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Background: The available in vitro evidences suggest the inherent instability and interconvertibility of [6]-gingerol and [6]-shogaol. However, limited data on their in vivo interconversion hinder understanding of their influence on the pharmacokinetic profiles. Purpose: This study presents the first comprehensive in vivo investigation aiming to determine the interconversion pharmacokinetics in rats, and elucidate the oral bioavailability, target distribution, biotransformation, and excretion profiles of the key ginger constituents, [6]-gingerol, [6]-shogaol, and zingerone. Methods: The pharmacokinetics was investigated through single intravenous (3 mg/kg) or oral (30 mg/kg) administration of [6]-gingerol, [6]-shogaol, or zingerone, followed by the determination of their tissue distribution after oral dosing (30 mg/kg). Intravenous pharmacokinetics was leveraged to evaluate the interconversion, circumventing potential confounders associated with the oral route. Results: All rats tolerated these compounds throughout the pharmacokinetic study. The parent compounds exhibited rapid but partial absorption, and extensive organ distribution with substantial biotransformation, thereby limiting the oral bioavailability of each compound to below 2% when administered as pure compounds. Conversion of [6]-gingerol to [6]-shogaol after intravenous administration, demonstrated a significantly larger clearance compared to the reverse conversion ([6]-shogaol to [6]-gingerol). The irreversible metabolic clearance for both compounds was significantly greater than their reversible bioconversions. Furthermore, [6]-gingerol underwent biotransformation to zingerone. Conjugated glucuronides were eliminated partly through renal excretion, with minimal fecal excretion. Conclusion: This in vivo investigation demonstrates the influence of interconversion on the disposition kinetics of [6]-gingerol, [6]-shogaol, and zingerone, as evidenced by the findings in the systemic circulation. The study further highlights the importance of considering this interconversion and tissue distribution when determining the administration dosage of ginger constituent combinations for therapeutic benefits and clinical applications.

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Herein, we examined whether prolonged arsenic exposure altered tau phosphorylation in the brain of Sprague Dawley rats expressing endogenous wild-type tau. The results showed that daily intraperitoneal injections of 2.5 mg/kg BW sodium arsenite over 28 days caused arsenic accumulation in the rat brain. Interestingly, we found an increase in tau phosphorylation at the Tau 1 region (189-207) and S202 in the hippocampus, S404 in the cerebral cortex, and S396 and S404 in the cerebellum of arsenic-treated rats. Additionally, arsenic increased active ERK1/2 phosphorylation at T202/Y204 in the hippocampus, cerebral cortex, and cerebellum. Meanwhile, we detected increasing active JNK phosphorylation at T183/Y185 in the hippocampus and cerebellum. Moreover, p35, a neuron-specific activator of CDK5, was also elevated in the cerebellum of arsenic-treated rats, suggesting that CDK5 activity may be increased by arsenic. These results suggested that arsenic may induce tau phosphorylation through the activation of tau kinases, ERK1/2, JNK, and CDK5. Together, the findings from this study demonstrated that prolonged arsenic exposure is implicated in neurodegeneration by promoting tau phosphorylation in the rat brain and points toward a possible prevention strategy against neurodegeneration induced by environmental arsenic exposure.

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Andrographis paniculata is widely used in traditional herbal medicines for the treatment of common cold, fever and diarrhea, in many regions of Scandinavia and Asia, including Thailand. The pharmacological activities of A. paniculata are mainly attributed to active diterpenoids including 14-deoxyandrographolide, which is uniquely high in first true leaf ethanolic extract (FTLEE) of A. paniculata. In this study, the acute toxicity of the standardized FTLEE of A. paniculata was examined according to the OECD test guideline No. 420. Mice were divided into four groups of each sex and orally received the standardized FTLEE of A. paniculata (0, 300, 2000, or 5000 mg/kg BW). Post-treatment, body weight, signs of toxicity, and/or mortality were observed for 14 days. At Day 15, animals were euthanized, internal organs were observed grossly, and blood samples collected were subjected to hematology and clinical biochemistry analyses. The results showed that all treated animals survived and no apparent adverse effects were observed during the duration of the study. Gross necropsy observation revealed no lesion in any organ of all the standardized FTLEE-treated mice. Although significant alterations in BUN, lymphocytes, neutrophils, hematocrit and hemoglobin were observed, these alterations were not treatment-related toxic effects. Therefore, we concluded that a single oral administration of the standardized FTLEE of A. paniculata with an upper fixed dose of 5000 mg/kg BW has no significant acute toxicological effects.

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Arsenic exposure has been linked to an impaired immune response and inflammation. Our study investigated the effects of sodium arsenite on host immune response and vascular inflammation during malarial infection. Mice were divided into three groups: control (C), Plasmodium berghei infection (I) and sodium arsenite exposure with Plasmodium berghei infection (As-I). The results showed that splenocyte proliferation stimulated by lipopolysaccharide (LPS) and pokeweed mitogen (PWM) was suppressed in the I group, and the suppression was more pronounced in the As-I group, suggesting that acquired immunity in infected mice was worsening following arsenic exposure. ICAM-1, an adhesion protein involved in parasite-infected red blood cell (iRBC) binding to endothelium, and HIF-1α, a hypoxia marker protein in the descending aorta, were increased in the As-I group compared to the I group. Collectively, our results suggest that arsenic may increase host susceptibility to malaria through suppression of B cell proliferation and enhancement of adhesion between iRBC and endothelium by increasing ICAM-1.

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Longan seed extract (LSE) contains high levels of beneficial polyphenolic compounds. The present study evaluated acute and repeated dose (4 and 13 weeks) toxicological effects of aqueous extract of longan seed to ensure the safety of utilization of this extract. Our study revealed that all treated animals survived through the whole experimental periods without adverse effects observed in either sex of animals after acute and repeated dose (4 and 13 weeks) oral administration of LSE. Likewise, growth pattern (body weights, food consumption, and relative organ weights), hematology analysis, and clinical biochemistry analysis in all LSE-treated animals were in normal physiological ranges. Moreover, histopathological finding of LSE-treated animals in repeated dose studies demonstrated no obvious alterations. Although the significant increment in food consumption of female rats (100 mg/kg, Week 4) and % eosinophil of male rats (400 mg/kg), and decrement in food consumption of male rats (250 mg/kg, Week 3 and 9) were observed, these alterations were not dose- and time-response relationships. Therefore, we concluded that acute and repeated dose (4 and 13 weeks) oral administration of LSE has no significant toxicological effects;hence it may be safe to use with caution pending its chronic toxicity study and/or clinical trial.

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Gynostemma pentaphyllum Makino (GP) is a herbal tea widely grown in Southeast Asia. However, this herbal tea can be contaminated with some heavy metals, especially cadmium (Cd), from agricultural areas, which may affect human health. The objective of this study is to evaluate the immunomodulatory effects of Cd contaminated in GP herbal tea and inorganic Cd on rat splenocytes. Rats were divided into groups and treated with drinking water (control), high CdCl 2 in drinking water (HCd; 0.05 mg/L), GP herbal tea containing 0.05 mg/L Cd (GP-HCd) for 4 months, low CdCl 2 in drinking water (LCd; 0.006 mg/L), and GP herbal tea containing 0.006 mg/L Cd (GP-LCd) for 6 months. After the treatments, Cd accumulation in organs and blood was detected by using a graphite furnace atomic absorption spectrophotometer. In spleen, HCd-treated rats had 4-fold higher Cd accumulations than GP-HCd-treated rats. Cd accumulation in liver and kidney in the HCd group also increased significantly. There were no significant changes in total leucocyte and lymphocyte counts; however, these parameters tended to decrease slightly in LCd, GP-LCd, and GP-HCd groups. The HCd group (ex vivo) significantly produced suppressive effects on T cell mitogen-induced splenocyte proliferation, with 1 mug/mL Con A and PHA-P. In addition, 0.5 mug/mL PWM-induced B cell proliferation, through T cell functions, was also significantly inhibited by HCd as compared to the control group, while GP-HCd had no effects. However, both GP-LCd- and LCd-treated rats had a slight increase in Con A-stimulated splenocyte proliferation. This study indicated that high Cd contamination in drinking water alone had suppressive effects on T cell functions, but these effects could not be found with the same Cd level contamination in GP herbal tea.

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The protective effects of fruits and vegetables against chronic diseases have been attributed to the antioxidant properties of some secondary metabolites present in these foods. Plant polyphenols have been reported to exhibit bioactive properties, and in particular antioxidant activities. Longan seeds are found to contain high levels of some beneficial polyphenolic compounds such as corilagin, gallic acid and ellagic acid. The present study examined the free radical scavenging activity of longan seed extract by using three different assay methods. Longan extracts contained corilagin ranging from zero to 50.64 mg/g DW, gallic acid from 9.18 to 23.04 mg/g DW, and ellagic acid from 8.13 to 12.65 mg/g DW depending on the cultivars. Dried longan seed extracts of cultivar Edor contained high levels of gallic acid and ellagic acid and also exhibited the highest radical scavenging activities when comparing fresh seed and dried pulp extracts. For scavenging activity of DPPH and superoxide radicals, longan seed extract was found to be as effective as Japanese green tea extract while dried longan pulp and mulberry green tea extracts showed the least scavenging activities. In the ORAC assay, both fresh and dried longan seed also had higher activity than dried pulp and whole fruit. However, the results demonstrate that three polyphenolics may not be the major contributors of the high antioxidant activity of longan water extracts but this high activity may be due to other phenolic/flavonoid glycosides and ellagitannins present in longan fruit. In addition, longan seed also showed tyrosinase inhibitory activity with IC(50) values of 2.9-3.2 mg/ml. Therefore, the preliminary observations suggest that longan seed extract could be another potential source of potent natural dietary antioxidants and also in an application as a new natural skin-whitening agent.

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Andrographis paniculata has been widely used for the prevention and treatment of common cold especially in Asia and Scandinavia. The three active diterpenoids from this plant, including aqueous plant extracts, were investigated for the inhibitory effect on platelet aggregation in vitro. The results indicated that andrographolide (AP(1)) and 14-deoxy-11,12-didehydroandrographolide (AP(3)) significantly inhibited thrombin-induced platelet aggregation in a concentration-(1-100 microM) and time-dependent manner while neoandrographolide (AP(4)) had little or no activity. AP(3) exhibited higher antiplatelet activity than AP(1) with IC(50) values ranging from 10 to 50 microM. The inhibitory mechanism of AP(1) and AP(3) on platelet aggregation was also evaluated and the results indicated that the inhibition of extracellular signal-regulated kinase1/2 (ERK1/2) pathway may contribute to antiplatelet activity of these two compounds. In addition, standardized aqueous extracts of A. paniculata containing different amounts of AP(3) inhibited thrombin-induced aggregation to different degrees. The extracts significantly decreased platelet aggregation in a concentration-(10-100 microg/ml) and time-dependent manner. However, the extract with high level of AP(3) (Extract B) (IC(50) values=50-75 microg/ml) showed less inhibitory activity against thrombin than the extract with lower level of AP(3) (Extract A) (IC(50) values=25-50 microg/ml). These results indicate that the standardized A. paniculata extract may contain other antiplatelet compounds rather than AP(1) and AP(3), which contribute to high antiplatelet activity. Therefore, the consumption of A. paniculata products may help to prevent or treat some cardiovascular disorders i.e. thrombosis; however, it should be used with caution by patients with bleeding disorders.

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Regular consumption of fruit and vegetables is associated with a lower risk of some chronic diseases including various forms of cancer and cardiovascular diseases. The health-promoting potential of these foods may be due, in part, to the phytochemical bioactive compounds present in the plants. Fruit of Euphoria longana Lam. (longan) are consumed throughout Asia and are a major crop in Thailand. In the present study phytochemicals were extracted with 70% methanol from peel, pulp, and seed tissues of longan fruit, and the major components were identified as gallic acid, corilagin (an ellagitannin), and ellagic acid. A high-through-put reversed phase HPLC method was developed to determine the content of these three compounds in different parts of the longan fruit and among different cultivars. The analyses showed that there was a large variation in the contents of gallic acid, corilagin, and ellagic acid in different plant tissues and cultivars. Seed contained the highest levels of the three phenolics, and pulp contained the lowest. Among commercial cultivars, Biewkiew and Edor contained the highest levels of gallic and ellagic acid while Srichompoo contained the highest content of corilagin. These three cultivars may be used in directed breeding and cultivation programs and to develop concentrated longan seed extracts to promote good health. Utilization of this byproduct material will support the use of thousands of tons of waste longan seeds after the production of canned longan pulp.

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Effects of exposure to deltamethrin on host resistance to malaria infection (Plasmodium berghei) were examined in Swiss albino male mice. Four doses of deltamethrin were initially tested with two non-lethal doses, 5 and 10mg/kg, selected for more detailed study. Survival times of infected mice did not change when they were exposed to the compound for 14 days before the infection. However, survival times were shortened when they were exposed to the compound, particularly at the high-dose, after and during the initial infection. Percent parasitemia of these animals also elevated faster than that of the control. Deltamethrin exposure also caused alteration of white blood cell populations. Specifically, total white blood cell and lymphocyte counts significantly decreased in the high-dose treated mice. Granulocyte counts were comparatively lower in both treated groups than that in the control. Red blood cells, hemoglobin, and hematocrit were not affected. The obtained results suggest that deltamethrin exhibits an immunosuppressive effect and negatively impacts host resistance to malaria infection.