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J Ethnopharmacol [journal]
- Creative and innovative good practice in traditional Chinese medicine clinical studies: Strategies for sustainable development. [Journal Article]
- J Ethnopharmacol 2014 Sep 29; 155(3):1625-8.
- Neuroprotection or neurotoxicity? new insights into the effects of Acanthopanax senticosus harms on nervous system through cerebral metabolomics analysis. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Sep 12.
Acanthopanax senticosus harms (AS), also called "Ciwujia" in Chinese and "Siberian ginseng" in the Siberian Taiga region, is the herb used in traditional medicinal systems in China and Russia, etc., which has been applied to the treatment of various nervous and cerebrovascular diseases, such as depression, mental fatigue, and transient global cerebral ischemia, etc.The previous researches usually tended to focus on the neuroprotective effects of AS, but ignored its additional effects that are not entirely beneficial to the nervous system. Therefore, to discover the potential intervention targets of AS and evaluate their roles in the nervous system are the urgent problems.Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods were integrated to investigate the metabolic profiles of AS-treated rats. The analysis of possible pathways influenced by AS were performed by ingenuity pathway analysis (IPA) with MetPA.Treated with AS, 16 modulated metabolites were identified and considered as the potential intervention targets of AS, out of which 3 metabolites had protective effects on the nervous system, whereas 7 metabolites showed the neurotoxicity.These results may reveal that the effects of AS on nervous system had two sides, and it could not only exert the neuroprotection but also produce some potential neurotoxicity.
- Antinociceptive property of Olax Subscorpioidea OLIV (OLACACEAE) extract in mice. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Sep 8.
Olax subscorpioidea is a shrub or tree found in Nigeria, and other part of Africa. It is indicated in the management of inflammatory disorder, mental illness, convulsion, pain, and cancer. However, there is dearth of information on scientific basis for its folkloric use in the management of pain. Therefore, the study was designed to investigate antinociceptive property of the Extract of Olax subscorpioidea (EOS) leaves in mice.Antinociceptive activity of O. subscorpioidea (12.5-50mg/kg, i.p.) was investigated using acetic acid induced abdominal writhing, tail immersion, hot plate and formalin tests.O. subscorpioidea produced significant dose dependent inhibition of writhing frequency [F (4, 20)=155.9, p<0.0001] and significant dose dependent inhibition of neurogenic and inflammatory pains [F (4, 20)=116.7, p<0.0001; F (4, 20)=40.05, p<0.0001]. It also produced a significant dose dependent prolongation of the latent period and reaction times in tail immersion and hot plate tests in mice [F (4, 20)=19.49, p<0.0001; F (4, 20)=97.95, p<0.0001].O. subscorpioidea possessed potent analgesic action, mediated centrally and peripherally, thus justifying its use in the management of pain.
- Inhibiton of cytochrome P450 isoenzymes and P-gp activity by multiple extracts of Huang-Lian-Jie-Du decoction. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Sep 8.
Huang-Lian-Jie-Du-Decotion (HLJDD), an important traditional Chinese medicine formula, has been used for various diseases in clinical practice, and thus has high potential to induce cytochrome P450 (CYP) isoenzymes / P-glycoprotein (P-gp) mediated herb-drug interactions (HDIs) with other co-administered drugs.The purpose of this study was to investigate the in vitro effects of multiple extracts including aqueous extracts, total flavonoids, iridoids, alkaloids from HLJDD on the activities of CYPs in rats (CYP1A2, CYP2C6, CYP2D2, CYP2E1 and CYP3A1) and P-gp, and then to predict potential interactions with co-administered drugs.The effects of the four extracts from HLJDD on the CYPs activity were evaluated in rat liver microsomes incubation system, and then determined by LC-MS/MS-based CYPs probe substrate assay. Caco-2 cell monolayer was used to investigate the effect of the four extracts on the efflux of Rhodamine 123 to evaluate their influences on P-gp activity.The results show that total flavonoids and alkaloids exibited strong inhibition on rat CYP isoenzymes activities. Total flavonoids exhibited different inhibitory effects on CYPs activities with an order of CYP3A1>CYP2C6>CYP2E1>CYP1A2>CYP2D2, and the values of IC50 were 4.24, 8.16, 17.56, 19.03, 29.51μg/mL, respectively. Total alkaloids possessed similar inhibition on CYPs and could strongly inhibit the activity of CYP2D2 (IC50=2.38μg/mL), CYP3A1 (IC50=2.61μg/mL), CYP2E1 (IC50=22.35μg/mL), CYP1A2 (IC50=23.2μg/mL) and CYP2C6 (IC50=43.09μg/mL). Moderate degree of inhibition on CYPs activities was observed in aqueous and total iridoids extracts. Results from transport assay revealed that total flavonoids and alkaloids exhibited significant inhibitory effect on P-gp activity as evidenced by strong inhibition on the efflux of Rhodamine-123 with IC50 of 104.6 and 82.6μg/mL. But aqueous extract showed weak and iridoids had negligible effect on P-gp activity.This study clearly demonstrated that total flavonoids and alkaloids from HLJDD can significantly inhibit the activities of CYPs and P-gp, which should be taken into consideration to predict any potential HDIs when HLJDD and its bioactive components are co-administered with other therapeutic drugs metabolized by CYPs or transported by P-gp.
- Anti-HBV activity of the different extracts from Phyllanthus rheedei wight. in cell culture based assay systems. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Sep 8.
Phyllanthus rheedii Wight is a plant used by Muthuvan tribes of Kerala for liver related diseases.Analysis of the anti-Hepatitis B Virus (HBV) activity of water, ethanol and hexane extracts of Phyllanthus rheedii Wight by cell line based methods.The different extracts of P. rheedii was analysed on cell lines were viz, PLC/PRF, Hep3B, FLCII10 and HepG2215 for its anti HBV property. The analysis was done through ELISA, SQRT-PCR and immuno blotting.From the screening experiments it was shown that the ethanol extract of this plant has the maximum activity in lowering the viral markers like HBsAg, HBV Core and HBV X protein and whole virions with comparatively lesser cytotoxicity. The dose responses of this particular extract were further established.This study concluded that the ethanol extract of P. rheedii is very much effective in preventing the multiplication of HBV at the cellular level. This study scientifically validated the tribal claim of the use of this plant for severe liver disorders.
- UFLC/MS-IT-TOF guided isolation of anti-HBV active chlorogenic acid analogues from artemisia capillaris as a traditional Chinese herb for the treatment of hepatitis. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Sep 8.
Hepatitis B induced by HBV is a serious health problem. Artemisia capillaris (Yin-Chen) has long been used to treat hepatitis in traditional Chinese medicine. Coumarins, flavonoids and organic acids were revealed as its hepatoprotective and choleretic components, but its anti-HBV active components remain unknown. This current study focused on its anti-HBV active constituents by various chromatographic methods.LC/MS and bioassay-guided fractionation on the active extract of Artemisia capillaris led to the isolation of nine chlorogenic acid analogues. Structures of the isolates were elucidated by MS/MS and NMR techniques. Anti-HBV assay was performed on HepG 2.2.15 cell line in vitro: reduction of HBsAg and HBeAg secretions was measured by ELISA method; inhibition of HBV DNA replication was monitored by real-time quantitative PCR and cellular toxicity was assessed by MTT method.The 90% ethanol extract of A. capillaris (Fr. AC) showed significantly inhibitory activity on HBV DNA replication with an IC50 value of 76.1±3.9μg/mL and low cytotoxic effects (SI>20.1). To clarify its active constituents, the extract was further separated into 3 sub-fractions (AC-1, AC-2 and AC-3), of which Fr. AC-2 was the most active fraction against HBeAg secretion and HBV DNA replication with IC50 values of 44.2±2.8 and 23.2±1.9μg/mL. Nine chlorogenic acid analogues were detected from the active part (Fr. AC-2) by LC/MS technique and further separated by HPLC method. The isolates were determined as chlorogenic acid (1), cryptochlorogenic acid (2), neochlorogenic acid (3), 3,5-dicaffeoylquinic acid (4), 4,5-dicaffeoylquinic acid (5), 3,4-dicaffeoylquinic acid (6), chlorogenic acid methyl ester (7), cryptochlorogenic acid methyl ester (8), neochlorogenic acid methyl ester (9). Compounds 1-6 possessed potent activity against HBV DNA replication with IC50 values in the range of 5.5±0.9 to 13.7±1.3μM. Di-caffeoyl analogues (4-6) also exhibited activity against the secretions of HBsAg and HBeAg. Esterified analogues (7-9) showed dramatically decreased anti-HBV activity, indicating that carboxyl group is closely associated to the anti-HBV activity.This investigation was focused on the active fractions of A. capillaris and their active compositions, which showed that Fr. AC-2 was the main active section of A. capillaris and chlorogenic acid analogues were the main constituents contributed to its anti-HBV activity. These results support the ethnopharmacological use of A. capillaris as anti-HBV agents.
- Anti-diabetic and spasmolytic potential of Farsetia hamiltonii Royle from Cholistan desert. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Sep 8.
Folk herbal practitioners of the Cholistan desert claim Farsetia hamiltonii Royle (Brassicaceae) to treat diabetes, oxidative damages, diarrhea, fever, and abdominal cramps. The aim of this study was to scientifically find the potential of F. hamiltoni in treating diabetes and gastrointestinal diseases.In vivo anti-diabetic activity of F. hamiltonii was studied on alloxan induced diabetic rats to justify its traditional use. The in vitro antispasmodic activity on isolated tissues of rabbit jejunum was also evaluated. Additionally, several enzyme inhibition studies (lipoxygenase, tyrosinase, acetylcholinesterase (AchE), carbonic II anhydrase and phosphodiesterase I) and antioxidant activity of plant extracts were also conducted.In vivo experiments, F. hamiltonii methanol extract (300mg/kg) significantly lowered the fasting blood glucose (107.6±1.249mg/dL up to 4(th) day) comparable to positive control (Glibenclamide) throughout the study period. The in vitro antispasmodic activity on isolated tissues of rabbit jejunum on methanol extract showed concentration dependent (0.01-0.3mg/ml) relaxation of spontaneous contractions with EC50 value 0.011µM and high K(+) (80mM) induced contraction (0.01-0.1mg/ml) with EC50 value 0.066mg/ml. F. hamiltonii DCM and methanol extracts exhibited some antilipoxygenase activities while tyrosinase, acetylcholinesterase (AchE), carbonic II anhydrase, phosphodiesterase I, and antioxidant activity of plant extracts were not significant.Our results validate the traditional use of F. hamiltonii for the traditional therapeutic potential in treating diabetes and gastrointestinal diseases.
- Safety, tolerability, and pharmacokinetics of a single ascending dose of baicalein chewable tablets in healthy subjects. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Sep 8.
The root of Scutellaria baicalensis Georgi, has been used extensively in traditional Chinese medicine for the treatment of inflammation, fever, cough, dysentery, and hypertension. Baicalein is a flavonoid isolated from the root of Scutellaria baicalensis Georgi, and is a novel neuroprotective agent under development for the treatment of Parkinson's disease. We aimed to investigate the pharmacokinetic (PK) properties of baicalein and its main metabolite, bacalin, after single-dose administration in healthy Chinese subjects. The safety and tolerability of baicalein were also assessed.This was a Phase I, randomized, double-blind, single-dose trial of baicalein (100-2800mg) in 72 healthy adults. Samples of blood, urine and feces were collected at regular intervals up to 48h after administration of the study drug. Baicalein and baicalin were then analyzed using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The maximum concentration that the drug achieved after dosing (Cmax), time to Cmax (Tmax), terminal half-life (t1/2), area under the curve from time zero to time of last quantifiable concentration (AUC(0, t)), area under the curve from time zero to infinity (AUC(0, ∞)), apparent total plasma clearance (CL/F), and apparent total volume of distribution (V/F) were determined using non-compartmental models. Dose proportion was tested using a method combining the equivalence criterion and power model. Physical examinations, vital signs, ECG findings, hematology, and urinalysis were monitored before and at regular intervals after administration of the study drug.The PK profile of baicelein and baicelin was characterized by a median Tmax of 0.75h to 3.5h and 0.5h to 3h, respectively, followed by a multiphasic profile with a t1/2 of 1.90-15.01h and 4.22-10.80h, respectively. The estimates of the proportionality coefficient (90% CI) for Cmax, AUC0-t and AUC0-∞ were 0.83 (0.70-0.96), 0.91 (0.81-1.00) and 0.92 (0.82-1.02), respectively. All values overlapped within the pre-specified range of (0.89-1.11), (0.93-1.07), and (0.93-1.07), respectively. Dose proportionality was inconclusive for a baicalein dose range of 100-2800mg. The total urinary clearance of baicalein and baicalin was <1%. Approximately 27% of baicalein was eliminated as unchanged drug in feces. Baicalein was well tolerated. Eleven treatment-related adverse events were observed, and all were rated as "mild" and resolved without further treatment. No serious adverse events occurred.Single oral doses of 100mg to 2800mg of baicalein were safe and well tolerated by healthy subjects. Clinical laboratory assessments showed no signs of toxicity in the liver or kidney. The favorable safety profile and PK properties warrant further clinical studies for baicalein.
- Acute toxicity and genotoxicity study of fermented traditional herb formula Guibi-tang. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Sep 10.
Guibi-tang (Guipi-tang in Chinese and Kihi-to in Japanese) is a multi-herb traditional medicine commonly prescribed to treat psychoneurosis in East Asia. Although this medicine has been widely used, there is little available information on the safety and toxicity of Guibi-tang, especially on the fermented one.Guibi-tang, composed of 12 herbs, was fermented with bacteria and lyophilized. Single dose acute toxicity in rats was observed for 14 days after administration. Genetic toxicity of fermented Guibi-tang was evaluated on bacterial reverse mutation in Salmonella and Escherichia spp., chromosome aberrations in Chinese hamster ovary cells, and micronucleus formation in mice. Ingredients in FGBT were identified and quantified by high performance liquid chromatograph-mass spectrometry.In acute oral toxicity study, behavior, clinical signs and body weight changes were normal observing in all experimental animals. No revertant colonies were found in any bacterial cultures examined. Morphological or numerical anomalies and significant increased number of aberrant metaphases were not observed. Micronucleus assay showed no significant increases in the frequency of inducing micronuclei in any dose examined. Decursinol, decursin, glycyrrhizin, and 6-gingerol in fermented Guibi-tang were identified and quantitated. As a whole, no acute and genotoxic effects were found in all the assays and parameters analyzed.Fermented Guibi-tang was recognized as safe and non-toxic, and therefore can be used for applications of traditional medicine in modern complementary and alternative therapeutics and health care.
- In vivo distribution and pharmacokinetics of multiple active components from Danshen and Sanqi and their combination via inner ear administration. [JOURNAL ARTICLE]
- J Ethnopharmacol 2014 Sep 10.
Salvia miltiorrhiza Bunge (Labiatae sp. plant, Chinese name Danshen) and Panax notoginseng (Burk.) F. H. Chen (Araliaceae plant, Chinese name Sanqi), have a long history in treating coronary heart disease, cerebrovascular disease and inner ear disorders in traditional Chinese medicine. To provide a rational basis for the use of these herbs in clinical practice, we investigated the in vivo distribution and pharmacokinetics of marker agents in Danshen and Sanqi via intravenous and inner ear administration and explored the potential interactions of these agents in compound prescription.Guinea pigs were given Danshen extracts (salvianolic acid B, tanshinone IIA), Sanqi extracts (panax notoginseng saponins) and combination of the two extracts via intravenous and intratympanic administration (IT). Samples from the brain, inner ear perilymph (PL), cerebrospinal fluid (CSF) and plasma were collected at different time points. The concentration of salvianolic acid B (Sal B), tanshinone IIA (Ts IIA), notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1) and ginsenoside Rb1 (Rb1) were determined by high-performance liquid chromatography coupled with a diode array detector (DAD). Pharmacokinetic parameters were estimated using non-compartmental methods.Local drug application via inner ear greatly improved drug distribution within the PL, CSF and brain tissues compared with intravenous administration (IV). The values of Cmax and AUC (0-t) after IT were significantly higher than IV. In comparison with IT of Danshen and Sanqi alone, the pharmacokinetic parameters for R1, Rg1, Rb1, Sal B and Ts IIA were markedly different in the compound prescription. The compound compatibility enhanced the transport of Danshen components into the brain through the inner ear and apparently prolonged the retention time in CSF while decreasing the distribution of Sanqi components in the inner ear and brain.The results indicated that local drug application to the inner ear was a more effective delivery route than systemic administration. Co-administration of Danshen and Sanqi could cause significant pharmacokinetic herb-herb interactions in guinea pigs. The multiple active components via inner ear administration might be promising candidates for the treatment of inner ear and brain diseases.Salvianolic acid B (PubChem CID: 11629084); Tanshinone IIA (PubChem CID: 164676); Notoginsenoside R1 (PubChem CID: 441934); Ginsenoside Rg1 (PubChem CID: 441923); Ginsenoside Rb1 (PubChem CID: 9898279).