-Methyladenine (3-MA), chloroquine (CQ) and a specific inhibitor of ERK1/2, SCH772984, were used respectively to confirm the autophagic effect of ASP.
Results
The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocytes proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of ERK1/2 pathway.
Conclusion
ASP markedly rescued SNP-induced chondrocyte apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP a potential therapeutic supplementation for OA treatment.
Plant polysaccharides with multiple biological activities and health benefit effects are usually considered as natural active macromolecules in food and medicine dual purposes plant. Nerveless, there are still some problems with plant polysaccharides, such as the lack of concentration in the range of action, poor stability, rapid blood clearance and poor targeting, which affect the bioavailability and clinical application of plant polysaccharides. Over the last decade, researchers have increasingly turned their attention toward understanding the role of plant polysaccharides in normal cellular function and in disease, while opening up new research fronts in designing and developing nanomaterial delivery systems for the treatment of cancer, immune diseases and other diseases using plant polysaccharides as a carrier or object drug. However, deficiencies of NDDS research limits the application of polysaccharides in disease treatment. Herein, advances in the application of plant polysaccharides in nano-based drug delivery systems are reviewed. In addition, the further research on plant polysaccharides in nanotechnology was prospected.
Objective Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism.
Method Human primary chondrocytes isolated from articular cartilage of OA patients were treated with SNP alone or in combination with different dose of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3)-II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localisation and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile,activation of ERK 1/2 pathway was determined by western blot. The autophagy inhibitors 3-Methyladenine (3-MA), chloroquine (CQ) and a specific inhibitor of ERK1/2, SCH772984, were used respectively to confirm the autophagic effect of ASP.
Results The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocytes proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of ERK1/2 pathway.
Conclusion ASP markedly rescued SNP-induced chondrocyte apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP a potential therapeutic supplementation for OA treatment.
Worldwide, Helicobacter pylori (H. pylori) is regarded as the major etiological agent of peptic ulcer and gastric carcinoma. Claiming about 50 percent of the world population is infected with H. pylori while therapies for its eradication have failed because of many reasons including the acquired resistance against its antibiotics. Hence, the need to find new anti-H.pylori medications has become a hotspot with the urge of searching for alternative, more potent and safer inhibitors. In the recent drug technology scenario, medicinal plants are suggested as repositories for novel synthetic substances. Hitherto, is considered as ecofriendly, simple, more secure, easy, quick, and less toxic traditional treatment technique. This review is to highlight the anti-H. pylori medicinal plants, secondary metabolites and their mode of action with the aim of documenting such plants before they are effected by cultures and traditions that is expected as necessity.
The polysaccharide (PS) fractions isolated from fungi and higher plants have been shown as potent biological response modifiers exhibiting immunostimulating and antitumor activities through the functions involving activation of macrophages, cell-mediated immunity and cytokine induction. The primary structure of these PSs exhibits β(1->3), β(1->4)-linkage glycan as the common form of main chain, while the side chains involve β(1->3), β(1->4), β(1->6) or α(1->4) linkages. The hydrogen bond, tertiary structure of triple helix, and high molecular weight contribute to the stability and biological activities of the PSs. The degree of substitution on the backbone chain and the length of the side chains are important for the conformation of structure and their immunologic activity. Here we review the biochemical characterization, immunomodulating activities, and clinical application of important PSs isolated from fungi including Lentinus, Ganoderma, Hoelen, Polyporus, and Ascomyces and higher plants such as Radix Astragali, Angelica, Ginseng, and others. Immunomodulating PSs thus far have been used to prevent disease and promote restoration of the body's homeostasis, and current evaluations focus on treatment of pathogenic factors. Development of these polysaccharides into drugs for therapeutic use needs research on structure-activity relationship and quality assurance for polysaccharide molecules and final products. © 2004, Medical and Pharmaceutical Society for WAKAN-YAKU. All rights reserved.
The results of studies of medicinal plants are given. The peculiarity their biology, physiology and phytochemistry, reproduction and cultivation, use in medicine and industry was considered.
Plants continue to be significant sources of new chemical entities that are useful for combating a variety of human diseases. Several recent studies have documented the importance and potential of natural products chemistry in general (Cragg et al. 1997; Henkel et al. 1999) and of phytochemistry of plants in particular (Balandrin et al. 1993; Chadwick & Marsh 1990; Farnsworth 1988; Farnsworth & Bingel 1977; Farnsworth & Morris 1976; Farnsworth et al. 1985; Kinghorn 1994; Kinghorn & Balandrin 1993) for the discovery of medicinally useful agents. Plant based medicines have formed the foundation of most modern European and American medicinal therapies, particularly those that originated before World War II. At least 60 of the more important medicines in North America are still derived from higher plant materials. Natural medicines such as these have been developed principally from three botanical sources: bacteria (including blue-green algae), microscopic fungi and higher plants. Bacteria and fungi have been heavily studied because of their pathogenic properties. Many of these same properties led to the discovery of antibiotics and some anti-tumor agents. The need to understand infectious organisms therefore has led to the development of new pharmaceuticals in Europe and industrialized former European colonies. In other, non-European cultures, different disease pressures have led to development of drugs from different sources.
Background: The purpose of this study was to examine the effect of a leaf extract from A. archangelica on the growth of Crl mouse breast cancer cells in vitro and in vivo. Materials and Methods: The antiproliferative activity of the extract was measured by H-3-thymidine uptake in the Crl cells in vitro. Twenty mice were injected with the Crl cells, and 11 of them were fed A. archangelica leaf extract, and the progress of the tumours was followed. Results: The leaf extract was mildly antiproliferative on the Crl cells with an EC50 of 87.6,ug/ml. The antitumour activity of the extract was expressed in the mice by marked reduction in tumour growth. In the experimental animals, 9 out of 11 mice developed no or very small tumours, whereas control animals, not receiving the extract, developed significant larger tumours (p < 0.01), as estimated by Mann-Whitney U-test. The antitumour activity of the leaf extract could not be explained by the antiproliferative activity of furanocoumarins present in the extract. Conclusion: The results demonstrate the antiproliferative activity in vitro and antitumour activity in vivo of a leaf extract from A. archangelica.
Angiotensin converting enzyme (ACE) inhibitors are widely used in treatment of cardiovascular diseases. Their long term use causes development of anemia in patients with these diseases. Present study was designed to evaluate the protective hematopoietic potential of Angelica sinensis polysaccharides (ASP) against ACE inhibitor-induced anemia along with their toxic effects on kidney and liver cells. Adult male albino rats were randomly divided into five equal groups (n=6). Group I was control group and group II was administered with ACE inhibitor (20 mg/kg/day) to induce anemia. In group III, ACE inhibitor was administered (20 mg/kg/day) in combination with erythropoietin (EPO, 100 IU/kg/each). Group IV was administered with ASP at the dose rate of 1 g/kg/day. In Group V, ACE inhibitor (20 mg/kg/day) was administered in combination with ASP (1 g/kg/day). After 28 days, blood and tissue samples were collected for hematological and histopathological analysis respectively. The results showed that ACE inhibitors significantly reduced (P<0.05) the hemoglobin value (Hb), packed cell volume (PCV), red blood cell (RBC) count, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) values. In group treated with ASP, there was significant (P<0.05) increase in Hb value and RBC count. The combination of ACE inhibitor and ASP led to the significant (P<0.05) reduction in Hb, PCV, RBC count, MCV and MCH values. While histopathological examination of liver and kidney cells showed a mild degree of toxicity in ASP treated group. (c) 2015 PVJ. All rights reserved
The root of burdock (Arctium lappa L.) has long been cultivated as a popular vegetable in Taiwan and Japan for dietary use and folk medicine. The present study investigates the effects of Bao-Jian burdock extract powders (BJBEP), a commercialized burdock extract preparation, on gastric mucosal protection. In vitro study, BJBEP revealed significant protection on rat gastric mucosalcells, RGM1, from indomethacin (INDO)-caused cytotoxicity at the concentration of 125-1000 ppm, whose efficacy was comparable with that of sucralfate from a concentration point of view. In vivo study, ethanol-induced acute gastric mucosal lesions (AGML) were applied to assess the gastroprotective activity of BJBEP in rats. BJBEP was able to decrease significantly the AGML areas caused by ethanol at the dose of 260 to 2600 mg/kg/bw. Total polyphenols in BJBEP was in proportion to its free radical scavenging activity which could be involved in biological function of gastric mucosa protective activity. The overall results indicate that BJBEP has protective effect on INDO-induced gastric mucosal cytotoxicity in vitro and ethanol-induced AGML in rats.
Angelica sinensis has been widely used to treat some psychosomatic illnesses, amnesia, anemia, and gynecological diseases in traditional Chinese medicine for thousands years. In this paper, we determined the protective effect of Angelica sinensis volatile oil (ASVO) on primary culture cortical cells damaged by glutamate. Excitotoxicity induced by glutamate caused the production of reactive oxygen species (ROS), the decrease in antioxidant enzymes levels, the decline in mitochondrial transmembrane potential (MMP), and the increase in apoptosis and necrosis. When administered either before or after the glutamate insult, ASVO could increase the cell viability significantly and could maintain the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), all of which played important roles in the antioxidative defense mechanism. Flow cytometry analyse revealed ASVO could obviously alleviate apoptosis and necrosis induced by glutamate, the mechanism was probably involved with maintaining MMP, inhibiting Ca2+ influx, and increasing the expression of bcl-2 while suppressing the expression of bax. The results of this study demonstrated that AVSO possessed the activity to prevent the neurotoxicity induced by glutamate, implying that AVSO has a potential foreground in the therapy of neuro-excitotoxicity diseases.
The water-soluble crude polysaccharides were extracted from the safflower with hot water followed by precipitating with ethanol and drying. Then, the polysaccharides were hydrolyzed with sulfuric acid in the boiling water. The monosaccharide composition of polysaccharides from the safflower was analyzed by ion chromatography-pulsed amperometric detection. This method is simple, sensitive and selective without derivatization. Under the optimum conditions, our results show that the polysaccharide fraction is mainly composed of fucose, rhamnose, arabinose, mannose, glucose, galactose and fructose. The linear ranges of this method for these monosaccharides are in the range of 0.02 to 20 mg·L-1 with the correlation coefficients r≥0.999 2, whereas the detection limits calculated at S/N=3 are in the range of 3.70 to 11.35 μg·L-1. The recoveries are in the range of 87.2% to 111.6% with the relative standard deviations are from 1.26% to 3.61%.
The reversed-phase high performance liquid chromatographic (HPLC) method of precolumn-derivatization with 1-phenyl-3-methyl-5-pyrazolone(PMP) was developed to separate the traditional nine monosaccharides and detect the monosaccharide composition of Angelica polysaccharides with good reproducibility. In this study, it was found that sulfuric acid and trifluoroacetic acid possessed the same ability for hydrolyzing Angelica polysaccharides and the component monosaccharides were completely released from the polysaccharides until hydrolyzing for 8 h, and the whole drying processes of the acid hydrolysates and their PMP-derivatives could be omitted. The results of HPLC analysis showed that Angelica polysaccharides consisted of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabonose with the molar ratio of 0.57:1.00:0.13:3.06:8.16: 7.17:12.7. The HPLC method is simple, rapid, sensitive, convenient and can be applied to the quality control of Angelica polysaccharides.
Apply the univariate and orthogonal experiments, the purity of polysaccharide as index, to optimize the best purification conditions of natural clarifying agents ZTC1+1IIon Angelica polysaccharides. To determine the optimal temperature, the amount of clarifying agent, the concentration of the extracting solution of Angelica, flocculation time, to select stable and feasible polysaccharide purification process.
The dried root of Angelica sinensis is widely used in Chinese traditional medicine for its beneficial effects against several diseases, including osteoarthritis. In order to understand the mechanism of action, two main components of the plant, the phytochemical, sodium ferulate, and a polysaccharidic fraction have been tested on osteoarthritis animal models or in human chondrocytes stimulated by the pro-inflammatory cytokine, Interleukine-1β. The results showed that sodium ferulate exhibited marked anti-inflammatory and anti-apoptotic properties by inhibiting the TNF/TNFR signal transduction pathway. On the other hand, the polysaccharidic fraction which contains a mixture of various carbohydrates was found to promote proteoglycan biosynthesis in cartilage matrix by stimulating the activity of the UDP-glycosyltransferases that synthesize the chondroitin sulfate chains of aggrecans. It is suggested that the combined action of sodium ferulate and polysaccharidic fraction would prevent cartilage destruction in osteoarthritis and favor cartilage repair.
Angelica and Astragalus, Chinese herbal medicine, are used as immunostimulants for enriching the blood, anti-tumor and antioxidation effects. However, the synergistic mechanisms of antioxidant and antitumor effects have long been the object of intensive study. We investigated the deferring senile effect of polysaccharides from Angelica and Astragalus (AAP) on aging mice by determination of the contents of monoamine oxidase (MAO) in brain, hydroxyproline (Hyp) in skin. In addition, KM mice with murine H22 hepatocarcinoma cell model were used to study the in vivo antitumor efficacy of AAP by measuring inhibition rate of tumor and immune organs index. The obtained results showed that AAP decreased significantly the content of MAO, and enhanced the concentrations of Hyp in aging mice. No significant differences were found as compared with those of vitamin E. The results of anti-tumor showed that inhibition rate of the higher dose of AAP was 43.8%, and it could enhance immune organs index. Our study indicates that AAP has significant deferring senile effect on the aging mice and suppressing the growth of H22 solid tumor in mice.
Lycium barbarum and Astragalus membranaceus are two traditional medicinal herbs widely used in China for nourishing Yin and reinforcing Qi.
The purpose of the study was to investigate the prophylactic and curative effects of crude polysaccharides (QHPS) extracted from a two-herb formula composed of Lycium barbarum and Astragalus membranaceus at a ratio of 2:3 in colitis rats, and to further elucidate the potential mechanism of action in epithelial cell proliferation in vitro.
An acetic acid (AA)-induced ulcerative colitis rat model was applied in the study. Two independent protocols were used to assess the prophylactic and curative effects of QHPS respectively, in which rats were either pre-treated with QHPS (0.18g/kg) for 14 days prior to AA induction, or post-treated with QHPS for 7 days after AA induction. The stool consistency and weight loss were used to evaluate disease activity. The morphological changes in intestinal mucosa at the end of the experiments were observed. The serum levels of endotoxin (EDT), diamine oxidase (DAO) and D-lactate (DLA), important biochemical markers for evaluating intestinal mucosal structure and function, were measured. In the in vitro mechanistic studies, rat intestinal epithelial cells (IEC-6) was used to access for epithelium regeneration.
The intra-colonic instillation of AA induced ulcerative colitis in rat, as indicated by diarrhea, weight loss, and colonic mucosal damage. Both prophylactic and curative treatments effectively reduced the weight loss and diarrhea and attenuated the colonic mucosal damage associated with inducible colitis. The significant increase in serum levels of DAO, DLA and EDT were induced by AA and inhibited by QHPS treatment. Moreover, QHPS could significantly stimulate IEC-6 proliferation in a dose- dependent manner (p<0.05).
The present study indicated for the first time that polysaccharides extracted from this two-herb formula can protect against experimental ulcerative colitis, presumably by promoting the recovery of the intestinal barrier.
Decursinol is one of the coumarins purified from the dried roots of Angelica gigas Nakai (Umbelliferae) and has various pharmacological effects including an analgesic property. Although aspirin is widely used to reduce pain and inflammation, aspirin-induced gastric damage remains the major limitation to its use. Therefore, the anti-ulcer activity of decursinol in aspirininduced gastric ulcer in mice was examined. One group of mice was treated orally once daily with aspirin (300 mg/kg) and another group was co-administered with decursinol (10, 25, 50, and 100 mg/kg) and aspirin (300 mg/kg) orally once daily for 5 consecutive days. On day 6, the gastric mucosae were examined. Animal groups co-administered with decursinol and aspirin exhibited a dose-dependent reduction of gastric damage against aspirin-induced gastric ulceration. The extent of inhibitions for the respective doses employed was 11.1, 15.8, 50.3, and 70.4%, respectively. These results suggest that combination therapy with aspirin and decursinol may be useful to alleviate pain and inflammation without major gastrointestinal side effects.
The root of Angelica sinensis (Oliv.) Diels, a well-known Chinese herbal medicine, has been used historically as a tonic, hematopoietic and anti-inflammatory agent for thousands of years. Modern phytochemistry and pharmacological experiments have proved that polysaccharide is one of the major active ingredients in A. sinensis. It has been demonstrated that A. sinensis polysaccharides had various important biological activities, such as hematopoiesis, immunomodulation, antitumor, antioxidant, radioprotection and hypoglycemic activity. The purpose of the present review is to summarize previous and current references regarding extraction and purification techniques as well as structural characterization and biological activities of A. sinensis polysaccharides.
We have examined the gastric luminal content of Na+, K+, and protein and mucosal levels of myeloperoxidase in rats between the ages of 10 and 60 days in response to luminal instillation of ethanol (20 and 50% w/v). In control animals the appearances of ions and protein and myeloperoxidase activities were low and similar in all age groups. Luminal content of cations and protein increased in response to both 20 and 50% ethanol and were greater in animals older than 20 days when compared with younger rats. However, ethanol treatment resulted in a significant degree of mucosal cellular disruption and erosions in both young and mature rats. Myeloperoxidase activities in response to ethanol were not greater than control until animals were older than 20 days. Treatment of rats aged 10-60 days with intraperitoneal glycogen (1%) resulted in peritoneal granulocyte infiltration. The concentration of peritoneal cells increased as animals aged. With the exception of day 15, the myeloperoxidase content of the peritoneal leukocytes did not vary significantly at other ages examined. These data suggest that (1) mucosal efflux of Na+, K+, and protein in response to luminal ethanol increase as rats age from 10 to 60 days; (2) the ontogenic development of ethanol-induced cation and protein appearance parallel the increase in myeloperoxidase activity in the gastric mucosa; and (3) the increase in mucosal myeloperoxidase activity in response to ethanol likely reflects increased granulocyte infiltration as rats age.
The need for dextran fractions with a narrow molecular-weight distribution for clinical use is well known. The definition of such material has significantly improved by the use of gel permeation chromatography (GPC) techniques. However, an internationally accepted standard method of analysis giving accurate and reproducible results in different laboratories has yet to be defined. This paper reviews the GPC packings that can be or have been used for determining the molecular weight distribution of dextran polymers. The application of GPC to the determination of the molecular weight of dextrans on TSK PW type columns is described and its accuracy and reproducibility are discussed. This material appears to meet the criteria required for a standard method.
Tumor necrosis factor alpha (TNF-α) has been suggested to play a critical role in indomethacin-induced gastric mucosal damage, so we evaluated its mucosal level and its relationship with prostaglandin E2 and neutrophils in indomethacin-induced gastric mucosal injury in rats. Indomethacin caused a time- and dose-dependent increase in gastric mucosal erosion, which was accompanied by a reduction in prostaglandin E2 followed by an increase in TNF-α level and neutrophil infiltration in the gastric mucosa. Pretreatment with exogenous prostaglandin E2 totally abolished indomethacin-induced gastric mucosal injury and the TNF-α increase. Depletion of neutrophils by methotrexate or reduction of TNF-α concentration by pentoxifylline markedly reduced indomethacin-induced mucosal damage. Pentoxifylline but not methotrexate prevented the increase in mucosal TNF-α level induced by indomethacin. It is suggested that depletion of prostaglandin E2 followed by an increase of TNF-α production and neutrophil infiltration in the gastric mucosa are important sequential processes in indomethacin-induced ulceration. Prevention of one of these processes would inhibit ulcer formation.
The effects of a weakly acidic polysaccharide fraction, GL-4, from the leaves of Panax ginseng C. A. Meyer on various experimental gastric ulcer models in mice and rats have been studied. Oral administration of GL-4 at doses of 50 to 200 mg/kg inhibited the formation of the gastric lesions induced by necrotizing agents such as HCl/ethanol and ethanol in a dose-dependent manner. This protective effect was observed not only upon oral but also upon subcutaneous administration of GL-4 (50-100 mg/kg). GL-4 also inhibited the formation of gastric ulcers which were induced by water immersion stress, indomethacin, or pylorus-ligation. The contents of prostaglandin E2 in the gastric juice from rats were not influenced by oral administration of GL-4. The protective action of GL-4 against HCl/ethanol-induced gastric lesions was not abolished by pretreatment with indomethacin. When GL-4 (100 mg/kg, p.o.) was administered into pylorus-ligated rats, both gastric acidity and pepsin activity in the gastric juice decreased significantly.
The role of vagus in the actions of different acid inhibitors on ethanol-induced gastric damage and mucosal blood flow (GMBF) changes was studied in anaesthetized rats, using an ex vivo stomach chamber preparation. Subdiaphragmatic bilateral vagotomy decreased the basal gastric acid secretion and GMBF; it also intensified ethanol-evoked lesions in the glandular mucosa. Misoprostol, omeprazole and cimetidine produced a similar degree of reduction in acid output. Misoprostol given subcutaneously (s.c.) (50 micrograms/kg), or added to the incubation solution (12.5 micrograms) for 15 min, markedly prevented ethanol-induced lesion formation and reduction in GMBF. The reversing effect of s.c. injection of misoprostol on either lesion formation or on GMBF reduction was attenuated by vagotomy. Omeprazole protected against lesion formation only when present in the incubation solution (12.5 mg) of ex vivo chamber preparations of both vagus-intact and vagotomized animals, but the effect was significantly less in the latter group. The drug also prevented the depressive action of ethanol in vagus-intact animals. Cimetidine pretreatment (50 mg s.c. or 12.5 mg in incubation solution), however, did not modify the effects of ethanol on lesion formation and the GMBF. The findings indicate that the three different types of acid inhibitors exert different actions on ethanol-induced gastric mucosal damage, although they produced similar inhibition of acid output. Vagotomy lowers the GMBF and attenuates the antiulcer action of misoprostol and omeprazole, especially when the drugs are given by the parenteral route.
The involvement of endogenous prostaglandins (PGs) in modulating gastric mucosal blood flow (GMBF) is still unclear. The present study was designed to demonstrate the role of this autacoid in the basal GMBF and the restoration of blood flow after restriction of blood supply to the stomach. The ex-vivo gastric chamber was prepared and the GMBF was measured by a laser Doppler technique. 20% ethanol incubation for 10 min in the chamber increased the basal GMBF and lessened the reduction of blood flow induced by absolute ethanol. It also decreased lesion formation caused by ethanol. Indomethacin 5 mg/kg, given s.c 60 min before experimentation had the opposite effects. Ligation of the gastric artery for 20 min which reduced the GMBF by 60%, worsened ethanol ulceration. There was a marked rebound of the GMBF after the ligation was released. Indomethacin totally abolished the blood flow rebound and aggravated ethanol ulceration. However, 20% ethanol incubation significantly potentiated such a rebound in blood flow and reduced lesion formation. Indomethacin pretreatment reversed these actions, whereas misoprostol administration produced the similar effects as 20% ethanol. It is concluded that GMBF plays an important role in ethanol ulceration and both basal and rebound GMBF is probably modulated by endogenous PGs.
The effects of daily administration of ulcerogenic doses of the glucocorticoids, dexamethasone and prednisolone, on gastric prostaglandin and leukotriene synthesis were examined in the rat. Significant gastric damage was not observed until the fourth day of treatment with dexamethasone and until the sixth day of treatment with prednisolone. However, the onset of gastric damage was not accompanied by any significant effect of these drugs on gastric 6-keto prostaglandin Fl alpha synthesis. Conversely, both drugs caused a reduction in gastric leukotriene C4 synthesis, with dexamethasone producing a highly significant (p less than 0.001) effect. Furthermore, there was a highly significant (p less than 0.001) correlation between the ability of these drugs to inhibit gastric leukotriene C4 synthesis, and their ability to reduce gastric tissue levels of the neutrophilic enzyme myeloperoxidase. Thus, glucocorticoid-induced gastric damage does not appear to be related to inhibitory effects of these drugs on prostaglandin synthesis. Whether or not effects of these drugs on gastric leukotriene C4 synthesis and myeloperoxidase activity are relevant to the mechanism of ulceration is unclear.
The relation of blood flow stasis to the development of unequivocal histologic necrosis (loss of parietal cells from the column of contiguous cells) in ethanol-induced gastric mucosal injury was studied in anesthetized rats. The most rapid vascular change that occurred when the gastric mucosa was exposed to 100% ethanol was a severe segmental constriction of the large submucosal venules. At 22 sec, the average venular diameter was 52.2 +/- 6.0% of the original one. This was followed by complete superficial mucosal blood flow stasis at 49 +/- 4 sec and appearance of histologic evidence of necrosis in one of seven rats at 2.5 min, four of six rats at 10 min, and seven of seven rats at 60 min. We conclude that in ethanol-induced gastric mucosal injury, submucosal venular constriction occurs first, followed by cessation of mucosal blood flow to be followed later on with histologic evidence of necrosis.
Modifications to the Coomassie blue G dye-binding assay for protein are described which remove much of the variation previously observed in the response of this assay to different proteins. Increasing the concentration of dye in the assay solution, or decreasing the concentration of phosphoric acid, increased the color yield of a range of proteins to values close to that of the standard protein bovine serum albumin. The sensitivity of the assay was also increased so that a protein concentration of 2 μg/ml can be accurately determined in a sample volume of 50 μl.
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause clinically important gastric damage by several mechanisms. In order to evaluate the role of neutrophil infiltration in lesion formation, tissue myeloperoxidase activities were assessed in different gastric layers of the stomach both in rats with normal neutrophil levels and in neutropenic rats. Sprague-Dawley rats were treated either with indomethacin (Indo; 25 mg/kg, s.c.) or the vehicle. A group of rats were made neutropenic by administration of methotrexate (MTX; 2.5 mg/kg i.p.) once a day for 3 days. The stomachs were removed for the determination of lesion index, glutathione, lipid peroxide levels, protein oxidation and tissue myeloperoxidase activities. MTX treatment appeared to reduce neutrophil infiltration significantly while producing insignificant effects on eosinophils and macrophages. Indo administration caused multiple gastric lesions and treatment with MTX significantly reduced lesion index. In rats treated with Indo, neither glutathione nor LP levels showed any significant changes but the protein oxidation was significantly higher than that of other groups. The MPO level of gastric mucosa was increased in Indo-treated rats and reversed by MTX pretreatment. The results of the present study indicate that neutrophil infiltration in the gastric mucosa of rats may be involved in the pathogenesis of NSAID-induced gastric mucosal injury, but no correlation was found between lesion formation and protein oxidation in the gastric mucosa.
Cigarette smoking has been associated with peptic ulceration. However, the ulcerogenic mechanisms are still undefined. The aim of this study was to investigate the effects and possible mechanisms of cigarette smoke on ethanol- or cold-restraint stress-induced gastric damage.
Rats were exposed to cigarette smoke followed by either an ethanol (70%) challenge or cold-restraint stress. The severity of mucosal damage, levels of prostaglandin E2 and leukotriene C4, determined by radioimmunoassay, and neutrophil infiltration in the stomach were assessed.
Smoke dose-dependently potentiated ethanol-but not stress-induced ulcer. It reduced mucosal prostaglandin E2 and increased myeloperoxidase activity. Filtered cigarette smoke did not have these effects. The acidic fraction from the filters produced similar potentiating effects and also delayed ulcer healing. Mucosal leukotriene C4 and serum nicotine levels did not correlate with the mucosal injury in the stomach. Neutropenia abolished the ulcerogenic action and the increase of myeloperoxidase activity produced by both cigarette smoke and acidic fraction.
Reduction of prostaglandin E2 and increase in neutrophil accumulation in the gastric mucosa are responsible for the potentiating action of acute smoke exposure on ethanol-induced gastric damage. Substances other than nicotine could contribute to these adverse reactions in the stomach.
To investigate whether or not heparin can accelerate the healing process of acetic acid-induced gastric ulcers in rats and to identify the mechanisms for heparin to produce this effect, so that we can develop a new therapeutic application to heparin besides its traditional anticoagulant activity.
Male Sprague-Dawley rats were used to produce acetic acid-induced gastric ulcers. Heparin in the doses of 100, 500, and 1000 U/kg were administered intravenously through the tail vein once daily, starting 1 day after ulcer induction for 7 days in the dose-response experiment or heparin 1000 U/kg at a time schedule of 3, 5, and 7 days in the time-response study, respectively. The gastric mucosal blood flow (GMBF) was measured using a laser Doppler flowmeter under ether anesthesia. The rats were then sacrificed and the ulcer areas were measured. The gastric mucosa was then scraped for the determinations of mucosal prostaglandin E2 (PGE2) level and myeloper-oxidase (MPO) activity.
Heparin in the doses of 500 and 1000 U/kg accelerated the healing of acetic acid ulcers in a dose-dependent manner. The highest dose of heparin also reduced the ulcer areas in a time-dependent fashion. The effect was accompanied by an increase in gastric mucosal PGE2 levels. The same dose of heparin not only decreased the gastric mucosal MPO activity but also increased the GMBF in a time-related manner.
Heparin with the doses used in the present study accelerated the healing of acetic acid-induced gastric ulcers in rats in a dose- and time-dependent manner, and this action was related to its effects to increase the levels of gastric mucosal PGE2 and GMBF as well as to decrease the gastric mucosal MPO activity.