Peibo Li

Immuno-enhancement effects of Shenqi Fuzheng Injection on cyclophosphamide-induced immunosuppression in Balb/c mice

ETHNOPHARMACOLOGICAL RELEVANCE Radix Codonopsis and Radix Astragali, of which Shenqi Fuzheng Injection (SFI) is composed, are commonly used in traditional Chinese medicine to improve immune function against chronic diseases. AIM OF THE STUDY The present study was thus designed to systematically elucidate the in vivo immuno-enhancement effects of SFI in immunosuppressed mice induced by cyclophosphamide (Cy) treatment. MATERIALS AND METHODS Balb/c mice were injected intraperitoneally (i.p.) once daily with low-dose (2.5 g raw materials/kg), intermediate-dose (5 g raw materials/kg), high-dose (10 g raw materials/kg) of SFI for 10 consecutive days, respectively, accompanied by i.p. injection of Cy (80 mg/kg) on Days 4-6. RESULTS Compared with vehicle group, low-, intermediate- and high-dose SFI treatment accelerated recovery dose-dependently of spleen index, peripheral white blood cell and bone marrow cell counts, enhanced T cell and B cell proliferation responses, as well as splenic nature killer cell activity and peritoneal macrophage phagocytosis, and restored the level of interleukin-2 in the serum. Furthermore, SFI treatment promoted recovery of the amount of peripheral white blood cells on Day 6, rather than recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF) did. CONCLUSIONS These results demonstrate, for the first time, that chronic treatment with SFI results in accelerating recovery of immunosuppression in Cy-treated mice, which is competent in taking into consideration for both precautions and remedy. Our findings provide experimental evidences for further researches and clinical application in cancer patients undergoing chemotherapy.

Hepatoprotective effect of Hypericum japonicum extract and its fractions.

OBJECTIVE To investigate the hepatoprotective activity of different parts of Hypericum japonicum against carbon tetrachloride(CCl(4))-induced hepatitis and alpha-naphthyl-isothiocyanate (ANIT)-induced cholestasis. MATERIALS AND METHODS Mice were divided into groups and then administrated orally with solutions extracted from herbs before they were modeled in the experiments. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (T-BIL) in serum were evaluated. HPLC fingerprint was used for phytochemical analysis of the extracts. RESULTS The total aqueous extract of Hypericum japonicum had an obvious effect on the decreasing of AST, ALT and T-BIL levels in serum. The isolated fraction IV (F4) exhibited a preferable activity of ameliorating cholestasis, while Fraction V (F5) was more efficacious in protecting liver from injury. Chemical fingerprint indicated that F5 contained several flavonoids which might be the active chemicals against hepatotoxicity. CONCLUSION Different fractions of Hypericum japonicum manifest different effect, indicating their different potentials as candidacies of new drugs.

AlzPlatform: an Alzheimer's disease domain-specific chemogenomics knowledgebase for polypharmacology and target identification research.

Alzheimer’s disease (AD) is one of the most complicated progressive neurodegeneration diseases that involve many genes, proteins, and their complex interactions. No effective medicines or treatments are available yet to stop or reverse the progression of the disease due to its polygenic nature. To facilitate discovery of new AD drugs and better understand the AD neurosignaling pathways involved, we have constructed an Alzheimer’s disease domain-specific chemogenomics knowledgebase, AlzPlatform (www.cbligand.org/AD/) with cloud computing and sourcing functions. AlzPlatform is implemented with powerful computational algorithms, including our established TargetHunter, HTDocking, and BBB Predictor for target identification and polypharmacology analysis for AD research. The platform has assembled various AD-related chemogenomics data records, including 928 genes and 320 proteins related to AD, 194 AD drugs approved or in clinical trials, and 405 188 chemicals associated with 1 023 137 records of reported bioactivities from 38 284 corresponding bioassays and 10 050 references. Furthermore, we have demonstrated the application of the AlzPlatform in three case studies for identification of multitargets and polypharmacology analysis of FDA-approved drugs and also for screening and prediction of new AD active small chemical molecules and potential novel AD drug targets by our established TargetHunter and/or HTDocking programs. The predictions were confirmed by reported bioactivity data and our in vitro experimental validation. Overall, AlzPlatform will enrich our knowledge for AD target identification, drug discovery, and polypharmacology analyses and, also, facilitate the chemogenomics data sharing and information exchange/communications in aid of new anti-AD drug discovery and development.

A potent tyrosinase activator from Radix Polygoni multiflori and its melanogenesis stimulatory effect in B16 melanoma cells.

Tyrosinase is a key enzyme in melanin biosynthesis. Activators of tyrosinase with stimulatory effects on melanogenesis are beneficial for the treatment of hypopigmentation diseases. In the present study, mushroom tyrosinase activity assay was performed to screen tyrosinase activators from traditional Chinese herbs. Four components from Radix Polygoni multiflori were tested. The most active compound, 2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐d‐glucoside (THSG), was found to be a significant tyrosinase activator. The maximal activation was 126% at a concentration of 75.0 µg/mL. The three anthraquinones slightly activated tyrosinase with effects in the range 7–31%. All the compounds were tested in B16 melanoma cells, the anthraquinones were found to inhibit cell proliferation at a concentration of 0.1–2.5 µg/mL, and THSG was found to be non‐cytotoxic at a concentration of 0.1–12.5 µg/mL. THSG significantly increased the activity of murine tyrosinase and stimulated melanin biosynthesis in B16 melanoma cells. In conclusion, THSG is a potent tyrosinase activator and stimulator of melanogenesis with potential for the treatment of hypopigmentation disease. Copyright

Acute and 13 weeks subchronic toxicological evaluation of naringin in Sprague-Dawley rats.

Naringin is widely distributed in plant foods and has not previously been evaluated for safety through standard in vivo toxicological studies. In the present study, acute and subchronic oral toxicity studies of naringin were designed and conducted in Sprague-Dawley (SD) rats. Acute oral administration of naringin was done as a single bolus dose up to 16 g/kg and subchronic toxicity study for 13 weeks was done by oral administration at doses of 0 (control), 50, 250 and 1250 mg/kg in SD rats. There were no mortality, adverse clinical signs, abnormal changes in body weights or food consumption, toxicologically relevant changes in hematology, clinical biochemistry and macroscopic findings during 14 days of the acute toxicity study. During the subchronic oral toxicity study, no mortality and toxicologically significant changes in clinical signs, food consumption, opthalmoscopic examination, hematology, clinical biochemistry, serum sex hormone, macroscopic findings, organ weights and histopathological examination except for slight body weight decrease were noted and attributed to naringin administration. These observations suggest that naringin is practically non-toxic for SD rats in oral acute toxicity study and the no-observed-adverse-effect-level (NOAEL) of naringin in rats is greater than 1250 mg/kg/day when administered orally for 13 consecutive weeks.

Core bioactive components promoting blood circulation in the traditional Chinese medicine compound xueshuantong capsule (CXC) based on the relevance analysis between chemical HPLC fingerprint and in vivo biological effects.

Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation was designed to explore the core bioactive components promoting blood circulation in CXC using high-performance liquid chromatography (HPLC) and animal studies. CXC samples were prepared with different proportions of the 4 herbs according to a four-factor, nine-level uniform design. CXC samples were assessed with HPLC, which identified 21 components. For the animal experiments, rats were soaked in ice water during the time interval between two adrenaline hydrochloride injections to reduce blood circulation. We assessed whole-blood viscosity (WBV), erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI, respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR), activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on the hypothesis that CXC sample effects varied with differences in components, we performed grey relational analysis (GRA), principal component analysis (PCA), ridge regression (RR), and radial basis function (RBF) to evaluate the contribution of each identified component. Our results indicate that panaxytriol, ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and calycosin-7-O-β-D-glucoside are the core bioactive components, and that they might play different roles in the alleviation of circulation dysfunction. Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC) aggregation, angoroside C was related to platelet aggregation, protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd affected RBC deformability and plasma proteins, and calycosin-7-O-β-D-glucoside influenced extrinsic clotting activity. This study indicates that angoroside C, calycosin-7-O-β-D-glucoside, panaxytriol, and protocatechualdehyde may have novel therapeutic uses.

Six months chronic toxicological evaluation of naringin in Sprague-Dawley rats.

Naringin is a flavonoid showing variable pharmacological properties and is distributed ubiquitously in plant foods. There is a paucity of reported data regarding its safety profile. In the present study, chronic toxicity studies of naringin was designed and conducted by oral gavage at doses of 0, 50, 250 and 1250 mg/kg in Sprague-Dawley (SD) rats for six months followed by 1-month recovery period. During the 6-month treatment period and one month recovery period, no mortality and toxicologically significant changes in clinical signs, opthalmoscopic examination, hematology, clinical biochemistry, serumsexhormone, macroscopic findings, organ weights and histopathological examination were noted and attributed to naringin administration. Although consecutive and/or isolated periods of significant body weights and food consumption decreases were relevant to naringin administration, they were not considered toxicologically significant. In addition, slight, non-pathological and reversible hair loss was noted during the 6-month treatment period and considered as a kind of change possibly relevant to naringin administration; however, it was not considered adverse change and to be of toxicological significance. Based on the results of this study, the no-observed-adverse-effect-level (NOAEL) of naringin in rats is greater than 1250 mg/kg/day when administered orally for 6 consecutive months.

Antidiabetic activities of oligosaccharides of Ophiopogonis japonicus in experimental type 2 diabetic rats

The aim of the present study is to investigate the antidiabetic properties of oligosaccharides of Ophiopogonis japonicus (OOJ) in experimental type 2 diabetic rats. OOJ was administered orally in doses of 225 and 450 mg/kg body weight to high-fat diet and low-dose streptozotocin (STZ)-induced type 2 diabetic rats for 3 weeks. The results showed that OOJ treatment could increase body weight, decrease organ related weights of liver and kidney, reduce fasting blood glucose level, and improve oral glucose tolerance in diabetic rats. Moreover, increased glycogen content in liver and skeletal muscle, reduced urinary protein excretion, higher hepatic GCK enzyme activity, lower hepatic PEPCK enzyme activity, enhanced GLP-1 level, decreased glucagon level and alleviated histopathological changes of pancreas occurred in OOJ-treated diabetic rats by comparison with untreated diabetic rats. This study demonstrates, for the first time to our knowledge, that OOJ exerts remarkable antidiabetic effect in experimental type 2 diabetes mellitus, thus justifying its traditional usage.

Lifespan extension by n-butanol extract from seed of Platycladus orientalis in Caenorhabditis elegans.

AIM OF THE STUDY As a traditional Chinese medicine, seed of Platycladus orientalis(Linnaeus) Franco has been extensively used as a tonic and sedative remedy. The present study was conducted to investigate whether lifespan was extended and the mechanisms of n-butanol extract from seed of Platycladus orientalis (BSPO) in Caenorhabditis elegans. The findings could provide the pharmacological basis for a treatment in traditional medicine. MATERIALS AND METHODS Lifespan extension by BSPO was evaluated under normal culture conditions and in a stress test. A possible mechanism of the anti-aging effect of BSPO, a change in the stress-resistance of related proteins, was also investigated in C. elegans. RESULTS It has been shown that BSPO could significantly extend lifespan of C. elegans in a concentration dependent manner under normal culture conditions and stress. Further studies demonstrated that BSPO treatment significantly decreased reactive oxygen species (ROS) accumulation, up-regulated resistance to stress of related proteins, including glutathione S-transferase-4 (GST-4) and heat shock protein-16.2 (HSP-16.2), and reduced the amount of lipofuscin in transgenic C. elegans. CONCLUSION These results indicated that BSPO extended the lifespan, which could be attributed to its direct ROS scavenging activity, reducing the amount of lipofuscin and increasing the expression of gens associated with resistance to stress. These obtained data provided valuable support for traditional clinical practice to extend lifespan and to provide tonic remedy.

Fermentation effects of oligosaccharides of Radix Ophiopogonis on alloxan-induced diabetes in mice

In this study, oligosaccharides extracted from Ophiopogon japonicus vinegar (OOV) by alcoholic and acetic acid fermentation with water extracts from Radix Ophiopogon and oligosaccharides extracted from Radix Ophiopogonis (OOJ) were investigated. Characterization of the extracts indicated that OOV are proteoglycans, whereas OOJ are not. Moreover, compared with OOJ, monosaccharide compositions of OOV only include fructose and galactose and not glucose. MALDI-TOF-mass spectrometric results showed that the molecular weight of OOV was smaller after fermentation. Changes in the characteristics of OOV would inevitably lead to changes in its hypoglycemic properties. The OOV inhibition activity against α-glucosidase was stronger than that of OOJ. The inhibition activity became stronger with higher dosages of OOV. The hypoglycemic effect of OOV on alloxan-induced diabetic mice was stronger than that of OOJ. More important, the ability of OOV to reduce damage on islets in diabetic mice was stronger than that of OOJ. Overall, alcoholic and acetic acid fermentation improved the hypoglycemic activity of OOJ.