Search

Abstract 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.

Coronaviral disease 2019 (COVID-19) is a recent pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there are still cases of COVID-19 around the world that can develop into persistent symptoms after discharge. The constellation of symptoms, termed long COVID, persists for months and can lead to various diseases such as lung inflammation and cardiovascular disease, which may lead to considerable financial burden and possible risk to human health. Moreover, the molecular mechanisms underlying the post-pandemic syndrome of COVID-19 remain unclear. In this study, we aimed to explore the molecular mechanism, disease association, and possible health risks in convalescent COVID-19 patients. Gene expression data from a human convalescent COVID-19 data set was compared with a data set from healthy normal individuals in order to identify differentially expressed genes (DEGs). To determine biological function and potential pathway alterations, the GO and KEGG databases were used to analyze the DEGs. Disease association, tissue, and organ-specific analyses were used to identify possible health effects. A total of 250 DEGs were identified between healthy and convalescent COVID-19 subjects. The biological function alterations identified revealed cytokine interactions and increased inflammation through NF-κB1, RELA, JUN, STAT3, and SP1. Interestingly, the most significant pathways were cytokine-cytokine receptor interaction, altered lipid metabolism, and atherosclerosis that play a crucial role in convalescent COVID-19. In addition, we also found pneumonitis, dermatitis, and autoimmune diseases. Based on our study, convalescent COVID-19 is associated with inflammation in a variety of organs that could lead to autoimmune and inflammatory diseases, as well as atherosclerosis. These findings are a first step toward fully exploring the disease mechanisms in depth to understand the relationship between post-COVID-19 infection and potential health risks. This is necessary for the development of appropriate strategies for the prevention and treatment of long COVID.

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.

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

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.

Objectives: Antibacterial resistance (ABR) is a major global health security threat, with a disproportionate burden on lower-and middle-income countries (LMICs). It is not understood how ‘One Health’, where human health is co-dependent on animal health and the environment, might impact the burden of ABR in LMICs. Thailand's 2017 “National Strategic Plan on Antimicrobial Resistance” (NSP-AMR) aims to reduce AMR morbidity by 50% through 20% reductions in human and 30% in animal antibacterial use (ABU). There is a need to understand the implications of such a plan within a One Health perspective. Methods: A model of ABU, gut colonisation with extended-spectrum beta-lactamase (ESBL)-producing bacteria and transmission was calibrated using estimates of the prevalence of ESBL-producing bacteria in Thailand. This model was used to project the reduction in human ABR over 20 years (2020–2040) for each One Health driver, including individual transmission rates between humans, animals and the environment, and to estimate the long-term impact of the NSP-AMR intervention. Results: The model predicts that human ABU was the most important factor in reducing the colonisation of humans with resistant bacteria (maximum 65.7–99.7% reduction). The NSP-AMR is projected to reduce human colonisation by 6.0–18.8%, with more ambitious targets (30% reductions in human ABU) increasing this to 8.5–24.9%. Conclusions: Our model provides a simple framework to explain the mechanisms underpinning ABR, suggesting that future interventions targeting the simultaneous reduction of transmission and ABU would help to control ABR more effectively in Thailand.

Aim Insufficient 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.Objective This 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.Methods An 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.Results Pharmacokinetics 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 µg/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 µg/L for single and repeated doses, respectively). Safety evaluation revealed mild, transient adverse events, but all parameters remained within normal ranges.Conclusions This 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.