ABSTRACT Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34þ cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA=Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 0.06 g=100 g vs. 4.97 0.07 g=100 g; blood sugar levels at week 5, 16 1.30 mmol=L vs. 10.2 0.92 mmol=L; ejection fraction, 57.5 2.23 vs. 68.2 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.
In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.
OBJECTIVE: To review the literature concerning the physiology of the endocannabinoid system, current drug development of cannabinoid agonists, and current clinical research on the use of cannabinoid agonists for analgesia.
DATA SOURCES:Articles were identified through a search of MEDLINE (1966-August 2005) using the key words cannabis, cannabinoid, cannabi*, cannabidiol, nabilone, THC, pain, and analgesia. No search limits were included. Additional references were located through review of the bibliographies of the articles identified.
STUDY SELECTION AND DATA EXTRACTION:Studies of cannabinoid agonists for treatment of pain were selected and were not limited by pain type or etiology. Studies or reviews using animal models of pain were also included. Articles that related to the physiology and pharmacology of the endocannabinoid system were evaluated.
DATA SYNTHESIS:The discovery of cannabinoid receptors and endogenous ligands for these receptors has led to increased drug development of cannabinoid agonists. New cannabimimetic agents have been associated with fewer systemic adverse effects than delta-9-tetrahydrocannabinol, including recent development of cannabis medicinal extracts for sublingual use (approved in Canada), and have had promising results for analgesia in initial human trials. Several synthetic cannabinoids have also been studied in humans, including 2 cannabinoid agonists available on the international market.
CONCLUSIONS:Cannabinoids provide a potential approach to pain management with a novel therapeutic target and mechanism. Chronic pain often requires a polypharmaceutical approach to management, and cannabinoids are a potential addition to the arsenal of treatment options.
Hericium is a genus of mushrooms (fungus) in the Hericiaceae family. Hericium erinaceus (HE) has been used for the treatment of digestive diseases for over 2000 years in China. HE possesses many beneficial functions such as anticancer, antiulcer, antiinflammation and antimicrobial effects, immunomodulation and other activities. The aim of the studies was to evaluate the anticancer efficacy of two extracts (HTJ5 and HTJ5A) from the culture broth of HE against three gastrointestinal cancers such as liver, colorectal and gastric cancers in both of in vitro of cancer cell lines and in vivo of tumor xenografts and discover the active compounds.
MATERIALS AND METHODS:
Two HE extracts (HTJ5 and HTJ5A) were used for the studies. For the study of chemical constituents, the HTJ5 and HTJ5A were separated using a combination of macroporous resin with silica gel, HW-40 and LH-20 chromatography then purified by semipreparative high-performance liquid chromatography (HPLC) and determined by nuclear magnetic resonance (NMR) spectra. For the in vitro cytotoxicity studies, HepG2 and Huh-7 liver, HT-29 colon, and NCI-87 gastric cancer cell lines were used and MTT assay was performed to determine the in vitro cytotoxicity. For in vivo antitumor efficacy and toxicity studies, tumor xenograft models of SCID mice bearing liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 subcutaneously were used and the mice were treated with the vehicle control, HTJ5 and HTJ5A orally (500 and 1000mg/kg/day) and compared to 5-fluorouraci (5-FU) at the maximum tolerated dose (MTD, 25-30mg/kg/day) intraperitoneally daily for 5 days when the tumors reached about 180-200mg (mm(3)). Tumor volumes and body weight were measured daily during the first 10 days and 2-3 times a week thereafter to assess the tumor growth inhibition, tumor doubling time, partial and complete tumor response and toxicity.
Twenty-two compounds were obtained from the fractions of HTJ5/HTJ5A including seven cycli dipeptides, five indole, pyrimidines, amino acids and derivative, three flavones, one anthraquinone, and six small aromatic compounds. HTJ5 and HTJ5A exhibited concentration-dependent cytotoxicity in vitro against liver cancer HepG2 and Huh-7, colon cancer HT-29, and gastric cancer NCI-87 cells with the IC50 in 2.50±0.25 and 2.00±0.25, 0.80±0.08 and 1.50±0.28, 1.25±0.06 and 1.25±0.05, and 5.00±0.22 and 4.50±0.14mg/ml; respectively. For in vivo tumor xenograft studies, HTJ5 and HTJ5A showed significantly antitumor efficacy against all four xenograft models of HepG2, Huh-7, HT-29 and NCI-87 without toxicity to the host. Furthermore, HTJ5 and HTJ5A are more effective than that of 5-FU against the four tumors with less toxicity.
HE extracts (HTJ5 and HTJ5A) are active against liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 cells in vitro and tumor xenografts bearing in SCID mice in vivo. They are more effective and less toxic compared to 5-FU in all four in vivo tumor models. The compounds have the potential for development into anticancer agents for the treatment of gastrointestinal cancer used alone and/or in combination with clinical used chemotherapeutic drugs. However, further studies are required to find out the active chemical constituents and understand the mechanism of action associated with the super in vivo anticancer efficacy. In addition, future studies are needed to confirm our preliminary results of in vivo synergistic antitumor efficacy in animal models of tumor xenografts with the combination of HE extracts and clinical used anticancer drugs such as 5-FU, cisplatin and doxurubicin for the treatment of gastrointestinal cancers.
Bone marrow-derived stem cells have the ability to migrate to sites of tissue damage and participate in tissue regeneration. The number of circulatingstem cells has been shown to be a key parameter in this process. Therefore, stimulating the mobilization of bone marrow stem cells may accelerate tissue regeneration in various animal models of injury. In this study we investigated the effect of the bone marrow stem cells mobilizer StemEnhance (SE), a water-soluble extract of the cyanophyta Aphanizomenon flos-aquae (AFA), on hematopoietic recovery after myeloablation as well as recovery from cardiotoxin-induced injury of the anterior tibialis muscle in mice. Control and SE-treated female mice were irradiated, and then transplanted with GFP(+) bone marrow stem cells and allowed to recover. Immediately after transplant, animals were gavaged daily with 300 mg/kg of SE in PBS or a PBS control. After hematopoietic recovery (23 days), mice were injected with cardiotoxin in the anterior tibialis muscle. Five weeks later, the anterior tibialis muscles were analyzed for incorporation of GFP(+) bone marrow-derived cells using fluorescence imaging. SE significantly enhanced recovery from cardiotoxin-injury. However, StemEnhance did not affect the growth of the animal and did not affect hematopoietic recovery after myeloablation, when compared to control. This study suggests that inducing mobilization of stem cells from the bone marrow is a strategy for muscle regeneration.