Organochlorine pesticide residue in Chinese herbal medicine.

Over ten-year routine inspection results on organochlorine pesticide (OCP) residue were summarized, OCPs residues, including BHC isomers (α, ß, γ, and δ-BHC), DDT analogs (p,p'-DDD, p,p'-DDE, o,p'-DDT, and p,p'-DDT), and pentachloronitrobenzene (PCNB) and its metabolites (pentachloroaniline and methyl pentachlorophenyl sulfide (MPCPS)), in 1,665 samples for 37 types of Chinese herbal medicine (CHM) using the QuEChERS method coupled with the GC-ECD. Based on the maximal residue levels for OCPs set by Asian pharmacopeias, PCNB contamination in Ginseng radix as well as the total DDT and PCNB contamination in Panacis quinquefolii radix are of concern. OCP residues in different parts of Panax ginseng were also compared. The total BHC residue in leaf and fibrous root, as well as the total DDT and PCNB residue in all parts, exceeded MRL of 0.1 mg/kg. Overall, this study provided meaningful results about OCP residue in CHM for pharmaceutical industries and consumers.

Effects of Physical Properties and Processing Methods on Astragaloside IV and Flavonoids Content in Astragali radix.

The aim of this study was to investigate the effects of the physical properties (diameter size, powder particle size, composition of bark- and wood-tissue, and turnover rate) and processing methods on the content of active ingredients in Astragali radix (AR), a popular Chinese herbal medicine. The astragaloside IV and flavonoid contents increased with decreasing diameter size. Bark-tissue had significantly higher astragaloside IV and formononetin content than that in the wood-tissue. As a higher proportion of bark-tissue is associated with decreasing diameter, a strong correlation was also shown between bark- to wood-tissue ratio and active ingredients' content. Furthermore, an increase in astragaloside IV content was observed in thin powder as compared to coarse powder ground from the whole root. However, this association between active ingredients' content and powder particle size was abolished when isolating bark- and wood-tissue individually. Moreover, AR stir-frying with refined honey, a typical processing method of AR, increased formononetin content. The turnover rate of active constituents upon decoction ranged from 61.9-81.4%. Assessing the active constituent contents using its physical properties and processing methods allows for a more comprehensive understanding of optimizing and strengthening the therapeutic potentials of AR used in food and herbal supplements.

Investigation of toxic heavy metals content and estimation of potential health risks in Chinese herbal medicine.

The content of toxic heavy metals (THMs), including lead (Pb), arsenic (As), cadmium (Cd), and mercury (Hg), was determined in a total of 10,245 samples for 279 types of Chinese herbal medicine (CHM) using a validated inductively coupled plasma mass spectrometry method. The exceeding rate (ER) for the four THMs were calculated based on diverse permissible limits (PLs) established by different organizations and national pharmacopeias. Cluster analysis was used to classify the degree risk of THMs contamination according to the calculated ER. Results revealed that Cibotii rhizome, Selaginellae herba, Morindae officinalis radix, Asprellae ilicis radix, and Toxicodendri resina exhibited high-degree risk of Pb contamination. Eckloniae/Laminariae thallus, Spirodelae herba, and Naturalis indigo possessed high-degree risk of As contamination. Tetrapanacis medulla, Centipedae herba, Cyathulae radix, Linderae radix, Meretricis/Cyclinae concha, and Tabanus displayed high-degree risk of Cd contamination. Toxicodendri resina has high-degree risk of Hg contamination. In addition, six types of CHM, including Asprellae ilicis radix, Toxicodendri resina, Eckloniae/Laminariae thallus, Fossilia Ossis Mastodi, Haematitum, and Hedyotidis diffusae herba, may have non-carcinogenic health risk after consumption of raw materials because the calculated hazard quotient and hazard index were over 1.0. In summary, these data provide useful information about THMs contamination in CHM.

Dihydromyricetin-rich herbal mixture extracts as a potential prescription for treatment of metabolic syndrome in rats fed a high-fat diet and subacute toxicity assessment in rats.

Dihydromyricetin (DHM)-rich herbal mixture extracts, also called APF complex, comprised of Ampelopsis grossedentata, Pericarpium citri reticulatae, and Fructus crataegi. The content of DHM in APF complex was 362.7 ±â€¯12.5 mg/g. The aims of this study were to investigate the therapeutic effects of APF complex on metabolic syndrome in rats fed a high-fat diet (HFD) and evaluate the subacute toxicity of APF complex in rats. HFD significantly increased body weight gain, fat tissue (epididymal fat, mesenteric fat, and perirenal fat) deposition, body fat index, and hepatic triglyceride (TG) and total cholesterol (TC) accumulation as well as caused abnormal blood biochemical parameters, including TC, TG, low-density lipoprotein-cholesterol (LDL-C), free fatty acid (FFA), and glucose. APF complex has a tendency but not significance to limit HFD-induced body weight gain. APF complex also significantly improved HFD-induced body fat accumulation, as evidenced by decreasing fat tissue deposition and body fat index. In addition, APF complex significantly ameliorated HFD-induced hyperlipidemia and hyperglycemia, as evidenced by reducing levels of blood TG and TC as well as blood glucose and FFA, respectively. Furthermore, APF complex significantly decreased HFD-induced hepatic TG and TC accumulation. In subacute toxicity assessment, APF complex exhibited no toxicological signs, as evidenced by without affecting mortality, food and water consumption, body weight changes, absolute organ weights, hematological system, blood lipids and nutritional status, and electrolyte balance as well as non-toxic to liver and renal function. Overall, APF complex was considered as a non-toxic herbal prescription and could act as adjuvant therapy for metabolic syndrome.

Investigation of aflatoxins contamination in herbal materia medica in a Taiwan pharmaceutical factory.

During the years 2005-2016, a total of 1067 samples for 24 types of herbal materia medica were investigated for the presence of aflatoxins (AFs) using immunoaffinity column cleanup and HPLC-coupled to a fluorescence detector after post-column derivatization. AFs were detected in 373 (35%) out of the total samples. Among them, Platycladi Semen (65% for total AFs and 79% for AFB1), Corydalis Rhizoma (53% for total AFs and 32% for AFB1), Corni Fructus (3% for total AFs), Coicis Semen (3% for total AFs and AFB1), Nelumbinis Semen (6% for total AFs and 9% for AFB1), Arecae Semen (18% for AFB1), Polygalae Radix (5% for total AFs and AFB1), and Cassiae Semen (25% for total AFs and 38% for AFB1) exceeded the official limits of 5 and 10 µg/kg, for AFB1 and total AFs (the sum of AFB1, AFB2, AFG1, and AFG2), respectively, set by the Taiwan government. We concluded that Platycladi Semen, Corydalis Rhizoma, and Cassiae Semen are the most commonly contaminated by AFs.

Effects of herbal mixture extracts on obesity in rats fed a high-fat diet.

The aim of this study was to investigate and compare the effects of three herbal mixture extracts on obesity induced by high-fat diet (HFD) in rats. The prescriptions-Pericarpium citri reticulatae and Fructus crataegi-were used as matrix components and mixed with Ampelopsis grossedentata, Salvia miltiorrhiza, and epigallocatechin-3-gallate (EGCG) to form T1, T2, and T3 complexes, respectively. Results revealed that HFD feeding significantly increased body weight gain, fat deposition, plasma lipid profiles, hepatic lipid accumulation, and hepatic vacuoles formation, but decreased plasma levels of adiponectin in rats. Only the T1 complex showed the tendency, although not significantly so, for decreased HFD-induced body weight gain. T1 and T3 complexes significantly reduced HFD-induced fat deposition, and plasma levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol. Only the T1 complex significantly increased HFD-reduced adiponectin levels in plasma, but decreased HFD-increased triglyceride content in liver tissues. All complexes effectively inhibited HFD-induced vacuoles formation. The content of dihydromyricetin, salvianolic acid B, and EGCG in T1, T2, and T3 complexes was 18.25 ± 0.07%, 22.20 ± 0.10%, and 18.86 ± 0.04%, respectively. In summary, we demonstrated that herbal mixture extracts, especially T1 complex, exhibit antiobesity activity in HFD-fed rats.

Gastroprotective potential against indomethacin and safety assessment of the homology of medicine and food formula cuttlebone complex.

Cuttlebone complex (CBC), a homology of medicine and food formula, is comprised of five herbal medicines (Endoconcha Sepiae, Radix Paeoniae Rubra, fresh ginger, Fructus Amomi, and Radix Glycyrrhizae) and two food ingredients (Zingiber zerumbet and chitosan). Herein, the gastroprotective potential against indomethacin and a safety assessment of CBC were investigated. In a gastroprotective model, CBC effectively decreased the indomethacin-increased gastric ulcerous lesions, and increased the indomethacin-decreased prostaglandin E2 levels in the gastric mucosa. In genotoxicity tests, CBC treatment did not increase the numbers of revertant colonies in five Salmonella typhimurium strains and chromosome aberrations in Chinese hamster ovary CHO-K1 cells, with or without S9 metabolic activation. The oral supplementation of CBC did not increase micronucleus formation in the peripheral blood of mice. In a subacute toxicity study, the body weight and blood biochemical parameters observed in CBC-treated rats were normal. In conclusion, CBC was considered as a non-toxic formula and could be used to remedy indomethacin-induced gastric damage.

Alpha-carotene inhibits metastasis in Lewis lung carcinoma in vitro, and suppresses lung metastasis and tumor growth in combination with taxol in tumor xenografted C57BL/6 mice.

This study aimed to investigate the anti-metastatic activity of α-carotene (AC) in Lewis lung carcinoma (LLC) and in combination with taxol in LLC-xenografted C57BL/6 mice. Cell culture studies reveal that AC significantly inhibited invasion, migration and activities of matrix metalloproteinase (MMP)-2, -9 and urokinase plasminogen activator but increased protein expression of tissue inhibitor of MMP (TIMP)-1, -2 and plasminogen activator inhibitor (PAI)-1. These effects of AC are similar to those of ß-carotene at the same concentration (2.5 µM). AC (2.5 µM) also significantly inhibited integrin ß1-mediated phosphorylation of focal adhesion kinase (FAK) which then decreased the phosphorylation of MAPK family. Findings from the animal model reveal that AC treatment (5m g/kg) alone significantly decreased lung metastasis without affecting primary tumor growth, whereas taxol treatment (6 mg/kg) alone exhibited significant inhibition on both actions, as compared to tumor control group. AC treatment alone significantly decreased protein expression of integrin ß1 but increased protein expression of TIMP-1 and PAI-1 without affecting protein expression of TIMP-2 and phosphorylation of FAK in lung tissues, whereas taxol treatment alone significantly increased protein expression of TIMP-1, PAI-1 and TIMP-2 but decreased protein expression of integrin ß1 and phosphorylation of FAK. The combined treatment produced stronger actions on lung metastasis and lung tissues protein expression of TIMP-1, TIMP-2 and PAI-1. Overall, we demonstrate that AC effectively inhibits LLC metastasis and suppresses lung metastasis in combination with taxol in LLC-bearing mice, suggesting that AC could be used as an anti-metastatic agent or as an adjuvant for anti-cancer drugs.

Lycopene and the LXRα agonist T0901317 synergistically inhibit the proliferation of androgen-independent prostate cancer cells via the PPARγ-LXRα-ABCA1 pathway.

In our previous study, we demonstrated that lycopene can inhibit the proliferation of androgen-dependent prostate LNCaP cancer cells through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ)-liver X receptor alpha (LXRα)-ATP-binding cassette transporter 1 (ABCA1) pathway. However, it is still unclear whether lycopene possesses similar effects in androgen-independent prostate cancer cells DU145 and PC-3. As lycopene inhibited the proliferation of both cell types to a similar extent, we chose DU145 cells for most of the subsequent studies. We show that lycopene significantly increased protein and mRNA expression of PPARγ, LXRα and ABCA1 and cholesterol efflux (i.e., decreased cellular cholesterol and increased cholesterol in culture medium). Lycopene (10 µM) in the presence of a specific antagonist of PPARγ (GW9662) or of LXRα (GGPP) restored the proliferation of DU145 cells and significantly suppressed lycopene-induced protein and mRNA expression of PPARγ and LXRα and cholesterol efflux. Liver X receptor α knockdown by siRNA against LXRα significantly promoted the proliferation of DU145 cells, whereas si-LXRα knockdown followed by incubation with lycopene (10 µM) restored the proliferation to the control level. Furthermore, lycopene in combination with the LXRα agonist T0901317 exhibited synergistic effects on cell proliferation and protein expression of PPARγ, LXRα and ABCA1. These results demonstrate that lycopene can inhibit DU145 cell proliferation via PPARγ-LXRα-ABCA1 pathway and that lycopene and T0901317 exhibit synergistic effects.

Inhibitory effect of vitamin C in combination with vitamin K3 on tumor growth and metastasis of Lewis lung carcinoma xenografted in C57BL/6 mice.

Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation.

Growth inhibitory efficacy of lycopene and ß-carotene against androgen-independent prostate tumor cells xenografted in nude mice.

SCOPE: In this study, we evaluated the efficacy of lycopene against the growth of prostate cancer in vivo. METHODS AND RESULTS: Athymic nude mice were implanted subcutaneously with human androgen-independent prostate carcinoma PC-3 cells. They were supplemented with a low or a high dose of lycopene (4 and 16 mg/kg) and a single dose of ß-carotene (16 mg/kg) twice a week for 7 wk. At the end of the experiment, both lycopene and ß-carotene strongly inhibited the tumor growth, as evidenced by the decrease in tumor volume and tumor weight. High-dosage lycopene and ß-carotene significantly decreased the expression of proliferating cell nuclear antigen in tumor tissues and increased the levels of insulin-like growth factor-binding protein-3 in plasma. In addition, high-dosage lycopene supplementation significantly decreased the vascular endothelial growth factor (VEGF) levels in plasma. In contrast, ß-carotene supplementation significantly increased the VEGF levels, as compared with tumor control group. CONCLUSION: Lycopene and ß-carotene supplementation suppressed the growth of prostate tumor cells, and the effects are likely associated with reduction of proliferation (attenuation of proliferating cell nuclear antigen expression) and with interference of the insulin-like growth factor 1 signaling (increased plasma insulin-like growth factor-binding protein-3 levels). Furthermore, the inhibition of VEGF by lycopene suggests that the antitumor mechanisms of lycopene also involve anti-angiogenesis.

Anti-angiogenic effects and mechanisms of polysaccharides from Antrodia cinnamomea with different molecular weights.

ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia cinnamomea is a popular medicinal mushroom in Taiwan that has been widely used for treatment of various cancers and liver diseases. AIM OF THE STUDY: This study aimed to investigate the immunomodulatory effect on angiogenesis of polysaccharides from mycelia of Antrodia cinnamomea (PMAC). MATERIALS AND METHODS: PMAC were extracted in boiling water, precipitated with 95% ethanol, and separated into four different molecular weights (<5, 5-30, 30-100, > 100 kDa). Tube formation and chorioallantoic membrane (CAM) assay were used to determine the in vitro and ex vivo anti-angiogenic effects. RESULTS: Only the PMAC-mononuclear cells (MNCs)-conditioned medium (CM) with MW > 100 kDa significantly and concentration-dependently decreased the secretion of vascular endothelial growth factor in human leukemia cells and inhibited the matrigel tube formation in human umbilical vein endothelial cells. Similarly only the PMAC-MNC-CM with MW > 100 kDa significantly and concentration-dependently increased the levels of interleukin (IL)-12 and interferon-gamma (IFN-gamma). In addition, the ex vivo CAM assay revealed that only the PMAC with MW>100 kDa significantly and dose-dependently inhibited neovascularization. CONCLUSIONS: PMAC with MW > 100 kDa are anti-angiogenic in vitro and ex vivo, and the effects are likely through immunomodulation.