Comparison of diterpenoid contents and dissolution profiles of selected Andrographis paniculata crude and extract capsules.

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.

Comparative pharmacokinetics and safety evaluation of high dosage regimens of Andrographis paniculata aqueous extract after single and multiple oral administration in healthy participants.

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.

Sodium arsenite exposure impairs B cell proliferation and enhances vascular inflammation in Plasmodium berghei mouse model.

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.

In vitro antifungal activities of longan (Dimocarpus longan Lour.) seed extract.

Longan, Dimocarpus longan Lour., contains polyphenolic compounds which exhibit several pharmacological properties. This study aims to evaluate antifungal activities of longan fruit extract in comparison to its active compounds. The results showed that longan seed exhibited antifungal activity against the opportunistic yeasts (Candida species and Cryptococcus neoformans). In contrast, longan pulp and whole fruit did not demonstrate any inhibitory effects. Ellagic acid showed the most potent antifungal activity followed by corilagin and gallic acid, respectively. Ellagic acid inhibited Candida parapsilosis and C. neoformans more effectively than Candida krusei and also some Candida albicans clinical strains. Baidam cultivar possessed higher antifungal activity (MIC=500-4000 µg/ml) as it contained higher contents of ellagic acid and gallic acid than Edor (MIC=1000-8000 µg/ml). For antibacterial activity, only corilagin and gallic acid possessed weak to moderate inhibitory effects against Staphylococcus aureus and Streptococcus mutans, respectively. Longan seed was then applied in the oral care products. Longan effervescent granule (5% extract) significantly reduced adhesion of C. albicans to acrylic strips. Mouthwash containing 0.5% extract exhibited good antifungal activity compared to a commercial product. These findings indicated that longan seed extract and its polyphenolic compounds can be used as an antifungal agent in oral care products for the treatment of opportunistic yeast infection.