Introduction:Andrographis paniculata has been used in the management of COVID-19-related conditions during the SARS-CoV-2 pandemic. However, human pharmacokinetic-pharmacodynamic (PK/PD) evidence to support a rationale for safe and evidence-based dosing of standardized extracts in clinical use remains limited. This exploratory study aimed to investigate the pharmacokinetics, preliminary PK/PD relationship, and short-term safety profile of standardized A. paniculata aqueous extract capsules in patients with mild COVID-19. Methods:A single-center PK/PD clinical trial with two sequential phases (single-dose followed by multiple-dose) was conducted. Patients with mild COVID-19 received standardized A. paniculata aqueous extract capsules equivalent to 30 mg of andrographolide every 8 h (90 mg/day) for 5 consecutive days, alongside standard symptomatic treatment. Results:Rapid absorption and elimination with limited systemic exposure supported repeated dosing to maintain exposure over the 5-day period. PK/PD analysis demonstrated a sigmoidal, saturable exposure-response relationship. The mean area under the concentration-time curve (AUC0-4 h) on day 5 approached the estimated EAUC50 (half-maximal effective exposure) derived from the Emax model. A -2.96 log10 reduction in viral load was observed; however, without a placebo control group, it is not possible to conclusively attribute this reduction to the investigational A. paniculata aqueous extract capsules. Adverse events were mild, with no hepatotoxicity or renal toxicity observed. Conclusion:These findings provide preliminary evidence regarding the pharmacokinetics, dose-exposure characteristics, and short-term tolerability of standardized A. paniculata aqueous extract capsules, supporting further investigation in patients with mild COVID-19. Larger, placebo-controlled trials are warranted to establish causality and to evaluate clinical benefits.

There is increasing evidence of the health effects of germinated colored rice (GCR). Metastasis, namely the spread of cancer cells to distant sites in the body, is a serious problem for cancer therapy. This study aimed to explore the anti-metastatic potential of GCR extract in HT29 colorectal cancer cells through cell migration inhibition, and to identify target proteins by using proteomic approach. GCR extract at 4 mg/mL caused 87 % reduction in cell migration. Two-dimensional gel proteomic analysis revealed beta-actin downregulation in GCR-treated cells. GCR also affected gene expression of actin dynamic regulatory proteins including RHOA, RAC1, and CDC42 genes. Gamma-aminobutyric acid (GABA), a bioactive compound present in GCR extract, could decrease cell migration and downregulated beta-actin in the cells, but did not alter expression level of RHOA, RAC1, and CDC42 genes. This study reveals a potential of GCR to be developed as a functional food for assisting the cancer treatment.

This study investigated the contamination of perfluorooctane sulfonate (PFOS), its isomers, and perfluorooctanoic acid (PFOA) in seafood from Thailand to assess public health risks. A total of 144 samples from eight marine species were collected from three provinces—Rayong, Samut Sakhon, and Bangkok—between 2022 and 2023. Samples were analysed using a validated ultra–high performance liquid chromatography with tandem mass spectrometry (UHPLC–MS/MS) technique. PFOS and PFOA were detected in all samples, with concentrations ranging from < 24 to 623 ng/kg wet weight (ww) and < 48 to 419 ng/kg ww, respectively. PFOS was detected at a higher concentration than PFOA, and both compounds were found predominantly in cockles. Geographically, seafood from Rayong province revealed higher PFOS contamination, likely due to industrial activities. Linear PFOS was the most prevalent isomer, accounting for 84

AimInsufficient quality control and limited dissolution of Andrographis paniculata extract capsules restricts their bioavailability and hinder the clinical use for treating mild coronavirus disease 2019 (COVID-19) patients.ObjectiveThis study aims to investigate pharmacokinetics and safety of high-dosage A. paniculata ethanolic extract (equivalent to 180 or 360 mg/day of andrographolide), relevant dosages used for mild COVID-19 treatment.MethodsAn open-label, single-dose, and repeated-dose conducted in healthy volunteers. Subjects received capsules containing ethanolic extract equivalent to andrographolide dosage of either 60 or 120 mg per dose, taken every eight hours daily (totaling 180 or 360 mg/day). Safety was assessed through blood chemical analysis and adverse event monitoring after 7 days of ethanolic extract administration.ResultsPharmacokinetics of ethanolic extract indicated low plasma levels of the major diterpenoids. The maximum plasma concentration (Cmax) of andrographolide did not exhibit a dose-proportional increase, reaching 6.44 and 11.62 mu g/L for single and repeated doses of 60 mg/day, respectively. Doubling the dose (120 mg/day) only resulted in slightly higher Cmax (6.97 and 15.03 mu g/L for single and repeated doses, respectively). Safety evaluation revealed mild, transient adverse events, but all parameters remained within normal ranges.ConclusionsThis study highlights limitations in the pharmacokinetics of the ethanolic extract of A. paniculata. It indicated non-linear proportionality in the oral bioavailability of andrographolide. These findings suggest that current extraction process of ethanolic extract may hinder its effectiveness. Further research is warranted to explore alternative extraction methods or formulation developments that can enhance the bioavailability of andrographolide and its potential therapeutic effects for COVID-19 treatment.

INTRODUCTION:Andrographis paniculata (AP) has been approved by the Thai government for the treatment of mild cases of COVID-19 patients. Increasing use of AP products requires quality control to ensure efficacy and safety. At present, there is no requirement for dissolution test of AP products in the Thai Herbal Pharmacopoeia (THP). OBJECTIVE:This work aimed to examine the contents and dissolution profiles of active diterpenoids, andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3), neoandrographolide (AP4), and 14-deoxyandrographolide (AP6) in AP capsules available in Thai markets. MATERIALS AND METHODS:Four extract products (EXT. A-D) and three crude powder products (CRD. A-C) were tested for contents by using HPLC-DAD. Dissolution profiles of four diterpenoids were investigated in different media (pH 1.2, 4.5, 6.8, and 0.01 N HCl + SLS) with apparatus II (paddle type). RESULTS:The AP1 contents were 1.99%-2.90% w/w for crude capsules and 2.84%-16.27% w/w for extract capsules. In the dissolution test, the dissolution percentages of four diterpenoids from crude capsules were higher than those from extract capsules except EXT. A. AP1 in most extract products (EXT. B, C, D) was dissolved in all dissolution media at a lower percentage than the other three diterpenoids. EXT. A (aqueous extract) was the only extract capsule showing the amounts of all diterpenoids dissolved in all media >80% in 45 min. CONCLUSION:The study demonstrated that AP1 content in AP products complied with the acceptance criteria in the THP (80%-120%), and the weight variation also met the United States Pharmacopeia (USP) requirements. However, different dissolution profiles of AP products may lead to different bioavailability of diterpenoids and further affect their efficacy.

Information regarding per- and polyfluorinated substances concentrations in biological samples from the Thai population was still lacking. A sensitive bioanalytical method was developed and validated for the quantification of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) levels in human plasma. Simple protein precipitation and LC–MS/MS techniques were used with stable isotope internal standards of 13C8–PFOS and 13C8–PFOA. The validated method followed the ICH bioanalytical validation guideline, and the results showed good accuracy, precision, and reproducibility. The validated analytical method was then applied to determine PFOS and PFOA concentrations in 50 human plasma samples from the National Blood Center, Thai Red Cross Society. The concentrations were found to be in ranges of <0.91–6.27 ng/mL for PFOS and <0.49–2.72 ng/mL for PFOA. PFOS was also measured separately for its isomers, and the geometric means of the linear isomer (L–PFOS) and branched isomer (br–PFOS) in plasma samples were at 1.85 and 0.41 ng/mL, respectively. Both PFOS and PFOA concentrations were lower in comparison to previous reports from other countries. The present study showed the application of our reliable method to determine PFOS and PFOA in biological samples in order to monitor the human exposure of both chemicals in Thailand.

Background: The prolonged situation of the COVID-19 pandemic, with the emergence of new variants of SARS-CoV-2, not only imposes a financial burden on healthcare supports but also contributes to the issue of medication shortages, particularly in countries with limited access to medical resources or developing countries. To provide an alternative therapeutic approach during this crisis, there is an increasing research that has investigated the potential uses of Andrographis paniculata in supporting the application of herbal medicine for COVID-19. Purpose: This study aimed to investigate the safety profiles and clinical pharmacokinetics, specifically focusing on dose proportionality of the four major active diterpenoids of Andrographis paniculata aqueous extract following oral administration of two different high doses of andrographolide. Methods: The participants received the aqueous extract capsules equivalent to 60 or 120 mg of andrographolide; and as multiple doses administered three times daily, calculated as 180 or 360 mg/day of andrographolide. Safety evaluation was assessed following the oral administration of the multiple doses. Results: The results indicated a dose-dependent effect observed between the respective two doses. A twofold increase in the dose of the extract demonstrated twofold higher plasma concentrations of the four major parent compounds; 1) andrographolide, 2) 14-deoxy-11, 12-didehydroandrographolide, 3) neoandrographolide, and 4) 14-deoxyandrographolide, as well as their conjugated metabolites. The observed diterpenoids are biotransformed partly through a phase II metabolic pathway of conjugation, thus reducing in the parent compounds in the plasma and existing the majority as conjugated metabolites. These metabolites are then excreted through the hepatobiliary system and urinary elimination. For the results of the safety evaluation, the occasional adverse events experienced by individuals were of mild intensity, infrequent in occurrence, and reversible to the normal baseline. Safety consideration should be given to the individual patient’s pertinent health conditions when using this extract in patients with hepatic or kidney dysfunction. Clinical Trial Registration: https://www.thaiclinicaltrials.org/show/TCTR20210201005 ; Identifier: TCTR20210201005.

Andrographis paniculata, a medicinal plant in Thailand national list of essential medicines, has been proposed for treatment of patients with mild to moderate coronavirus disease 2019. This study aims to develop a highly selective and sensitive liquid chromatography triple quadrupole tandem mass spectrometry method for quantitative determination of major diterpenoids in plasma and urine with application in pharmacokinetics. Chromatographic separation was performed on C18 column using a gradient mobile phase of water and acetonitrile. Mass spectrometry was analyzed using multiple reaction monitoring with negative ionization mode. This validated analytical method was very sensitive, less time consuming in analysis, and allowed the reliability and reproducibility on its application. The clinical pharmacokinetics was evaluated after single oral administration of A. paniculata extract (calculated as 60 mg of andrographolide). The disposition kinetics demonstrated that major diterpenoids could enter into systemic circulation, but they are mostly biotransformed (phase II) into conjugated glucuronide and sulfate metabolites. These metabolites are predominantly found in plasma and then extremely eliminated, in part through urinary excretion. The successful application of this analytical method supports its suitable uses in further clinical benefits after oral administration of A. paniculata.

Coronavirus disease 2019 (COVID-19) is a present global health crisis that is driving the investigation of alternative phytomedicines for antiviral purposes. The evidence suggests that Andrographis paniculata crude or extract is a promising candidate for treating symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review aims to consolidate the available reports on the disposition kinetics of andrographolide, a main active component of A. paniculata. The second objective of this review is to summarize the available reports on an appropriate oral dosage for the use of andrographolide in upper respiratory tract infections (URTIs) and other viral infectious diseases. The data were collected from the literature on absorption, distribution, biotransformation, and excretion of andrographolide, and information was also obtained from scientific databases about the use of A. paniculata. The finding of this review on pharmacokinetics indicates that andrographolide is slightly absorbed into the blood circulation and exhibits poor oral bioavailability, whereas its distribution process is unrestricted. In the termination phase, andrographolide preferentially undergoes biotransformation partly through phase I hydroxylation and phase II conjugation, and it is then eliminated via the renal excretion and hepatobiliary system. The key summary of the recommended dosage for andrographolide in uncomplicated URTI treatment is 30 mg/day for children and 60 mg/day for adults. The dose for adult patients with pharyngotonsillitis could be increased to 180 mg/day, but not exceed 360 mg/day. Co-treatment with A. paniculata in concert with the standard supportive care for influenza reduced the severity of symptoms, shortened treatment duration, and decreased the risk of developing post-influenza complications. The recommended starting dose for use in patients with mild COVID-19 is 180 mg/day of andrographolide, based on the dose used in patients experiencing a URTI with inflammation. This review is not only applicable for evaluating the appropriate doses of andrographolide for antiviral treatments but also encourages future research evaluating the effectiveness of these recommended dosages during the COVID-19 pandemic.

Andrographis paniculata is an annual herbaceous plant widely used in many East Asian countries to help relieve symptoms of the common cold, fever, and non-infectious diarrhea. It is often co-administered with prescribed drugs. The present work aimed to study the interactive effects of A. paniculata extracts and the cancer chemotherapeutic drug, 5-Flurouracil (5-FU), on the expression of four common drug metabolizing cytochrome P450 s (CYP450), including CYP1A2, CYP3A4, CYP2C9, and CYP2D6, in human hepatocellular carcinoma HepG2 cells. Two different types of A. paniculata extracts were tested, the ethanolic extract at the first true leaf stage (FTLEE) and the water extract at the mature leaf stage (MLWE), along with their major phytochemical compound, andrographolide (AP1). The results showed that FTLEE, MLWE, and AP1 sensitized HepG2 cells to the cytotoxicity of 5-FU. Western Blotting assay demonstrated that both extracts and AP1 single treatments decreased CYP2C9 and CYP2D6 but increased CYP3A4 levels. 5-FU single treatment reduced the level of CYP1A2 and CYP2D6. Combination of 5-FU only with FTLEE produced an increase in CYP1A2 level compared to 5-FU treatment alone. Combination of either extracts or AP1 with 5-FU produced a further reduction of CYP2D6 levels. The data suggest the influence of harvesting stage of A. paniculata on CYP1A2 induction, and the synergistic effect of A. paniculata and 5-FU on CYP2D6 reduction. The combinations of A. paniculata with anti-cancer drugs should be critically considered. However, the interactive effects of A. paniculata extracts or AP1 with 5-FU on CYP450 s need more preclinical studies.

Paraquat (1,1'-dimethyl, 4,4'-bipyridinium dichloride; PQ), a commonly used herbicide worldwide, is both toxic and mutagenic. The mutagenic effect of PQ stems from its ability to redox-cycle, generating oxidative stress and subsequently oxidative DNA damage, which miscodes when replication is attempted. Andrographolide (AP1), the major constituent in the leaves of the herbaceous plant Andrographis paniculata, is a diterpenoid with reported antioxidant activity. The present study employed the mammalian cell line AS52 to investigate the protective effect of AP1 against PQ-induced mutagenesis. AP1 induced cytotoxicity in AS52 cells in a dose-dependent manner (IC50 = 15.7 µM), which allowed the selection of a non-lethal dose for the mutagenesis studies. While PQ was mutagenic in AS52 cells as evidenced by the increased levels of 6-TGr mutants, AP1 by itself did not increase the mutation frequency. However, co-treatment with AP1 (1-5 µM) or the antioxidant N-acetylcysteine (2 mM) almost completely counteracted the mutagenicity of PQ (10-100 µM) in AS52 cells. Taken together, these findings suggest that AP1, and likely by extension, A. paniculata extracts, are effective antioxidants that can protect against PQ-induced mutations, and thus could be a promising alternative treatment for PQ poisoning.

This initial study aimed to determine the concentrations of perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) in seafood, bottled drinking water, and surface and tap water collected from Map Ta Phut Industrial Estate in Rayong province, Thailand. Samples were collected during dry (January) and wet (June) seasons, 2019. The perfluorinated compounds were cleaned up by solid phase extraction and analysed by ultra-performance liquid chromatography-tandem mass spectrometry with stable isotopic labelled internal standards (13C8-PFOS and 13C8-PFOA). This study reports concentrations of PFOS and PFOA in seafood at levels between 29-6724 and <48-421 ng/kg wet weight, respectively. Surface water samples from rivers and the coastal sea had PFOS and PFOA between 0.60-465.65 and <0.25-59.29 ng/L, respectively. Contamination of PFOS and PFOA in bottled drinking water (<0.125-0.454 and <0.25-0.621 ng/L, respectively) did not exceed the USEPA standard of 70 ng/L. Concentrations of PFOS and PFOA in seafood and water samples between seasons did not show any definite trend. Seafood dietary assessments of PFOS exposure in the seafood eater population raised a health concern, as the exposure exceeded the latest EFSA tolerable weekly intake value for PFAS mixtures (4.4 ng/kg body weight/week). Therefore, environmental and food samples from Map Ta Phut area should be closely monitored to ensure the safety of people living in and around this area.

Rice cultivation under flooded conditions enhances arsenic (As) solubility and favors As accumulation in rice grain that poses an indisputable threat to human health worldwide. The reduction of sulfur may induce processes that decrease As solubility, but its impact on rice grain As species remains unresolved. Herein, we investigated the influence of sulfur (S)-containing materials, including chicken manure and elemental sulfur powder on As accumulation and speciation in rice grain as well as the dynamics of the porewater chemistry and solid-phase As solubility throughout the entire growth stage under continuous flooding and intermittent flooding conditions in pot experiments. The S amendments (200 mg S kg(-1)) to the soil significantly decreased inorganic As in rice grain under continuous flooding (-65% decrease) as well as under intermittent flooding (-70% decrease). The chicken manure amendment promoted sulfur reduction and enhanced dissolvable Mn, Fe, and As at an earlier growth stage. The sequential extraction results corroborated a decrease in the soluble and exchangeable As (F1) and an increase in residual As (F5) fractions in the S-amended treatments. Solubility data suggested that As adsorption onto Fe oxides was the primary mechanism controlling As solubility rather than the formation of As-Fe sulfides. Porewater As, considered to represent the most bioavailable As fraction, failed to explain the grain As accumulation. The time-averaged concentration of oxalate-extractable As explained grain arsenite best, suggesting that poorly crystalline Fe oxides may be the primary dissolvable reactive phases that control As bioavailability in the soil-rice system. Our results suggest that the application of S-containing soil amendments can effectively decrease inorganic As accumulation in rice grains grown under the flooded conditions, which are most widely applied in paddy rice production. (C) 2021 Elsevier B.V. All rights reserved.

Germinated brown rice (GBR) with unpolishing, soaking, and germinating processes can improve the texture, flavor, and nutritional value, including GABA and phenolic contents. The effect of GBR was first investigated in vascular cognitive impaired mice and glutamate-induced toxicity in HT22 cells with respect to standard pure GABA. Feeding mice with GBR for 5 weeks showed neuroprotection. In this study, the modified bilateral common carotid artery occlusion mice model was mild but a significant difference in cognitive impairment was still shown. Like pure GABA, GBR decreased cognitive deficits in memory behavioral tests and significantly attenuated hippocampal neuronal cell death at P < 0.001. Similarly to 0.125 μM of GABA, 100 μg/mL of GBR increased HT22 cell viability after glutamate toxicity. GBR affected less apoptotic cell death and less blocking by the GABAA antangonist bicuculline in comparison to GABA. When the results are taken together, the underlying mechanism of GBR protection may mediate though the GABAA receptor and its phenolic contents.

Exposure to arsenic (As) through rice consumption potentially threatens millions of people worldwide. Understanding is still lacking the recycling impacts of rice residues on As phytoavailability in paddy soils and is of indisputable importance in providing a sustainable and effective measure to decrease As accumulation in rice grain. Herein, we examined the effects of rice husk biochar (RHB) and rice husk ash (RHA) on As grain speciation, and As dynamics in the soil porewater and solid-phase fractions. The results corroborated that both the RHB and RHA (0.64% w/w) treatments significantly (p < 0.05) decreased inorganic As accumulation in rice grain to 027-0.29 mg k(-1), which was below the maximum inorganic As level in husked rice (0.35 mg kg(-1)) established by the Codex. The residual phase (F6 = 90% of total soil As) as quantified by the sequential extraction was the dominant As pool; the fractions were subsequently transformed into several As pools associated with soluble and exchangeable (F1), organically bound (F2), Mn oxides (F3), poorly crystalline (F4) and crystalline (F5) Fe oxides during the rice growing periods. The Si-rich amendments enhanced the residual phase formation upon soil flooding, which decreased the As availability to rice plant. The inorganic grain-As concentrations were well explained by the soil-extractable As concentrations in the F2, F3, F5, and F6 fractions. The pore-water analysis indicated that Mn oxides were important sources and sinks for As released to the soil solution. Our findings shed light on the beneficial role of RHB and RHA in alleviating inorganic As uptake in paddy rice. (C) 2019 Elsevier B.V. All rights reserved.

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.

Human exposure to environmental contaminants such as persistent chlorinated organics, heavy metals, pesticides, phthalates, flame retardants, electronic waste and airborne pollutants around the world, and especially in Southeast Asian regions, are significant and require urgent attention. Given this widespread contamination and abundance of such toxins as persistent organic pollutants (POPs) in the ecosystem, it is unlikely that remediation alone will be sufficient to address the health impacts associated with this exposure. Furthermore, we must assume that the impact on health of some of these contaminants results in populations with extraordinary vulnerabilities to disease risks. Further exacerbating risk; infectious diseases, poverty and malnutrition are common in the Southeast Asian regions of the world. Thus, exploring preventive measures of environmental exposure and disease risk through new paradigms of environmental toxicology, optimal and/or healthful nutrition and health is essential. For example, folic acid supplementation can lower blood arsenic levels, and plant-derived bioactive nutrients can lower cardiovascular and cancer risks linked to pollutant exposure. Data also indicate that diets enriched with bioactive food components such as polyphenols and omega-3 polyunsaturated fatty acids can prevent or decrease toxicant-induced inflammation. Thus, consuming healthy diets that exhibit high levels of antioxidant and anti-inflammatory properties, is a meaningful way to reduce the vulnerability to non-communicable diseases linked to environmental toxic insults. This nutritional paradigm in environmental toxicology requires further study in order to improve our understanding of the relationship between nutrition or other lifestyle modifications and toxicant-induced diseases. Understanding mechanistic relationships between nutritional modulation of environmental toxicants and susceptibility to disease development are important for both cumulative risk assessment and the design and implementation of future public health programs and behavioral interventions.

Despite its nutritional values, rice also contains arsenic. There has been increasing concern about health implications associated with exposure to arsenic through rice consumption. The present study evaluated arsenic accumulation and its speciation in selected organs of Wistar rats after 28 day repeated oral administrations of polished or unpolished rice and their control arsenic compounds (sodium arsenite or dimethylarsinic acid; DMA). Only the treatment of sodium arsenite (2 μg/kg body weight), significantly increased total arsenic concentrations in blood when compared to the distilled water control group. In all groups, total arsenic concentrations were highest in kidney (1.54-1.90 mg/kg) followed by liver (0.85-1.52 mg/kg), and the predominant arsenic form in these organs was DMA. However, there was no significant difference in arsenic accumulation in the measured organs among the control and rice-treated groups. Therefore, the repeated 28 day administration of arsenic-contaminated rice did not cause significant arsenic accumulation in the animal organs.

Hijiki seaweed (Hijikia fusiformes) contains high levels of inorganic arsenic, a known carcinogen. However, scientific reports on carcinogenic risks associated with the consumption of this seaweed are limited. This study investigated the effects of seaweed extracts contaminated with arsenic on two colorectal cancer cell lines. Two seaweed extracts, including Hijiki and red seaweed, induced H508 but not HT29 cell proliferation. Growth induction of H508 cells after treatments with Hijiki and sodium arsenite at concentrations equivalent to arsenic found in Hijiki was observed by both MTT and BrdU assays. Hijiki and sodium arsenite induced epidermal growth factor receptor (EGFR) and ERK1/2 activations. AG1478, an EGFR inhibitor, decreased the activation of EGFR and ERK1/2 induced by Hijiki and sodium arsenite. U0126, an ERK1/2 upstream inhibitor, and atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, but not AG1478 completely inhibited the proliferative effect of Hijiki. Altogether, the results suggest that the presence of arsenic in seaweed may partly contribute to the proliferation of colorectal cancer cells. EGFR-dependent, and -independent ERK1/2 signaling pathways, and mAChR may be involved in the growth stimulation by Hijiki. These results raise concern regarding the potential colorectal cancer risks from regular consumption of Hijiki containing high contents of inorganic arsenic.

Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata, 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person.