Bao-Kang Huang

Bioactivity-guided fractionation for anti-fatigue property of Acanthopanax senticosus.

ETHNOPHARMACOLOGICAL RELEVANCE The root of Acanthopanax senticosus (also called Eleutherococcus senticosus or Siberian ginseng) has been used extensively in China, Russia and Japan as an adaptogen to fight against stress and fatigue. AIM OF THE STUDY The present study was designed to ascertain the anti-fatigue property of Acanthopanax senticosus by load-weighted swimming test, sleep deprivation test, also to isolate and characterize the active constituents. MATERIALS AND METHODS Animals were orally administered with the extract of Acanthopanax senticosus. The anti-fatigue effects of the four fractions with different polarities from the 80% ethanol extract, and the different eluates collected from D101 macroporous resin chromatography and eleutheroside E, were examined based on the weight-loaded swimming capacity (physical fatigue) and the change of biochemical parameters in ICR mice. Moreover, the active fraction was later submitted to sleep-deprived mice (mental fatigue). RESULTS The results shown that the n-butanol fraction significant extends the swimming time of mice to exhaustion. Furthermore, the 60% ethanol-water eluate, more purified eleutherosides (including eleutheroside E, E(2) and derivatives), were the exactly active constituents. Two compounds were isolated, which were identified as eleutheroside E, E(2). CONCLUSIONS The eleutherosides possess the potent abilities to alleviate fatigue both in physical and mental fatigue. Eleutheroside E may be responsible for the pharmacological effect of anti-fatigue. Furthermore, the possible mechanisms were reduced the level of TG by increasing fat utilization, delayed the accumulation of blood urea nitrogen (BUN), and increased the LDH to reduce the accumulation of lactic acid in muscle and then protect the muscle tissue.

Comparative research of chemical constituents, antifungal and antitumor properties of ether extracts of Panax ginseng and its endophytic fungus.

The chemical compositions and bioactivities of ether extracts of an endophytic fungus Paecilomyces sp. isolated from Panax ginseng were reported, and the comparative analysis of the constituents, antifungal and antitumor properties of the ether extracts from this fungus and its host ginseng were also conducted. By means of GC/MS technique, 51 compounds of Panax ginseng and 38 compounds of Paecilomyce sp. were determined. It is attractive that the extracts derived from Paecilomyce sp. and ginseng samples contained the same compound falcarinol, a natural pesticide and anti-cancer agent. The ether extracts of Paecilomyce sp., tested at 7.8 microg/ml, completely inhibited the visible growth of Pyricularia oryzae. Furthermore, both extracts were tested against four human pathogenic fungi and showed the IC(80) of Paecilomyce sp. was 4 microg/ml against Trichophyton rubrum, equally to the control. Finally, the in vitro antitumor experience showed that the most of the IC(50) values were all being below 20 microg/ml.

Lipid-lowering effects of polydatin from Polygonum cuspidatum in hyperlipidemic hamsters.

Hyperlipidaemias are common in obese people, and they increase the risk of cardiovascular diseases such as coronary heart disease (CHD) and atherosclerosis (AS). Previous studies have shown that several drugs can depress serum cholesterol. However, they could cause serious side effects in various clinical settings. The objective of the present study was to evaluate the lipid-lowering effects of polydatin in high-fat/cholesterol (HFC)-fed hamsters. The levels of lipids in hamsters were measured enzymatically before and after the administration of polydatin. Significant differences between HFC and HFC+polydatin were detected for those concentrations. Decreased levels of serum TC, TG and LDL-C and the concentrations of hepatic TG were found. Experimental results also showed that polydatin elevated LDL-C/HDL-C and TC/HDL-C ratios. In concert with other effects, serum cholesterol-lowering effect in hamsters may contribute to the regulation properties attributed to polydatin.

Anti-inflammatory diterpenes from the seeds of Vitex negundo.

Phytochemical investigation of a dichloromethane-soluble extract of Vitexnegundo seeds led to the isolation of five labdane diterpenes, negundoins A-E (1-5), a 9,10-seco-abietane diterpene, negundoin F (6), a sandaracopimara-7,15-diene diterpene, negundoin G (7), and two known diterpene derivatives (8, 9). Their chemical structures were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. The anti-inflammatory effects of metabolites 1-7 were also evaluated in vitro. Compounds 3 and 5 were among the most potent inhibitors on nitric oxide production by LPS-stimulated RAW 264.7 macrophages, with IC(50) values of 0.12 and 0.23 microM, respectively. Further studies revealed that compounds 3 and 5 (5 microM) significantly reduced the levels of the iNOS protein to 0.40+/-0.13% and 41.02+/-6.02%, respectively, and COX-2 protein to 2.06+/-0.53% and 26.40+/-7.43%, respectively.

Nitric oxide scavenging lignans from Vitex negundo seeds.

A new phenyldihydronaphthalene-type lignan, vitexdoin A (1), a new phenylnaphthalene-type lignan alkaloid, vitedoamine B (2), four new phenylnaphthalene-type lignans, vitexdoins B-E (3-6), and four known lignan derivatives (7-10) were isolated from Vitex negundo seeds. Their structures were elucidated by detailed analyses of NMR, IR, and MS data. The ability of the isolates to prevent nitric oxide (NO) production by LPS-stimulated RAW 264.7 macrophages in a concentration-dependent manner was also studied. Compounds 5, 6, and 9 were among the most potent NO production inhibitors, with IC(50) values of 0.13, 0.15, and 0.11 microM, respectively. The introduction of free hydroxy groups plays a vital role in the potency of these compounds.

Bioactivity-guided fractionation for analgesic properties and constituents of Vitex negundo L. seeds.

This study was undertaken to ascertain the analgesic properties of Vitex negundo L. seeds and to isolate and characterize the active constituents. Among the 80% ethanol extract and some fractions with different polarity, the acetoacetate fraction showed the highest anti-nociceptive activity in acetic acid-induced writhing test in ICR mice. The analgesic bioguided isolation of the acetoacetate fraction yielded two major lignans: 6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydroxymethyl-7-methoxy-3,4-dihydro-2-naphthaldehyde (1) and vitedoamine A (2). Given orally, compound (1), which was more productive, produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin injections and exhibited notable anti-inflammatory activities in dimethyl benzene-induced ear edema test in a dose-dependent manner. Since co-administration of naloxone fails to antagonize the analgesic activity of compound (1) in the formalin test, we suggest that compound (1) possesses potent analgesic effects which are most likely to be mediated by its anti-inflammatory activity rather than through opioid receptor system and therefore could partially explain the anti-nociceptive effect of V. negundo L. seeds.

Regulative effects of essential oil from Atractylodes lancea on delayed gastric emptying in stress-induced rats.

Gastric motor dysfunction induced by psychological stress results in many symptoms of functional dyspepsia (FD). There are a number of herbal medicines that are reported to improve gastrointestinal motor. However, the mechanisms of considerable herbal medicines are not explicit. In the present study, the effects of an essential oil (EO) extracted from Atractylodes lancea on delayed gastric emptying, gastrointestinal hormone and hypothalamic corticotropin-releasing factor (CRF) abnormalities induced by restraint stress in rats were investigated and the mechanism of the EO is also explored. Oral administration of EO for 7 days did not affect normal gastric emptying, but accelerated delayed gastric emptying induced by restraint stress in rats. The EO significantly increased the levels of motilin (MTL) and gastrin (GAS) and decreased the levels of somatostatin (SS) and CRF. The EO did not modify gastric emptying in vagotomized rats that underwent restraint stress, but antagonized delayed gastric emptying induced by intracisternal injection of CRF. These results suggest that the regulative effects of the EO on delayed gastric emptying are preformed mainly via inhibition of the release of central CRF and activation of vagal pathway, which are also involved in the release of gastrointestinal hormones such as MTL, GAS and SS.

Traditional Chinese medicine formulas for the treatment of osteoporosis: Implication for antiosteoporotic drug discovery

ETHNOPHARMACOLOGICAL RELEVANCE Osteoporosis is a chronic epidemic which can leads to enhanced bone fragility and consequent an increase in fracture risk. Traditional Chinese medicine (TCM) formulas have a long history of use in the prevention and treatment of osteoporosis. Antiosteoporotic TCM formulas have conspicuous advantage over single drugs. Systematic data mining of the existing antiosteoporotic TCM formulas database can certainly help the drug discovery processes and help the identification of safe candidates with synergistic formulations. In this review, the authors summarize the clinical use and animal experiments of TCM formulas and their mechanism of action, and discuss the potential antiosteoporotic activity and the active constituents of commonly used herbs in TCM formulas for the therapy of osteoporosis. MATERIALS AND METHODS The literature was searched from Medline, Pubmed, ScienceDirect, Spring Link, Web of Science, CNKI and VIP database from 1989 to 2015, and also collected from Chinese traditional books and Chinese Pharmacopoeia with key words such as osteoporosis, osteoblast, osteoclast, traditional Chinese medicine formulas to identify studies on the antiosteoporotic effects of TCM formulas, herbs and chemical constituents, and also their possible mechanisms. RESULTS Thirty-three TCM formulas were commonly used to treat osteoporosis, and showed significant antiosteoporotic effects in human and animal. The herb medicines and their chemical constituents in TCM formulas were summarized, the pharmacological effects and chemical constituents of commonly used herbs in TCM formulas were described in detail. The action mechanisms of TCM formulas and their chemical constituents were described. Finally, the implication for the discovery of antiosteoporotic leads and combinatory ingredients from TCM formulas were prospectively discussed. CONCLUSIONS Clinical practice and animal experiments indicate that TCM formulas provide a definite therapeutic effect on osteoporosis. The active constituents in TCM formulas are diverse in chemical structure, and include flavonoids, lignans, saponins and iridoid glycosides. Antiosteoporotic mechanism of TCM formulas and herbs involves multi regulatory pathways, such as Wnt/β-catenin, BMP/Smad, MAPK pathway and RANKL/OPG system. Phytochemicals from TCM formulas and their compositional herb medicines offer great potential for the development of novel antiosteoporotic drugs. The active ingredients in TCM formulas can be developed in combination as potent drugs, which may exhibit better antiosteoporotic effects compared to the individual compound.

Antifatigue activity of the liposoluble fraction from Acanthopanax senticosus.

The crude extract of Acanthopanax senticosus (AS) has been used extensively in Russia, China, Korea and Japan as an adaptogenic agent to fight against stress and fatigue. However, whether the liposoluble fraction possesses antifatigue activity or not is still unclear. A liposoluble fraction was administered orally to mice for 9 days. The swimming time to exhaustion was longer in the treatment groups (22.2 ± 3.3, 25.5 ± 4.8 min) than in the control group (13.7 ± 1.2 min, p < 0.05). The plasma TG (triglyceride) and BUN (blood urea nitrogen) levels in the high dose (500 mg/kg) groups were decreased significantly compared with the control group. Plasma lactate dehydrogenase (LDH) was lower in the treatment groups than in the control group. Chemical analysis from GC/MS revealed that the main components of the liposoluble fraction of AS were saturated fatty acid (12.98%), unsaturated fatty acid (33.13%), unsaturated alcohol (27.46%) and diolefine (15.76%). In conclusion, the liposoluble fraction enhanced the forced swimming capacity of mice by decreasing muscle damage, effectively preventing the increase in BUN concentration and increasing fat utilization. It is proposed that the antioxidant effect may be one of the antifatigue mechanisms of the liposoluble fraction of AS. Copyright

Correlation between the genetic diversity and variation of total phenolic acids contents in Fructus Xanthii from different populations in China.

Fructus Xanthii (Cang-Er-Zi) is a traditional Chinese medicine that is used in curing nasal diseases and headache according to the Chinese Pharmacopoeia. For the effective quality control of its medicinal values, reflected by chemical variation patterns, in addition to the relationship with genetic diversity, analyses based on UV spectrophotometry, HPLC fingerprinting and inter-simple sequence repeat (ISSR) molecular markers were carried out, involving 16 Xanthium populations from different locations in China. The HPLC data showed considerable variation of chemical constituents among the 16 Xanthium populations, and they were classified to three chemotypes by hierarchical clustering analysis. Abundant genetic diversity was detected among the Xanthium populations, which were also clustered into three groups based on their ISSR data and varied according to different species. Combining the genetic divergence and chemical differences showed an important result that, in the two chemotypes, the higher contents of total phenolic acids (TPA) in Fructus Xanthii showed greater genetic diversity (I). We suggest that genetic diversity affects the contents of TPA. Since variable phenolic acid contents may affect therapeutic efficacy, it is important to point out that combining the use of genetic base with chemotype will help control the favourable chemotypes and breed new cultivars with more desirable chemical constituents.